148: Medications Used in the Neonatal Intensive Care Unit

This section provides a description of medications used in the contemporary care of sick newborn infants.^a It is not intended to be an exhaustive list of all drugs available for infants, nor is it intended to be an in-depth source of information about neonatal pharmacology. Readers are encouraged to consult with their institutional pharmacists regarding issues of pharmacokinetics, drug interactions, drug elimination and metabolism, and monitoring drug serum levels. Information on medications and breast-feeding and pregnancy can be found in Chapter 149.

When the designations of neonate/newborn or infant are used for medication doses, it refers to the following:

• Neonate/Newborn: Birth to 28 days postnatal age.

• Infant: >28 days (1 month) to 1 year of age.

INDICATIONS AND USE: Analgesic, antipyretic.

ACTIONS: Analgesic effect—inhibition of prostaglandin synthesis in the central nervous system (CNS) and peripherally, blocking pain impulse generation. Antipyretic effect—inhibition of hypothalamic heat-regulating center.

DOSAGE: PO, PR.

• Preterm infants 28–32 weeks: 10–12 mg/kg/dose PO every 6–8 hours or 20 mg/kg/dose PR every 12 hours. Maximum daily dose: 40 mg/kg.

• Preterm infants 33–37 weeks; term neonates <10 days: 10–15 mg/kg/dose PO every 6 hours or 30 mg/kg PR loading dose; then 15 mg/kg/dose every 8 hours. Maximum daily dose: 60 mg/kg.

• Term infants ≥10 days: 10–15 mg/kg/dose PO every 4–6 hours or 30 mg/kg PR loading dose; then 20 mg/kg/dose every 6–8 hours. Maximum daily dose: 90 mg/kg.

ADVERSE EFFECTS: Rash, blood dyscrasias (neutropenia, leukopenia, and thrombocytopenia), and hepatic necrosis with overdose; renal injury may occur with chronic use.

PHARMACOLOGY: Extensively metabolized by the liver primarily by sulfonation, and by glucuronidation to a much lesser extent. Excretion by the kidney with elimination half-life: term infants—~3 hours, preterm infants >32 weeks—5 hours, and in premature infants <32 weeks—up to 11 hours. Prolonged elimination with liver dysfunction.

COMMENTS: Rectal administration may result in inaccurate dosing. Prophylactic use during vaccination may result in potential reduction in antibody response. Beginning 2011 into 2012—transition to one pediatric concentration 160 mg/5 mL and elimination of 80 mg/0.8 mL infant drops per U.S. Food and Drug Administration (FDA) recommendations. N-acetylcysteine is the antidote of choice for acetaminophen poisoning.

INDICATIONS AND USE: Reduce intraocular pressure in glaucoma; an anticonvulsant in refractory neonatal seizures; decrease cerebrospinal fluid (CSF) production in posthemorrhagic hydrocephalus; treatment of renal tubular acidosis.

ACTIONS: Competitive, reversible, carbonic anhydrase inhibitor; increases renal excretion of sodium, potassium, bicarbonate, and water, resulting in the production of acidosis. Decreases the production of aqueous humor and reduces abnormal discharge from central nervous system (CNS) neurons.

DOSAGE: IV, PO.

• Glaucoma: 8–30 mg/kg/day PO divided every 8 hours or IV 20–40 mg/kg/day divided every 6 hours; maximum 1 gram/day.

• Anticonvulsant: 4–16 mg/kg/day PO divided every 6–8 hours not to exceed 30 mg/kg/day or 1 gram/day.

• Alkalinize urine: 5 mg/kg/dose PO 2–3 times over 24 hours.

• Decrease CSF production: 5 mg/kg/dose IV/PO every 6 hours; increased by 25 mg/kg/day to a maximum of 100 mg/kg/day. Furosemide has been used in combination.

ADVERSE EFFECTS: Gastrointestinal (GI) irritation, transient hypokalemia, hyperchloremic metabolic acidosis, growth retardation, bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia, drowsiness, and paresthesia.

PHARMACOLOGY: Unchanged in urine. Half-life is 4–10 hours.

COMMENTS: Currently, rarely used in neonates; a 1998 study failed to show efficacy in slowing the progression of posthemorrhagic hydrocephalus in neonates and infants. In neonates, use is limited to the treatment of glaucoma. Used as an adjunct to other medications in refractory seizures. Tolerance to diuretic effect may occur with long-term use. Oral solution may be compounded by using tablets.

ACTION AND SPECTRUM: Treatment and prophylaxis of herpes simplex virus (HSV-1 and HSV-2) infections, herpes simplex encephalitis, herpes zoster infections, and varicella-zoster infections.

DOSAGE: PO, IV.

• Herpes simplex (based on AAP Red Book, 2012):

  • Neonatal: 20 mg/kg/dose IV every 8 hours for 14–21 days. Treat central nervous system (CNS) infections for 21 days and all other infections for 14 days. Reduce dosing interval to every 12 hours in neonates <30 weeks' gestational age.

  • Dosing in renal impairment:

    • Serum creatinine 0.8–1.1 mg/dL: 20 mg/kg IV every 12 hours.

    • Serum creatinine 1.2–1.5 mg/dL: 20 mg/kg IV every 24 hours.

    • Serum creatinine >1.5 mg/dL: 10 mg/kg IV every 24 hours.

• Herpes zoster (shingles):

  • Infants and children: 10 mg/kg/dose IV every 8 hours for 7–10 days. In immunocompromised host, the AIDS information guidelines recommend duration of therapy of 10–14 days.

• Varicella-zoster (chickenpox) in immunocompromised host:

  • Infants <1 year: 10 mg/kg/dose IV every 8 hours for 7–10 days.

ADVERSE EFFECTS: Generally well tolerated. Thrombophlebitis and inflammation of injection site. Acute renal failure/acute kidney injury, increased blood urea nitrogen (BUN) and serum creatinine, nephrotoxicity. Increased liver transaminases. Neutropenia, thrombocytopenia, anemia, thrombocytosis, leukocytosis, and neutrophilia. Neutropenia may necessitate reduction in dose or treatment with granulocyte colony-stimulating factor (G-CSF) if absolute neutrophil count (ANC) remains <500/mm³. Adequate hydration and infusion rate of at least 1 hour reduces risk of transient renal impairment and crystalluria.

PHARMACOLOGY: Inhibits DNA synthesis and viral replication. Oral absorption is 15–30%, cerebrospinal fluid (CSF) concentrations are 50% of serum and primarily excreted by the kidneys.

COMMENTS: Infuse over at least 1 hour; concentration <7 mg/mL, 5 mg/mL is preferred. Do not refrigerate. Monitor complete blood cell count (CBC) and renal and liver function.

INDICATIONS AND USE: Acute treatment of sustained paroxysmal supraventricular tachycardia for conversion to normal sinus rhythm.

ACTIONS: A purine nucleoside that slows conduction time through the atrioventricular (AV) node and interrupts reentry pathways through the AV node to restore normal sinus rhythm. Effects are mediated by depression of calcium slow-channel conduction, an increase in potassium conductance, and possibly indirect antiadrenergic effects.

DOSAGE: IV.

• 0.05–0.2 mg/kg by rapid IV push over 1–2 seconds. Repeat bolus doses at 2-minute intervals by increasing increments of 0.05–0.1 mg/kg until sinus rhythm is achieved or until a maximum dose of 0.3 mg/kg is reached. Infuse as close as possible to IV site and immediately flush IV with saline to ensure dose enters circulation. For doses <0.2 mL, prepare dilution using normal saline (NS) to final concentration of 300 mcg/mL.

ADVERSE EFFECTS: Contraindicated in heart block. Transient arrhythmias, flushing, dyspnea, and hypotension. May cause bronchoconstriction; use with caution in patients with history of bronchospasm.

PHARMACOLOGY: Rapid onset of action; half-life is <10 seconds; duration is 20–30 seconds.

COMMENTS: Methylxanthines (caffeine and theophylline) are competitive antagonists; larger adenosine doses may be required.

INDICATIONS AND USE: Treatment of hypovolemia, maintenance of cardiac output in shock, plasma volume expansion, hypoproteinemia associated with generalized edema or decreased intravascular volume; acute nephrotic syndrome in premature infants. Not recommended for initial volume expansion; use isotonic crystalloid solutions—0.9% NaCl or lactated Ringer's (Pediatric Advanced Life Support [PALS] and Neonatal Resuscitation Program [NRP] guidelines).

ACTIONS: Increases intravascular oncotic pressure, which results in a mobilization of fluid from the interstitial spaces into the intravascular space.

DOSAGE: IV.

• Neonates, infants, and children: 0.5–1 gram/kg IV (or 10–20 mL/kg of 5% IV bolus) repeated as necessary. Maximum: 6 grams/kg/day. Five percent solutions should be used in hypovolemic or intravascularly depleted patients; 25% solutions should be used in cases of fluid or sodium restriction.

• Hypoproteinemia in neonates: Dose may be added to hyperalimentation solutions; however, may increase potential for growth of bacteria or fungi.

ADVERSE EFFECTS: Rapid infusion may cause vascular overload and precipitation of congestive heart failure or pulmonary edema. The 25% solution should be used with extreme caution in premature neonates due to increased risk of intraventricular hemorrhage.

PHARMACOLOGY: Duration of volume expansion is ~24 hours.

COMMENTS: Refer to individual product information for use of correct in-line IV filter. A 5% concentration is osmotically equivalent to equal volume of plasma, and 25% concentration is osmotically equivalent to 5 times its volume of plasma. If unavailable, 5% solutions can be prepared by diluting the 25% solution with normal saline (NS) or 5% dextrose in water (D5W). Do not use sterile water to prepare dilution; this may cause hypotonic-associated hemolysis, which can be fatal.

INDICATIONS AND USE: Prevention and treatment of bronchospasm; bronchodilator in respiratory distress syndrome (RDS) and bronchopulmonary dysplasia/chronic lung disease (BPD/CLD). Used for treatment of hyperkalemia.

ACTIONS: Primarily β₂-adrenergic stimulation (bronchodilation and vasodilation) with minor β₁ stimulation (increased myocardial contractility and conduction).

DOSAGE: Inhalation, nebulization.

• Nebulization: 0.1–0.5 mg/kg/dose (minimum of 2.5 mg) every 2–6 hours as needed.

• Inhalation: Metered dose inhaler (MDI) 90 mcg/spray: 1–2 puffs every 2–6 hours as needed.

ADVERSE EFFECTS: Tachycardia, tremors, central nervous system (CNS) stimulation, hypokalemia, hyperglycemia, and hypertension.

COMMENTS: Duration of action is ~2–5 hours. Titrate dose according to the effect on heart rate and improvement in respiratory symptoms.

INDICATIONS AND USE: Any clinical condition in which blood flow must be maintained through the ductus arteriosus to sustain either pulmonary or systemic circulation until corrective or palliative surgery can be performed. Examples are pulmonary atresia, pulmonary stenosis, tricuspid atresia, transposition of the great arteries, aortic arch interruption, coarctation of the aorta, and severe tetralogy of Fallot (TOF).

ACTIONS: Causes vasodilation of all vascular smooth muscle including the ductus arteriosus.

DOSAGE: IV.

• Initial: 0.05–0.1 mcg/kg/minute by continuous infusion. Gradually titrate to maintain acceptable oxygen levels without adverse effects. Use the lowest rate to maintain improved oxygenation response.

• Maintenance: 0.01–0.4 mcg/kg/minute.

ADVERSE EFFECTS: See black box warning. May cause gastric outlet obstruction and reversible cortical proliferation of the long bones after prolonged treatment. Hypotension, cutaneous vasodilation, bradycardia, inhibits platelet aggregation, hypoventilation, seizure-like activity, jitteriness, temperature elevation, hypocalcemia, hypoglycemia.

COMMENTS: Decreased response after 96 hours of infusion. Maximal improvement in Pao₂, usually within 30 minutes in cyanotic infants and 1.5–3 hours in acyanotic infants. Use cautiously in infants with bleeding tendencies.

INDICATIONS AND USE: Used to restore patency of occluded central venous catheters and for the dissolution of large-vessel thrombus (systemic use). (See also Chapters 79 and 87.)

ACTIONS: Alteplase is a thrombolytic. It enhances conversion of plasminogen to plasmin, which then cleaves fibrin, fibrinogen, factor V, and factor VIII, resulting in clot dissolution.

DOSAGE: IV.

• Occluded central venous catheter:

  • Manufacturer's recommendations (CathFlo, Activase): Postnatal age ≥14 days, use 1 mg/mL; instill a volume equal to 110% of the internal lumen volume; do not exceed 2 mg in 2 mL; leave in lumen for up to 2 hours and then aspirate out of catheter. May repeat process if lumen is still occluded. Check the catheter product literature or manufacturer for catheter volume.

  • Chest, 2008 dosing recommendations (Monagle et al, 2008): 0.5 mg diluted in a volume of normal saline (NS) equal to the catheter lumen internal volume; instill over 1–2 minutes; dwell time is 1–2 hours. Aspirate solution from catheter and then flush catheter with NS.

• Dissolution of large vessel thrombus (systemic use):

  • Dose is controversial and optimal dose has not been established. May consider fresh frozen plasma (FFP) prior to administration of alteplase.

  • Chest, 2008 recommendations (Monagle et al, 2008): 0.1–0.6 mg/kg/hour for 6 hours. Dose must be titrated to effect; some patients require longer or shorter duration of therapy.

ADVERSE EFFECTS: The risk of complications increases at rates >0.4 mg/kg/hour. Systemic use is not recommended with preexisting intraventricular hemorrhage or cerebral ischemic changes. Bleeding from venipuncture sites may occur. During the treatment of occluded central venous catheter, bleeding may occur if excess alteplase is inadvertently injected into the systemic circulation. Excessive pressure during instillation may force clot into systemic circulation.

COMMENTS: Increases risk of bleeding in infants concurrently on heparin, warfarin, or indomethacin. Monitor prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and fibrin split products prior to the initiation of therapy and at least daily through the duration of therapy. Fibrinogen levels should be maintained >100 mg/dL and platelets >50,000/mm³.

ACTION AND SPECTRUM: Active against gram-negative bacteria, including most Pseudomonas, Klebsiella, Enterobacter, Proteus, Escherichia coli, and Serratia spp. No activity against anaerobic organisms. Reserve for treatment of gram-negative organisms resistant to gentamicin and tobramycin. Treatment of susceptible mycobacterial organisms.

DOSAGE: IM, IV. Infuse over 30 minutes. Dosage should be monitored and adjusted by use of pharmacokinetics. Initial empirical dosing based on body weight:

• Neonates 0–4 weeks and <1.2 kg: 7.5 mg/kg/dose every 18–24 hours.

• Postnatal age <7 days:

  • 1.2–2 kg: 7.5 mg/kg/dose every 12 hours.

  • >2 kg: 7.5–10 mg/kg/dose every 12 hours.

• Postnatal age ≥7 days:

  • 1.2–2 kg: 7.5–10 mg/kg/dose every 8–12 hours.

  • >2 kg: 10 mg/kg/dose every 8 hours.

• Infants and children: 15–22.5 mg/kg/day divided every 8 hours; some patients may require higher doses of 30 mg/kg/day divided every 8 hours.

• Treatment of nontuberculous mycobacterial infection: 15–30 mg/kg/day divided every 12–24 hours as a part of a multidrug regimen.

