MNGHA NEOMEDBOOK (December 2021)

MNGHA Neonatal Drug Reference 2021

MNGHA Neonatal Drug Reference NEOMEDBOOK 6th Edition December 2021

2021 NEOMED BOOK 2

NEOMEDBOOK Dosage Guidelines is for term and preterm infants up to 3 to 6 months chronological age respectively. The dosing for older infants may be different, so please consult your Clinical Pharmacist or other medication reference for Pediatric dosing. Notes: Preterm Infants born at 25 weeks gestation will reach term at 3 months chronological age. This medication reference will be suitable until s/he is 6 months chronological age. 3

2021 NEOMED BOOK 4

Table of Contents Preface........................................................................................................................................................ 7 Acknowledgements ............................................................................................................................ 8 Good Prescribing Habits....................................................................................................................... 9 Commonly-used Abbreviations ........................................................................................................ 10 Chapters: General Dosing Guidelines 1: Neonatal Drug Dosing Guidelines........................................................................................... 11 - 47 2: Antimicrobial Therapy Drug Dosage Guidelines................................................................ 48 - 65 3: Guidelines for the Continuous Infusion of Critical Care Drugs...................................... 66 - 71 4: Vancomycin Monitoring Guidelines........................................................................................ 72 - 75 5: Aminoglycoside Monitoring Guidelines................................................................................ 76 - 78 6: Retinopathy of Prematurity (ROP) Medications.................................................................. 79 - 80 Metabolic Medication Guidelines 7: Emergency Management of Acute Hyperammonemia................................................... 81 - 82 8: Common Inborn Errors of Metabolism Medication and Cofactors.............................. 83 - 87 Management Guidelines of Neonatal Electrolyte Disturbance 9: Initial Fluid Requirement in Neonates.................................................................................... 88 - 90 10: Why it is not safe to use ¼ Normal Saline?......................................................................... 91 - 93 11: Sodium and Potassium Acetate Infusion............................................................................ 94 - 95 12: Management of Hypokalemia................................................................................................ 96 - 98 13: Management of Hyperkalemia............................................................................................... 99 - 100 14: Calcium Dosing in Neonates.................................................................................................... 101 - 104 15: Guidelines for the Administration of Magnesium in Neonates................................... 105 - 108 16: Guidelines for the Administration of Phosphorus in Neonates................................... 109 - 111 17: Parenteral Nutrition in Neonates............................................................................................ 112 - 119 5

2021 NEOMED BOOK Immunization Guidelines 18: General Information about Immunization......................................................................... 120 - 123 19: Ministry of Health (KSA) Recommended Schedule for Immunization of Infants and Children....................................................................... 124 - 125 20: Guidelines for Immunization of preterm infants.............................................................. 126 - 127 21: Guidelines in treating Neonates with Hepatitis B Mothers........................................... 128 - 130 22: Use of Immunoglobulin (IVIG) and HBIG in Neonates.................................................... 131 - 134 Other Guidelines 23: Rotavirus......................................................................................................................................... 135 - 138 24: Treatment of Community-acquired Pneumonia in Childhood................................... 139 - 140 25: Guidelines for the Treatment of Brucellosis....................................................................... 141 - 142 26: Glucocorticoids............................................................................................................................ 143 - 147 27: Guidelines for Warfarin Therapy for INR of 2-3 in Pediatrics........................................ 148 - 149 28: Sodium Nitroprusside............................................................................................................... 150 - 151 29: Drugs to avoid in G6PD Deficiency...................................................................................... 152 - 154 30: Clinical relevant parameters for each antiepileptic drug and assessment of their lactation risk............................................................ 155 - 158 31: Management guidelines of Neonates with HIV-positive mothers............................ 159 - 161 Appendices I: Cardiovascular Drug Compatibility Chart............................................................................... 162 - 164 II: Summary of medications for various Inborn Errors of Metabolism.............................. 165 - 190 III: Composition of Milk Formula per 100mL............................................................................... 191 - 192 IV: Sample of TPN Sheet..................................................................................................................... 193 - 194 V: List of Topical Medications ......................................................................................................... 195 - 197 6

Preface The NEOMEDBOOK project is the collective effort of the medical, nursing, and allied healthcare experts in the field of Neonatology all over the kingdom of Saudi Arabia. This initiative started in 2006 when a Clinical Pharmacist in Pediatrics, Dr. Kwame Amoh, worked with esteemed Neonatologists in the institution to create an updated, accessible, easy-to-follow medication guidelines for our Neonatal Healthcare providers. For many years, the Neonatal drug reference called the “Kwame Book” be- came well-known and widely-used not just in the MNGHA Central Region, but also in other Neonatal units across the kingdom. The Neonatology team continued its efforts in updating the Neonatal Med- ication guidelines, even after Dr. Kwame’s separation from the institution. In early 2019, Neonatology department leaders from all MNGHA Hospitals have agreed to update the Kwame Book and use it as the official and central- ized Neonatal drug reference for all MNGHA Regions. In 2020, after a thorough review by Neonatology and other Pediatric sub- specialties, the Kwame Book was officially renamed as NEOMEDBOOK. 7

2021 NEOMED BOOK Acknowledgement The authors would like to acknowledge the help of all our colleagues involved in the review and update of this drug manual. First, the authors would like to thank each one of the reviewers for their contributions and their time and expertise to this book. Our sincere gratitude goes to DR. KWAME AMOH Pediatric Clinical Pharmacy specialist (from 1996 – 2016) KAMC, Riyadh, KSA who inspired our Neonatology experts to create a centralized, updated, evi- dence-based drug reference. We also thank our first reviewers, the Medical and Nursing Leaders in Neonatal Intensive Care Department of King Abdulaziz Medical City-Riyadh, who worked tirelessly in the initial updates of this book. Many thanks to our esteemed experts from Pediatric Endocrinology, Infectious Dis- eases, and Genetics Divisions who contributed to this project greatly and consistent- ly for many years. The authors would also like to thank the Pharmaceutical Reviewing Committee who took part in the review process. Without their support, this book would not have become a reality. Finally, we would like to thank MNGHA Quality Management, whose guidance and support have become instrumental in the completion of this project. 8

Good Prescribing Habits 1. Write orders legibly. 2. Provide date and time for all orders. 3. Sign all orders appropriately. 4. Write badge number and pager number clearly. 5. If an error is made while writing an order or one is noticed after an order has been written, the order can be cancelled by crossing it out with a single line and initialing it. 6. On the other hand, if an incorrect order has already been forwarded to the pharmacy and needs to be cancelled, then a complete discontinuation order has to be written to that effect. 7. Avoid prohibited abbreviations (eg, write “discontinue” instead of DC; “Micrograms” or “mcg” instead of µg, etc) 8. Spell out “units” and “micrograms” 9. Writing orders for doses < 1: Begin with a zero e.g. 0.5mg; 0.5micrograms; 0.5units etc. 10. Avoid trailing zeros (eg, orders greater than 1 should not be written as 1.0 11. Types of physician orders: a.) STAT Orders: these are orders that should be ready for delivery 5 – 30 minutes following receipt of the order in the pharmacy. b.) ASAP or Now orders: these are orders that should be ready for delivery 2 hours after receipt of the order in the pharmacy. c.) Routine orders: these are orders that should be ready for delivery within 4 hours follow ing receipt of the order in the pharmacy. 12. Writing orders for critical care drugs (eg, dopamine, fentanyl, midazolam, etc): a.) Indicate dose in parenthesis at the end of the order :(mcg/kg/min; mcg/kg/hr; mg/kg/hr; units/kg/hr etc.) 13. Rounding off orders a.) Drugs with wide therapeutic index: these drugs can be rounded up to the next whole number since the difference between therapeutic concentration and toxic concentration is wide (eg. penicillins, cephalosporins, erythromycins, etc). b.) Drugs with narrow therapeutic index: these drugs should be ordered exactly as calculat ed since the difference between the therapeutic concentration and toxic concentration is narrow (eg, aminoglycosides, digoxin, etc). 9

2021 NEOMED BOOK C o m m o n ly -u s e d A b b r e v ia t io n s AAP : American Academy of Pediatrics KCl : potassium chloride ACTH : adrenocorticotropic hormone LD : loading dose ALT : alanine transaminase  LFT : liver function test aPTT : activated partial thromboplastin time Max : maximum ARV : antiretrovirals  mcg : microgram AST : aspartate aminotransferase mcmol : micromol BP : blood pressure MD : maintenance dose BSA : body surface area mEq : miliequivalent BUD : beyond used date mg : miligram BUN : blood urea nitrogen mL : mililiter CBC : complete blood count mmol : milimol CDC : Center for Disease Control and Prevention mOsm : miliosmole CHD : congenital heart disease MRSA : Methicillin-resistant Staph aureus CHO : carbohydrate Na : sodium CMV : Cytomegalovirus NaCl : sodium chloride CNS : central nervous system NEC : Necrotising enterocolitis CPAP : Continuous positive airway pressure NG : nasogastric (insertion) CrCl : creatinine clearance nmol : nanomol D.bili : direct bilirubin NS : normal saline D/C : discharge OG : orogastric (insertion) DL : drug library (BBraun) PICC : peripherally-inserted central catheter D_%W : dextrose(_%)water PDA : Patent ductus arteriosus EBM : express breastmilk PMA : post menstrual age (corrected GA) ECG : electrocardiogram PNA : postnatal age (age after birth) ELBW : extremely low birthweight PO : per os (oral) ETT : endotracheal tube PR : per rectum (rectal) Fe : Iron PRN : pro renata (as needed) G6PD : Glucose-6-phosphate dehydrogenase  PTH : Parathyroid hormone GA : Gestational Age RDS : respiratory distress syndrome GERD : Gastroesophageal reflux disease RR : respiratory rate GFR : Glomerular filtration rate  RSV : Respiratory Syncytial Virus GI : gastrointestinal Scr : serum creatitine GIR : glucose infusion rate SMOF : Soya, MCT, Olive, and Fish Oil HBsAg : Hepatitis B surface antigen SUBQ : subcutaneous HCl : hydrochloride T.bili : total bilirubin HMF : Human milk fortifier T3 : triiodothyronine HR : heart rate T4 : thyroxine IM : Intramuscular TPN : total parenteral nutrition INH : Isonicotinic acid hydrazide TSH : thyroid-stimulating hormone iNO : inhaled nitric oxide UAC : umbilical artery catheter INR : international normalized ratio  UTI : urinary track infection IO : introsseous UVC : umbilical venous catheter IU : International Unit VLBW : very low birthweight IV : Intravenous VRE : vancomycin-resistant enterococcus Kcal : kilocalorie VUR : Vesicoureteral reflux  10

Chapter 1 NEONATAL DRUG DOSING GUIDELINES All recommended dosing are verified to ensure consistency with MNGHA’s Medical Record System (BestCare) and the BBraun Drug Library. 11

