MNGHA NEOMEDBOOK (December 2021)

2021 NEOMED BOOK Chapter 28 SODIUM NITROPRUSSIDE 150

To prevent cyanide toxicity from long-term administration of sodium nitroprusside infusion, do the following: Mix each 100mg of sodium nitroprusside with 1 gram of sodium thiosulfate and protect bag or bottle from light. The mixture is stable for 7 days if protected from light. Determine the amount of sodium nitroprusside required based on physician’s order and add the appropri ate amount of sodium thiosulfate. For example, sodium nitroprusside 50 milligrams should be mixed with 500 milligrams of sodium thiosulfate and 25 milligrams of sodium nitroprusside is to be mixed with sodium thiosulfate 250 milligrams. Example: If a 3kg infant is prescribed sodium nitiroprusside 2mcg/kg/min, how much sodium thiosulfate should be mixed with the 24-hour requirement of sodium nitroprusside? First, calculate the 24-hour requirement of sodium nitroprusside, thus: 2mcg x 3kg x 60min x 24hrs = 8.64mg. Therefore, the amount of sodium thiosulfate to be mixed with 8.64mg sodium nitroprusside is given by: Xmg (sodium thiosulfate) = 1000mg sodium thiosulfate 8.64mg sodium nitroprusside 100mg of sodium nitroprusside Thus, Xmg sod. Thiosulfate = (8.64mg sod. Nitroprusside) (1000 mg sod. Thiosulfate) 100mg of sodium nitroprusside So that Xmg sodium thiosulfate needed = 86.4mg ***References: 1. Lexicomp Online®, Pediatric & Neonatal Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc.; September 10, 2020 Sodium Nitroprusside | 151

2021 NEOMED BOOK Chapter 29 DRUGS TO AVOID IN G6PD DEFICIENCY 152

DEFINITE RISK OF HAEMOLYSIS POSSIBLE RISK OF HAEMOLYSIS Pharmacological Class Drugs* Pharmacological Class Drugs* Anthelmintics • ß-Naphthol Analgesics • (Aspirin) • Niridazole • Acetanilide • Stibophen • Paracetamol (Acetaminophen) • Aminophenazone (Aminopyrine) • Dipyrone (Metamizole) • Phenacetin • Phenazone (Antipyrine) • Phenylbutazone • Tiaprofenic acid Antibiotics • Nitrofurans Antibiotics • Furazolidone - Nitrofurantoin • Streptomycin Antimalarials - Nitrofurazone Anticonvulsants • Sulfonamides Antimethemo- Antidiabetics globinaemic Agents • Quinolones Antidotes - Sulfacytine Antimycobacterials - Ciprofloxacin - Sulfaguanidine - Moxifloxacin Antihistamines - Sulfamerazine - Nalidixic acid - Sulfamethoxypyri - Norfloxacin Antihypertensives - Ofloxacin dazole • Phenytoin • Chloramphenicol • Glibenclamide • Sulfonamides • Dimercaprol (BAL) - Co-trimoxazole • Antazoline (Antistine) (Sulfamethoxazole + • Diphenhydramine Trimethoprim) • Tripelennamine - Sulfacetamide • Hydralazine - Sulfadiazine • Methyldopa - Sulfadimidine • Chloroquine & - Sulfamethoxazole - Sulfanilamide derivatives - Sulfapyridine • Proguanil - Sulfasalazine (Salazo • Pyrimethamine • Quinidine sulfapyridine) • Quinine - Sulfisoxazole (Sulfa furazole) • Mepacrine • Pamaquine • Pentaquine • Primaquine • Methylene blue • Dapsone Antimalarials • Para-aminosalicylic acid Drugs to avoid in G6PD Deficiency | 153

2021 NEOMED BOOK DEFINITE RISK OF HAEMOLYSIS POSSIBLE RISK OF HAEMOLYSIS Pharmacological Class Drugs* Pharmacological Class Drugs* Antimycobacterials • Isoniazid Antimycobacterials • Sulfones • Trihexyphenidyl - Aldesulfone sodium (Benzhexol) (Sulfoxone) - Glucosulfone Antiparkinsonism Agents - Thiazosulfone • Doxorubicin Cardiovascular Drugs • Dopamine (L-dopa) Antineoplastic Adjuncts • Rasburicase • Procainamide • Quinidine Genitourinary Analgesics • Phenazopyridine Diagnostic Agent • Toluidine blue (Pyridium) for Cancer Detection • Colchicine • Probenecid Others • Acetylphenylhydrazine Gout Preparations • Phenylhydrazine Hormonal Contraceptives • Mestranol Nitrates • Isobutyl nitrite Vitamin K Substance • Menadiol Na sulfate Vitamins • Menadione • Menadione Na bisulfite Others • Phytomenadione • Ascorbic acid (Vit C) (rare) • Arsine • Berberine (in Coptis chinensis) • Fava beans • Naphthalene (in moth balls) • Para-aminobenzoic acid 154 | Drugs to Avoid in G6PD Deficiency