PHARMACOLOGY: Displays concentration-dependent killing; bactericidal activity. Renal elimination (glomerular filtration); half-life is 4–8 hours; volume of distribution is 0.6 L/kg.

ADVERSE EFFECTS: Possible nephrotoxicity and ototoxicity. Toxicities may be potentiated when used with furosemide or vancomycin, and neuromuscular blockade is increased if used with pancuronium or with coexisting hypermagnesemia.

COMMENTS: Monitor serum levels when treating >48 hours, in patients with decreased or changing renal function, with signs of nephrotoxicity or ototoxicity, with concomitant use of other nephrotoxic agents, and in patients who may require higher doses. Adjust the dosage according to serum peak and trough levels. Therapeutic peak level is 15–40 mcg/mL depending on type of infection, and trough level is <5–8 mcg/mL. Nephrotoxicity is associated with serum trough concentrations >10 mcg/mL; ototoxicity, with serum peak concentrations >35–40 mg/mL (more cochlear damage than vestibular).

INDICATIONS AND USE: To reduce frequency and severity of apnea of prematurity, following extubation or during alprostadil administration. A bronchodilator in the treatment of bronchopulmonary dysplasia/chronic lung disease. Caffeine is more effective and safer for the treatment of apnea of prematurity. Caffeine also has the advantage of once-a-day dosing. Aminophylline/theophylline has greater bronchodilator effects.

ACTIONS: Theophylline (the active component of aminophylline) causes relaxation of bronchial smooth muscle; increases the force of contraction of the diaphragmatic muscles; dilates the pulmonary, coronary, and renal arteries; causes mild diuretic action; causes increased sensitivity of the central nervous system (CNS) medullary respiratory centers to CO₂; stimulates central respiratory drive and peripheral chemoreceptors; and increases sensitivity to catecholamines resulting in increased cardiac output and improved oxygenation. Aminophylline is ~80% theophylline. Neonates have a unique ability to convert theophylline to caffeine in a ratio of 1:0.3. Caffeine may account for as much as 50% of the theophylline level.

DOSAGE: PO, IV.

• IV loading dose: 5–8 mg/kg, slowly over 30 minutes. IV maintenance dosage is 1.5–3.0 mg/kg/dose every 8–12 hours starting 8–12 hours after loading dose.

• PO (use immediate-release dosage form) loading dose: Same as IV. PO maintenance dose as theophylline is 4–22 mg/kg/day divided every 6–8 hours. Older infants may need higher doses as clearance rate increases with increased postnatal age, possibly up to 25–30 mg/kg/day.

ADVERSE EFFECTS: Hyperglycemia, dehydration, diuresis, and feeding intolerance. CNS effects include jitteriness, hyperreflexia, and seizures. Most common side effects are cardiovascular with tachycardia (heart rate ≥180 beats/min) and other tachyarrhythmias.

COMMENTS: Therapeutic levels—apnea 6–14 mcg/mL; bronchospasm 10–20 mcg/mL. Toxicity usually >20 mcg/mL. Monitor serum levels at a peak 1 hour after IV dosing or 2 hours after PO dosing. Take trough levels 30 minutes before next dose. Serum levels should be monitored any time toxicity is suspected or when apneic episodes are increased.

INDICATIONS AND USE: Treatment of resistant life-threatening ventricular arrhythmias unresponsive to other agents; prevention and suppression of supraventricular arrhythmias (especially those associated with Wolff-Parkinson-White [WPW] syndrome) and postoperative junctional ectopic tachycardia (JET).

ACTIONS: An iodinated benzofuran that prolongs the action potential and increases the effective refractory period. It decreases afterload (causes peripheral and coronary vasodilation), and demonstrates α- and β-blocking properties and calcium channel inhibition. It slows the heart rate (decreases A-V node and sinus node conduction–negative inotropic effects).

DOSAGE: IV. Limited data are available. Generally not first line due to high incidence of adverse effects. Recommend consultation with pediatric cardiologist prior to use.

• IV loading dose: 5 mg/kg over 30–60 minutes; do not exceed 0.25 mg/kg/minute unless clinically indicated; central venous access is recommended. May repeat dose up to total loading dose of 15 mg/kg.

• Maintenance: 5 mcg/kg/minute gradually increasing as needed to 15 mcg/kg/minute.

• PO loading dose: 10–20 mg/kg/day divided into 2 doses per day for 7–10 days or until adequate control of arrhythmia is achieved or significant adverse effects occur. Reduce dose to 5–10 mg/kg/day given once daily for several weeks. Attempt to reduce dose to lowest possible without the recurrence of arrhythmia: 2.5 mg/kg/day.

ADVERSE EFFECTS: Bradycardia and hypotension (may be related to rate of infusion), proarrhythmias (including torsade de pointes), heart block, congestive heart failure (CHF), and paroxysmal ventricular tachycardia. Amiodarone may cause hypo/hyperthyroidism (may partially inhibit the peripheral conversion of T₄ to T₃; serum T₄, and rT3 concentrations may be increased, and serum T₃ may be decreased). Amiodarone HCl contains 37% iodine by weight and is a potential source of iodine; ~3 mg of inorganic iodine/100 mg of amiodarone is released into the circulation. Elevated liver enzymes, elevated bilirubin. Phlebitis and local injection site irritation: avoid concentrations >2 mg/mL, administer through central vein.

PHARMACOLOGY: Adult data: onset of oral antiarrhythmic effects may take up to 3–6 weeks. Duration of antiarrhythmic effects may persist for 30–90 days or longer following discontinuation of therapy. Protein binding: 96%. Metabolized in liver.

COMMENTS: Potential drug interactions may occur. Amiodarone inhibits certain cytochrome P450 enzymes and may increase serum levels of digoxin, flecainide, lidocaine, theophylline, procainamide, quinidine, warfarin, and phenytoin. To avoid toxicities with these agents, dosage reduction and serum concentration monitoring is recommended. Dosage reductions of 30–50% have been recommended. Concurrent administration of amiodarone with β-blockers, digoxin, or calcium channel blockers may result in bradycardia, sinus arrest, and heart block.

ACTION AND SPECTRUM: Antifungal agent that acts by binding to sterols and disrupting the fungal cell membranes. Broad spectrum of activity against Candida spp. and other fungi.

DOSAGE: IV, intrathecal, intraventricular.

• Conventional amphotericin B:

  • Initial dose: 0.5 mg/kg IV over 2–6 hours. Use a 0.1 mg/mL concentration in 5% dextrose in water (D5W). Incompatible with NaCl.

  • Maintenance: 1–1.5 mg/kg IV every 24 hours for 2–6 weeks or longer, but a lower dose may suffice. Infuse over 2–6 hours, but infusion over 1–2 hours may be used if tolerated.

  • Intrathecal or intraventricular: Reconstitute with sterile water at 0.25 mg/mL; dilute with cerebrospinal fluid (CSF) and reinfuse. Usual dose: 25–100 mcg every 48–72 hours; increase to 500 mcg as tolerated.

• Liposomal amphotericin B:

  • Concentrates in liver and spleen, but penetrates the central nervous system (CNS) less than conventional amphotericin B. Used when refractory to or intolerant of conventional amphotericin B.

  • 5–7 mg/kg/dose IV infused over 2 hours. May be diluted with D5W, D10W, or D20W to a final concentration of 1–2 mg/mL; concentrations of 0.2–0.5 mg/mL may be needed to provide sufficient volume for infusion.

• Amphotericin B lipid complex:

  • Used when refractory to or intolerant of conventional amphotericin B. Less nephrotoxic.

  • 5 mg/kg/dose IV every 24 hours infused over 2 hours. Dilute with D5W to final concentration of 1 mg/mL; a maximum concentration of 2 mg/mL. Manufacturer recommends that an in-line filter should not be used.

PHARMACOKINETICS: Slow renal excretion.

ADVERSE EFFECTS: Fewer adverse effects in neonates as compared to adults. May cause fever, chills, vomiting, thrombophlebitis at injection sites, renal tubular acidosis, renal failure, hypomagnesemia, hypokalemia, bone marrow suppression with reversible decline in hematocrit, hypotension, hypertension, wheezing, and hypoxemia.

COMMENTS: Protect the solution from light. Monitor serum potassium, magnesium, blood urea nitrogen (BUN), creatinine, and urine output at least every other day until the dosage is stabilized, then every week. Monitor complete blood cell count (CBC) and liver function every week. Discontinue if BUN is >40 mg/dL, serum creatinine is >3 mg/dL, or liver function tests are abnormal.

ACTION AND SPECTRUM: Semisynthetic penicillinase-sensitive penicillin that is bactericidal and acts by inhibiting the late stages of cell wall synthesis. Treatment of susceptible bacterial infections caused by streptococci, pneumococci, enterococci, nonpenicillinase-producing staphylococci, Listeria, meningococci; some strains of Haemophilus influenzae, Proteus mirabilis, Salmonella, Shigella, Escherichia coli, Enterobacter, and Klebsiella; used in combination with an aminoglycoside or cefotaxime in neonates for prevention and treatment of infections due to group B streptococci, Listeria, and E. coli.

DOSAGE: IM, IV, PO (only for children).

• Postnatal age ≤7 days:

  • ≤2 kg: 50 mg/kg/day IM, IV divided every 12 hours. Meningitis: 100 mg/kg/day divided every 12 hours.

  • >2 kg: 75 mg/kg/day IM, IV divided every 8 hours. Meningitis: 150 mg/kg/day divided every 8 hours.

  • Group B streptococcal meningitis: 200–300 mg/kg/day IM, IV divided every 8 hours.

• Postnatal age >7 days:

  • <1.2 kg: 50 mg/kg/day IM, IV divided every 12 hours. Meningitis: 100 mg/kg/day divided every 12 hours.

  • 1.2–2 kg: 75 mg/kg/day IM, IV divided every 8 hours. Meningitis: 150 mg/kg/day divided every 8 hours.

  • >2 kg: 100 mg/kg/day IM, IV divided every 6 hours. Meningitis: 200 mg/kg/day divided every 6 hours.

  • Group B streptococcal meningitis: 300 mg/kg/day IM, IV divided every 6 hours.

• Infants and children:

  • 100–200 mg/kg/day IM, IV divided every 6 hours.

  • Meningitis: 200–400 mg/kg/day IM, IV divided every 6 hours. Maximum dose: 12 grams/day.

  • Oral dosing in children: 50–100 mg/kg/day PO divided every 6 hours. Maximum dose: 2–3 grams/day.

ADVERSE EFFECTS: Hypersensitivity, rash, abdominal discomfort, nausea, vomiting, diarrhea, hemolytic anemia, thrombocytopenia, neutropenia, prolongation of bleeding time, interstitial nephritis, and eosinophilia. Large doses may cause central nervous system (CNS) excitation or seizures.

ACTION AND SPECTRUM: Combination β-lactamase inhibitor and β-lactam. The bactericidal spectrum of ampicillin that is extended by the addition of sulbactam, a β-lactamase inhibitor; includes organisms producing β-lactamases such as Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Klebsiella, Acinetobacter, Enterobacter, and anaerobes.

DOSAGE: IV, IM. Dose based on ampicillin component.

• Preterm infants and neonates during the first week of life (0–7 days):

  • 100 mg ampicillin/kg/day IM/IV divided every 12 hours.

• Neonates >7 days:

  • 100 mg ampicillin/kg/day IM/IV divided every 6–8 hours.

• Infants ≥1 month:

  • 100–150 mg ampicillin/kg/day IM/IV divided every 6 hours.

• Meningitis

  • 200–300 mg ampicillin/kg/day IM/IV divided every 6 hours.

ADVERSE EFFECTS: Elevated blood urea nitrogen (BUN) and serum creatinine. See Ampicillin.

COMMENTS: Modify dosage in patients with renal impairment.

INDICATIONS AND USE: Treatment of severe metabolic alkalosis after other treatment has failed, pituitary function test (stimulant for the release of growth hormone), and treatment of certain neonatal-onset urea cycle disorders.

ACTIONS: Corrects severe hypochloremic metabolic alkalosis resulting from the high chloride content of arginine. Arginine stimulates pituitary release of growth hormone and prolactin and the pancreatic release of glucagon and insulin.

DOSAGE: IV.

• Metabolic alkalosis in infants and children:

  • Arginine HCl dose (mEq) = 0.5 × weight (kg) × [HCO₃^– – 24] where HCO₃^– = the patient's serum bicarbonate concentration in mEq/L; give one-half to two-thirds of calculated dose and reevaluate.

• Correct hypochloremia in infants and children:

  • Arginine HCl dose (mEq) = 0.2 × weight (kg) × [103 – Cl⁻] where Cl⁻ = the patient's serum Cl^– concentration in mEq/L; give one-half to two-thirds of the calculated dose, then reevaluate.

  • IV: May use undiluted (irritating to tissues) or dilute with normal saline (NS) or dextrose. Administer through a central line. Infuse over at least 30 minutes or over 24 hours in maintenance IV. Maximum: 1 gram/kg/hour (= 10 mL/kg/hour of 10% solution). PO: May use the injectable form, diluted.

• Growth hormone reserve test:

  • IV 500 mg/kg (= 5 mL/kg of the 10% solution) infused IV over 30 minutes. (Use only IV, not PO administration, for this test.)

• Urea cycle disorders

  • Consult specialists in metabolic disorders if a urea cycle disorder is suspected.

ADVERSE EFFECTS: Not a first-line treatment for metabolic alkalosis and should never be used as initial therapy; try sodium, potassium, or ammonium chlorides first. May be toxic in infants with arginase deficiency. Do not use in patients sensitive to arginine HCl or in those with hepatic or renal failure. May cause hyperchloremic metabolic acidosis, elevated gastrin, glucagon, and growth hormone; flushing and gastrointestinal (GI) upset with rapid IV administration; hyperglycemia, hypoglycemia, hyperkalemia; tissue necrosis on extravasation, vein irritation; allergic reactions; elevated blood urea nitrogen (BUN) and creatinine.

COMMENTS: Monitor IV site, blood glucose, chloride, and blood pressure.

INDICATIONS AND USE: Sinus bradycardia, in conjunction with neostigmine for the reversal of nondepolarizing neuromuscular blockade. Used preoperatively to inhibit salivation and reduce excessive secretions of the respiratory tract.

ACTIONS: A competitive antagonist of acetylcholine at parasympathetic sites in smooth muscle, cardiac muscle, and various glandular cells, leading to increased heart rate, increased cardiac output, reduced gastrointestinal (GI) motility and tone, urinary retention, cycloplegia, and decreased salivation and sweating.

DOSAGE: IM, IV, ETT, PO.

• Bradycardia in infants and children:

  • 0.02 mg/kg/dose; may repeat once in 3–5 minutes; reserve use for those patients unresponsive to improved oxygenation and epinephrine. No longer part of AHA neonatal resuscitation algorithm.

• Preanesthetic:

  • 0.02 mg/kg/dose 30–60 minutes preoperatively, then every 4–6 hours as needed.

• Reversal of neuromuscular blockade:

  • Neostigmine 0.06 mg/kg/dose with atropine 0.02 mg/kg/dose.

• Intubation, nonemergent (preferred vagolytic):

  • 0.02 mg/kg/dose IM/IV.