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Acetaminophen (Paracetamol F e v e r /P a in : • May cause hemolysis at large O ral: doses in type A G6PD deficiency. G A 2 8 -3 2 w k s : 1 0 to 1 2 m g /k g /d o s e , Q 6 -8 h ; Has no anti- inflammatory activity. M a x im u m d o s e : 40 m g /kg /d ay • Monitor LFTs, T.bili & D.bili, BUN G A 3 3 -3 7 w k s o r t e r m <1 0 d a y s : and creatinine. 1 0 -1 5 m g /k g /d o s e , Q 6 h ; M a x im u m d o s e : 60 m g /kg /d ay • Administer IV over 15 min T e r m n e o n a t e s ≥1 0 d a y s : • Some experts do not recom- 1 0 -1 5 m g /k g /d o s e , Q 4 -6 h mend the use of IV acetaminophen (d o n o t e x c e e d 5 d o se s in 2 4 h o u rs); in premature neonates <32 weeks M a x im u m d o s e : 75 m g /kg /d ay GA until pharmacokinetic and pharmacodynamic studies have IV : been conducted in this age group G A 2 8 -3 2 w k s : 7 .5 m g /k g /d o se , Q 8 h ; *Note: Echo should be done after M a x im u m d o s e : 2 2 .5 m g /k g /d a y 3 days of acetaminophen course. If the PDA does not close after 3 G A ≥3 2 w e e k s : days, you may extend up to 7 days. P N A ≤4 w k s : 1 2 .5 m g /k g /d o s e , Q 6 h ; M a x im u m d o s e : 50 m g /kg /d ay P N A >4 w k s : 1 0 -1 5 m g /k g /d o s e , Q 6 h ; M a x im u m d o s e : 60 m g /kg /d ay R ectal: G A 2 8 -3 2 w k s : 2 0 m g /k g /d o se , Q 1 2 h ; M a x im u m d o s e : 40 m g /kg /d ay G A 3 3 -3 7 w k s o r t e r m <1 0 d a y s : 15 m g /kg /d o se, Q 8h ; M a x im u m d o s e : 60 m g /kg /d ay T e r m ≥1 0 d a y s : 2 0 m g /k g /d o s e , Q 6 -8 h (d o n o t e x c e e d 5 d o se s in 2 4 h ); M a x im u m d o s e : 75 m g /kg /d ay P a te n t D u c tu s A r te rio s u s (P D A ) C lo s u re : Preterm in fants: 15 m g /kg /d o se o rally/IV, Q 6h fo r 3 d ays* P a in (m ild to m o d e ra te ) o r fe v e r: O r a l: 1 0 to 1 5 m g /k g /d o s e , Q 4 -6 h P R N (d o n o t exceed 5 d o ses in 24h ; M ax im u m d o se: 7 5 m g /k g /d a y n o t to e x c e e d 4 ,0 0 0 m g /d a y IV : In f a n t s : 7 .5 m g /k g /d o se q 6 h ; M a x im u m d o s e : 60m g /kg /d ay 12 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Acetazolamide Acetylcysteine M etab o lic alk alo sis: Side effects: Sulfa allergy cross (N- Acetylcysteine) IV, O ral: reactivity, GI, irritation, paresthesia, P M A ≥3 0 w k s : polyuria, drowsiness, vomiting, NAC 3 to 5 mg/kg/dose every 6 to 8 hours, for 3 to 4 diarrhea, electrolytes imbalance Doses, infuse over 5 – 30 minutes (hypokalemia, hyponatremia) and Adenosine metabolic acidosis, may occur with M eco n iu m ileu s: long-term therapy. Albumin PO 200–400 mg (2 – 4 mL of 10% acetylcyste- • Side effects: Bronchospasm, (5%, 20%) ine) up to 3 times a day if required. stomatitis, rhinorrhea, nausea, Rectally, 200-400 mg of 5% acetylcysteine (4-8 vomiting and hemoptysis. mL) given 3-4 times a day, as required. • Prior hydration is essential for R esp irato ry co n d itio n s, ad ju vant th erap y: meconium ileus treatment ** Infants: • **Patients should receive an Nebulizer 2 to 4 mL of ***10% solution (undi- aerosolized bronchodilator 10 to luted); Q8-6h*** 15 min prior to acetylcysteine. Intratrach eal ad m in istratio n fo r Lu n g A telectasis: • Nebulized inhalation: May be given by direct instillation into the ***may be further diluted with trachea with salbutamol and atropine. sodium chloride or sterile water for Dose: 2-4mL of 5% intratracheal Q4 – 8 H inhalation Paroxysmal Supraventricular Tachycardia (SVT) Conversion Note: Suctioning the trachea Initial dose: 50 to 100 mcg/kg (0.05 to 0.1 mg/ should be done at least 10 minutes kg) rapid IV push from the intratracheal instillation Repeat doses: repeat with increments of 50 to of NAC. 100 mcg/kg/dose (0.05 to 0.1 mg/kg/dose) IV Administration: every 1 to 2 min as needed; • Infuse directly into a vein or as Maximum dose: 0.3 mg/kg/dose or 12 mg/ close to the patient as possible. dose • Follow each dose with a rapid saline flush. Ascites with hypoalbuminemia: • IO is an option during resusci- 20% albumin: IV: 0.5 - 1 g/kg/dose over 2 to tation 3 hours (can be followed by Lasix if there is • Bedside Dilution (300 mcg/mL): edema); may repeat up to 3 times per day until • Use 1 mL (3000 mcg) of adenos- albumin is > 2.5 g/dL ine with 9 mL NS to make final concentration of 300 mcg/mL • Side Effects: Flushing, dyspnea and irritability occur frequently. May cause bronchoconstriction, bradycardia, pulmonary edema, and hypotension. • Caffeine diminish adenosine effect by competitive antagonism • Monitor parameters: continuous ECG,HR,BP,RR Note: • Albumin 5% should be used in hypovolemic or intravascular depleted patients Neonatal Drug Dosing Guidelines | 13

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Albumin (5%, 20%) H em o lytic d isease o f th e n ew b o rn : • Albumin 20% should be used (cont’d) 2 0 % a l b u m i n : I V : 1 g/kg/dose administer prior in patients with fluid or sodium to or during plasma exchange restrictions (eg, patients with Alphacalcidol H y p o vo lem ia, p lasm a vo lu m e ex p an sio n : hypoproteinemia and generalized (one-alpha drops) 5 % a l b u m i n I V : 0.5 to 1 g/kg/dose (10 to 20 edema, or nephrotic syndrome). mL/kg/dose) over 60 min • Normal saline (or blood) are 2mcg/mL ; H yp o ten sio n : preferred for volume expansion 1 drop = 5 % a l b u m i n : I V : 0.5 g/kg/dose (10 mL/kg/ in the delivery room 0.1 mcg dose) over 15 to 20 min; • Allergic reactions consisting of shaking, chills, fever, urticaria, Aminophylline changes in blood pressure, nausea, vomiting, pulmonary edema, and hypotension. Monitoring • Closely monitor for circulatory overload during administration. • Closely monitor hemodynamic parameters after administering for evidence of cardiac or respiratory failure, renal failure or increasing intracranial pressure Neonates: 0.05 - 0.1 mcg / kg / day PO Q24H Monitor serum calcium, phos- Premature Infants: 0.1 mcg/kg/day PO Q24 H phorus and alkaline phosphatase Children: <20 kg: 0.05 mcg/kg/day PO Q24H levels regularly. Maintenance dosage range: 0.25 – 1 mcg PO Patients receiving barbiturates (eg: daily Phenobarbital) or other anticon- vulsants concomitantly may need larger doses of alphacalcidol to produce the desired effect. A p n ea o f p rem atu rity Side effects: Nausea, vomiting, Loading dose (LD): 5 - 8 mg/kg ulceration, reflux, tachycardia, IV infused over 30 minutes or PO 5 – 6 mg/kg hypokalemia, hyperglycemia, Do not give more than 6 mg/kg/ IV as bolus seizures, rash and restlessness. if heart rate is 160 ± 5 bpm. Do serum level on 5th day, and Maintenance dose: 1-2 mg/kg/dose IV/PO then once weekly. Q6-8H * Therapeutic level for apnea: 33 – Usual Maintenance dose: 72 mcmol/L 5 mg/kg/day Q6 – 8H IV/PO To start 8-12 hrs after LD * Keep same dose when switching from IV Aminophylline to oral theophylline. Note: When serum theophylline levels are sub- therapeutic and patient continues to be symptomatic, therapy can be optimized by 14 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Aminophylline making use of the fact that each 1.25 mg/kg • Correct hypokalemia, hypomag- (cont’d) of aminophylline or 1mg/kg of theophylline nesemia, and hypocalcemia prior Amiodarone would raise the serum theophylline level by 11 to initiating treatment mcmol/L. • Side effects: Anorexia, nausea, Amlodipine Supraventricular tachycardia: vomiting, dizziness, paresthesia, Oral: Loading dose: 10 to 20 mg/kg/day in 2 ataxia, tremor, hypothyroidism divided doses for 7 to 10 days; then decrease or hyperthyroidism, altered LFT, to 5 to 10 mg/kg/day q24h and continued for pulmonary fibrosis, risk of ana- 2 to 7 month phylaxis, photosensitivity and skin discoloration (blue-gray skin). May Tachyarrhythmia, including junctional ecto- also cause worsening of pre-exist- pic tachycardia (JET), paroxysmal supraven- ing arrhythmias with bradycardia tricular tachycardia (PSVT): and AV block. • Dilute IV continuous infusion IV: solution with D5W. Loading dose: 5 mg/kg given over 60 min; • Infusions lasting longer than 2 Maximum total initial load: 10 mg/kg; hours should be administered in glass or polyolefin bottles contain- Do not exceed total daily bolus of 15 mg/kg/ ing D5W day • For peripheral administration do not exceed 2 mg/mL. Continuous IV infusion • Continuous EKG and blood Initial: 5 mcg/kg/min; pressure (for IV). Range: 5 to 15 mcg/kg/min • Follow AST and ALT. • Monitor T3, T4, and TSH • Check drug interaction and drug food interaction before start drug Hypertension • Young children (0-6 years) may re- 0– 6 years: quire high dose and Q12Hr dosing Initial: 0.1 mg/kg/dose PO, Q24H. Titrate as to achieve blood pressure control needed (Flynn 2000) Maximum Dose:10 mg/day • Use with caution in combina- Usual Dosage Range: 0.14 – 0.63 mg/kg/day tion with other antihypertensive PO Q12-24H agents. Hypertension control may Following initial dose, allow 5 – 7 days of con- be better in children with BID tinuous therapy before dosage adjustments. dosing regimen. • Side effects include nausea, headache, abdominal pain and somnolence. Dose-related side effects include edema, dizziness, flushing, fatigue and palpitations. Neonatal Drug Dosing Guidelines | 15

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Atropine Sulfate 0.01-0.03 mg/kg/dose IV over 1 min or IM. Side effects: Cardiac arrhythmias, May repeat dose Q10 – 15 minutes to achieve cardiac conduction defects, hyper- desired effect. tensive crises, sedation, seizures, paralytic ileus, mydriasis and cyclo- Maximum total dose 0.04 mg/kg plegia. esophageal reflux. ET: 0.01 to 0.03 mg/kg/dose followed immedi- ately by 1 mL NS. Intubation: 0.02 mg/kg IV 1 to 2 minutes prior to intuba- tion. Maximum single dose of 0.5 mg Neonates: • Monitor LFT’s. May cause Persistent Pulmonary Hypertension (PPHN) hypotension, peripheral edema, 1 mg/kg/dose PO Q12H then increase to 2 mg/ flushing, nausea, vomiting, anemia kg/dose Q12H and thrombocytopenia. Check drug interaction before start Bosentan medication Budesonide F o r p o s t-e x t u b a t io n s t r id o r : (Racemic cocktail Salbutamol 1mg plus budesonide 125 mcg plus racemic epinephrine 0.05 mL/kg (Max: 0.5 epinephrine) mL); then add NS to bring total volume to 3 mL Q 4-6H PRN. Bumetanide Edema (diuresis): • Dose equivalency: Bumetanide Preterm and term: Oral, IM, IV: 1mg = furosemide 40mg = ethac- 0.01 to 0.06 mg/kg/dose, Q12-24 hr; rynic acid 50mg Administer over 1-2 minutes • Cross –allergenicity may occur in Maximum Dose: 0.1 mg/kg/dose patients allergic to sulfonamides. * Continuous IV infusion: 1 to 8mcg/kg/hour. • Reduce dosage in patients with hepatic dysfunction. Give oral doses with food. • Side effects include hypoten- sion, cramps, dizziness, ototoxcity electrolyte disturbances, and metabolic alkalosis. • Monitor sign of diuretic resistance Caffeine Citrate Doses are expressed in mg of Caffeine citrate. • Side effects include: tachycar- caffeine base is 1/2 the dose of the caffeine dia, flushing, cardiac arrhythmias, citrate reduce splanchnic blood flow, rash, Apnea of Prematurity: Loading dose: IV/PO: dry skin, acidosis, hypokalemia, 20 mg/kg Caffeine citrate for one time over 30 gastrointestinal disturbances, close minutes monitor for the development of Maintenance dose: IV/PO: NEC, hyperglycemia, hypoglyce- Start with 10mg/kg/dose over 10-15 minutes mia, cerebral hemorrhage, and Range: 5-20mg/kg/dose Caffeine citrate once hypertension. daily to begin 24 hours after loading dose. • May lower seizure threshold lead Hold dose if heart rate is >180 bpm. to new onset or breakthrough seizure activity 16 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Calcitriol Hypocalcemia secondary to hypoparathyroid- ism: Oral: 1 mcg once daily for the first 5 days of life Alternate regimen: Oral: 0.02 to 0.06 mcg/kg/ day; Hypocalcemic tetany: Oral: Initial: 0.25 mcg/dose once daily, followed by 0.01 to 0.1 mcg/kg/day divided in 2 doses Calcium Gluconate Maximum Daily Dose: 2 mcg Indications for loading dose are: (10%) Symptomatic Hypocalcemia (seizure) or Ar- - Symptomatic Hypocalcaemia rhythmia due do hyperkalemia - Arrhythmia due do hyperkalemia Loading dose: Side effects: Venous thrombosis, Elemental Calcium 9.3-18.6 mg/kg (1-2mL/kg) cardiac arrhythmias, hypertension, IV infused over 20-30 minutes. lethargy, muscle weakness, consti- Dilution: Dilute with D5W or NS to final con- pation, hypercalcemia, nephroli- centration of: < 20 mg Ca gluconate/mL (2 mg/ thiasis, anorexia, nausea, vomiting mL of elemental calcium). and ocular toxicity. Monitoring for bradycardia: Stop infusion if • Serum electrolyte levels should heart rate is less than 100 beats/minute be obtained prior to initiating ther- Maintenance dose: apy and monitored during calcium Symptomatic patient - 2 mg elemental calci- administration. um/ kg/hr IV as continuous infusion • Recheck level no sooner than two Asymptomatic patient - 1 mg elemental calci- hours post-infusion. um/ kg/hr IV as continuous infusion • Monitor vital signs, bradycardia, *Not to exceed: hypotension, and dysrhythmias. Peripheral Line: 20mg elemental calcium in • Closely monitor for extravasation. 100mL • Avoid infusing calcium through IV Central Line: 80mg/kg/day elemental calcium catheters with thin access or those Maintenance (PO): in veins of the scalp, hands, or feet. Elemental calcium • Ca salts are contraindicated in Neonates: 50-150 mg/kg/day elemental calci- patients with ventricular fibrillation um in 4 to 6 divided doses. or hypercalcemia or infants less Preterm Neonatal Enteral Nutrition, Mainte- than 28 days old and receiving nance required (dietary intake plus medica- ceftriaxone. tion) • Chronic oral calcium and vitamin Oral: 150 – 200mg/kg/day D therapy may be required if un- Children: 50-100 mg/kg/day elemental calcium derlying condition is not corrected. in 4 divided doses. • Give PO Ca after meals to maxi- mize solubility and absorption Caution: Intra-arterial infusion will sudden severe ischemic changes and necrosis of distal tissues. Maximum: 1 g/day Neonatal Drug Dosing Guidelines | 17

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Calcium Gluconate Parenteral nutrition, elemental calcium: IV: Or < 20 mg Ca chloride/mL or < 2 (10%) Central Line: 40-80 mg elemental calcium/ mg elemental calcium/mL. (cont’d) kg/day * Ensure normal serum magne- Peripheral Line: 20mg per 100 mL sium level. Captopril 1 mL of 10% Calcium Gluconate Hyperkalemia: = 9 mg of Elemental Calcium= Calcium gluconate (10%): 100mg of Calcium Gluconate * Hyaluronidase should be a 50-100 mg/kg (4.5 – 9 mg/kg of elemental standby as it can used as antidote calcium), to be given IV over 15-20 minutes for line site extravasation and should be diluted in 5-10mL of D5% (don’t * Infusion site has to be inspected flush it) every 30 minutes Heart failure (afterload reduction); hyperten- • Side effects: Skin rash, angioede- sion: ma, proteinuria, neutropenia, hypotension, taste impairment, Preterm and (term neonates PNA ≤7 days): cough, gastrointestinal complaints Oral: and hyperkalemia. Initial: 0.01 mg/kg/dose q8-12h; • Need dose renal adjustment Usual range: 0.01 to 0.05 mg/kg/dose q8-12h • Check drug drug interaction that increase risk of hyperkalemia Term neonates PNA >7 days: • Contraindicated in patients with Oral: bilateral renovascular disease or Initial: 0.05 to 0.1 mg/kg/dose q8- 24h; with unilateral renal artery stenosis Max dose 0.5 mg/kg/dose q6-24h in a solitary kidney. Carvedilol Hypertension: Side effects: May cause aplastic Infants: anemia, atriventricular block, hep- Oral: Initial: 0.05 mg/kg/dose every 6 to 24 atotoxicity, and thrombocytopenia hours; higher initial doses of 0.15 to 0.3 mg/kg/ or may worsen heart failure. dose every 6 to 24 hours titrate dose carefully • Not to be given to asthmatic upward as needed to maximum of 6 mg/kg/ patients or patients with 2nd & 3rd day degree AV block Infants/children: Heart failure: Oral: Initial: 0.075-0.08 mg/kg/dose twice daily; titrate as tolerated; may increase dose by typically 50% every 2 weeks; usual reported maintenance (target) Dose range: • Patients taking b-blockers may 0.3-0.75 mg/kg/dose twice daily; the usual be unresponsive to epinephrine titration time to reach target dose was 11-14 during anaphylactic reactions weeks Maximum Daily Dose: 50 mg/day. 18 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Carbamazepine Seizure disorder: • Monitor risk of anemia or agran- Chloral Hydrate Oral: ulocytosis, hepatotoxicity and Cholecalciferol Infants and Children <6 years: hyponatremia Suspension: Initial: 10 to 20 mg/kg/day divided • Serum levels of carbamazepine q6h;titrate at weekly intervals; maintenance may be increase by erythromycin, doses administered q6-8h; verapamil, cefixime, itraconazole Maximum Dose: 35 mg/kg/day and isoniazid • Carbamazepine may decrease Sedation, procedural (eg, echocardiogram or activity of warfarin, cyclosporine, EEG): phenytoin, benzodiazepines, and Oral: 25 to 50 mg/kg/dose once at least one valproic acid hour prior to procedure • Do not crush or chew extended- 10-25 mg/kg/day PO÷ Q6-8H PRN release dosage forms. Hypnotic: • Therapeutic level: 17- 42 mcmol/L 50 mg/kg/dose PO single dose • Conversion from immediate-re- Pre-procedure and Agitation: lease tablet to suspension: Use the 25 - 50 mg/kg/ dose same daily dose and divide q8h; 30 - 60 minutes prior to procedure. • Conversion from immediate-re- Breastfed / Partially breastfed infants / Non lease tablets to extended-release: breastfed infants ingesting less than 1000 mL/ Use the same daily dose divided day of Vitamin D fortified formula or milk. q12h PO: 400 International Unit PO once daily • Side effects: Gastric irritation, Vitamin D deficiency and/or rickets cardiac arrhythmias, respiratory/ I. <3 m o nths myocardial depression paradoxical If Vitamin D level between 25-50nmol/L, start excitation, apnea, and hypoten- on 1000 International Unit PO daily for 6 sion. weeks (*) • *Chronic administration in neo- If Vitamin D level between 50-75nmol/L, start nates can lead to accumulation of on 400 International Unit PO daily active metabolites. • *Avoid use in patients with hepat- ic or renal disease. • At 1 month: Monitor serum calcium, phosphorus and alkaline phosphatase. Then at 2 or 3 months, monitor serum calcium, magnesium, phosphate, alkaline phosphatise, 25- hydroxy Vitamin D and parathyroid hormone. Obtain wrist x-ray to assess healing of rickets. Check serum 25- hy- droxyvitamin D level annually. • 1 mcg = 40 International Unit • Normal Vitamin D Level: 75-150 nmol/L Neonatal Drug Dosing Guidelines | 19

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Cholecalciferol II. From Birth to 12 months (*) Check Vitamin D level after 6 (cont’d) If Vitamin D level is less than 25 nmol/L, start weeks from treatment and consult Cholestyramine on 1500 International Unit PO daily for 6 Pediatric Endocrinology. weeks (*) • Give other oral medications Cisatracurium Dyslipidemia: 4 – 6 hours after cholestyramine 240 mg/kg/day in 3 divided doses; or 1 hour before dose to prevent Clonazepam maximum daily dose: 8 g/day decreased absorption. Clonidine • Mix powder with 60-240 mL of Pruritus secondary to cholestasis: water, noncarbonated liquid, or Infants: applesauce 240 mg/kg/day in 2 or 3 divided doses, higher • Side effects: Constipation, doses were associated with increased steator- abdominal distension, vomiting, rhea and required dosage reduction fat-soluble vitamin deficiencies (A, D, E, K) & rash. Diarrhea secondary to intestinal failure, • Risk of hyperchloremic acidosis short-bowel syndrome: Oral: 240 mg/kg/day in 3 divided doses; maxi- Onset and recovery times after mum daily dose: 8 g/day 0.15mg/kg/dose IV is somewhat Neuromuscular blockade: IV (not to be used shorter in infants and children than IM): in adults. Infants and Children <2 years: 0.15 mg/kg/dose IV over 5 to 10 seconds Infants >1 month of age Continuous infusion: 1-4 mcg/kg/min. Patient must be ventilated. Maximum of 10 mcg/kg/min • Side effects: CNS depression, Seizure disorders: ataxia and drowsiness are com- Infants and Children <10 years or ≤30 kg: mon. May cause behavioral chang- Oral, Initial: 0.01 to 0.03 mg/kg/day divided es, increased bronchial secretions q8-12h; and hematopoietic toxicity. • Contraindicated in severe liver Maximum Initial Daily Dose: 0.05 mg/kg/day; disease and acute narrow angle increase by ≤0.25 to 0.5 mg/day every 3rd day glaucoma. until seizures are controlled or adverse effects observed Maintenance: 0.1 to maximum of 0.2 mg/kg/ • Side effects include dry mouth, day divided q8h; dizziness, drowsiness, fatigue, Neonatal abstinence syndrome (opioid with- constipation and arrhythmias. drawal): • May cause mild metabolic acido- sis and may not be able to relieve Oral: 0.5 to 1 mcg/kg/dose followed by 0.5 to poor sleeping. 1.25 mcg/kg/dose q4-6h 20 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Cosyntropin Infantile spasms: 10 International Uni ACTH = 10 ACTH 150 units (15 mcg/kg) /m2/day IM/IV Q24H x 2 mcg Cosyntropin (synacthen) (0.25 weeks then taper. ACTH stimulation test Note: Please discuss with Pediatric mg/mL) Low dose: 0.1 – 3.5 mcg/kg/dose IV, Endocrine before doing this Fixed dose: 1 mcg/kg/dose dynamic test Standard-dose: IV: 15 mcg/kg; Maximum dose: 125 mcg/dose over 2 min- Dilute in NS. Stable for 12 hrs at RT. utes. Cortisol levels are measured at 0, 30, and 60 mins. 1 mcg/mL (final vol. 1mL) and 0.5 mcg/mL (final vol. 2mL) given IV over 2 mins. Darbepoetin Neuroprotection in Neonatal Encephalopathy Alfa Preterm: 10mcg/kg once weekly for 2 doses, can be given IV or Subcutaneous. Administer first dose as soon as possible within 12 hours. Anemia associated with chronic kidney disease (CKD) Initial: IV (preferred), SUBQ: 0.45 mcg/kg once weekly Desmopressin Cranial diabetes insipidus • Use with precaution in neonates acetate Neonates: may lead to severe hyponatremia, (DDAVP) Nasal solution can be given orally: 1 - 4 mcg PO adjust dose based on hydration once to three times a day. status, Na level and urine output. Infants: • Doses can be adjusted according Intranasally: to the response. 0.1 – 0.5 mcg (usual dose 1.25 – 10 mcg daily in • Switching from nasal spray to 1-2 divided doses). nasal solution: 1:1 Subcutaneous: • One puff nasal spray (10mcg) 0.1 mcg once daily. = 0.1mL nasal solution (10mcg). • Switching from nasal spray to sublingual tablets: Nasal spray dose is 10 to 40 time more potent than the sublingual tablets. Neonatal Drug Dosing Guidelines | 21

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Dexamethasone BPD, facilitation of ventilator wean • Side effects: Insomnia, irritability, Dextrose PNA ≥7 days: Oral, IV “DART Protocol”: hypertension, hyperkinesia, adre- Dextrose 30% nal suppression, hyperglycemia, DART PROTOCOL gastrointestinal hemorrhage, pulmonary edema, peptic ulcers, 0.075 mg/kg/dose Q12H x 3 days allergic contact dermatitis, arrhyth- mias, PVCs. 0.05 mg/kg/dose Q12H x 3 days • Omeprazole may be added 0.025 mg/kg/dose Q12H x 2 days simultaneously (only in patient > 1500 g or more than 32 weeks). 0.01 mg/kg/dose Q12H x 2 days - Low dose DEXAMETHASONE treatment Total of Dexamethasone of 0.89 mg /kg over 10 days Airway edema or extubation Neonates: IV: 0.25 to 0.5 mg/kg/dose q8h for 3 doses, start 4-12 hours prior to extubate Maximum dose: 1.5 mg/kg/day Infants (>1 month corrected gestational age): 0.5 mg/kg/dose (Maximum: 10mg/dose) IV or IM, administered 6-12 hours before extubation for 6 doses. Total dexamethasone dose: 3mg/kg Rebound hypoglycemia, hyper- Neonatal Hypoglycemia glycemia, glycosuria, local vein Symptomatic infant: irritation with hypertonic dextrose. Give slow push of 2 mL/kg of 10% dextrose in water (D10W) IV. Following bolus infusion, increase dextrose infusion to 8 mg/kg/min to maintain optimal serum glucose (>3 mmol/l ) up to a maximum infusion rate of 12 mg/kg/min. If greater than 12 mg/kg/min of dextrose is re- Sucrose is preferable if available. quired, then consult Pediatric endocrinologist. Taper IV dextrose infusion slowly. For pain relief: 0.6 mL/kg (max: 2mL) into paci- fier cavity or dip pacifier into solution and have infant suck on it. Other pain reduction or comforting mea- sures such as paracetamol, distraction, holding, feeding and so on can be used in conjunction with dextrose 30% adminis- tration to provide additional comfort for infants. For painful procedure to give dextrose 2 minutes prior to procedure. 22 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Diazoxide Congenital hyperinsulinism • Rare complications include hyper- Digoxin Oral: Initial: 10 mg/kg/day divided q8h; grad- uricemia, leukopenia, neutropenia, ually titrate; fluid retention, and (rarely) pulmo- Dobutamine Usual range: 8 to 15 mg/kg/day divided q8-12h nary hypertension. Domperidone Hyperinsulinemic hypoglycemia • For long term therapy, CBC and Oral: Initial: 5 mg/kg/day in divided q8h; serum uric acid concentrations Usual range: 8 to 15 mg/kg should be monitored periodically. Maximum dose: 20 mg/kg/day divided q8-12h • Discontinue if no effect after 2-3 weeks Important: Digitalizing Dose is Digitalizing doses is not rec- Optional ommended and needs to be approved by Pediatric Cardiology Age Total Digitalizing Dose TDD due to its risks. Administer in 3 divided dose(mcg/kg) For dosing purposes, please follow the Pediatric Cardiology’s recom- Oral Solution IV mendations. Nausea, vomiting, anorexia, Preterm 20 to 30 15 to 25 arrhythmias, conduction defects, abdominal pain, thrombocyto- Full-term 25 to 35 20 to 30 penia 1 to 24 35 to 60 30 to 50 months Give 1/2 TDD, then 1/4 TDD Q12H for 2 doses Age Total Daily Maintenance Dose doses every 12 hours (mcg/kg/day) Preterm Oral Solution IV neonates 5 to 7.5 4 to 6 Full-term 8 to 10 5 to 8 neonates 10-15 9-15 1 to 24 months Hemodynamic support: Hypertension, increased heart rate, IV infusion: start: 0.5-1 mcg/kg/minute; usual arrhythmias. range: 2-20 mcg/kg/minute *Contraindicated in idiopathic Usual dose: 2-20 mcg/kg/min IV subaortic stenosis and atrial Maximum recommended dose: 25 mcg/kg/min fibrillation. Compatibilities: Side effects include dry mouth, D5W, NaCl 0.9%, D5 NaCl 0.45%, D5 NaCl 0.9% transient skin rash, itching, thirst, Nausea/vomiting abdominal cramps, diarrhea, and Oral: 0.25mg/kg/dose q8h drowsiness, extrapyramidal symp- Maximum Dose: 10mg/dose q8h toms are rare (prolonged QT). Post-prandial indigestion: Children: 0.2 – 0.4mg/kg/dose PO Q 6-8H Neonatal Drug Dosing Guidelines | 23