• Endotracheal tube (ETT):

  • 0.04–0.06 mg/kg/dose; may repeat once if needed. Flush with 1–5 mL normal saline (NS) based on patient size.

• Oral:

  • Initial dose: 0.02 mg/kg/dose given every 4–6 hours. May increase gradually to 0.09 mg/kg/dose.

ADVERSE EFFECTS: Xerostomia, blurred vision, mydriasis, tachycardia, palpitations, constipation, urinary retention, ataxia, tremor, and hyperthermia. Toxic effects are especially likely in children receiving low doses.

COMMENTS: Contraindicated in thyrotoxicosis, tachycardia secondary to cardiac insufficiency, and obstructive GI disease. In low doses, it may cause paradoxic bradycardia secondary to its central actions.

ACTION AND SPECTRUM: Treatment of upper respiratory tract infections due to Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Streptococcus pneumoniae, Chlamydia trachomatis, Neisseria gonorrhoeae, Staphylococcus aureus, Mycobacterium avium complex, Chlamydophila psittaci, and Mycoplasma hominis. Has also been used for treatment of pertussis.

DOSAGE: PO.

• Infants <6 months:

  • Pertussis: 10 mg/kg/dose PO once daily for 5 days (based on AAP Red Book, 2012). Azithromycin is drug of choice for age <1 month because of idiopathic hypertrophic pyloric stenosis with erythromycin.

• Children ≥6 months:

  • Respiratory tract infections: 10 mg/kg on day 1 (maximum dose 500 mg) followed by 5 mg/kg/day (maximum dose 250 mg) once daily on days 2–5.

  • Pertussis: 10 mg/kg on day 1 (maximum dose 500 mg) followed by 5 mg/kg/day (maximum dose 250 mg) once daily on days 2–5 (based on AAP Red Book, 2012).

ADVERSE EFFECTS: Diarrhea, vomiting, irritability, rash.

PHARMACOLOGY: Macrolide antibiotic; half-life of ~80 hours.

COMMENTS: Limited data in neonates.

ACTION AND SPECTRUM: Monobactam antibiotic that is bactericidal against most Enterobacteriaceae, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Serratia, Haemophilus influenzae, and Citrobacter spp., but essentially no activity against gram-positive aerobic or anaerobic bacteria.

DOSAGE: IV, IM.

• Neonates postnatal age <7 days:

  • ≤2 kg: 30 mg/kg/dose every 12 hours.

  • >2 kg: 30 mg/kg/dose every 8 hours.

• Neonates postnatal age ≥7 days:

  • <1.2 kg: 30 mg/kg/dose every 12 hours.

  • 1.2–2 kg: 30 mg/kg/dose every 8 hours.

  • >2 kg: 30 mg/kg/dose every 6 hours.

• Children >1 month:

  • 90–120 mg/kg/day divided every 6–8 hours.

ADVERSE EFFECTS: Diarrhea, nausea, vomiting, rash, hypoglycemia, irritation at the infusion site. May cause transient eosinophilia, leukopenia, thrombocytopenia, hypoglycemia, and elevated liver enzymes.

PHARMACOLOGY: Renal elimination as unchanged drug. Half-life is 3–9 hours in neonates. Widely distributed into body tissues, cerebrospinal fluid, bronchial secretions, peritoneal fluid, bile, bone.

COMMENTS: Demonstrates synergistic activity with aminoglycosides against most strains of P. aeruginosa, many strains of Enterobacteriaceae, and other gram-negative aerobic bacilli.

INDICATIONS AND USE: Prevention and treatment of respiratory distress syndrome in preterm infants.

ACTIONS: A natural bovine lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins to which dipalmitoylphosphatidylcholine (DPPC), palmitic acid, and tripalmitin are added to mimic the surface tension–lowering properties of natural lung surfactant. Surfactant lowers surface tension on alveolar surfaces during respiration and stabilizes the alveoli against collapse.

DOSAGE: ETT.

• 4 mL/kg (100 mg of phospholipids/kg) birthweight. Divide dose into 4 aliquots, repositioning the infant with each dose. Inject each aliquot gently into the catheter over 2–3 seconds. Ventilate the infant after each one-quarter dose for at least 30 seconds or until stable. Four doses of 4 mL/kg can be given in the first 48 hours of life, no more frequently than every 6 hours. Wean ventilator settings rapidly after administration.

ADVERSE EFFECTS: Most adverse effects are associated while administering the beractant to the infant: transient bradycardia, oxygen desaturation, endotracheal tube (ETT) reflux, pallor, vasoconstriction, hypotension, endotracheal blockage, hypertension, hypocarbia, hypercarbia, and apnea. Pulmonary hemorrhage has been reported, especially in very low birthweight infants.

INDICATIONS AND USE: A potent loop diuretic used for the management of edema associated with congenital heart disease, congestive heart failure, and hepatic or renal disease.

ACTIONS: Inhibition of sodium and chloride in the ascending loop of Henle and proximal renal tubule. Urinary excretion of sodium, chloride, potassium, hydrogen, calcium, magnesium, ammonium, phosphate, and bicarbonate increases with bumetanide-induced diuresis. Renal blood flow increases substantially as a result of renovascular dilation and increases prostaglandin secretion.

DOSAGE: IV, IM, PO.

• Neonates: 0.005–0.1 mg/kg/dose every 12–24 hours.

• Infants and children: 0.015 mg/kg/dose up to 0.1 mg/kg/dose every 6–24 hours (maximum dose is 10 mg/kg/day).

ADVERSE EFFECTS: Hypokalemia, hypochloremia, hyponatremia, metabolic alkalosis, and hypotension. Potentially ototoxic but less so than furosemide.

COMMENTS: Patients refractory to furosemide may respond to bumetanide for diuretic therapy. Although patients may respond differently, bumetanide is ~40 times more potent on a milligram-per-milligram basis than furosemide. Follow electrolytes.

INDICATIONS AND USE: Treatment of apnea of prematurity; postextubation and postanesthesia apnea.

ACTIONS: Similar to other methylxanthine drugs (eg, aminophylline and theophylline). Caffeine appears to be more active on and less toxic to the central nervous system (CNS) and the respiratory system. Proposed mechanisms of action include increased production of adenosine 3′,5′-cyclic monophosphate (cAMP) alterations of intracellular calcium concentrations. Stimulates the CNS, which increases the medullary respiratory center sensitivity to carbon dioxide, stimulates central inspiratory drive, and improves diaphragmatic contractility. Caffeine exerts a positive inotropic effect on the myocardium, increases renal blood flow and glomerular filtration rate, and stimulates glycogenolysis and lipolysis.

DOSAGE: IV, PO.

• Loading dose: 20–25 mg/kg of caffeine citrate IV or PO (equivalent to 10–12.5 mg of caffeine base).

• Maintenance: 5–10 mg/kg/day caffeine citrate IV or PO every 24 hours, starting 24 hours after loading dose (equivalent to 2.5–5 mg of caffeine base).

ADVERSE EFFECTS: Nausea, vomiting, gastric irritation, agitation, tachycardia (if heart rate >180 beats/min may consider holding dose), and diuresis. Symptoms of overdosage include arrhythmias and tonic-clonic seizures.

PHARMACOLOGY: Therapeutic serum trough levels 5–25 mcg/mL; severe toxicity is with levels >50 mcg/mL. Draw trough on day 5 of treatment. The serum half-life in neonates ranges from 40 to 230 hours and decreases with increased postnatal age; in infants >9 months half-life is ~5 hours. Half-life is prolonged with cholestasis.

INDICATIONS AND USE: Acute treatment of symptomatic hypocalcemia, treatment of hypermagnesemia, cardiac disturbances of hyperkalemia, hypocalcemia, or calcium channel blocker toxicity and prevention of hypocalcemia.

ACTIONS: Calcium is essential for the functional integrity of the nervous, muscular, skeletal, and cardiac systems and for clotting function.

DOSAGE: IV. Dosage expressed in milligrams of calcium chloride.

• Acute treatment of symptomatic hypocalcemia: 10–20 mg/kg per dose, dilute in appropriate fluid and infuse IV over 10 minutes.

• Cardiac arrest in the presence of hyperkalemia or hypocalcemia, magnesium toxicity, or calcium antagonist toxicity: 20 mg/kg/dose IV every 10 minutes as needed. If effective, consider IV infusion 20–50 mg/kg/hour.

• Tetany: IV: 10 mg/kg over 5–10 minutes; may repeat after 6 hours or follow with an infusion with a maximum dose of 200 mg/kg/day.

ADVERSE EFFECTS: Arrhythmias (in particular, bradycardia) and deterioration of cardiovascular function; may potentiate digoxin-related arrhythmias; may increase risk of metabolic acidosis. Calcium chloride is contraindicated in ventricular fibrillation or hypercalcemia. Extravasation may cause severe tissue damage (sloughing and necrosis).

COMMENTS: Supplied as a 10% solution (10 mL) (equivalent to elemental calcium 27 mg [1.36 mEq]/mL). Chloride salt is preferred to the gluconate form in cardiac arrest because it may be more bioavailable. Calcium chloride precipitates when mixed with sodium bicarbonate. Warning: Multiple salt forms of calcium exist; when ordering and administering calcium, incorrect selection or substitution of one salt for another without proper dosage adjustment may result in serious over- or under-dosing. There is a 3-fold difference in the primary cation concentration between calcium chloride (1 gram = 13.6 mEq [270 mg] of elemental Ca⁺⁺) and calcium gluconate (1 gram = 4.65 mEq [90 mg] of elemental Ca⁺⁺).

INDICATIONS AND USE: Treatment and prevention of hypocalcemia and prevention of hypocalcemia during exchange transfusion.

ACTIONS: See Calcium Chloride. Calcium gluconate must be metabolized to release calcium ion.

DOSAGE: IV, PO (dosage expressed in milligrams of calcium gluconate).

• Acute treatment of symptomatic hypocalcemia: 100–200 mg/kg/dose IV diluted in appropriate fluid and administered over 10–30 minutes.

• Maintenance IV: 200–800 mg/kg/day divided every 6 hours or as infusion; maximum rate: 50–100 mg/minute of calcium gluconate. Continuous infusion is more efficacious than intermittent infusion due to less renal calcium loss.

• Maintenance PO: 200–800 mg/kg/day divided every 6 hours, mixed in feedings.

• Exchange transfusion: 100 mg calcium gluconate/100 mL of citrated blood exchanged infused IV over 10 minutes.

ADVERSE EFFECTS: See Calcium Chloride. Oral administration may cause gastrointestinal (GI) irritation; dilute and use with caution in infants at risk for necrotizing enterocolitis.

INDICATIONS AND USE: Prevention and treatment of neonatal respiratory distress syndrome (RDS).

ACTIONS: Natural, preservative-free calf lung extract that contains phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins B and C. Each milliliter of calfactant contains 35 mg of total phospholipids and 0.65 mg of proteins (0.26 mg of protein B). Calfactant decreases the surface tension on alveolar surfaces, stabilizing the alveoli and preventing collapse. This results in improved ventilation, lung compliance, and gas exchange.

DOSAGE: ETT.

• Prophylactic initial dose for RDS: As soon as possible after birth, give 3 mL/kg/dose, divided into two 1.5–mL/kg aliquots. After the instillation of each aliquot, position infant either on the right or left side. Ventilation is continued during administration over 20–30 seconds. The 2 aliquots should be separated by a pause to evaluate respiratory status and reposition the patient.

• The initial dose may be followed by 3 subsequent doses of 3 mL/kg/dose at 12-hour intervals, if necessary.

ADVERSE EFFECTS: Bradycardia, cyanosis, airway obstruction, pneumothorax, pulmonary hemorrhage, and apnea. Most adverse effects occur during administration of dose.

COMMENTS: Following administration, lung compliance and oxygenation often rapidly improve. Patients should be closely monitored and appropriate changes in ventilatory support should be made as clinically indicated.

INDICATIONS AND USE: Moderate to severe congestive heart failure (reduction of afterload) and hypertension.

ACTIONS: Competitive inhibitor of angiotensin-converting enzyme. Causes a decrease in angiotensin II and aldosterone levels; increases plasma and tissue renin activity; decreases systemic vascular resistance without reflex tachycardia and augmentation of cardiac output.

DOSAGE: PO.

• Premature and term neonates, postnatal age (PNA) ≤7 days: Initial dose: 0.01 mg/kg/dose every 8–12 hours; titrate dose and interval based on response.

• Term neonates, PNA >7 days: Initial dose: 0.05–0.1 mg/kg/dose every 8–24 hours; titrate dose up to maximum 0.5 mg/kg/dose given every 6–24 hours.

• Infants: Initial dose: 0.15–0.3 mg/kg/dose; titrate dose up to 6 mg/kg/day divided in 2–4 doses.

ADVERSE EFFECTS: Hypotension, rash, fever, eosinophilia, angioedema, neutropenia, gastrointestinal (GI) disturbances, and hyperkalemia. Significant decreases in cerebral and renal blood flow have occurred in premature infants who have chronic hypertension and received higher doses (0.15–0.3 mg/kg/dose); may result in neurologic complications including seizures, apnea and lethargy, and oliguria.

COMMENTS: Administer 1 hour before or 2 hours after feedings if possible; food decreases absorption. Contraindicated in patients with bilateral renovascular disease. Use with caution in patients with low renal perfusion pressure. Reduce the dose with renal impairment and in sodium- and water-depleted patients (use with caution if on concurrent diuretic therapy).

INDICATIONS AND USE: Anticonvulsant. Treatment of partial (especially complex partial), primary generalized tonic-clonic seizures and mixed partial or generalized seizures.

ACTIONS: Decrease synaptic transmission, limits influx of sodium ions across cell membrane.

DOSAGE: PO.

• 10–20 mg/kg/day of oral suspension, initially divided 4 times a day; may increase weekly to optimal response, then to a maximum of 35 mg/kg/day. Administer daily dose in 3–4 divided doses with feedings.

ADVERSE EFFECTS: Nausea, vomiting, leukopenia, thrombocytopenia, aplastic anemia and agranulocytosis, congestive heart failure (CHF), heart block, dystonia, drowsiness, and behavioral changes, syndrome of inappropriate antidiuretic hormone secretion (SIADH), hyponatremia, hepatitis and cholestasis, rash and Stevens-Johnson syndrome, urine retention, azotemia, oliguria, and anuria. Monitor complete blood cell count (CBC), liver function, and urinalysis; perform periodic eye examination. Do not discontinue abruptly because seizures may result in epileptic patients.

PHARMACOLOGY: Metabolized in liver by cytochrome P450 3A4. Induces liver enzymes and increases its own metabolism. Half-life in neonates is 8–28 hours. Therapeutic range is 4–12 mcg/mL.

COMMENTS: Avoid switching between Tegretol and generic carbamazepine; changes in serum concentration and seizure activity may result; monitor serum concentrations. Interactions are numerous. Erythromycin, isoniazid, and cimetidine may inhibit hepatic metabolism of carbamazepine, resulting in increased carbamazepine serum concentrations. Concurrent phenobarbital may lower carbamazepine serum levels. Carbamazepine may induce metabolism of warfarin, phenytoin, theophylline, benzodiazepines, and corticosteroids.

ACTION AND SPECTRUM: Treatment of invasive aspergillosis that is refractory to other antifungal agents or in patients intolerant of other agents; infections caused by susceptible Candida species.

DOSAGE: IV.

• Preterm neonates—infants <3 months: 25 mg/m² (or equivalent to ~2 mg/kg)/dose IV every 24 hours; infuse over at least 1 hour via syringe pump.

• Infants ≥3 months: Initial dose of 70 mg/m²/dose IV followed by 50 mg/m²/dose IV every 24 hours starting day 2. May increase to 70 mg/m²/dose IV every 24 hours if clinical response is inadequate. Maximum dose is 70 mg/day.

• Length of therapy: At least 14 days after last positive culture.

ADVERSE EFFECTS: Hypokalemia, hypercalcemia, elevated liver enzymes, thrombocytopenia, direct hyperbilirubinemia, thrombophlebitis, hypotension, fever, and rash.

PHARMACOLOGY: An echinocandin acts by inhibiting the synthesis of β-(1,3)-D-glucan, an important component of the fungal cell wall. Fungicidal against Candida species and fungistatic against Aspergillus. Metabolized by the liver, not cytochrome P450 enzymes; results in fewer drug-drug interactions than the azole class of antifungal agents. Serum concentrations of caspofungin may be lower if concomitant therapy with dexamethasone, phenytoin, carbamazepine, nevirapine, and rifampin. Caspofungin clearance is induced and higher doses may be required: 70 mg/m²/dose.

COMMENTS: Note: Dosing information based on very limited pharmacokinetic data of 18 neonates and infants (Saez-Liorens, 2009). Do not use diluents containing dextrose for reconstitution.

ACTION AND SPECTRUM: First-generation cephalosporin; a broad-spectrum semisynthetic β-lactam antibiotic with bactericidal activity. Activity against susceptible gram-positive cocci (except enterococci), including penicillinase-producing staphylococci; some gram-negative coverage of susceptible Escherichia coli, Klebsiella, and Proteus. Primarily used in neonates for urinary tract infections, perioperative prophylaxis, and soft tissue infections.

DOSAGE: IV.

• Neonates:

  • Postnatal age ≤7 days: 40 mg/kg/day divided every 12 hours.

  • Postnatal age >7 days: ≤2 kg: 40 mg/kg/day divided every 12 hours; >2 kg: 60 mg/kg/day divided every 8 hours.

• Infants and children:

  • 50–100 mg/kg/day divided every 8 hours; maximum dose: 6 grams/day.

ADVERSE EFFECTS: Infrequent; fever, rash, and urticaria. May cause eosinophilia, leukopenia, neutropenia, and thrombocytopenia. Excessive dosage (especially in renal impairment) may result in central nervous system (CNS) irritation with seizure activity.

PHARMACOLOGY: 80–100% excreted unchanged in urine. Half-life is 3–5 hours in neonates.

COMMENTS: Dosage reduction is required in moderate to severe renal failure.

ACTION AND SPECTRUM: Fourth-generation cephalosporin used for treatment of infections caused by susceptible gram-negative bacteria: Escherichia coli, Haemophilus influenzae, Enterobacter, Klebsiella, Providencia, Serratia, Proteus, Morganella, Neisseria, Pseudomonas aeruginosa, Acinetobacter, and Citrobacter. Treatment of infections caused by susceptible gram-positive bacteria: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Streptococcus agalactiae.

DOSAGE: IV.

• Neonates and infants ≤8 days of age: 30 mg/kg/dose IV every 12 hours.

• Infants >28 days of age: 50 mg/kg/dose every 12 hours.

• For meningitis or infections due to Pseudomonas or Enterobacter: 50 mg/kg/dose every 12 hours.

ADVERSE EFFECTS: Rash, elevated hepatic transaminase enzymes, prothrombin time (PT), partial thromboplastin time (PTT), thrombocytopenia, leukopenia, neutropenia, eosinophilia, and hypophosphatemia.

PHARMACOLOGY: Distributes well into body tissues and fluids. Low protein binding; primarily excreted in urine unchanged.

COMMENTS: Manufacturer does not recommend use for treatment of serious infections due to H. influenzae type b for suspected meningitis.

ACTION AND SPECTRUM: Third-generation cephalosporin with bactericidal activity against susceptible gram-negative organisms (except Pseudomonas), including Escherichia coli, Enterobacter, Klebsiella, Haemophilus influenzae (including ampicillin-resistant strains), Proteus, Serratia, Neisseria gonorrhoeae, and Neisseria meningitidis. Generally poor activity against gram-positive aerobic organisms.

DOSAGE: IV, IM.

• Neonates:

  • 0–4 weeks and <1.2 kg: 100 mg/kg/day divided every 12 hours.

• Postnatal age ≤7 days:

  • 1.2–2 kg: 100 mg/kg/day divided every 12 hours.

  • >2 kg: 100–150 mg/kg/day divided every 8–12 hours.

• Postnatal age >7 days:

  • 1.2–2 kg: 150 mg/kg/day divided every 8 hours.

  • >2 kg: 150–200 mg/kg/day divided every 6–8 hours.

• Infants and children 1 month to 12 years:

  • <50 kg: 100–200 mg/kg/day divided every 6–8 hours.

  • Meningitis: 200 mg/kg/day divided every 6 hours; 225–300 mg/kg/day divided every 6–8 hours has been used to treat invasive pneumococcal meningitis.

  • Disseminated gonococcal infection and scalp abscesses: The Centers for Disease Control and Prevention (CDC) recommends cefotaxime as an alternative to ceftriaxone in the treatment of disseminated gonococcal infection and gonococcal scalp abscesses in newborns. The dose of cefotaxime is 25 mg/kg in a single daily dose IM or IV for 7 days; duration is 10–14 days for meningitis.

  • Gonococcal ophthalmia prophylaxis in newborns of mothers with gonorrhea at delivery: 100 mg/kg IV or IM as a single dose (topical antibiotic therapy alone is inadequate).

ADVERSE EFFECTS: Arrhythmias; transient neutropenia, thrombocytopenia, eosinophilia, leukopenia; transient hepatic and renal dysfunction.

PHARMACOLOGY: Excreted principally unchanged in the urine. Half-life in neonates is 1–4 hours.

COMMENTS: Reserved for suspected or documented gram-negative meningitis or sepsis. When used as empiric therapy, combine with ampicillin or penicillin to provide gram-positive coverage (ie, group B streptococci, pneumococci, and Listeria monocytogenes). Third-generation cephalosporins induce the emergence of multidrug-resistant bacteria or fungal infection when used excessively and without proper clinical indications.

ACTIONS AND SPECTRUM: Second-generation cephalosporin used for infections from gram-negative enteric organisms Escherichia coli, Klebsiella, and Proteus; active against many strains of Neisseria gonorrhoeae, ampicillin-resistant Haemophilus influenzae, and anaerobic bacteria, including Bacteroides species of the gastrointestinal (GI) tract.

DOSAGE: IV.

• Neonates:

  • 90–100 mg/kg/day divided every 8 hours.

• Infants ≥3 months and children:

  • Mild-moderate infection: 80–100 mg/kg/day divided every 6–8 hours.

  • Severe infection: 100–160 mg/kg/day divided every 4–6 hours; maximum dose: 12 grams/day.

PHARMACOLOGY: Highly protein bound and renally excreted essentially unchanged.

ADVERSE EFFECTS: Usually well tolerated. May cause rash, thrombophlebitis; transient leukopenia, thrombocytopenia, neutropenia, anemia, and eosinophilia, and transient elevation of blood urea nitrogen (BUN), serum creatinine, and liver enzymes.

COMMENTS: Not inactivated by β-lactamase. Has poor central nervous system (CNS) penetration. The safety and efficacy in infants <3 months have not been established.

ACTION AND SPECTRUM: Third-generation cephalosporin with bactericidal activity against gram-negative aerobic bacteria, including Neisseria, Haemophilus influenzae, some Enterobacteriaceae, and Pseudomonas. Pseudomonal infections in patients at risk of developing aminoglycoside-induced nephrotoxicity and/or ototoxicity. Poor gram-positive activity. Aminoglycosides act synergistically with ceftazidime.

DOSAGE: IV.

• Neonates:

  • 0–4 weeks and <1.2 kg: 100 mg/kg/day divided every 12 hours.

• Postnatal age <7 days:

  • 1.2–2 kg: 100 mg/kg/day divided every 12 hours.

  • >2 kg: 100–150 mg/kg/day divided every 8–12 hours.

• Postnatal age ≥7 days and ≥1.2 kg:

  • 150 mg/kg/day divided every 8 hours.

• Infants and children 1 month to 12 years:

  • 100–150 mg/kg/day divided every 8 hours; maximum dose: 6 grams/day.

• Meningitis:

  • 150 mg/kg/day divided every 8 hours; maximum dose: 6 grams/day.

ADVERSE EFFECTS: Infrequent except for fever, rash, urticaria. May cause transient leukopenia, neutropenia, thrombocytopenia, and hemolytic anemia; transient elevation in liver enzymes, hyperbilirubinemia, transient elevation of blood urea nitrogen (BUN) and serum creatinine.

PHARMACOLOGY: Renally excreted 80–90% unchanged. Half-life is 2.2–4.7 hours; penetrates well into cerebrospinal fluid (CSF).

ACTION AND SPECTRUM: Third-generation cephalosporin with activity against gram-negative aerobic bacteria, Haemophilus influenzae, Enterobacteriaceae, and Neisseria, and activity against gram-positive cocci, methicillin-susceptible Staphylococcus and Streptococcus. No activity against Pseudomonas aeruginosa, Chlamydia trachomatis, methicillin-resistant staphylococci, and enterococci.

DOSAGE: IV, IM.

• Neonates:

  • Postnatal age <7 days: 50 mg/kg/day every 24 hours.

  • Postnatal age ≥7 days:

    • ≤2 kg: 50 mg/kg/day every 24 hours.

    • >2 kg: 50–75 mg/kg/day every 24 hours.

• Gonococcal prophylaxis:

  • 25–50 mg/kg as a single dose (dose not to exceed 125 mg).

• Gonococcal infection:

  • 25–50 mg/kg/day (maximum dose 125 mg) every 24 hours for 7 days; up to 10–14 days if meningitis is documented. (Note: Use cefotaxime in place of ceftriaxone in hyperbilirubinemic neonates.)

• Ophthalmia neonatorum:

  • 25–50 mg/kg as a single dose (maximum dose 125 mg).

• Infants and children:

  • 50–75 mg/kg/day divided every 12–24 hours.

• Meningitis:

  • 80–100 mg/kg/day divided every 12–24 hours; loading dose of 75 mg/kg may be administered at the start of therapy; maximum dose 4 grams/day.

ADVERSE EFFECTS: Diarrhea, cholelithiasis, gallbladder sludging. May also cause neutropenia, eosinophilia, hemolytic anemia, increased prothrombin times, rash, thrombophlebitis, elevated liver enzymes, jaundice, hyperbilirubinemia; use with caution in infants with hyperbilirubinemia.

PHARMACOLOGY: Biliary and renal excretion. Half-life is 5–19 hours.

COMMENTS: Warning: Ceftriaxone is incompatible with calcium-containing solutions. Calcium-containing solutions or products must not be administered within 48 hours of the ceftriaxone dose due to the fatal reaction involving calcium-ceftriaxone precipitates in the lungs and kidneys of neonates. Dosage reduction is required only in patients with both renal and hepatic dysfunction.

ACTION AND SPECTRUM: Second-generation cephalosporin with activity against susceptible staphylococci, group B streptococci, pneumococci, Haemophilus influenzae (type A and B), Escherichia coli, Enterobacter, and Klebsiella.

DOSAGE: IM, IV.

• Neonates: 50–100 mg/kg/day divided every 12 hours.

• Children: 75–150 mg/kg/day divided every 8 hours; maximum dose 6 grams/day.

• Meningitis: Not recommended due to reports of treatment failures and slower bacteriologic response time.

ADVERSE EFFECTS: Fever, seizures, rash, thrombophlebitis, diarrhea, hemolytic anemia, transient neutropenia and leukopenia, eosinophilia, increased prothrombin time. Transient elevation in liver enzymes, hepatitis, and cholestasis; elevation in blood urea nitrogen (BUN) and serum creatinine.

PHARMACOLOGY: Primarily excreted unchanged in the urine. Half-life is 5.1–5.8 hours in infants <3 days old and 1–4.2 hours in infants >8 days of age.

COMMENTS: Decrease the dosage in renal failure. Limited experience in neonates. Safety and efficacy in infants <3 months of age have not been established.

INDICATIONS AND USE: Short-term sedative and hypnotic; central nervous system (CNS) depressant.

DOSAGE: PO, PR. Use the lowest effective dose.

• Usual dose 25–50 mg/kg/dose PO or PR every 6–8 hours as needed.

• Sedation prior to electroencephalography and other procedures: 25–75 mg/kg/dose once PO or PR. Typical dose: 50 mg/kg/dose once; repeat 25 mg/kg/dose once if needed.

ADVERSE EFFECTS: Gastrointestinal irritation resulting in nausea, vomiting, and diarrhea; paradoxic excitation; and respiratory depression, particularly if administered with opiates and barbiturates. May cause direct hyperbilirubinemia with chronic use (active metabolite 2,2,2-trichloroethanol [TCE]); competes with bilirubin for glucuronide conjugation in the liver); overdose can be lethal.

COMMENTS: Contraindicated with marked renal or hepatic impairment. Syrup may contain sodium benzoate; benzoic acid (benzoate) is a metabolite of benzyl alcohol.

ACTION AND SPECTRUM: Broad-spectrum bacteriostatic agent, reserved for serious infections due to organisms resistant to other less toxic agent due to Haemophilus influenzae, Neisseria meningitides, and Escherichia coli; Klebsiella, Serratia, Enterobacter, Salmonella, Shigella, Neisseria gonorrhoeae, staphylococci, Streptococcus pneumoniae, and Bacteroides; active against many vancomycin-resistant enterococci.

DOSAGE: IV.

• Neonates:

  • Loading dose: 20 mg/kg IV.

  • Maintenance dose: 12 hours after the loading dose.

    • ≤7 days: 25 mg/kg/day IV once every 24 hours.

    • >7 days, ≤2 kg: 25 mg/kg/day IV once every 24 hours.

    • >7 days, >2 kg: 50 mg/kg/day IV divided every 12 hours.

• Infants and children:

  • Meningitis: 75–100 mg/kg/day IV divided every 6 hours.

  • Other infections: 50–75 mg/kg/day IV divided every 6 hours. Maximum daily dose 4 grams/day.

ADVERSE EFFECTS: Idiosyncratic reactions result in aplastic anemia (irreversible and rare), reversible bone marrow suppression (dose related), allergy (rash and fever), diarrhea, vomiting, stomatitis, glossitis, fungal overgrowth, “gray baby” syndrome (early signs are hyperammonemia and unexplained metabolic acidosis; other signs are abdominal distention, hypotonia, gray skin color, and cardiorespiratory collapse), and cardiotoxicity due to left ventricular dysfunction. Use with extreme caution in neonates.

PHARMACOLOGY: Metabolized by hepatic glucuronyl transferase. Half-life is 10–24 hours in neonates.

COMMENTS: Must monitor serum levels. Desired peak is 10–25 mcg/mL; levels >50 mcg/mL are strongly associated with “gray baby” syndrome. Monitor complete blood cell count (CBC) with differential, platelet count, and reticulocyte count every 3 days.