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Dopamine Hemodynamic support: Tachycardia, arrhythmias, ventricu- Edrophonium IV infusion: lar premature beats, extrasystoles, chloride start: 10 mcg/kg/minute; usual range: 5-20 nausea, vomiting, polyuria, extrav- mcg/kg/minute asation, hypertension. Enoxaparin Low-dose dopamine would not be expected Low molecular to improve renal failure and this has been *Treat extravasation with phen- weight heparin demonstrated by the lack of efficacy in clini- tolamine. cal trials. (LWH) (see Phentolamine) Usual dose: 2-20 mcg/kg/min Preparation and compatibility: D5W, NaCl 0.9%, D5 NaCl 0.45%, D5 NaCl 0.9% Dopaminergic effects 2-5 mcg/kg/min vasodilation in renal, mesen- teric, coronary and intracerebral vascular beds with minimal effect on other blood vessels or on the heart. beta-1 effects 5-10 mcg/kg/min. mainly inotropic effects with some chronotropic effects. alpha-1 effects 10 - 20 mcg/kg/min potent vasoconstriction in most vascular beds. Maximum recommended dose: 25-30 mcg/ kg/min Tensilon test for myasthenia gravis: • May precipitate cholinergic crisis, Neonate: arrhythmias, and bronchospasm. 0.1 mg IV as single dose Infant: 0.04 mg/kg/ • Antidote: atropine dose IV x 1 • Ensure atropine is available in Maximum dose: 1mg syringe and have resuscitation Reduce dose in chronic renal failure. equipment ready. • Contraindicated in GU or GI Thrombosis treatment: obstruction on arrhythmias. Preterm: SUBQ: • Monitor anti-factor Xa levels. 2 mg/kg/dose every 12 hours. Full-term neonates: SUBQ: • Adjust dosage to achieve target Initial Treatment: anti-factor Xa levels of 0.5 – 1 unit/ 1.75mg/kg/dose every 12 hours mL in a sample taken 4 hours Maximum: 3mg/kg/dose every 12 hours (range 3-5 hours) following a Infants 1 to <2 months: SUBQ: subcutaneous injection. 1.5 mg/kg/dose every 12 hours • Treatment target anti-factor Xa levels of 0.5 – 1 unit/mL. Infants ≥2 months: SUBQ: 1 mg/kg/dose q12h 24 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Enoxaparin Thrombosis prophylaxis: • Prophylaxis: 0.1 to 0.3 units/mL Low molecular Infants 1 to <2 months: SUBQ: weight heparin 0.75 mg/kg/dose every 12 hours Anti-Factor Dose Change Xa Level (LWH) Infants ≥2 months, Children, and Adoles- (cont’d) cents: SUBQ: 0.5 mg/kg/dose q12h <0.35 Increase by units/mL 25% Epinephrine (1:10,000; 0.1 mg/ 0.35-0.49 Increase by units/mL 10% mL) Epinephrine 1.1 – 1.5 units/ Decrease by (1:10,000; 0.1 mg/ mL 20% mL) 1.6 – 2.0 units/ Decrease by mL 30% Cardiac Resuscitation: Tachycardia, arrhythmias, tremor, IV, IO: 0.01 to 0.03 mg/kg (0.1–0.3 mL/kg/dose) anxiety, bradycardia, hyperten- every 3 to 5 minutes as needed sion, hyperkalemia, myocardial ET: 0.05 to 0.1 mg/kg (0.5 mL-1mL/kg/dose) ischemia, metabolic acidosis, every 3 to 5 minutes nephrotoxicity, seizures, pulmo- Hemodynamic support: nary edema and extravasation. 0.05-2mcg/kg/min Compatibility: D5W, D10W, NaCl 0.9% Epinephrine, Airway edema Tachycardia, tremor hypertension. racemic Nebulization: 0.05 to 0.1 mL/kg (maximum dose: 0.5 mL/ (2.25% solution for dose) diluted in 2 to 3 mL NS, may repeat dose inhalation) every 20 minutes Erythropoietin Alfa Neuroprotection in Neonatal Encephalopathy Side effects Hypertension, throm- (Short Acting) Dose: 1,000 u/kg/dose IV or SUBQ given in bosis, chills, fever, rash, urticaria, conjunction with hypothermia on day 1, 2, 3, 5 pruritis, hypokalemia, hyperglyce- and 7 for a total of 5 doses. mia, leukopenia, upper respiratory Administer first dose as soon as possible within infection, nausea and vomiting 12 hours of birth. Esomeprazole (Administer the preservative-free erythro- • Routine use (for GERD) is not rec- poietin preparation intravenously (IV) over ommended in preterm neonates 5 minutes, followed by normal saline flush) as per AAP 2018 For preterm and term neonates with clinical • Common side effects are nausea, symptoms of GERD: vomiting, and diarrhea. Decrease IV: 0.5 mg/kg/dose once daily, infuse over 30 serum theophylline levels while in- mins creasing the half-life of phenytoin. 6 weeks treatment course • Give all doses before meals. Caution: Not recommended for (Switch to oral omeprazole as soon as pa- infants weighing < 1500g because tient tolerates oral therapy). of the potential to increase the risk of NEC and late-onset sepsis. Neonatal Drug Dosing Guidelines | 25

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Factor VII (Novoseven) Neonatal dosing: In addition, dose and frequency Factor VII deficiency or Prolonged PT & INR: of injections should be adapted to Fentanyl 15-30 mcg/kg/dose IV over 2 – 5 minutes each individual. every Q4-6H for 2 doses. Then, check PT, INR Ferrous Sulfate For patients who are not refractory, (Iron) Glanzmann’s thrombasthenia: platelets are the first line treatment 90 mcg/kg/dose IV over 2-5 minutes Q2H for Glanzmann’s thrombasthenia. Flecainide Dose can be repeated Q4 – 6H until hemostasis Novoseven dilution: is achieved. - in sterile water, stable for 24H Dose and frequency of injections should be (strongly recommended) adapted to each individual. - in NS, stable for 30 minutes Intermittent IV : Side effects: Respiratory depres- 1-2 mcg/kg/dose Q2-4H PRN slow IV push, over sion and apnea, muscle rigidity 3 - 5 minutes and chest wall spasm (occur Children < 2 years : following rapid IV administration), 1 -2 mcg/kg/dose IV Q1 – 2H PRN over 3-5 hypotension, bradycardia, seizures, minute laryngospasm, urine retention may Continuous Infusion: occur with continuous infusions 0.5 - 5 mcg/kg/hr and tolerance may develop to an- Compatibility: D5W, D10W, NS algesic doses with prolonged use. Antidote: Naloxone 0.25mL/kg (Ampoule With continuous infusion for 5 days concentration: 0.4mg/mL) or longer, significant withdrawal symptoms may occur. Dilution : 1mL of Fentanyl in 4 mL NS = • Give with meals or after meals to 10mcg/mL lessen GI irritation. Iron – Deficiency Anemia – Prophylaxis: • May cause constipation, dark Preterm/Term Infants stools, nausea, and epigastric pain. 2 mg elemental Fe/kg/day divided Q8-24H PO. • ANTACIDS may decrease iron ab- Iron-deficiency Anemia –Treatment: sorption. Iron and TETRACYCLINE Neonates: inhibit each other’s absorption. 3-6 mg elemental Fe/kg/day divided Q12-24H • For preterm infant begin iron PO. prophylaxis at 2-4 weeks PNA • For term infant consider addition- Supraventricular tachycardia (SVT), suppres- al supplement not earlier than 4-6 sion months Infants: PO: Initial : 2 mg/kg/day divided Q12H • Reserved for resistant dysrhyth- Titrate up to 6- 8 mg/kg/day divided Q12H mias, milk products may decrease IV: 0.5 – 2 mg/kg over 2- 10 min bio-availability. For Infants Arrhythmias: • Side effects include blurred Oral: Initial: 1 to 3 mg/kg/day divided every 8 vision, nausea, dyspnea, headache, hours; may titrate dose at 4-day dizziness and may cause AV block. Intervals; usual maintenance range: 3-6 mg/ • Note: May worsen LV failure, kg/day sinus, bradycardia, pre-existing ventricular arrhythmias. 26 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Fludrocortisone Congenital Adrenal Hyperplasia: Sodium retention, potassium acetate Recommended dose in infants is excretion, hypertension, fluid (0.1 mg tablets) 0.05 – 0.2 mg/day given Q24H PO retention causing edema, dyspnea, weight gain, GI ulcers and growth Flumazenil suppression. (Anexate®) Folic acid Reversal of benzodiazepine sedation: Please consult endocrine before Furosemide Start with 0.01 mg/kg (max dose: 0.2mg) given starting over 15 seconds, then 0.01 mg/kg (max. dose: Benzodiazepine antidote. Does not Glucagon 0.2mg) administered Q 1 minute to a maxi- reverse effects of narcotics. mum cumulative dose of 0.05 mg/kg or 1mg whichever is lower. Reverses effects of benzodiaze- pines (midazolam, lorazepam, diaz- epam, etc.) in 1 – 3 minutes. May cause seizures, especially in patients taking benzodiazepines for seizure control. Hereditary spherocytosis: 500 mcg/day PO, High dose of folic acid may de- OD Q24H crease absorption of phenytoin. Anemia: 100 mcg/day PO once daily • Hypotensin, hyperglycemia, Intermittent IV dose, Oral hyperuricemia, hypokalemia, Neonates: IV dose: 0.5 – 2 mg/kg/dose Q8 – hyper- calciuria, nephrotoxicity, 24H. hypo- magnesemia, metabolic alkalosis, g.i. effects (nausea, Infants: vomiting, oral and gastric irritation, Initial: 0.5 – 2 mg/kg/dose every 6 to 12 H. diarrhea, constipation). May increase by 1mg/kg/dose; • Monitor serum electrolytes at Max. 6mg/kg/dose least once weekly. Continuous IV infusion: Adverse effects include nausea, Neonates: 0.1 – 0.4 mg/kg/hour vomiting, tachycardia, ileus, hypo- Infants: 0.05 – 0.4 mg/kg/hour natremia and thrombocytopenia. Hypoglycemia, persistent: IM, IV, SUBQ: 0.02 - 0.2 mg/kg/dose Q20 min PRN Maximum dose: 1mg/dose Congenital hyperinsulinism, Continuous IV infusion: 0.5 to 1 mg infused over 24 hours (1- 20 mcg/kg/hour) Monitor blood glucose closely and watch for rebound hypoglycemia. beta-blocker or Calcium channel blocker overdose: 0.05 mg/kg as a single dose, repeat dose if no response Continuous IV infusion: 0.05-0.1 mg/kg/hour Compatibility: 1mg or 2mg in 25mL D5W, NS Neonatal Drug Dosing Guidelines | 27

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Glycopyrrolate Respiratory antisecretory: Drowsiness, tachycardia, dry IV /IM /SUBQ: 4 – 10 mcg/kg/dose Q4–8H mouth, mydriasis, nausea and PO: 40 – 100 mcg/kg/dose Q8 – 12H constipation. As an adjunct for reversal of Neuromuscular * Use with caution in hepatic or Blockade: 0.2 mg for each 1 mg of Neostig- renal disease, ileus or urinary mine IV retention. Prophylaxis UAC/UVC patency: Side effects: Excessive bleeding, Continuous infusion: tissue necrosis, thrombocytopenia, final concentration: (0.25 to 1 unit/mL); 25- vasospasm, hyperkalemia and 200 units/kg/day (Rate 0.25 -0.5 mL/hour) hypersensitivity. Preterm Infants: Use smaller dose for UAV/UVC in Less than 1kg: 0.25 unit/mL preterm infants to prevent the risk More than or equal to 1kg: 0.5 unit/mL of IVH or bleeding. Heparin Term Infants: 0.5 (preferred) – 1 unit/mL Antidote: Protamine sulfate Thromboprophylaxis in CHD, Continuous IV 1 mg IV protamine will neutralize infusion: 10 to 15 units/kg/hour 100 units of beef lung heparin. Thrombosis; treatment, Continuous IV infusion: Consider time of heparin and 75 units/kg over 10 min followed by 28 units/ antidote administration: kg/hr. Adjust dose to maintain If protamine given immediately aPTT of 60 – 85 seconds or anti-Xa of 0.35 to after heparin: give 1-1.5 x dose 0.7 units/mL above. Anticoagulation: Intravenous bolus 50 units/kg If given within 0.5-1hr: give 50% of followed by maintenance of 10-25 units/kg/hr. above dose. If > 2 hrs: give 25% of Intermittent dosing: 50 – 100 u/kg/dose IV above dose. Q4h. Max. Rate: 5mg/min Hydralazine Hypertension: Adverse effects include diarrhea, IV: 0.1 to 0.5 mg/kg/dose q6-8h. Increase grad- emesis and transient agranulocy- ually as required for blood pressure control to a tosis. Assess blood pressure and max. dose: 2 mg/kg/dose every 6 hours heart rate frequently for long term Acute severe hypertension: treatment, monitor CBC periodi- 0.15 to 0.6 mg/kg/dose every 4 hours cally. Oral: 0.25 to 1 mg/kg/dose q6-8h ; Hydrochlorothiazide Maximum daily dose: 7.5 mg/kg/day Side Effects/Comments Bronchopulmonary dysplasia (BPD) Hypokalemia, hyperglycemia, hy- Neonates: Oral: 1 – 2 mg/kg/dose Q12H peruricemia, hypercalcemia, hypo- Infants: Oral: 3 – 4 mg/kg/day divided q12h chloremic alkalosis, hypomagnese- mia, hyponatremia, Hypotension Edema, Hypertension: Oral: 1 – 2 mg/kg/dose divided q12h 28 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Hydrochlorothiazide Reduction of diazoxide-induced Na and water Side Effects/Comments (cont’d) retention, Potentiating the glyacaemic effect of Hypokalemia, hyperglycemia, hy- diazoxide Oral: 3-5 mg/kg/dose divided q12h peruricemia, hypercalcemia, hypo- Hydrocortisone chloremic alkalosis, hypomagnese- Congenital Hyperinsulinism: mia, hyponatremia, Hypotension 7-10 mg/kg/day ÷ Q12H Congenital Adrenal Hyperplasia: Edema, growth suppression, gas- 10 – 20 mg/m2/day divided Q8H PO tro- intestinal distress, hypokale- mia, hyperthyroidism, hyperglyce- Adrenal crisis (shock) and pre-op: mia, hypertension, salt and water 50 - 100 mg/m2 IV retention. BSA (m2) = 0.05 x wt (kg) + 0.05 Physiologic Replacement: (Applicable to infants with weight 7 – 9 mg/m2/day IV, PO divided Q8 – 12H < 10 kg) Ibuprofen Hypotension, refractory; For Stress dose, see page 145. For Term and Preterm Neonates: • Contraindicated in patients Start with 2mg/kg, then 1mg/kg/dose IV Q6 – with active GI bleeding and ulcer 12H for 3 – 5 days disease. Patent Ductus Arteriosus (PDA) closure (Neo- • Use with caution in patients profen®): with aspirin hypersensitivity, Neonates: renal or hepatic insufficiency, and Low Dose: 10 mg/kg IV on day 1 followed by in patients being treated with 5mg/kg IV at 24 and 48 hours anti-coagulants. High Dose: 20 mg/kg IV on day 1 followed by • MILK reduces GI distress. 10mg/kg IV at 24 and 48 hours Infuse each dose over 30 to 60 minutes. PO: 10mg/kg/dose followed by two doses of 5mg/kg/dose at 24 and 48 hours Iloprost Infants: Side effects include nausea, Immune Globulin Analgesic / Antipyretic: vomiting, diarrhea, cramping pain, 5 – 10 mg/kg/dose PO Q6 – 8H, flushing vasodilatation, and hypo- (IgG) (Human) Maximum dose: 40 mg/kg/day PO tension. May cause brochospasm. Pulmonary arterial hypertension (PAH): Backache, nausea, skin reactions, Nebulizer with ultrasonic machine: tachycardia, respiratory distress, 2.5 (mcg) for the first dose, if well tolerated, shock, cardiac or respiratory arrest dosing may be increased to 5 (mcg) and main- tained at that dose, taken 6 to 9 times per day (adjusted according to response). Adjuvant treatment of hemolytic jaundice and immune thrombocytopenia (ITP): 500 – 1000 mg/kg/dose IV over 2– 6 hours Acute Viral myocarditis: 2000 mg/kg once as a single dose Immune thrombocytopenia (ITP): Acute: 400 – 1000 mg/kg/dose IV for 2-5 consecutive 5 days (Total cumulative dose 2000mg/kg) Viral myocarditis: 2 g/kg IV infused over 24 hrs Neonatal Drug Dosing Guidelines | 29

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Insulin, Regular Isoproterenol Hyperglycemia • Allergic reactions, hypoglycemia, Intermittent IV : hypothermia. Ketamine 0.05 - 0.1 unit/kg IV push every 4-6 hours Lactulose • Neonates are extremely sensitive Lamotrigine Continuous Infusion: 0.01- 0.5 unit/kg/hr and to the effect of insulin; initiate ther- titrate to desired effect. apy at the lower end of infusion Drug Library Hardlimit dose: 0.6 unit/kg/hr rate and monitor closely. Hyperkalemia Flushing, tachycardia, tremor, Give 0.1 unit/kg with glucose as 400mg/kg (5 weakness, gastrointestinal ulcer- mL/kg of D10W) over 30 minutes. May repeat ation, arrhythmia, hypoglycemia, this dose in 30 – 60 minutes, if needed. rebound, bronchospasm. Bradycardia; increase cardiac output • Rapid IV administration may 0.05 – 0.5 mcg/kg/min as continuous infusion. cause respiratory depression or Maximum dose: 2 mcg/kg/min apnea. • Not recommended for long-term Adjust infusion rate to clinical response. use for infusion (more than 24 Sedation/analgesia: hours) For infants >3 months of age: • Weaning can be fast. Bolus: 0.5 to 2 mg/kg/dose IV Infusion: 5-20 mcg/kg/min Mechanically-ventilated children with severe bronchospasm Start with 8 mcg/kg/min and titrate to desired clinical effect. Maximum dose: 32 mcg/kg/min • Contraindication in GALACTOSE- Constipation: MIA. Use with caution in diabetes 1.5 – 3 mL/kg/day PO divided Q12-24 mellitus, Monitor serum ammonia, >6 months: 1 – 2 mL/kg/day PO Q8-12H serum potassium and fluid status Portal systemic encephalopathy in patients with portal systemic Infants: encephalopathy. 2.5 – 10 mL/day PO in divided Q6 – 8H • GI discomfort and diarrhea may occur. Anticonvulsant: Adjunctive (add-on) therapy • May take up to 48 hours to act. for refractory seizures • Side effects: Fatigue, drowsiness, Initial: ataxia, rash, headache, nausea, 2 mg/kg/dose once daily, may increase by 2 vomiting and abdominal pain. mg/kg/day at intervals of at least 7 days Other reported side effects include Maximum Dose: 10 mg/kg/day diplopia, nystagmus and alopecia. For intractable convulsions in the newborn • Maintenance dose should be Neonates (already receiving enzyme-inducing reduced in renal failure. agents): 5 – 10 mg/kg/day PO ÷ Q12H. 30 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Lamotrigine Infants: • In liver dysfunction, reduce (cont’d) 1 – 12 months of age taking enzyme- inducing all doses (initial, escalation and agents: 10 – 20 mg/kg/day PO ÷ Q12H. maintenance) as follows: moderate Levetiracetam 1 – 12 months of age receiving valproate and dysfunction: decrease dose by (Keppra) enzyme-inducers: 5 – 10 mg/kg/day PO ÷ 50%; severe dysfunction: decrease Q12H. dose by about 75%. 1 – 12 months of age taking valproate alone: • Discontinue by tapering over > 5mg/kg/day PO ÷ Q12H. 2 weeks period (approximately Refractory epilepsy: reducing by 50% per week) as 1 – 12 yrs: 2 – 15 mg/kg/day PO ÷ Q12H. sudden discontinuation may cause Patients on enzyme-inducing antiepileptic withdrawal symptoms. Lamotrig- drugs should receive maximum of 15 mg/ ine levels kg/day PO ÷ Q12H. • May be decreased by acetamino- Patients receiving valproate alone should phen, carbamazepine, phenobar- be given 5 mg/kg/day PO ÷ Q12H. bital, phenytoin, rifampin and oral contraceptives. Valproic acid may Neonatal Seizure increase serum levels. Initial: IV, PO: 10mg/kg/day divided q12h. • Do not exceed the recommended Increase dose by 10mg/kg/day over three days initial dose or the recommended to 30mg/kg/day, dose escalation to reduce the risk Additional increase up to 45-60mg/kg/day of serious skin rash have been used with persistent seizure activity • May be decreased by acetamino- or clinical EEG findings. phen, carbamazepine, phenobar- Status Epilepticus bital, phenytoin, rifampin and oral Neonates: Loading Dose: 20-150mg/kg/day in contraceptives. Valproic acid may divided smaller doses increase serum levels. Maintenance dose: Side effects: Constipation, 5-100mg/kg/day IV/PO Q12H diarrhea, nausea, vomiting, loss of Children: appetite and gastroenteritis. Loading Dose: 60mg/kg as single dose; Other reported side effects Maximum Dose: 4,500 mg/dose include neutropenia, leukopenia, Maintenance dose: based clinical response and thrombocytopenia, pancytopenia, type of seizure disorder hepatitis, abnormal liver function tests, ataxia, confusion, dizziness, headache and amnesia. Neonates: LD :10-50mg/kg/ IV over 15 mins. PO can also be used. MD: 10-30mg/kg/dose IV/PO Q24H in neonates and Q12H in infants. Partial onset seizures: Infants 1 to <6 months: IV, Oral Initial: 7 mg/kg/dose twice daily; increase dosage q2 wks by 7mg/kg/dose q12h based on response to 21 mg/kg/dose q12h. Neonatal Drug Dosing Guidelines | 31

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Levothyroxine Congenital hypothyroidism Coronary vasospasm, cardiac In most term neonates, initial doses 37.5 – 50 arrest, hypothyroidism, hyperthy- mcg/day. Titrate as rapidly as possible (less roidism, pituitary suppression and than 2 weeks after initiation of therapy to osteomalacia, rash, growth distur- achieve target serum T4 concentration). bances, hypertension, arrhythmias, Then, maintain on 10-15 mcg/kg/dose PO once diarrhea and weight loss. daily. Note: Pediatric endocrine needs to IV/IM dose: 75-80% of oral dose Q24H be informed before starting IV. Hypothyroidism (acquired or congenital): 1 to 3 months: 10 to 15 mcg/kg/dose once daily Lorazepam >3 to 6 months: • Respiratory depression, sedation, Magnesium Sulfate 8 to 10 mcg/kg/dose once daily mild ataxia, rash, GI symptoms, ap- Neonatal Seizure nea, hypotension and bradycardia. 0.05 – 0.1 mg/kg IV over 1- 5 minutes. May • *Injectable preparation may be repeat dose after 15-20 minutes up to a total given rectally. of 3 doses • Flumazenil is the antidote. Maximum total dose= 0.15mg/kg . • Caution: Can cause severe hypo- tension. Sedation • Elemental magnesium: 0.05 – 0.1 mg/kg/dose IV Q 4 – 6h PRN > 1 meq/kg/dose may cause Hypomagnesemia: (refer to Chapter 15, page diarrhea 105) • 1 mmol of magnesium (Mg) = IV:25-50 mg/kg/dose (2.5–5 mg/kg/dose as 250 mg salt Mg sulfate = 25 mg elemental Magnesium Sulfate) over 3-4 hours elemental Mg Q8-12 H for 2-3 doses • 1mmol of Mg = 2 Meq Mg IM: 25-50 mg/kg/dose (2.5–5 mg/kg/dose as • 1 Meq = 12.5 mg of elemental Mg elemental Magnesium Sulfate) = 0.12 -0.25 • 50% Mg Sulfate = 500 mg/mL mL/kg of 20% Magnesium Sulfate solution of magnesium sulfate= 50 mg elemental magnesium= 4 mEq PO: elemental magnesium 25-50 mg/kg/dose (2.5–5 mg / kg / dose as Note: For dilution of Mg Sulfate, elemental Magnesium Sulfate) orally from one use a compatible solution (D5 or to four times daily (about only 30% of dose NS) absorbed by gut) for 5 days. Maximum: 75 mg/kg/dose (7.5 mg / kg / dose as elemental Magnesium Sulfate) PO Q 6 – 8 H For persistent Pulmonary Hypertension of the Newborn (PPHN) Loading dose: 200 mg/kg, (20 mg / kg / dose as elemental Magnesium Sulfate) to be given over 20–30 minutes, then (by continuous intravenous infusion) 20–75 mg/ kg/hour (2 –7.5 mg / kg / dose as elemental Magnesium Sulfate) for up to 5 days if response occurs after initial dose (to maintain plasma magnesium concentration between 3.5–5.5 mmol/L). 32 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Methylene blue Methemoglobinemia: • Use with caution in G6PD defi- Methylprednisolone LV, I.O: 1 mg/kg/dose over 5 – 30 minutes ciency or renal insufficiency. • Side effects: Nausea, vomiting, May repeat in 30 – 60 minutes if needed. dizziness, headache, diaphoresis, stained skin and abdominal pain. Consider alternative treatment if no resolution Causes blue-green discoloration of after 2 doses urine and feces. Status asthmaticus: Side effects: Hypertension, gastro- Loading dose: 2 mg/kg IV X 1 dose intestinal bleeding, hyperglycemia Maintenance dose: 0.5 - 1mg/kg/dose IV Q6-8H and adrenal axis suppression. May increase cyclosporine and tacroli- Anti-inflammatory/immunosuppressive: mus levels. PO/IM/IV: 0.5 – 1.7 mg/kg/day ÷ Q6-12H Pulse therapy: 15-30 mg/kg/dose IV q24h for 3-5 days. Metolazone Maximum dose: 1000mg • Contraindicated in patients with Midazolam Edema: anuria, hepatic coma or hyper- Infants and Children: sensitivity to sulfonamides or PO 0.2 – 0.4 mg/kg/day ÷ Q12 – 24H in combi- thiazides. nation with furosemide. • Side effects: Electrolyte imbal- Adjust dose to minimal effective dose for ance, hyperglycemia, hyperurice- maintenance mia, chills, marrow suppression, hepatitis and rash. Sedation: Minimal cardiovascular effects, Intermittent: 0.05-0.1 mg/kg/dose Repeat prolonged sedation can occur, as PRN, usually Q2 – 4H to be given over 5 respiratory depression, apnea, minutes phlebitis and injection site pain, For ventilated infants: 0.2 mg/kg/dose IV Q hypotension, bradycardia. 6-8H Intranasally: 0.2 - 0.3 mg/kg/dose x 1 • *Use flumazenil to reverse effects. (See flumazenil) Continuous infusion: GA ≤ 32 weeks: Initial: 0.1- 0.5 mcg/kg/min, Titrate to clinical response GA >32 weeks: Initial: 0.5- 1 mcg/kg/min, Titrate to clinical response. Maximum dose: 2 mcg/kg/min. Morphine Sulfate Seizures: Continuous infusion: 1-6 mcg/kg/min • CNS and respiratory depression, Sedation/Analgesia dependence, nausea, vomiting, 0.05 – 0.1 mg/kg/dose IV/IM/SUBQ Q4-8H PRN. constipation, hypotension, brady- Give IV over at least 5 minutes. cardia, urinary retention allergy • Naloxone may be used to re- Continuous infusion: verse respiratory depression. Non-Ventilated Patients: 0.01 – 0.03 mg/kg/hr (10 – 30 mcg/kg/hr) Neonatal Drug Dosing Guidelines | 33