INDICATIONS AND USE: Mild to moderate edema, and hypertension.

ACTIONS: Thiazide diuretic; inhibits sodium reabsorption in the distal renal tubules. Sodium, potassium, bicarbonate, magnesium, phosphate, and chloride excretion are increased, whereas calcium excretion is decreased.

DOSAGE: PO, IV. Note: IV dosage in infants and children has not been established. IV doses in infants and children are based on anecdotal reports. The IV dosing regimens have been extrapolated from oral dosing regimens considering only 10–20% of an oral dose is absorbed.

• Neonates and infants <6 months:

  • Oral: 20–40 mg/kg/day PO divided every 12 hours; maximum 375 mg/day.

  • IV: 2–8 mg/kg/day IV divided every 12 hours; doses up to 20 mg/kg/day have been used.

• Infants >6 months and children:

  • Oral: 20 mg/kg/day PO divided every 12 hours; maximum 1 gram/day.

  • IV: 4 mg/kg/day IV divided in 1–2 doses; doses up to 20 mg/kg/day have been used.

ADVERSE EFFECTS: Hypokalemia, hypochloremic alkalosis, dehydration and prerenal azotemia, hyperuricemia, hyperglycemia, hypermagnesemia, hyperlipidemia.

PHARMACOLOGY: Duration of action 6–12 hours; onset of action is within 2 hours.

COMMENTS: Do not use in patients with anuria or severe hepatic dysfunction.

INDICATIONS AND USE: A resin-binding agent in patients with chronic diarrhea and short-gut syndrome to decrease fecal output.

ACTION: Cholestyramine resin binds to bile acids in the intestine, forms a nonabsorbable complex preventing the reabsorption and enterohepatic recirculation of bile salts, and releases chloride ions in the process.

DOSAGE: PO.

• Children: 240 mg/kg/day in 3 divided doses. Titrate dose depending on the indication.

ADVERSE EFFECTS: Constipation. High doses can cause hyperchloremic acidosis and increase urinary calcium excretion.

PHARMACOKINETICS: Not absorbed; excreted in the feces.

COMMENTS: May bind concurrent oral medications, in particular levothyroxine.

INDICATIONS AND USE: Prevention and treatment of duodenal and gastric ulcers, gastroesophageal reflux, esophagitis, and hypersecretory conditions.

ACTIONS: A histamine (H₂)-receptor antagonist; competitively inhibits the action of histamine on the gastric parietal cells, decreasing gastric acid secretion.

DOSAGE: PO.

• Neonates: 5–10 mg/kg/day PO divided every 8–12 hours.

• Infants: 10–20 mg/kg/day PO divided every 6–12 hours.

• Children: 20–40 mg/kg/day PO divided every 6 hours.

ADVERSE EFFECTS: Central nervous system (CNS) toxicity such as agitation and alterations in consciousness, neutropenia, agranulocytosis, thrombocytopenia, antiandrogenic effects; elevated aspartate transaminase (AST), alanine transaminase (ALT), and creatinine levels.

PHARMACOLOGY: Cimetidine reduces the hepatic metabolism of drugs metabolized by the cytochrome P450 pathway, which may result in decreased elimination of diazepam, theophylline, phenytoin, propranolol, and carbamazepine. Doses of these drugs may need to be decreased.

COMMENTS: Limited use in neonates.

INDICATIONS AND USE: Treatment of metabolic acidosis or as a urinary alkalinizing agent for conditions that require the maintenance of alkaline urine.

ACTIONS: Sodium and potassium citrate salts have the capability to buffer gastric acidity (pH >2.5) and are metabolized to bicarbonate to act as systemic alkalinizers.

DOSAGE: PO.

• 2–3 mEq/kg/day of bicarbonate in divided doses 3–4 times per day with water.

ADVERSE EFFECTS: Metabolic alkalosis, hypernatremia (if sodium salt used), hypocalcemia, hyperkalemia (if potassium salt used), diarrhea, nausea, vomiting.

COMMENTS: Supplied as oral solutions: Bicitra and Oracit contain 1 mEq of sodium and 1 mEq of bicarbonate equivalent per milliliter; Polycitra contains 1 mEq of sodium and 1 mEq of potassium and 2 mEq of bicarbonate equivalents per milliliter; Polycitra-K contains 2 mEq of potassium and 2 mEq of bicarbonate equivalents per milliliter. Conversion to bicarbonate may be impaired in patients with hepatic failure.

ACTION AND SPECTRUM: Bacteriostatic agent active against most aerobic gram-positive staphylococci and streptococci (except enterococci); Fusobacterium, Bacteroides spp., Actinomyces, and certain anaerobic gram-positive organisms.

DOSAGE: IM, IV.

• Neonates

  • Postnatal age <7 days:

    • ≤2 kg: 10 mg/kg/day IM/IV divided every 12 hours.

    • >2 kg: 15 mg/kg/day IM/IV divided every 8 hours.

• Postnatal age ≥7 days:

  • <1.2 kg: 10 mg/kg/day IM/IV divided every 12 hours.

  • 1.2–2 kg: 15 mg/kg/day IM/IV divided every 8 hours.

  • >2 kg: 20–30 mg/kg/day IM/IV divided every 6–8 hours.

• Infants and children:

  • 25–40 mg/kg/day IM/IV divided every 6–8 hours; doses as high as 4.8 grams/day have been given IV in life-threatening situations or 10–30 mg/kg/day PO divided every 6–8 hours; maximum dose 1.8 grams/day.

ADVERSE EFFECTS: Diarrhea, colitis, pseudomembranous colitis rash, pruritus, neutropenia, granulocytopenia and thrombocytopenia, hypersensitivity reactions, and elevated liver enzymes. Sterile abscess formation at the IM injection site.

PHARMACOLOGY: Primarily hepatic metabolism, highly protein bound.

COMMENTS: Does not cross the blood-brain barrier; therefore, do not use to treat meningitis.

INDICATIONS AND USE: For the treatment of petit mal, Lennox-Gastaut, infantile spasms, and akinetic and myoclonic seizures, either as a single agent or as adjunctive therapy.

ACTIONS: Depresses all levels of the central nervous system (CNS) including the limbic and reticular formation by binding to the benzodiazepine site on the γ-aminobutyric acid (GABA) receptor complex; suppresses the spike-and-wave discharge in absence seizures by depressing nerve transmission in the motor cortex.

DOSAGE: PO.

• Seizure disorders

  • Infants and children <10 years or 30 kg.

  • Initial daily dose: 0.01–0.03 mg/kg/day PO (maximum 0.05 mg/kg/day) given in 2–3 divided doses; increase by no more than 0.5 mg every third day until seizures are controlled or adverse effects occur.

  • Maintenance: 0.1–0.2 mg/kg/day PO divided into 3 doses; do not exceed 0.2 mg/kg/day.

ADVERSE EFFECTS: Hypotension, drowsiness, hypotonia, thrombocytopenia, anemia, leukopenia, eosinophilia, tremor, choreiform movements, bronchial hypersecretion, respiratory depression.

PHARMACOLOGY: Cytochrome P450 isoenzyme CYP3A3/4 substrate. CNS depressants increase sedation; phenytoin, carbamazepine, rifampin, and barbiturates increase clonazepam clearance; drugs that inhibit cytochrome P450 isoenzyme CYP3A3/4 may increase levels and effects of clonazepam (monitor for altered benzodiazepine response); concurrent use with valproic acid may result in absence status.

COMMENTS: Caution in patients with chronic respiratory disease, hepatic disease, or impaired renal function. Abrupt discontinuation of clonazepam may precipitate withdrawal symptoms, status epilepticus, or seizures. (Withdraw gradually when discontinuing therapy in children. Safely reduce by ≤0.04 mg/kg/week and discontinue when the daily dose is ≤0.04 mg/kg/day.) Worsening of seizures may occur when clonazepam is added to patients with multiple seizure types.

INDICATIONS AND USE: Adjunctive treatment of neonatal abstinence syndrome (NAS) and iatrogenic narcotic dependency.

ACTIONS: Stimulates central nervous system (CNS) α₂-adrenergic receptors which results in decreased sympathetic outflow, peripheral vascular resistance, systolic and diastolic blood pressure, and heart rate. Clonidine reduces circulating plasma renin levels.

DOSAGE: PO.

• Neonatal abstinence syndrome (opioid withdrawal):

  • Preterm neonate: 0.5–1 mcg/kg/dose PO every 6 hours. Taper dose when stabilized by 0.25 mcg/kg/dose PO every 6 hours (Leikin et al, 2009).

  • Full-term neonate: 1 mcg/kg/dose PO every 4 hours in combination with diluted opium tincture. A randomized, controlled, comparative trial in 80 neonates (gestational age [GA]: ≥35 weeks) with NAS demonstrated a decreased length of therapy and opioid doses in the combination treatment (clonidine plus diluted opium tincture) as compared to diluted tincture of opium alone (Agthe et al, 2009).

  • Alternate dosing: Initial dose of 0.5–1 mcg/kg/dose every 3–6 hours; maximum dose 1 mcg/kg/dose every 3 hours (AAP Clinical Report—Neonatal Drug Withdrawal, 2012).

ADVERSE EFFECTS: Very few side effects reported when used to treat NAS. Observe for hypotension and bradycardia and avoid abrupt discontinuation.

COMMENTS: More experience is needed before clonidine is routinely used to treat opioid withdrawal in infants.

INDICATIONS AND USE: Aid in the diagnosis of adrenocortical insufficiency; used in the diagnosis of congenital adrenal hyperplasia.

ACTIONS: Stimulates the adrenal cortex to secrete cortisol (hydrocortisone and cortisone), androgenic substances, and a small amount of aldosterone.

DOSAGE: IM/IV. Diagnostic test doses.

• Adrenocortical insufficiency:

  • Preterm neonates: Not well defined; 0.1 mcg/kg, 0.2 mcg/kg, 1 mcg/kg, and 3.5 mcg/kg have been used.

  • Neonates: 15 mcg/kg (1 dose only).

  • Children ≤2 years: 0.125 mg.

• Congenital adrenal hyperplasia evaluation:

  • 1 mg/m²/dose up to a maximum of 1 mg.

COMMENTS: Plasma cortisol concentrations should be measured immediately before and exactly 30 minutes after administration of cosyntropin; dose should be given in early morning; 0.25 mg of cosyntropin = 25 USP units of corticotropin.

INDICATIONS AND USE: For diagnostic and therapeutic ophthalmologic procedures that require mydriasis and cycloplegia.

ACTIONS: Causes pupillary dilatation by inhibition of the cholinergic response of the ciliary body muscle and sphincter muscle of iris.

DOSAGE: Ocular.

• One to two drops into the eye 10–30 minutes prior to procedure; usually used in conjunction with phenylephrine 2.5%. The 0.5% concentration is recommended for neonates.

ADVERSE EFFECTS: Tachycardia, vasodilatation, restlessness, delayed gastric emptying, urinary retention.

PHARMACOLOGY: Maximal effect occurs 30–60 minutes after administration, with pharmacologic effects lasting 6–24 hours.

COMMENTS: Consider holding feeds for 4 hours after procedure.

INDICATIONS: Treatment of airway edema prior to extubation. Used in infants with bronchopulmonary dysplasia/chronic lung disease to facilitate weaning from the ventilator.

ACTIONS: Long-acting, potent glucocorticoid without mineralocorticoid properties; prevents or suppresses inflammatory and immune responses in pharmacologic doses. Inhibits leukocyte infiltration at site of inflammation, interferes in function of mediators of inflammatory response, and suppresses humoral immune responses. May reduce edema and scar tissue formation; reversal of increased capillary permeability, and general suppression in immune response.

DOSAGE: IV, PO.

• Neonates:

  • Airway edema or extubation: Usual dose: 0.25 mg/kg/dose IV given ~4 hours prior to scheduled extubation and then every 8 hours for 3 doses total. Range: 0.25–1 mg/kg/dose for 1–3 doses. Maximum dose: 1 mg/kg/day. Note: A longer duration of therapy may be needed with more severe cases.

  • Bronchopulmonary dysplasia/chronic lung disease (facilitate ventilator weaning):

    • Numerous dosing schedules proposed: Range: 0.5–0.6 mg/kg/day given in divided doses PO or IV every 12 hours for 3–7 days, then taper over 1–6 weeks.

    • DART trial protocol (Doyle et al, 2006): 0.075 mg/kg/dose every 12 hours for 3 days, 0.05 mg/kg/dose every 12 hours for 3 days, 0.025 mg/kg/dose every 12 hours for 2 days, 0.01 mg/kg/dose every 12 hours for 2 days.

ADVERSE EFFECTS: With long-term use, increased susceptibility to infection, osteoporosis, growth retardation, hyperglycemia, fluid and electrolyte disturbances, cataracts, myopathy, gastrointestinal perforation and hemorrhage, hypertension, and acute adrenal insufficiency. Dexamethasone use for low birthweight infants has come under close scrutiny because of increasing numbers of reports indicating neurodevelopmental compromise (see Comments).

COMMENTS: Please review the important statement from the American Academy of Pediatrics, Committee on Fetus and Newborn, and Canadian Pediatric Society, Fetus and Newborn Committee (2002).

INDICATIONS: Alternative choice to lorazepam for status epilepticus. Treatment of seizures refractory to other combined anticonvulsant agents. Reduces anxiety, and can use for preoperative or preprocedural sedation.

ACTIONS: Exact action is unknown; acts as a central nervous system (CNS) depressant. Like other benzodiazepines, diazepam increases the activity of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) by binding the benzodiazepine receptor sites in the CNS.

DOSAGE: IV, PO.

• Status epilepticus:

  • Neonates: 0.1–0.3 mg/kg/dose IV given over 3–5 minutes, every 15–30 minutes to a maximum total dose of 2 mg. (Not recommended as first line; injection contains benzoic acid, benzyl alcohol, and sodium benzoate.)

  • Infants >30 days and children <5 years: 0.1–0.3 mg/kg/dose given over 3–5 minutes, every 5–10 minutes to a maximum total dose of 5 mg, or 0.2–0.5 mg/dose every 2–5 minutes to a maximum total dose of 5 mg; repeat in 2–4 hours as needed.

• Conscious sedation for procedures:

  • IV: Initial: 0.05-0.1 mg/kg over 3–5 minutes, titrate slowly to effect (maximum total dose 0.25 mg/kg) (Krauss and Green, 2006).

  • PO: 0.2–0.3 mg/kg (maximum dose 10 mg) 45–60 minutes prior to procedure.

• Sedation or muscle relaxation or anxiety:

  • Oral: 0.12–0.8 mg/kg/day in divided doses every 6–8 hours.

  • IV: 0.04–0.3 mg/kg/dose every 2–4 hours to a maximum of 0.6 mg/kg within an 8-hour period if needed.

ADVERSE EFFECTS: May cause rash, vasodilation, bradycardia, respiratory arrest, and hypotension. Use with caution in patients receiving other CNS depressants; may have additive CNS and respiratory depressant effects.

COMMENTS: Observe for and be prepared to manage respiratory arrest. Rapid IV push may cause sudden respiratory depression, apnea, or hypotension. Use of the rectal gel formulation in infants <6 months is not recommended; for use in children <2 years, the safety and efficacy have not been studied; contains benzoic acid, benzyl alcohol, ethanol 10%, propylene glycol, and sodium benzoate.