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Morphine Sulfate Ventilated Patients: • Note: Infants <3 months are more Naloxone 10 – 50 mcg/kg/hr susceptible to respiratory depres- Neostigmine Maximum dose: 100 mcg/kg/hr sion. Patients should have contin- Nitroglycerin P.O : 0.05 – 0.08 mg/kg/dose Q4-6H PRN uous respiratory monitoring (eg, Neonatal abstinence syndrome pulse oximetry) and be in a setting Oral: Initial: 0.04 mg/kg/dose q3-4h; increase that permits rapid management of by 0.04 mg/kg/dose if symptoms are not respiratory insufficiency. controlled; • Use lower dose of infusion in case of renal impairment. Maximum dose: 0.2 mg/kg/dose • Prolonged PT, hypotension, Opioid intoxication/overdose (full reversal): hypertension, arrhythmias, pulmo- IV, IO: 0.01- 0.1 mg/kg/dose, nary edema, ventricular fibrillation, May repeat Q2 – 3 minutes PRN hepatotoxicity, opiate withdrawal E.T.: 2-3 times the IV dose symptoms. Possible seizures with repeated doses. Reversal of respiratory depression from thera- • Do not use in infants whose peutic opioid dosing: mothers are suspected of having IV: 0.001-0.005 mg/kg/dose, titrate to effect recently abused narcotic drugs 0.1mg/kg or 0.25mL/kg IV/IM/SUBQ/ETT since it may precipitate withdrawal May repeat Q3 – 5 minutes PRN signs in such infants • Multiple doses may be required Neuromuscular Blockade Reversal for very large ingestions. Do not 0.03 to 0.07 mg/kg IV atropine or glycopy- use in infants whose mothers rrolate should be administered prior to or are suspected of having recently concomitantly with neostigmine abused narcotic drugs since it may * Use with caution in patients with broncho- precipitate withdrawal signs in spasm or cardiac arrhythmias. such infants Vasodilation; perioperative, congenital • Bradycardia, restlessness, heart defect repair agitation, anxiety, constipation, Start with 0.25-0.5 mcg/kg/min IV, increase by abdominal distension and fecal 0.5-1 mcg/kg/min every 3-5 minutes impaction, salivation, muscle Usual dose: 1-3mcg/kg/min weakness, tremors, hypotension, Usual Maximum: 5 mcg/kg/min respiratory depression, bron- Arterial Associated Peripheral Ischemia: chospasm, diarrhea, diaphoresis, Topical 2% ointment: nausea and vomiting. 4 mm/kg applied as a thin layer to the affected Methemoglobinemia, flushing, areas; every 8 hours, approximately 2 cm proxi- thrombocytopenia, bradycardia, mal to the line of pallor reflux esophagitis, GI upset, con- tact dermatitis and tolerance. Can cause hypotension. Use with caution in severe renal impairment, increased ICP and hepatic failure. 34 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Nitroglycerin patch Topical application: Can cause hypotension. Apply ¼ of 5mg patch to affected site. Q8-12H (5mg) Nystatin See Chapter 2, Page 60 Octreotide Hypoglycemia Hyperglycemia, hypoglycemia, Omeprazole Intermittent: nausea, diarrhea, abdominal dis- Palivizumab 5-25 mcg/kg/day divided Q6 – 8H IV/SUBQ comfort, cholelithiasis, rash, fever, (Monoclonal Max. dose: 40 mcg/kg/day divided Q6H IV/ oliguria, hypothyroidism, and SUBQ Necrotizing Enterocolitis (NEC). antibody) Continuous infusion: * Tachyphylaxis may occur. Initial: subQ 5 mcg/kg/day delivered over 24 hours; titrate to response, increase by 5 mcg/ Note : The most effective dose in kg/day; usual effective range: 5 to 25 mcg/kg/ treating chylotorax is 20 mcg/kg/ day; hour (based on Japanese and our Maximum daily dose: 35 mcg/kg/day experience). Congenital and Post-operative Chylothorax: Continuous infusion IV: 39,40 Start with 1-2 mcg/kg/hr and titrate to desired response. Range: 1 to 12 mcg/kg/hour) Maximum: 20 mcg/kg/hr • Routine use (for GERD) is not rec- Median duration: 9 days (range 4-47 days) ommended in preterm neonates For preterm and term neonates with clinical as per AAP 2018 symptoms of GERD: • Common side effects are nausea, PO: 0.7 mg/kg/dose once daily. vomiting, and diarrhea. Decrease 4-8 weeks treatment course serum theophylline levels while in- Higher doses of 1 - 2.5 mg/kg once daily has creasing the half-life of phenytoin. been reported. • Give all doses before meals. Infants weighing 3 - 5 kg: • Caution: Not recommended for Oral: 2.5 mg once daily up to six weeks infants weighing < 1500g because of the potential to increase the risk RSV Prophylaxis of NEC and late-onset sepsis. 15 mg/kg/dose IM Q 28 Days just before and • Side effects: Rash, pain, rhinitis, during the RSV season (November – March), increased liver enzymes, cough, for 5 doses. wheeze, diarrhea, vomiting, con- junctivitis and anemia. If total injection volume >1 mL, it is recom- • Caution: Use with caution in mended to divide doses. Dose should be patients with thrombocytopenia or administered within 6 hours of reconstitution. any coagulation disorder because Recommendations: of IM route of administration. (based on AAP 2014 Guidelines with some modifications) Neonatal Drug Dosing Guidelines | 35

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Palivizumab (Monoclonal 1. Infants <2 years of age with chronic lung • Side effects: Rash, pain, rhinitis, disease on Oxygen or chronic steroid use, increased liver enzymes, cough, antibody) profoundly immune-compromised during wheeze, diarrhea, vomiting, con- (cont’d) RSV season (e.g., solid organ or hematopoietic junctivitis and anemia. stem cell transplantation, chemotherapy, • Caution: Use with caution in Pancuronium severe combined immunodeficiency, chronic patients with thrombocytope- bromide granulomatous disease), undergoing cardiac nia or any coagulation disorder Phenobar- transplantation during RSV season. because of IM route of adminis- Bital 2. Infants <12 months of age, all premature tration. infants (less than 29 weeks GA) • *Hemodynamically significant 3. Infants <6 months of age, premature infants heart disease: receiving medica- (29 – 32 weeks’ GA with risk factors*) tion to control congestive heart 4. Infants <12 months of age, or hemody- failure who will require cardiac namically significant cyanotic and acyanotic surgical procedures, patient with congenital heart disease. moderate to severe pulmonary hypertension. 5. All Diaphragmatic Hernia or Neuromuscular If infant with RDS needs: disease at any gestational age (if <12 months > Intubation at the start of RSV season. > CPAP for > 1 week If breakthrough RSV hospitalization occur, you > Need Oxygen > 2 weeks may either: • If total injection volume>1 mL, it • discontinue giving the palivizumab course is recommended to divide doses. (American school of thought), or Dose should be administered with- • continue giving the palivizumab course (Euro- in 6 hours of reconstitution. pean school of thought) Paralysis/Skeletal Muscle Relaxation: • Increased heart rate and blood Initial: 0.05 – 0.1 mg/kg/dose IV pressure hypotension, excessive Intermittent: 0.05–0.1 mg/kg/dose IV PRN salivation, sweating and wheezing. Q1-2H • Antidote: Neostigmine (with Max. dose: 0.15 mg/kg/dose IV atropine or glycopyrrolate). Continuous infusion: • Hypoxemia may occur with inad- Infants: 0.4 to 0.6 mcg/kg/minute equate mechanical ventilation Children: 0.5 to 1 mcg/kg/minute • Tachycardia, and blood pres- sure changes (hypertension and Seizures hypotension), excessive salivation, Loading Dose IV: sweating and wheezing. 20 mg/kg at a rate of 1mg/kg/min • Drowsiness, ataxia, respiratory VLBW ( < 1500 g) : 15 mg/kg/dose IV depression, hypotension and rash. Additional dose of 5-10 mg/kg/dose as • For long term monitoring, do required serum trough level once every 2 Q20-30 min up to TOTAL of 40 mg/kg weeks Maintenance dose: • Therapeutic level: 65 – 172 Start 12 hours after the loading dose mcmol/L. 3-5 mg/kg/day Q12 - 24H, IV, PO 36 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Phenobar- Intractable seizures • *If a loading dose is required to Bital Loading Dose : control the seizure, then do serum 20 mg/kg IV followed by 10 mg/kg IV followed phenobarbital level 12 h after the Phentolamine by another 10 mg/kg IV if needed last loading dose before starting (Regitine®) the maintenance dose. Max. total dose: 40 mg/kg • Dilution: 1mL Phenobarbital in 5 Phenytoin mL of NS. Extravasation of sympathomimetics vasopres- • Most effective within 12 hours sors (Dopamine, epinephrine, norepinephrine, after extravasation. Inject 1 mL (in metaraminol, phenylephrine): 5 divided doses of 0.2 mL SUBQ To be used as soon as possible within 12 hr of around site of extravasation). extravasation • Hypotension could potentially Preparation: Mix 5 mg with 9.5 mL or 19.5 mL occur if a very large dose is admin- normal saline (0.25-0.5 mg/mL). istered Dose: Inject 1 mL (in 5 divided doses of 0.2 mL SUBQ around site of extravasation). Blanching Side Effects: Lethargy, ataxia, should reverse immediately. Monitor site. If nystagmus, hirsutism, dermatitis, blanching should recur, additional injections of gingival hyperplasia and lymph- phentolamine may be needed. adenopathy. Cardiac arrhythmias. Status epilepticus May cause cardiovascular collapse. Loading Dose IV: 15-20 mg/kg to in a single or divided dose Maintenance dose: IV, PO: 5mg/kg/day in 2 divided doses. Maintenance dose to start 12 hours after loading dose. Usual Range: IV, PO If dilution needed, use normal 4 - 8 mg/kg/day in 2 divided doses saline but NOT D5%W. *Dilution: Can be administered undiluted or Therapeutic level: 40 – 79 mcmol/L diluted in NS Rate of intravenous administration: 0.5 mg/ kg/min Phosphorus sodium Acute Management of Hypophosphatemia • Hypocalcemia, hypomagnesemia, or potassium 0.08-0.36 mmol/kg/dose IV over 4-6 hours. hyperphosphatemia, severe hypo- Refer to phosphate guideline for further tension and acute renal failure. phosphate (Inorgan- details • May cause cardiovascular col- ic Phosphate) Maintenance lapse. Sodium Glycero IV: 0.5-1.5 mmol/kg/day • Dilute sodium or potassium phosphate: Oral (Sodium Dihydrogen Phosphate): phosphate in IV fluids to a final 1-3 mmol/kg/day divided Q6 – 8H concentration of 0.05 mmol/mL or (Organic Phosphate) Parenteral nutrition, maintenance phosphorus 1.5 mg/mL and infuse at a rate not Phosphorus sodium requirement: greater than 0.2 mmol/kg/hr IV: 1-2 mmol/kg/day as an additive to parenter- • Each 1mmol of Potassium or potassium al nutrition solution. Phosphate provides 1.5 meq of phosphate (Inorgan- Sodium Glycerophosphate: Potassium. IV: 1-1.5 mmol/kg/dose infused over 8- 24H • One (1) mmol of Phosphate = 31 ic Phosphate) Dilute in D5W or NS to 0.05mmol/mL for mg Phosphate peripheral lV line and 0.12mmol/mL for central IV line administration. Neonatal Drug Dosing Guidelines | 37