INDICATIONS AND USE: Persistent hyperinsulinemic neonatal hypoglycemia (oral).

ACTIONS: Nondiuretic thiazide with antihypertensive and hyperglycemic effects. Inhibits the release of insulin from the pancreas and reduces total peripheral vascular resistance by direct relaxation of arteriolar smooth muscle, which results in a decrease in blood pressure and reflex increase in heart rate and cardiac output.

DOSAGE: PO.

• Hyperinsulinemic hypoglycemia:

  • Neonates: Initial: 10 mg/kg/day PO in divided doses every 8 hours; usual range: 5–15 mg/kg/day in divided doses every 8 hours.

  • Infants: Initial: 10 mg/kg/day in divided doses every 8 hours; usual range: 5–20 mg/kg/day in divided doses every 8 hours (Hussain et al, 2004; Kapoor et al, 2009).

ADVERSE EFFECTS: Tachycardia; sodium and fluid retention is common; congestive heart failure (CHF) may cause bilirubin displacement from albumin, hypotension, hyperglycemia, hyperuricemia, rash, fever, leukopenia, thrombocytopenia, and ketosis.

COMMENTS: Oral solution contains propylene glycol and sodium benzoate.

INDICATIONS AND USE: Treatment of potentially life-threatening digoxin or digitoxin toxicity in carefully selected patients; use in life-threatening ventricular arrhythmias secondary to digoxin, acute digoxin ingestion (ie, >4 mg in children), and hyperkalemia (serum potassium >5 mEq/L) in the setting of digoxin toxicity.

ACTIONS: Binds with molecules of free (unbound) digoxin or digitoxin and then is removed from the body by renal excretion.

DOSAGE: IV.

• Dose determination:

  • Determine the dose by determining the total body-loading dose of digoxin (TBL) using either method 1 or method 2.

    • Method 1: An approximation of the amount ingested:

      • TBL of digoxin (in mg) = C (in ng/mL) × 5.6 × body weight (in kg)/1000 or TBL = mg of digoxin ingested (as tablets or elixir) × 0.8.

      • Dose of Digibind (in mg) IV = TB × 76.

      • Dose of digoxin immune Fab (Digibind) (number of vials) IV = TBL/0.5.

    • Method 2: A postdistribution serum digoxin concentration C determination (Table 148–1).

• Acute digoxin toxicity:

  • Ingestion of known amount of digoxin: Each vial (38 mg) IV binds ~0.5 mg digoxin. Bioavailability of digoxin is 0.8 for 0.25 mg tablets or 1 for 0.2 Lanoxicaps.

  • Use the following formula: Dose (in vials) = digoxin ingested (mg) × bioavailability/0.5 mg of digoxin bound/vial.

• Chronic digoxin toxicity:

  • Infants and small children: Single vial (38 mg) IV initially.

  • Or use the following formula: Number of vials needed = (serum digoxin concentration in ng/mL) × (wt in kg)/100, then dose (in mg) = number of vials × 38 mg/vial.

ADVERSE EFFECTS: Caution in renal or cardiac failure; allergic reactions possible; epinephrine should be immediately available; patients may deteriorate due to withdrawal of digoxin and may require IV inotropic support (eg, dobutamine) or vasodilators. Hypokalemia reported following reversal of digitalis intoxication; monitor serum potassium levels.

PHARMACOLOGY: Volume of distribution: Digibind—0.3 L/kg; half-life: Digibind—15–20 hours; renal impairment prolongs the half-life of both agents. Improvement in signs and symptoms occurs within 2–30 minutes following IV infusion.

INDICATIONS AND USE: Treatment of congestive heart failure, atrial fibrillation or flutter, and supraventricular tachycardia.

ACTIONS: Exerts a positive inotropic effect (increased myocardial contractility). Its negative chronotropic effects (antiarrhythmic actions/decrease in heart rate) are due to the slowing of conduction through the sinoatrial (SA) and atrioventricular (AV) nodes caused by vagal stimulation.

DOSAGE: IV, PO. Total digitalizing dose (TDD) to be divided one-half, one-fourth, and one-fourth every 8 hours. Note: Oral doses (elixir) are ~25% higher than IV doses listed in the following.

• Preterm neonates:

  • TDD: 15–25 mcg/kg IV or 20–30 mcg/kg PO.

  • Daily maintenance: 4–6 mcg/kg/dose IV every 24 hours or 5–7.5 mcg/kg/dose PO every 24 hours.

• Full-term neonates:

  • TDD: 20–30 mcg/kg IV, 25–35 mcg/kg PO.

  • Daily maintenance: 5–8 mcg/kg/day IV divided every 12 hours or 6–10 mcg/kg/day PO divided every 12 hours.

• 1 month to 2 years:

  • TDD: 30–50 mcg/kg IV or 35–60 PO mcg/kg.

  • Daily maintenance: 7.5–12 mcg/kg/day IV or 10–15 mcg/kg/day PO divided every 12 hours.

ADVERSE EFFECTS: Sinus bradycardia may be a sign of digoxin toxicity. Any dysrhythmias (paroxysmal ventricular contractions, bradycardia, tachycardia) in a child on digoxin should be considered as digoxin toxicity. The gastrointestinal (GI) and central nervous system (CNS) symptoms are not frequently seen in children. To manage toxicity, see Digibind.

COMMENTS: Therapeutic levels: 0.5–2.0 ng/mL. Considerable overlap exists between toxic and therapeutic serum levels. Digoxin-like immunoreactive substance (DLIS) may cross-react with digoxin immunoassay and falsely increases serum concentrations; DLIS has been found in neonates. Use with caution and reduce dosage in patients with renal impairment; use with caution in patients with sinus nodal disease (may worsen condition). Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Hypercalcemia may increase the risk of digoxin toxicity. Contraindicated in second- and third-degree block, idiopathic hypertrophic subaortic stenosis, and atrial flutter or fibrillation with slow ventricular rates.

INDICATIONS AND USE: To increase cardiac output during states of depressed contractility, such as septic shock, organic heart disease, or cardiac surgical procedures. Treat hypotension and hypoperfusion related to myocardial dysfunction.

ACTIONS: A direct β₁-agonist that increases myocardial contractility, oxygen delivery, and oxygen consumption; actions on β₂- and α-adrenergic receptors are much less marked than those of dopamine. Unlike dopamine, dobutamine does not cause release of endogenous norepinephrine, nor does it have any effect on dopaminergic receptors.

DOSAGE: IV.

• 2–20 mcg/kg/minute by continuous infusion and titrate to desired response. Maximum: 40 mcg/kg/minute.

ADVERSE EFFECTS: Tachycardia and arrhythmias at higher doses, hypotension if patient is hypovolemic, ectopic heartbeats, and elevated blood pressure.

PHARMACOLOGY: Has more prominent effect on cardiac output than dopamine and less effect on blood pressure. Onset of action 1–2 minutes; peak effect in 10 minutes. Serum half-life is several minutes. Metabolized in liver and renally excreted.

COMMENTS: Correct hypovolemia prior to initiation of therapy; contraindicated in idiopathic subaortic stenosis and atrial fibrillation.

INDICATIONS AND USE: To increase cardiac output, blood pressure, renal perfusion, and glomerular filtration rate (GFR) (low dosages), which persists despite volume resuscitation.

ACTIONS: Actions are dose dependent. Low doses act directly on dopaminergic receptors to produce renal and mesenteric vasodilation. In moderate doses, β₁-adrenergic effects become prominent, resulting in a positive inotropic effect on the myocardium. High doses stimulate α-adrenergic receptors, producing increased peripheral resistance (vasoconstriction and increased blood pressure) and renal vasoconstriction.

DOSAGE: IV. Note: Dose-effect relationship is speculative in neonates.

• Continuous IV infusion:

  • 1–20 mcg/kg/minute; titrate to desired response.

  • Low: 1–5 mcg/kg/minute may increase renal perfusion and urine output.

  • Moderate: 5–15 mcg/kg/minute facilitates increased cardiac output, renal blood flow, heart rate, cardiac contractility, blood pressure.

  • High: >15 mcg/kg/minute causes systemic vasoconstriction and blood pressure.

ADVERSE EFFECTS: Dopamine may cause ectopic heartbeats, tachycardia, ventricular arrhythmias, hypertension, and azotemia. Gangrene of the extremities has occurred with high doses over prolonged periods. Extravasation may cause tissue necrosis and sloughing of surrounding tissues; if this occurs, infiltrate area with a small amount (1 mL) of phentolamine, made by diluting 2.5–5 mg in 10 mL preservative-free normal saline (NS); do not exceed 0.1 mg/kg or 2.5 mg total for neonates and 0.1–0.2 mg/kg or 5 mg total for infants (see Chapter 31).

PHARMACOLOGY: Rapidly metabolized; serum half-life 2–5 minutes, variable clearance. Individual developmental differences in endogenous norepinephrine stores; α-adrenergic, β-adrenergic, and dopaminergic receptor function and the ability of the neonatal heart to increase stroke volume will affect response to different dopamine doses.

COMMENTS: Administration of phenytoin IV to patients receiving dopamine may result in severe hypotension and bradycardia; therefore, use with extreme caution. Do not infuse through umbilical arterial catheter or other arterial catheter.

INDICATIONS AND USE: Reduce frequency of pulmonary infections and improve pulmonary function in cystic fibrosis patients; treatment of atelectasis as a result of mucous plugging that has failed to respond to conventional therapies.

ACTIONS: Selectively cleaves DNA resulting in a reduction of the viscosity of mucus in pulmonary secretions.

DOSAGE: ETT.

• 1.25–2.5 mL/dose administered once or twice daily nebulized; instillation into endotracheal tube.

ADVERSE EFFECTS: Airway obstruction secondary to mobilization of secretions in airway, desaturations, fever, cough, dyspnea, wheezing.

PHARMACOLOGY: Recombinant human DNA enzyme; hydrolyzes DNA released by degenerating leukocytes from purulent pulmonary secretions resulting in decreased viscosity.

COMMENTS: Not approved for use in infants and children ≤5 years of age; however, studies with small numbers of children as young as 3 months have shown efficacy and similar side effect profile.

INDICATIONS AND USE: Apnea of prematurity unresponsive to methylxanthine therapy.

ACTIONS: Stimulates respiration through action on central respiratory centers and reflex stimulation of carotid, aortic, or other peripheral chemoreceptors; decreases Pco₂ and increases minute ventilation and tidal volume without changing respiratory rate or inspiratory and expiratory times.

DOSAGE: IV.

• Loading dose: 2.5–3 mg/kg IV over 30 minutes followed by maintenance dose.

• Continuous IV infusion: 0.5–1.5 mg/kg/hour (maximum 2.5 mg/kg/hour); decrease the infusion rate when control of apnea is achieved.

ADVERSE EFFECTS: Hypertension, QT prolongation with heart block, tachycardia, skeletal muscle hyperactivity, abdominal distention, increased gastric residuals, bloody stools, necrotizing enterocolitis, vomiting, jitteriness, hyperglycemia, and glycosuria.

PHARMACOLOGY: Therapeutic range: 1.5–3 mcg/mL (<5 mcg/mL). Onset of respiratory stimulation is 20–40 seconds; maximum effect is 1–2 minutes; duration is 5–12 minutes.

COMMENTS: Use cautiously in premature neonates because of its side effects. Avoid use during the first few days of life, when hypertensive episodes may be associated with increased risk of intraventricular hemorrhage; contraindicated in cardiovascular and seizure disorders. Doxapram contains benzyl alcohol.

INDICATIONS AND USE: Treatment of moderate to severe hypertension and heart failure by reducing left ventricular preload and afterload.

ACTIONS: An angiotensin-converting enzyme (ACE) inhibitor that acts by inhibiting the conversion of angiotensin I to angiotensin II and results in lower levels of angiotensin II, which causes an increase in plasma renin activity and a reduction in aldosterone secretion and the breakdown of bradykinin, causing vasodilation. Enalapril increases sodium and fluid loss, and serum potassium.

DOSAGE: IV, PO.

• IV: 5–10 mcg/kg/dose every 8–24 hours. The frequency depends on blood pressure response. Monitor patient closely.

• PO: Initial: 0.04–0.1 mg/kg/day given every 24 hours; initiate at the lower end of the range and titrate to effect as required every few days; may need to dose every 6 hours. Maximum dose is typically 0.15 mg/kg/dose as frequently as every 6 hours.

ADVERSE EFFECTS: Hypotension, hyperkalemia, decreased renal function, oliguria, cough, anemia, neutropenia, and angioedema.

PHARMACOLOGY: Onset of action after oral dose is 1–2 hours. The duration of action is variable (8–24 hours).

COMMENTS: Use with extreme caution in renal dysfunction; reduce dose. Use a low initial dose to avoid a profound drop in blood pressure, especially in patients on diuretics who are hyponatremic or hypovolemic. Monitor blood pressure hourly for the first 12 hours. Note that the IV dose is much smaller than the PO dose; use caution to adjust the dose when changing route of administration.

INDICATIONS AND USE: Prophylaxis and treatment of thromboembolic disorders. (See Chapter 87.)

ACTIONS: Low molecular weight heparin that potentiates the action of antithrombin III and inactivates coagulation factor Xa and factor IIa (thrombin).

DOSAGE: Subcutaneous.

• Initial treatment:

  • Infants <2 months: 1.5 mg/kg subcutaneous every 12 hours.

  • Infants >2 months and children ≤18 years: 1 mg/kg subcutaneous every 12 hours.

  • Maintenance: Adjust dose to maintain antifactor Xa level between 0.5 and 1.0 units/mL. It may take several days to reach target range. Preterm infants may require higher doses to maintain antifactor Xa levels in target range: mean dose of 2 mg/kg every 12 hours, range of 0.8–3 mg/kg every 12 hours.

• Initial prophylaxis:

  • Infants <2 months: 0.75 mg/kg subcutaneous every 12 hours.

  • Infants >2 months and children ≤18 years: 0.5 mg/kg subcutaneous every 12 hours.

  • Maintenance: Adjust to maintain antifactor Xa level between 0.1 and 0.4 units/mL.

ADVERSE EFFECTS: Bleeding, intracranial hemorrhage, thrombocytopenia (incidence of heparin-induced thrombocytopenia is less than that with heparin therapy). Hematoma, irritation, ecchymosis, and erythema can occur at the injection site.

PHARMACOLOGY: Measure antifactor Xa levels 4 hours after a dose. After target level is reached, dosage adjustments may be required once or twice a month. Preterm infants and infants with hepatic or renal dysfunction may require more frequent adjustments.

COMMENTS: Compared with standard heparin, enoxaparin has much less activity against thrombin. Low antithrombin plasma concentration reduces the efficacy in neonates. Enoxaparin is less likely to cause thrombocytopenia and osteoporosis.

INDICATIONS AND USE: Bradycardia, cardiac arrest, cardiogenic shock, anaphylactic reactions, and bronchospasm.

ACTIONS: Acts directly on both α- and β-adrenergic receptors; β₂ effects predominate at lower doses. Exerts both positive chronotropic and inotropic effects on the heart, and relaxes bronchial smooth muscle. The α-adrenergic stimulation increases systolic blood pressure and constricts renal blood vessels.

DOSAGE: IV, ETT.