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Sodium Glycero PO: 1-2 mmol/kg/day q 6-12H • One (1) Sodium Glycerophos- phosphate: Parenteral nutrition, maintenance phosphorus phate will provide 1 mmol Phos- (cont’d) requirement: phate and 2 meq Sodium IV: 1-2 mmol/kg/day as an additive to parenter- Potassium Chloride al nutrition solution. • 1 mmol Potassium Chloride = (2 mmol/mL) Peripheral IV administration: 1 meq Bolus infusion: • May cause irritation, pain, phlebi- Usual Concentration: tis at the infusion site. 20-40 mmol/L (0.02 – 0.04 mmol/mL) • Rapid intravenous administration Maximum of 60 mmol/L (0.06mmol/mL) may cause cardiac arrhythmias Infusion dose: 0.2 mmol/kg/hr (arrest). Range: 0.1 - 0.3 mmol/kg/hr • The infant must be in cardiac monitor (ECG) during infusion. In exceptional circumstances, up to 0.5 mmol/ • In the presence of severe hypoka- kg/hour) lemia, see guidelines for potassium Central IV administration: IV bolus. Bolus infusion: • Serum concentration should be Usual concentration: monitored at 1-2 hours after the Greater than 60 mmol/L or 0.06 mmol/mL dose. Can be used 120 – 150 mmol/L (0.12 – • In extreme low birthweight in- 0.15mmol/mL) fants, (BW <1000 g), no potassium Maximum concentration: supplements should be added to 200 mmol/L or 0.2 mmol/mL the IV fluid or TPN in the first 48 hours of age. Rate of infusion: • Side Effects: Bradycardia, 0.5-1 mmol/kg/dose over 1 hr bronchospasm, hypoglycemia, Maintenance dose: hypotension, nausea, vomiting and Oral, IV: 2 – 5 mmol/kg/day divided Q2 – 8H heart block. Treatment of hypokalemia: Neonates, infants and children: Oral: 1 – 5 mmol/kg/day Q2 – 8H, not exceed 1-2 mmol/kg as a single dose. Tachyarrhythmias and Hypertension IV: Start with 0.01 mg/kg/dose given over 10 minutes Q6-8H. Titrate to desired response up to Maximum Dose: 0.15 mg/kg/dose Q6-8H. Propranolol PO: 0.25 – 10.5 mg/kg/dose Q6-8H • Treatment can be continued for 1 Maximum Dose: 3.5 mg/kg/dose Q6H year UNLESS complete resolution Thyrotoxicosis/congenital hyperthyrodism: occurs earlier. Following resolution, PO: 0.5-1mg/kg/dose Q6-8 H taper over 4 weeks by reducing Infantile Hemangioma (IH): dose by 50% for 2 weeks then NOT approved in infants younger than 5 weeks another 50% dose reduction for Start with 0.5 mg/kg/day PO Q8H for 1 week, the last 2 weeks. then 1mg/kg/day PO Q8H for the following week then 2 mg/kg/day PO Q8H for the re- maining duration of treatment. 38 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Ductus arteriosus patency Acute Side Effects: Apnea, fever, Initial: 0.05-0.1 mcg/kg/min flushing, bradycardia, hypogly- cemia, hypocalcemia, seizures, Maintenance: hypotension diarrhea, decreased Titrate to lowest effective dose based on re- platelet aggregation. sponse; may be as low as 0.01 mcg/kg/min. Side effects of prolonged use (more than 5 days): Prostaglandin E1 > Gastric outlet obstruction (PGE1) > Reversible cortical proliferation of long bones (Alprostadil) Side effects of long-term therapy (more than 3 months): Cortical hyperostosis and perios- titis. These changes resolve over weeks after discontinuation of therapy. Stable in D5%W, D10%W and NS. Heparin overdosage 1 mg IV protamine will neutralize ~100 units of heparin Adjust the protamine dose depending upon the duration of time since heparin administra- tion as follows: Protamine sulfate Time Since Last Dose of Protamine Pyridostigmine Heparin Dose (min) (mg) to Neutralize 100 units of Heparin <30 1 30to 60 0.5 to 0.75 60 to 120 0.375 to 0.5 >120 0.25 to 0.375 Maximum protamine dose: 50 mg/dose May cause nausea, vomiting, diar- Maximum Rate: 5 mg/min. rhea, rash, and muscle cramps. Myasthenia Gravis (congenital): Antidote: Atropine PO: 0.5-1mg/kg/dose Q4 – 6H while awake, Usual range: 4 to 5 mg/kg/day in 4 to 6 divided doses; Maximum dose: 7 mg/kg/day divided in 5 to 6 doses IM/IV: 0.05 – 0.15mg/kg/dose Q4 – 6H Max. single IM/IV dose: 10 mg Neonatal Drug Dosing Guidelines | 39

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Pyridoxine Rifampin Pyridoxine-dependent Seizures • With prolonged therapy, pe- IV: 100 mg IV push (preferred) ripheral sensory neuropathy has Rocuronium PO: 30 mg/kg/day for several days (when IV not been reported. With high doses: feasible) gastrointestinal disturbances, Maintenance dose: If clinical response estab- folic acid deficiency, sedation and lished, start oral pyridoxine 15-30 mg/kg/day, hypotonia/respiratory distress in given once daily infants, and skin reactions. Prophylaxis: 1 – 2 mg/kg/day PO once daily Does not alter level of conscious- Maximum dose: 50 mg/day ness or provide analgesia or See Chapter 2, Page 62 amnesia. Alternative to succinyl- Intubation (Surgical): choline for rapid intubation when Note: Patient must be ventilated succinylcholine is contraindicated. Initial: 0.45-0.6 mg/kg IV Duration of block is generally 30 – 45 minutes and is dose-de- Maintenance: pendent. Endotracheal intubation Intermittent: generally occurs in 45-60 seconds 0.075-0.15 mg/kg repeat as needed after administration. Continuous IV infusion: 7-10 mcg/kg/min (0.42-0.6 mg/kg/hour) Intubation(nonemergent): • Must be accompanied by ade- IV: 0.6-1.2 mg/kg quate analgesia and/or sedation Antidote: Increases pulmonary vascular resis- Sugammadex 2 mg/kg/dose IV single dose tance, prolong QT, and tachycardia Salbutamol Bronchodilation: Prolonged use may cause tachy- Salbutamol Nebulizer: 0.1-0.5 mg/kg/dose Q2-6 hours cardia. Budesonide One metered-dose inhaler MDI Q2-6 hours via Other side effects include arrhyth- (Racemic cocktail MDI with spacer device mia, tremor, hypokalemia, and epinephrine) Continuous nebulization for acute asthmatic irritable behavior. attack: 4 mg/kg in 200 mL NS to be given by Oral dose can only be used in nebulizer at rate 18 mL/hr (0.36 mg/kg/hr). Myasthenia Gravis DOK-7: Treatment of Hyperkalemia: 0.1 to 0.3 mg/kg/dose orally every 1. Nebulizer: 0.4 mg/dose in 2mL NS Q2 hours 6 to 8 hours until serum K decreases to desired level 2. Intravenous: 4 micrograms/kg over 10 min For post-extubation stridor: Salbutamol 1mg plus budesonide 125 mcg plus racemic epinephrine 0.05 mL/kg (Max: 0.5 mL); then add NS to bring total volume to 3 mL Q 4-6H PRN. 40 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Sildenafil Pulmonary hypertension: Reduction in blood pressure, Full-term neonates: headache, flushing, stomach upset, Sinemet Oral, Usual range: 0.5 to 3 mg/kg/dose q6-12h nasal congestion, diarrhea, urinary (Levodopa / Maximum Dose: 3mg/kg/dose PO Q6H. tract infection, blurred vision and Carbidopa) IV, Loading Dose: priapism (in male infants). 0.4 mg/kg over 3 hours followed by continuous infusion 1.6 mg/kg/day for up to 7 days. Pulmonary hypertension: facilitation of in- • Side effects include orthostatic haled nitric oxide (iNO) wean (in patients who hypotension, dyskinesia, neuro- previously failed iNO wean): leptic malignant syndrome, rash, Oral: Full-term neonates hyperglycemia, nausea, vomiting, Single dose: ~0.3 mg/kg/dose given once 70 to hyponatremia, constipation, diar- 90 minutes prior to iNO discontinuation rhea and seizures. Multiple dose: Initial: 0.3 mg/kg/dose (range: 0.22 to 0.47 mg/kg/dose) every 6 hours (aver- age duration: 28 days Tetrahydrobiopterin deficiencies; dopamine deficiency Dose based on L-dopa component: 0.25-0.5 mg/kg/day divided Q8-12 hours Maintenance: Oral: 2.5–3 mg/kg q6h Sodium Bicarbonate Bolus dose: 1-2 meq/kg IV infusion over 30 – 60 May cause hypernatremia, meta- minutes. bolic alkalosis, hypocalcemia and Maximum dose: 8 meq/kg/24 hrs OR meq local tissue necrosis. Rapid infusion NaHC03 needed = B.W. (kg) x base deficit of hypertonic solution may cause (meq/L) x 0.3 L/kg. IVH. Administer as 0.5 meq/mL dilution i.e., 4.2% • Dilute the 8.4% preparation 1:1 NaHC03. with sterile water to obtain a 4.2% Continuous drip: 0.25-1 meq/kg/hr (0.5 meq/mL) preparation for Monitor patient closely and alter dosing based direct slow IV administration. on acid-base status. • Urine alkalinization (PO): 1 -10meq/kg/day divided Q6 - 8H • Titrate to desired urinary PH. Sodium Chloride 3% Myasthenia Gravis (congenital): • Continuous IV infusion maximum (3% NaCl; 0.5 IV: Na deficit = (target serum – actual serum) x rate:1meq/kg/hr mmol/mL) 0.6 L/kg x weight given over 8 hours; followed • Hypertonic saline (3% Saline) can by 0.2 – 1 mmol/kg/hr be used in case of hyponatremia • If NaCl 3% is used, infusion is to be given <120 mEq/L and patient experi- through Central Line (preferred). encing symptoms • If no central line you need the consultant • Normal saline can be used if approval to use peripheral line. patient has no Central Line. Maintenance dose: Oral: 2 – 5 mmol/kg/day divided doses Q2 – 8H Neonatal Drug Dosing Guidelines | 41

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Sodium Chloride (0.9% NaCL = 0.154 Premature neonates: 2 – 8 mmol/kg/day IV • Hypokalemia, hypomagnesemia, Q2 – 8H hypocalcemia, nausea, vomiting, mmol/mL) constipation, sodium retention, Term Neonates: 2– 4 mmol/kg/day IV/ PO Q2 fecal impaction and gastrointesti- – 8H nal obstruction. • Monitor serum potassium (K+). Infants: 3– 4 mmol/kg/day IV/ PO Q2 – 8H • Oral administration in neonates Hyperkalemia, treatment and use in neonates with reduced Rectal: 1 g/kg/dose with a 15 to 30 minute gut motility (postoperatively or retention every 4 to 6 hours drug-induced) is contraindicated. • Alternatively; pretreatment of Sodium Polystyrene Infants: infant formula or EBM with Kayex- Sulfonate Oral: 1 gm/kg/dose Q6H PO alate to decrease K load for renal Rectal: 1 gm/kg/dose Q2-6H PR failure patients (Kayexalate) Exchange ratio: 1 meq per 1 gm resin • Baseline QTc interval and CrCl must be determined prior to Note: Not recommended for infants < 1500 initiation. gms. • Bradycardia, hypotension • Note: it is not necessary to Sotalol 80mg Tablet Supraventricular tachycardia (SVT): increase to target dosage if desired Initial dose: clinical effect has been achieved. PO: 2 mg/kg/day divided every 8 hours. If needed, increase dosage gradually by 1-2 mg/kg/day increments; allow at least 3 days between dosage increments to achieve new steady-state and to monitor clinical response, heart rate, and QTc intervals Proposed target dose: Neonates: PO: 4 mg/kg/ day divided every 8 hours. Spironolactone Infants: • Side effects: Nausea, vomit- 6 mg/kg/day divided every 8 hours ing, gastritis, gastric bleeding, Bronchopulmonary dysplasia BPD, Edema: thrombocytopenia, hyperkalemia, 1 to 3 mg/kg/day divided Q12- 24H PO acidosis, ulceration and hepatitis. • Side effects: Hypotension, bra- Succinylcholine Paralysis for intubation: dycardia, arrhythmia, malignant IV dosing: hyperthermia. (Use dantrolene to Neonates: 1 – 2 mg/kg/dose x 1 treat) and hyperkalemia. Infants ≤6 months: 2 to 3 mg/kg/dose • Contraindicated with previous IM dosing: history of malignant hyperther- Neonates: 4–5 mg/kg/dose x1 mia, severe burns, spinal cord Infants <6 months: 4 - 5 mg/kg injury, neuromuscular disease or myopathies. • Not recommended for continu- ous infusion. 42 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Sucrose 24 % (Tootsweet) For the reduction of procedural pain in infants Pacifier dipped into 24% sucrose 10 drops = 0.5 mL such as: = 0.1 mL. 2 drops = 0.1 mL blood tests by heel pricks, venipuncture or Contraindications: arterial stabs; intravenous catheter insertion; • Infants at high risk for NEC lumbar puncture; suture removal; dressings; • Asphyxiated infants circumcision; urinary catheter insertion; IM or • Infants with feeding intolerance SUBQ injections; eye examination; NG or OG • Infants without bowel sounds insertion and adhesive tape removal. • Infants with CHD that are not on established feeds Preterm: Administer 2 drops (0.1 mL) onto the • Infants with esophageal atresia or tip of the infant’s tongue OR have infant suck tracheal esophageal fistula on pacifier dipped into 24% sucrose 2 minutes • Infants who are sedated or on before procedure. If needed, subsequent doses other pain medications that are at may be given every 2 minutes based on pain risk for aspiration CUES such as crying time, increased heart rate, • Post-op infants who need to decreased oxygen desaturation, facial expres- avoid excessive saliva production sion ( brow bulge, eye squeeze, nasolabial • Infants with active PPHN furrow and open mouth). • Patients on ketogenic diet Maximum dose per day: 0.5 mL = 10 drops. Term up to 18 months. : Initial dose: Give 4 drops (0.2 mL) onto the tip of infant’s tongue OR have infant suck on pacifier dipped into 24% sucrose. If necessary, give subsequent doses 4 drops (0.2 mL) at a time every 2 min- utes based on pain CUES as described above. Maximum dose per day : 2 mL = 40 drops. Infants: 0.2 to 0.5 mL of 24% sucrose solution placed on the tongue or buccal surface or dip pacifier in sucrose solution and allow infant to suck. Tetanus Immuno- Prophylaxis Indication: if infant born outside globulin Human Tetanus immune globulin (TIG) 250 U IM the hospital and cord cut in unster- ile condition. Topiramate Neonatal seizures; refractory: • May be taken with or without Immediate release: food. Use with caution in renal and Initial: 0.5 to 1 mg/kg/day titrated up daily hepatic dysfunction. Reduce dose or every other day by 0.5 to 1 mg/kg/day to by 50% if creatinine clearance in achieve effective dose 3.5-8 mg/kg/day. less than 70 mL/min. Adjunctive therapy for primary generalized • Common side effects include tonic-clonic or partial seizures and Lennox- ataxia, dizziness, nystagmus, cogni- Gastaut Syndrome. tive dysfunction, sedation, visual disturbances, nausea, dyspepsia, paresthesia and kidney stones. Neonatal Drug Dosing Guidelines | 43

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Tromethamine For the reduction of procedural pain in infants • Side effects: Respiratory (THAM(R)) such as: depression, thrombophlebitis, (0.3molar) Dose (mL) of 0.3 M, THAM = body wt. (kg) x venospasm, alkalosis, transient Ursodeoxy- base deficit (meq/L) (IV) hypocalcemia, hypoglycemia and cholic Acid Maximum dose in neonates with normal renal hyperkalemia, extravasation. Valproic Acid function: 5 – 7 mmol (5.6 – 7.8 mL of 0.3M)/ • DO NOT ADMINISTER VIA UAC kg/day • Not indicated for metabolic acidosis caused by bicarbonate Parenteral nutrition-associated cholestasis deficiency. 15 – 30 mg/kg/day ÷ Q 8 – 12H PO. • Contraindicated in anuric, uremic • Use with caution in patients with renal impairment, Use ECG monitoring and monitor serum potassium. May cause GI disturbance, rash and elevated liver enzymes. For Biliary Atresia, post-Kasai procedure: • Side Effects: May cause GI, liver, 10 – 20 mg/kg/day in 2-3 divided doses. blood and CNS toxicity; weight Maximum dose: 30 mg/kg/day gain, transient alopecia; pancre- Refractory seizures: atitis; nausea; sedation; vomiting; Oral: headache; thrombocytopenia; Loading dose: 20 mg/kg, followed by a platelet dysfunction; rash and Maintenance Dose: 5 to 10 mg/kg/dose every hyperammonemia. 12 hours. • CONTRAINDICATED in liver disease. Refractory status epilepticus: • Neonatal: reserve use in refracto- IV: ry cases only. Loading dose: 20 to 40 mg/kg followed by a • Not preferred in patients < 2 years Continuous IV infusion of 5 mg/kg/hour; once old due to hepatotoxicity. patients were seizure-free for 12 hours and no • (Children on other anticonvul- longer had seizure activity on EEG, the infusion sants may require higher doses rate was decreased every 2 hours by 1 mg/kg/ because of drug interactions) hour • For protection of infants of mothers with • Side effects: Pain, erythema, varicella-zoster infections (chicken pox) within swelling, and rash at the site of 5 days before or 48 hours after delivery. injection; rarely, anaphylaxis. Varicella Zoster • For protection of postnatally exposed • Best results are achieved if VZIG Immune Globulin preterm infants under 1000g or under 28 is given within 96 hours after weeks regardless of maternal history. exposure and within 10 days after (VZIG) • For protection of postnatally exposed prema- exposure. ture infants whose maternal history is negative • High risk susceptible patients for varicella infection. who are re-exposed more than 3 weeks after prior dose of VZIG should receive another full dose. 44 | Neonatal Drug Dosing Guidelines

DRUG DOSAGE COMMENTS Varicella Zoster Immune Globulin Prophylaxis: 1 mL/kg (25 IU/kg) IV given immediately after (VZIG) virus contact but preferably within the first 4 (cont’d) days. Rate of infusion: 0.1 mL/kg/hr Maximum: 1 mL/kg/hr Treatment: 1-2 mL/kg (25 – 50 IU/kg) IV to be given as infusion at rate 0.1 mL/kg/hr. Maximum: 1 mL/ kg/hr Vecuronium Paralysis/skeletal muscle relaxation • Side effects: Rash, arrhythmias, Intermittent IV and bronchospasm. Use with cau- Initial dose: 0.1 mg/kg/dose IV x 1 tion in infants with renal or hepatic Maintenance: 0.03 – 0.15 mg/kg/dose IV Q impairment or neuromuscular 1-2H PRN. disease. Continuous IV infusion: • Dosing in obese patients should Initial: 1.7 mcg/kg/minute (0.1 mg/kg/hour) be calculated using ideal body weight • If intubation is performed using succinylcholine, the initial dose of vecuronium may be reduced to 0.04 to 0.06 mg/kg with inhalation anesthesia and 0.05 to 0.06 mg/kg with balanced anesthesia. Vigabatrin Infantile spasms: • Needs renal adjustment. Vitamin K Initial Dose: 25 mg/kg/dose twice daily • Side effects include skin rash, fa- May titrate upwards by 25 to 50 mg/kg/day cial flushing, weight gain, nausea, increments every 3 days based on response vomiting, epigastric pain, constipa- and tolerability tion, gingival hyperplasia, decrease hg. Others include hepatotoxicity, Vitamin K deficiency bleeding encephalopathy, headache, ataxia, Prevention: confusion and dizziness. Diplopia, Birth weight <1,000 g: visual field defects and optic atro- 0.3 to 0.5 mg/kg (IM, IV) phy plus retinal Birth weight ≥1,000 g and term infants : • Infantile spasms: Withdraw ther- 0.5 to 1 mg (IM) apy in 2 to 4 weeks if a substantial Treatment: SUBQ, IM: 1 to 2 mg/day clinical benefit is not observed or D/C treatment if treatment failure becomes obvious earlier than 2 to 4 weeks. • Relatively nontoxic, hemolytic anemia and kernicterus have been reported in neonates given mena- diol sodium diphosphate (Vitamin K3; Synkayvite), however, Vitamin K1 has not been associated with toxic symptoms or hypersensitivity. Neonatal Drug Dosing Guidelines | 45

2021 NEOMED BOOK DRUG DOSAGE COMMENTS Vitamin K Vitamin K deficiency, prevention and supple- K1 has not been associated with (con’t) mentation toxic symptoms or hypersensitivity. Zinc Sulfate Biliary atresia Infants < 6 months: • For IV administration: Dilute in Zoledronic acid INR >1.2 to 1.5: 2.5 mg once daily orally D5W to 0.18mg/mL and infuse INR >1.5-1.8: slowly over 30 to 60 minutes. Initial: 2 to 5 mg IM once followed by 2.5 mg • Fatal hypersensitivity reactions, once daily orally including anaphylaxis, have oc- INR >1.8 curred with parenteral use; onset Initial: 2 to 5 mg IM once followed by 5 mg may occur during or immediately once daily orally after intravenous (IV) or intramus- cular (IM) administration. Cholestasis: Oral: 2.4 to 15 mg/day Cystic fibrosis: Oral: 0.3 to 0.5 mg/day Liver disease: Oral: 2.5 to 5 mg/day Reversal of Vitamin K antagonists (eg, warfa- Oral Zinc may cause gastrointesti- rin): nal upset. IV: 0.03 mg/kg/dose for INR >8; no evidence of bleeding) Zinc deficiency; treatment: Dosage expressed in terms of elemental zinc Acquired (eg, secondary to cystic fibrosis, In treatment of classic acroderma- liver disease, sickle cell disease, short-bowel titis enterohepatica, permanent syndrome, intestinal failure, etc): Zinc therapy is needed to achieve and maintain a complete clinical Oral: 0.5 to 2 mg/kg/day remission.. • Needs renal adjustment. Classic acrodermatitis enterohepathica, • Evaluate the change in lumbar Neonates: Oral: 3 mg/kg/day;. spine Infants: Oral: 20-30 mg/day • Bone mineral density Z-score at Osteogenesis imperfecta (OI) 24 months relative to baseline. Neonates: • Monitor serum ionized calcium Initial infusion: 0.0125mg/kg given over 45 level. minutes, followed by a dose of 0.025mg/kg • Acetaminophen or ibuprofen given as infusion over 30 to 45 minutes every 3 30 minutes prior to infusion and months for 24 months. 6 hours after is recommended to reduce acute phase reactions (eg, Infants: flu-like symptoms including low- First dose: IV: 0.0125 mg/kg/dose. grade fever, nausea, myalgias, and Maintenance (3 months after 1st dose): fatigue).. IV: 0.025 mg/kg/dose every 3 months. 46 | Neonatal Drug Dosing Guidelines

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2021 NEOMED BOOK Chapter 2 ANTIMICROBIAL THERAPY DRUG DOSAGE GUIDELINES All recommended dosing are verified to ensure consistency with MNGHA’s Medical Record System (BestCare) and the BBraun Drug Library. 48 | Antimicrobial Therapy Drug Dosage Guidelines

DRUG DOSAGE SIDE EFFECTS/COMMENTS Acyclovir HSV Infection, Treatment and Preemptive Begin suppressive therapy Amikacin Therapy: immediately after completion of PMA<30 weeks IV treatment and continue for 6 20mg/kg/dose every 12hours. months. PMA > 30 weeks 20mg/kg/dose every 8 hours. Note: Due to increased risk of HSV Infection, Chronic suppression: neurotoxicity and nephrotoxicity, 300/m2/dose orally every 8 hours. higher doses (20 mg/kg) are not Varicella-Zoster Virus Infection: routinely recommended 10 to 15 mg/kg/dose IV every 8 hours for 5 to • Keep the patient well hydrated 10 days • Adverse Events Cytomegalovirus (CMV) prophylaxis: • Hepatic: increased LFT Oral: Infants <40 kg: - Local: Inflammation at injection 600 mg/m2/dose q6h ; max. dose: 800 mg/ site, phlebitis dose. - Renal: Acute renal failure, in- HSV encephalitis, treatment: creased BUN, SCr Infants: - Neutropenia IV: 10 to 15 mg/kg/dose every 8 hours • Dose Adjustments: GA (wks) Postnatal Dose Interval - CrCl >50 mL/minute/1.73 m2: No (days) (mg/kg) (hours) adjustments necessary. <29* - CrCl 25 to 50 mL/minute/1.73 30 to 34 <14 15 48 m2: Administer the recommended >15 15 24 dose q12h >35 <60 15 24 - CrCl 10 to <25 mL/minute/1.73 <7 15 24 m2: Administer the recommended >8 17.5 24 dose q24h. - CrCl <10 mL/minute/1.73 m2: Ad- minister 50% of the recommended dose q24h Compatible With D5W, D10W or NS. Infuse over at least one hour. Recommended final concentration for administration is 7 mg/mL or less. Keep patient well hydrat- ed. Monitor IV site for phlebitis. Also, monitor renal and hepatic function. Incompatible with: TPN, Intralipid, dopamine, dobutamine, piperacil- lin /tazobactam Timing of serum samples: (See Chap. 5, pg. 77-79) •Trough before 2nd dose and Peak after 2nd dose for neonates •Trough before 4th dose and Peak after 3rd dose for q8h dosing Antimicrobial Therapy Drug Dosage Guidelines | 49