• IV bolus: (1:10,000) 0.01–0.03 mg/kg (0.1–0.3 mL/kg) every 3–5 minutes PRN. Follow administration with a flush of 0.5–1 mL of normal saline (NS).

• IV infusion: Initial rate: 0.1 mcg/kg/minute; titrate to desired response to a maximum of 1 mcg/kg/minute.

• Endotracheal: 0.05–0.1 mg/kg (0.5–1 mL/kg of 1:10,000 solution) every 3–5 minutes until IV access is established or return of spontaneous circulation; immediately followed by 1 mL NS.

• Nebulization: 0.25–0.5 mL of 2.25% racemic epinephrine diluted in 3 mL of NS.

ADVERSE EFFECTS: Hypertension, tachycardia, nausea, pallor, tremor, cardiac arrhythmias, increased myocardial oxygen consumption, and decreased renal and splanchnic blood flow.

ACTION AND SPECTRUM: Macrolide antibiotic; bactericidal or bacteriostatic depending on the tissue concentration of drug and the microorganism. Spectrum of activity is broad and includes susceptible streptococci and staphylococci; also Mycoplasma, Legionella, pertussis, Chlamydia, and Campylobacter gastroenteritis.

DOSAGE: PO, IV, ocular.

• Neonates:

  • Oral ethylsuccinate form, postnatal age:

    • <7 days: 20 mg/kg/day PO divided every 12 hours.

    • >7 days:

      • <1.2 kg: 20 mg/kg/day PO divided every 12 hours.

      • 1.2–2 kg: 30 mg/kg/day PO divided every 8 hours.

      • >2 kg: 30–40 mg/kg/day PO divided every 6–8 hours.

    • IV lactobionate form: 5–10 mg/kg/dose every 6 hours for severe infections or when PO route is unavailable.

  • Chlamydial conjunctivitis or pneumonia: Oral: ethylsuccinate—50 mg/kg/day divided every 6 hours for 14 days (based on AAP Red Book, 2012).

• Infants and children:

  • Oral base and ethylsuccinate: 30–50 mg/kg/day PO divided every 6–8 hours; do not exceed 2 grams/day (as base) or 3.2 grams/day (as ethylsuccinate). Note: 200 mg erythromycin ethylsuccinate produces the same serum levels as 125 mg erythromycin base due to absorptive differences.

  • IV lactobionate: 15–50 mg/kg/day IV divided every 6 hours, not to exceed 4 grams/day.

  • Stearate: 30–50 mg/kg/day PO divided every 6 hours; maximum 2 grams/day.

  • Chlamydia trachomatis: Child <45 kg: 50 mg/kg/day PO divided every 6 hours for 14 days; maximum 2 grams/day.

  • Pertussis treatment or postexposure prophylaxis: Ethylsuccinate: 40 mg/kg/day divided every 6 hours for 14 days. Note: Azithromycin considered first-line agent in infants <1 month of age; erythromycin is associated with infantile hypertrophic pyloric stenosis in neonates (based on AAP Red Book. 2012).

  • Ophthalmic prophylaxis: 0.5 to 1-cm ribbon in each eye once.

  • Ophthalmic for acute infection: 0.5 to 1-cm ribbon in each eye every 6 hours.

  • Gastrointestinal motility disorders: 10 mg/kg/dose PO every 8 hours, 30 minutes before feedings; in neonates up to 2 weeks old, exposure to high doses (30–50 mg/kg/day) for ≥14 days has been associated with a 10-fold increase in the risk of hypertrophic pyloric stenosis. May be given IV 1–3 mg/kg infused over 60 minutes, but PO is preferred route.

ADVERSE EFFECTS: Infantile hypertrophic pyloric stenosis, stomatitis, epigastric distress, transient cholestatic hepatitis, and allergic reactions occur rarely. Cardiac toxicity requiring cardiopulmonary resuscitation (CPR) may occur with IV erythromycin; reduce risk of arrhythmias by slowly infusing over 1 hour.

PHARMACOLOGY: Hepatic metabolism, excreted via the bile and kidneys. Half-life is 1.5–3 hours (prolonged in renal failure). May cause increased serum levels of theophylline, digoxin, and carbamazepine.

COMMENTS: Parenteral forms are painful and irritating; dilute to 5 mg/mL and infuse >60 minutes. Do not use IM.

INDICATIONS AND USE: To stimulate erythropoiesis and decrease the need for erythrocyte transfusions (rEpo) in preterm infants; treatment of anemia of prematurity.

ACTIONS: Epoetin alfa (EPO) induces erythropoiesis by stimulating division and differentiation of committed erythroid progenitor cells; induces release of reticulocytes from the bone marrow into the bloodstream where they mature to erythrocytes (dose-response relationship).

DOSAGE: Subcutaneous.

• 200–400 units/kg/dose, 3–5 times per week, for 2–6 weeks. Total dose per week: 600–1400 units/kg/week. Short course: 300 units/kg/dose daily × 10 days.

ADVERSE EFFECTS: May cause hypertension, edema, fever, rash, possible seizures, transient early thrombocytosis and late neutropenia, polycythemia, and local skin reaction at injection site.

PHARMACOLOGY: Noticeable effects on hematocrit and reticulocyte counts occur within 2 weeks. Half-life in neonates: subcutaneous—17.6 hours on day 3 of therapy, 11.2 hours on day 10 of therapy.

COMMENTS: Supplement with oral iron therapy 3–8 mg/kg/day; optimal response is achieved when iron stores are adequate. EPO should be used in conjunction with restrictive transfusion guidelines and minimizing of phlebotomy losses. EPO is not a substitute for emergency blood transfusion. Do not use in patients with uncontrolled hypertension.

INDICATIONS AND USE: Treatment of supraventricular tachycardia (SVT); acute management of postoperative tachycardia and hypertension.

ACTIONS: Competitively blocks response to β_1-adrenergic stimulation with little or no effect on β₂-receptors except at high doses.

DOSAGE: IV.

• Neonatal (limited data available):

  • SVT: 100 mcg/kg/minute by continuous infusion; adjust dose based on individual clinical response and tolerance. Increase by 50–100 mcg/kg/minute every 5 minutes until ventricular rate is controlled.

  • Postoperative tachycardia and hypertension: 50 mcg/kg/minute by continuous infusion; increase by 25–50 mcg/kg/minute every 5 minutes until target blood pressure is reached.

  • Maximum dosage: 200 mcg/kg/minute.

• Infants and children (limited data available):

  • SVT: 100–500 mcg/kg over 1 minute; titrate infusion rate by 50–100 mcg/kg/minute every 5–10 minutes until ventricular rate is controlled.

  • Postoperative tachycardia and hypertension: Loading dose of 500 mcg/kg/minute over 1 minute followed by continuous infusion of 50–250 mcg/kg/minute; titrate infusion rate by 50 mcg/kg/minute every 10 minutes until target blood pressure is reached.

  • Maximum dose: 1000 mcg/kg/minute.

ADVERSE EFFECTS: Hypotension and bradycardia at higher doses; peripheral ischemia, agitation, local induration, inflammation phlebitis, and skin necrosis after extravasation.

PHARMACOLOGY: Ultra-short-acting β₁-selective blocking agent with half-life of 2.8–4.5 minutes and duration of action of 10–30 minutes. Onset of action ranges from 2 to 10 minutes; shorter if loading dose is given.

COMMENTS: Monitor IV site for infiltration, especially with the use of concentrations >10 mg/mL.

INDICATIONS AND USE: Reserved for use only when other diuretics have failed to produce effective diuresis due to toxicities.

ACTIONS: Loop diuretic that inhibits reabsorption of sodium and chloride in ascending loop of Henle and distal tubules, resulting in increased excretion of water, sodium, chloride, magnesium, and calcium. The inhibition of sodium reabsorption is greater than that of other diuretics. Also, there is not a direct effect on the pulmonary vasculature, as seen with furosemide.

DOSAGE: IV, PO.

• IV: 0.5–1 mg/kg/dose. Repeat doses are not routinely recommended; however, if indicated, repeat doses every 8–12 hours.

• PO: 1 mg/kg/dose once daily; increase at intervals of 2–3 days to a maximum of 3 mg/kg/day.

ADVERSE EFFECTS: Inject IV dose slowly over several minutes; may cause hypotension, dehydration, electrolyte depletion, diarrhea, gastrointestinal (GI) bleeding, hearing loss, rash, local irritation and pain, hematuria, and, rarely, hypoglycemia and neutropenia.

COMMENTS: Close medical supervision and dose evaluation is required; may increase risk of gastric hemorrhage associated with corticosteroid treatment.

INDICATIONS AND USE: Prevention and short-term treatment of gastroesophageal reflux disease (GERD), stress, gastric and duodenal ulcers, and gastrointestinal (GI) hemorrhage.

ACTIONS: Inhibits gastric acid secretion by reversible, competitive antagonism of histamine on the H2 receptor of the gastric parietal cells.

DOSAGE: IV, PO.

• Neonates and infants <3 months: 0.25–0.5 mg/kg/dose every 24 hours slow IV push.

• GERD: <3 months: 0.5 mg/kg PO once daily for up to 8 weeks; 3–12 months: 0.5 mg/kg PO twice daily for up to 8 weeks.

ADVERSE EFFECTS: Hypotension and cardiac arrhythmias with rapid IV administration; bradycardia, tachycardia, hypertension, thrombocytopenia, elevated liver enzymes, cholestatic jaundice, elevated blood urea nitrogen (BUN) and creatinine, and proteinuria.

PHARMACOLOGY: Onset of GI effect is within 1 hour. Duration is 10–12 hours. Elimination 65–70% unchanged in urine.

COMMENTS: Limited experience in infants and children. Famotidine does not inhibit cytochrome P450.

INDICATIONS AND USE: Analgesia, anesthesia, and sedation.

ACTIONS: A synthetic opiate agonist that binds to the opioid μ-receptors within the central nervous system, (CNS), increases the pain threshold, alters pain reception, and inhibits ascending pain pathway. Acts similarly to morphine and meperidine but without the cardiovascular effects of those drugs and with shorter respiratory depressant effects.

DOSAGE: IV.

• Neonates:

  • Analgesia: International Evidence-Based Group for Neonatal Pain recommendations (Anand et al, 2001).

    • Intermittent doses: Slow IV push: 0.5–3 mcg/kg/dose.

    • Continuous infusion: 0.5–2 mcg/kg/hour.

• Neonates and younger infants:

  • Analgesia/sedation: 1–4 mcg/kg/dose slow IV push every 2–4 hours as needed.

  • Continuous analgesia/sedation: Initial 1–2 mcg/kg IV bolus then 0.5–1mcg/kg/hour; titrate upward.

  • Continuous sedation/analgesia during extracorporeal membrane oxygenation/extracorporeal life support (ECMO/ECLS): Initial IV bolus: 5–10 mcg/kg slow IV push over 10 minutes, then 1–5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO/ECLS.

  • Anesthesia: 5–50 mcg/kg/dose.

ADVERSE EFFECTS: CNS and respiratory depression; bradycardia; skeletal muscle and chest wall rigidity with reduced pulmonary compliance, apnea, and laryngospasm, which is reversible with naloxone. Tolerance and withdrawal symptoms reported with continuous use. Urinary retention, gastrointestinal symptoms, and biliary spasms may occur.

PHARMACOLOGY: Metabolized in liver by CYP3A4 enzyme and excreted by kidneys. Liver failure prolongs serum half-life; 80–85% protein bound; lipid soluble. The volume of distribution and half-life are highly variable.

COMMENTS: Synthetic opioid narcotic analgesic that is 50–100 times more potent on a weight basis than morphine. Concurrent ventilatory assistance is suggested with its use. Tachyphylaxis occurs after several days of therapy. Adheres to ECMO/ECLS filter membranes; may have to adjust the dose.

INDICATIONS AND USE: Treatment and prevention of iron deficiency anemia; supplemental therapy for patients receiving epoetin alfa.

ACTIONS: Iron is required for production of heme proteins. Iron is released from the plasma to replenish the depleted stores in the bone marrow where it is incorporated into hemoglobin.

DOSAGE: PO. Recommendations of the American Academy of Pediatrics (AAP) for treatment and prevention of iron deficiency; dosages are for elemental iron.

• Term infants: 1 mg elemental iron/kg/day divided every 12–24 hours. Begin at 4 months of age.

• Preterm infants: 2–4 mg elemental iron/kg/day divided every 12–24 hours. Begin therapy by 1 month of age.

• Iron deficiency anemia: 6 mg/kg/day in 3 divided doses.

• Iron supplementation with erythropoietin: 6 mg/kg/day in 1 or 2 divided doses.

ADVERSE EFFECTS: Gastrointestinal irritation (vomiting, diarrhea, constipation, and darkened stool color).

COMMENTS: The use of iron-fortified formulas during the first year of life usually prevents iron deficiency anemia in both preterm and term infants. Iron-fortified formulas can be fed safely to preterm infants. Of the ferrous salts available (sulfate, fumarate, and gluconate), sulfate is preferred. Note: Multiple concentrations of ferrous sulfate oral liquid exist. Caution parents to guard against iron poisoning from accidental ingestion. Antidote is chelation with deferoxamine; consult specialized references and regional Poison Control Center for further information.

INDICATIONS AND USE: For the reduction of neutropenia in neonates with sepsis.

ACTIONS: Stimulates the production, maturation, and activation of neutrophil granulocytes and activates neutrophils to enhance both their migration and cytotoxicity.

DOSAGE: IV or subcutaneous.

• Neonates: 5–10 mcg/kg/day IV/subcutaneous once daily for 3–5 days has been administered to neutropenic neonates with sepsis. Refer to individual protocols.

ADVERSE EFFECTS: Thrombocytopenia, leukocytosis, transient decrease in blood pressure.

PHARMACOLOGY: There is an immediate transient leukopenia with nadir occurring 5–15 minutes after an IV dose or 30–60 minutes after a subcutaneous dose followed by a sustained elevation in neutrophil levels within the first 24 hours, which plateaus in 3–5 days. Following discontinuation of G-CSF, absolute neutrophil count (ANC) decreases by 50% within 2 days and returns to pretreatment levels within 1 week; white blood cell (WBC) counts return to normal range in 4–7 days.

INDICATIONS AND USE: Prevention and treatment of sustained, life-threatening ventricular arrhythmias; prophylaxis of paroxysmal atrial flutter and fibrillation and supraventricular tachycardia. Contraindicated in patients with structural heart disease.

ACTIONS: Class 1C antiarrhythmic that slows conduction throughout the myocardium, with the greatest effect on the His-Purkinje system.

DOSAGE: PO.

• Initial dose: 1–3 mg/kg/day divided into 2 or 3 doses; maintenance dose of 3–6 mg/kg/day up to 8 mg/kg/day divided into 2 or 3 doses. Titrate dose based on response. Higher doses have been associated with increased risk of pro-arrhythmias.

ADVERSE EFFECTS: May cause new or worsening ventricular arrhythmias, heart block, bradycardia, torsade de pointes, dizziness, blurred vision, headache, blood dyscrasias, and hepatic dysfunction.

PHARMACOLOGY: Demonstrates both local anesthetic and moderate inotropic effects. Reduction in conduction throughout the myocardium results in increased PR, QRS, and QT intervals. Infant formula and milk products may inhibit absorption. Elimination half-life in children <1 year of age is ~11–12 hours and in newborns and after maternal administration is ~29 hours. Half-life increased with congestive heart failure (CHF) or renal impairment.

COMMENTS: Therapeutic levels: 0.2–1 mcg/mL.

INDICATIONS AND USE: Antifungal agent for treatment of susceptible fungal infections including oropharyngeal and esophageal candidiasis; treatment of systemic candidal infections including urinary tract infection, peritonitis, cystitis, and pneumonia. There continues to be an increased number of strains of Candida isolated with decreased susceptibility to fluconazole. Fluconazole is more active against C. albicans than other candida strains like C. parapsilosis, C. glabrata, and C. tropicalis; alternative to amphotericin B in patients with preexisting renal impairment or when requiring concomitant therapy with other potentially nephrotoxic drugs.

ACTIONS: Interferes with fungal cytochrome P450 and sterol C-14 α-demethylation, resulting in a fungistatic effect.

DOSAGE: IV, PO.

• Systemic infections, including meningitis:

  • ≤29 weeks' gestation:

    • Postnatal age 0–14 days: 12–25 mg/kg loading dose, then 6–12 mg/kg IV/PO every 48 hours.

    • Postnatal age >14 days: 12–25 mg/kg loading dose, then 6–12 mg/kg IV/PO every 24 hours.

• 30 weeks' gestation and older:

  • Postnatal age 0–7 days: 12–25 mg/kg loading dose, then 6–12 mg/kg IV/PO every 48 hours.

  • Postnatal age >7 days: 12–25 mg/kg loading dose, then 6–12 mg/kg IV/PO every 24 hours.

• Neonates >14 days, infants, and children:

  • Oropharyngeal candidiasis IV or PO: Day 1: 6 mg/kg IV/PO, then 3 mg/kg IV/PO minimum 14 days.

  • Esophageal candidiasis IV or PO: As above but 21-day minimum.

  • Candidiasis prophylaxis: 3–6 mg/kg/dose IV infusion twice weekly has been used in extremely low birthweight (ELBW) infants at increased risk of invasive fungal infection. Dose of 6 mg/kg may be used if targeting Candida strains with higher minimal inhibitory concentrations (MICs) of 4–8 mcg/mL.

ADVERSE EFFECTS: Usually well tolerated. Vomiting, diarrhea, rash, and elevations in liver transaminases. Eosinophilia, leukopenia, thrombocytopenia, neutropenia.

PHARMACOLOGY: Good oral bioavailability; absorption not affected by food with peak serum concentrations achieved within 1 hour; good penetration into tissues and body fluids including cerebrospinal fluid (CSF). Less than 12% protein bound, primarily excreted unchanged in urine.

COMMENTS: Reduce dose in renal dysfunction. Use caution in preexisting renal dysfunction. Monitor liver function tests. Cimetidine and rifampin decrease fluconazole levels. Hydrochlorothiazide increases fluconazole area under the curve (AUC). Fluconazole interferes with the metabolism of barbiturates, theophylline, midazolam, phenytoin, and zidovudine. Contraindicated in patients receiving cisapride.

ACTION AND SPECTRUM: Antifungal agent that penetrates fungal cells and is converted to fluorouracil, which competes with uracil interfering with fungal RNA and protein synthesis. Used in combination with amphotericin B in the treatment of serious candida or cryptococcal pulmonary or urinary tract infections, sepsis, meningitis, or endocarditis (resistance emerges if flucytosine is used as a single agent); used in combination with another antifungal agent for treatment of chromomycosis and aspergillosis.

DOSAGE: PO. Administer in combination with amphotericin B due to development of resistance.

• Neonates: Initial: 25–100 mg/kg/day PO in divided doses every 12–24 hours.

• Infants and children: 50–150 mg/kg/day PO divided every 6 hours.

• Renal impairment: Use lower initial dose.

  • Creatinine clearance 20–40 mL/minute: Usual dose every 12 hours.

  • Creatinine clearance 10–20 mL/minute: Usual dose every 24 hours.

  • Creatinine clearance <10 mL/minute: Usual dose every 24–48 hours.

ADVERSE EFFECTS: Vomiting, diarrhea, rash, anemia, leukopenia, thrombocytopenia, elevated liver enzymes and bilirubin, increased blood urea nitrogen (BUN) and creatinine, and central nervous system (CNS) disturbances.

PHARMACOLOGY: Desired peak serum concentrations: 25–100 mcg/mL. Half-life, neonates: 4–34 hours. Renal elimination.

COMMENTS: Toxicities related to serum concentration >100 mcg/mL and usually reversible when drug is discontinued or dose is reduced. Amphotericin B may increase toxicity by decreasing renal excretion.

INDICATIONS AND USE: Used for partial replacement therapy for adrenocortical insufficiency and treatment of salt-losing forms of congenital adrenogenital syndrome, usually used with concurrent hydrocortisone in patients with salt-losing forms of congenital adrenogenital syndrome.

ACTIONS: Fludrocortisone is a potent mineralocorticoid with glucocorticoid activity that acts on the distal tubule to increase loss of potassium and hydrogen ion and increases reabsorption of sodium with subsequent water retention.

DOSAGE: PO.

• Usual: 0.05–0.1 mg/day (50–100 mcg/day) as a single daily dose. (Note: Doses are the same regardless of patient weight or age. Newborns are insensitive to the drug and may require larger doses than adults). May administer with feedings.

• Congenital adrenal hyperplasia (salt losers): Maintenance: 0.05–0.3 mg/day (American Academy of Pediatrics, Section on Endocrinology and Committee on Genetics, 2000).

ADVERSE EFFECTS: Hypertension, congestive heart failure, gastrointestinal upset, hypokalemia, growth suppression, hyperglycemia, salt and water retention, edema, hypothalamic-pituitary-adrenal suppression, osteoporosis, and muscle weakness resulting from excessive potassium loss. Monitor serum electrolytes (particularly sodium and potassium).

COMMENTS: Fludrocortisone 0.1 mg has a sodium retention activity equal to deoxycorticosterone acetate (DOCA) 1 mg.

INDICATIONS AND USE: Reversal of benzodiazepine sedative effect; management of benzodiazepine overdose.

ACTIONS: Competitive inhibition of effects of benzodiazepines on the γ-aminobutyric acid (GABA)/benzodiazepine receptor complex.

DOSAGE: IV.

• 5–10 mcg/kg/dose IV over 15 seconds; may repeat every 45 seconds until patient is awake. The maximum total cumulative dose is 50 mcg/kg (0.05 mg/kg) or 1 mg, whichever is lower. Administer IV through a large vein to minimize pain on injection and phlebitis. Monitor injection site for extravasation.

ADVERSE EFFECTS: Very limited data in neonates; hypotension, arrhythmias reported in adults. Use with caution in patients with preexisting seizure disorders. May precipitate acute withdrawal in patients with long-term benzodiazepine exposure.

PHARMACOLOGY: Highly lipid soluble. In children, peak concentration is achieved in 3 minutes and half-life is 20–75 minutes. There are very limited data in neonates.

INDICATIONS AND USE: Treatment of anemia due to nutritional deficit, prematurity, megaloblastic anemia, or macrocytic anemia.

ACTIONS: Required for formation of a number of coenzymes in many metabolic systems, specifically for purine and pyrimidine synthesis, nucleoprotein synthesis, and maintenance of erythropoiesis. Also stimulates white blood cell (WBC) and platelet production in folate deficiency anemia.

DOSAGE: PO, IM, IV, subcutaneous.

• Recommended daily allowance:

  • Premature neonates: 50 mcg/day PO (~15 mcg/kg/day).

  • Neonates to 6 months: 25–35 mcg/day PO.

  • Children 6 months to 3 years: 150 mcg/day PO.

• Folic acid deficiency (PO, IM, IV, subcutaneous):

  • Infants: 0.1 mg/day.

  • Children <4 years: Up to 0.3 mg/day.

ADVERSE EFFECTS: Generally well tolerated.

PHARMACOLOGY: Absorbed in the proximal portion of small intestine; metabolized in the liver.

CAUTION: May be confused with folic acid.

INDICATIONS: Adjunctive treatment with sulfadiazine and pyrimethamine to prevent hematologic toxicity; antidote for folic acid antagonist overdosage.

ACTIONS: Folinic acid is a derivative of tetrahydrofolic acid, a reduced form of folic acid; enables purine and thymidine synthesis, required for normal erythropoiesis.

DOSAGE: PO, IV.

• Folic acid antagonist overdosage (eg, pyrimethamine, trimethoprim):

  • 5–15 mg PO/IV per day for 3 days or until blood counts are normal or 5 mg PO/IV every 3 days; doses of 6 mg/day are needed for patients with platelet counts <100,000/mm³.

• Adjunctive treatment with sulfadiazine to prevent hematologic toxicity (for toxoplasmosis):

  • Infants and children: 5–10 mg PO/IV once daily; repeat every 3 days.

ADVERSE EFFECT: Thrombocytosis.

PHARMACOLOGY: Onset of action following oral dose is within 30 minutes; IV administration is within 5 minutes. Metabolism: Folinic acid is rapidly converted to 5-methyl-tetrahydrofolate (5MTHF), an active metabolite, in the intestinal mucosa and the liver.

INDICATIONS AND USE: Management of generalized convulsive status epilepticus; used for short-term parenteral administration of phenytoin, prevention and management of seizures.

ACTIONS AND SPECTRUM: Fosphenytoin is a water-soluble prodrug of phenytoin that is rapidly converted by phosphatases in blood and tissues.

DOSAGE: IM, IV (fosphenytoin 1 mg phenytoin equivalent [PE] = phenytoin 1 mg).

• Loading dose: 15–20 mg PE/kg IM or IV infusion over at least 10 minutes.

• Maintenance dose: 4–8 mg PE/kg every 24 hours IM or IV slow push. Start maintenance dose 24 hours after loading dose.

• Term infants >1 week of age: May require doses up to 8 mg PE/kg/dose every 8–12 hours.

ADVERSE EFFECTS: Hypotension (with rapid IV administration), vasodilation, tachycardia, bradycardia, drowsiness.

PHARMACOLOGY: Conversion to phenytoin half-life is ~7 minutes. Fosphenytoin is highly protein bound. (Caution in neonates with hyperbilirubinemia: Both fosphenytoin and bilirubin displace phenytoin from protein-binding sites, which results in increased serum-free phenytoin concentrations.)

COMMENTS: Dilute with 5% dextrose in water (D5W) or normal saline (NS) to 1.5–25 mg PE/mL. Maximum rate of infusion is 1.5 mg PE/kg/minute. Flush IV with saline pre- and postadministration. Monitor blood pressure during infusion.

INDICATIONS AND USE: Fluid overload, pulmonary edema, congestive heart failure, and hypertension.

ACTIONS: Inhibits reabsorption of sodium and chloride in the ascending limb of the loop of Henle and distal rental tubule. Furosemide-induced diuresis results in enhanced excretion of sodium, chloride, potassium, calcium, magnesium, bicarbonate, ammonium, hydrogen, and possibly phosphate. Nondiuretic effects include decreased pulmonary transvascular fluid filtration and improved pulmonary function.

DOSAGE: PO, IM, IV.

• Neonates, premature:

  • PO: 1–4 mg/kg/dose 1–2 times a day as initial dose has been used, and increase slowly if needed; highly variable oral bioavailability.

  • IV or IM: 1 mg/kg/dose every 12–24 hours.

• Infants and children:

  • Oral: 2 mg/kg PO once daily; if effective, may increase in increments of 1–2 mg/kg/dose every 6–8 hours; not to exceed 6 mg/kg/dose. In most cases, it is unnecessary to exceed individual doses of 4 mg/kg or a dosing frequency of once or twice daily.

  • IM, IV: 1–2 mg/kg/dose every 6–12 hours.

  • Continuous infusion: 0.05–0.2 mg/kg/hour; titrate in 0.1 mg/kg/hour increments every 12–24 hours to a maximum infusion rate of 0.4 mg/kg/hour.

ADVERSE EFFECTS: Hypokalemia, hypocalcemia, hyponatremia, and hypercalciuria and with prolonged use nephrocalcinosis and hypochloremic metabolic alkalosis. Ototoxicity is possible especially in association with concurrent use of aminoglycosides.

PHARMACOLOGY: Onset of action: oral within 30–60 minutes; IV: 5 minutes. Duration of action: oral dose is 6–8 hours; IV dose is 2 hours.

INDICATIONS AND USE: Symptomatic congenital cytomegalovirus (CMV) infection for the prevention of progressive hearing loss decreased developmental delay.

ACTIONS AND SPECTRUM: An acyclic nucleoside structurally related to acyclovir, possesses antiviral activity against herpes viruses. Ganciclovir is a prodrug that is phosphorylated to a substrate that inhibits viral DNA synthesis by competitive inhibition of viral DNA polymerases and incorporation into viral DNA resulting in eventual termination of viral DNA elongation. Ganciclovir is preferentially metabolized in virus-infected cells.

DOSAGE: IV.

• Neonates: 6 mg/kg/dose every 12 hours IV, infused over 1 hour. Treat for a minimum of 6 weeks. Reduce dose by half for significant neutropenia (<500 cells/mm³).

ADVERSE EFFECTS: Edema, arrhythmias, hypertension; seizures, sedation; vomiting, diarrhea; neutropenia, thrombocytopenia, leukopenia, anemia, eosinophilia; elevated liver enzymes; phlebitis; retinal detachment in patients with CMV retinitis; hematuria, elevated blood urea nitrogen (BUN), and serum creatinine and dyspnea.

PHARMACOLOGY: Oral bioavailability is poor. Renal excretion is the major route of elimination; primarily excreted unchanged in the urine via glomerular filtration and active tubular secretion.

COMMENTS: Handle and dispose according to guidelines issued for cytotoxic drugs; avoid direct contact of skin or mucous membranes with the powder contained in capsules or the IV solution. Dosage adjustment or interruption of ganciclovir therapy may be necessary in patients with neutropenia and/or thrombocytopenia and patients with impaired renal function.

ACTION AND SPECTRUM: Aminoglycoside with bactericidal activity against gram-negative aerobic bacteria, including most Pseudomonas, Proteus, and Serratia. Some activity against coagulase-positive staphylococci, but ineffective against anaerobes and streptococci.

DOSAGE: IV, IM, intrathecal, intraventricular. Base the initial dose on body weight, then monitor levels and adjust using pharmacokinetics. Many dosing strategies exist such as extended interval, age based, weight based, and traditional.

• Age based:

  • ≤29 weeks postmenstrual age (PMA):

    • 0–7 days: 5 mg/kg/dose IV/IM every 48 hours.

    • 8–28 days: 4 mg/kg/dose IV/IM every 36 hours.

    • ≥29 days: 4 mg/kg/dose IV/IM every 24 hours.

  • 30–34 weeks PMA:

    • 0–7 days: 4.5 mg/kg/dose IV/IM every 36 hours.

    • >7 days: 4 mg/kg/dose IV/IM every 24 hours.

  • ≥35 weeks PMA: 4 mg/kg/dose IV/IM every 24 hours.

• Intrathecal or intraventricular (use preservative-free):

  • Newborns: 1 mg/day.

  • Infants >3 months and children: 1–2 mg/day.

• Ophthalmic solution: 1 drop into each eye every 4 hours.

• Ophthalmic ointment: Apply 2–3 times a day.