Chapter 30 CLINICAL RELEVANT PARAMETERS FOR EACH ANTIEPILEPTIC DRUG AND ASSESSMENT OF THEIR LACTATION RISK 155

2021 NEOMED BOOK Drug Assessment of the lactation risk according to: Carbamazepine LactMed 2013 (including adverse drug reactions) Present study • CBZ levels are relatively high in breast milk. Safe • Breastfed infants have serum levels that are usually below the therapeutic range. • Side effects were rarely reported as sedation, decreased sick ling, withdrawal reactions and 3 cases of liver dysfunction. • Infant should be monitored for jaundice, drowsiness, ade quate weight gain, and development milestones especially in premature infants, exclusively breastfed and in combina tion with other antipsychotics. Clonazepam • Monitor growth, sedation, developmental milestones, espe Contraindicated Diazepam cially in preterm neonates, exclusively breastfed infants and if Contraindicated mother is receiving psychotropic drugs. • Monitoring of serum concentration • Accumulates in maternal milk and serum of breastfed infant. Other agents are preferred, especially while nursing a new born or preterm infant. • Single dose does not require delaying feeding. Ethosuximide • Monitor infant for drowsiness, adequate weight gain and Contraindicated Gabapentin psychomotor development. Moderately safe Lamotrigine Moderately safe Levetiracetam • Measurement of an infant serum level might help rule out Moderately safe Oxcarbazepine toxicity, if there is a concern. Moderately safe Phenobarbital • Monitor the infant for drowsiness, adequate weight gain, and Safe developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvul sant or psychotropic drugs. • It is not necessary to discontinue breastfeeding, but any ad verse effects such as apnoea, rash, drowsiness, decreased sucking are to be monitored and serum levels are to be measured. • Monitor infant for appearance of sleepiness, increase appro priate weight, normal psychomotor development. • Monitor the infant for drowsiness and decreased feeding, and development milestones especially in the first 2 months of life. • The presence of phenobarbital in breast milk may mitigate possible neonatal abstinence. • Monitor the breastfed infant for the possible onset of drows iness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants and antie pileptic polytherapy. • Measurement of the infant’s serum drug concentration might help rule out toxicity. Phenytoin • The proportion ingested by infants is small and generally Safe brings about no problems except in rare cases of idiosyncratic reactions. 156 | Clinical Relevant Parameters for each Antiepileptic Drugs and Assessment of their Lactiation Risk

Drug Assessment of the lactation risk according to: Pregabalin LactMed 2013 (including adverse drug reactions) Present study Primidone • Compatible with breastfeeding. Moderately safe Tiagabine • An alternate drug may be preferred, especially while nursing a Topiramate Valproate newborn or preterm infant. Vigabatrin Zonisamide • The presence of phenobarbital in breast milk may mitigate Safe possible neonatal abstinence. Moderately safe • Monitor the breastfed infant for the possible onset of drows Moderately safe iness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants and antie Safe pileptic polytherapy. Moderately safe Contraindicated • Measurement of the infant’s serum drug concentration might help rule out toxicity. • Monitor the infant for the onset of drowsiness, for adequate weight gain and development milestones especially in young er, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs. • Other drugs should be preferred especially while nursing a newborn or preterm baby. • Monitor the infant for the onset of diarrhea, drowsiness, increase appropriate weight and psychomotor development. • Breastfed infants are at risk for hepatoxicity. • Monitor the infant for unusual bleeding (a case of thrombocy topenia has been reported) • Until more data are available, vigabatrin should only be used with careful monitoring during breastfeeding. • Monitor infant for drowsiness, adequate weight gain and psychomotor development. • Measurement of an infant serum level might help rule out toxicity if there is a concern. Clinical Relevant Parameters for each Antiepileptic Drugs and Assessment of their Lactiation Risk | 157

2021 NEOMED BOOK Antimicrobial and lactation Compatibility Compatible with breast Effects during breast feeding Effects not known/to be feeding are not known used with caution • Acyclovir • Antiretrovirals • Chloramphenicol • Amantadine • Famciclovir • Clindamycin • Valacyclovir • Foscarnet • Dapsone • Ketoconazole • Ganciclovir • Mandelic acid • Chloroquine • Amphotericin • Metronidazole (low dose) • Hydroxychloroquine. • Fluconazole • Nalidixic acid • Quinine • Flucytosine • Nitrofurantoin • Aminoglycosides • Itraconazole • Penicillins • Amoxycillin • Mefloquine • Tetracyclines • Amoxycillin-clavulanate • Pentamidine NOT RECOMMENDED • Metronidazole (single high • Antitubercular drugs • Proguanil • Cephalosporins • Primaquine dose). • Macrolides • Pyrimethamine • Quinolones • Trimethoprim- sulphame- • Mebendazole thoxazole • Pyrantel pamoate • Praziquantel • Quinacrine antihelminth • Thiabendazole • Piperazine ***References: 1. Italian Journal of Pediatrics 2013; 39:50 2. Postgrad Med J 2004; 80: 196-200 158 | Clinical Relevant Parameters for each Antiepileptic Drugs and Assessment of their Lactiation Risk

Chapter 31 MANAGEMENT GUIDELINES OF NEONATES WITH HIV-POSITIVE MOTHERS 159

2021 NEOMED BOOK Level of HIV Description Neonatal Management Transmission Risk Mothers who received ARV during pregnancy with Zidovudine for 4 weeks Low Risk of Perinatal sustained viral suppression (defined as a confirmed HIV HIV Transmission RNA level < 50 copies/mL) near delivery and no concerns related to adherence Higher Risk of 1. Mothers who received neither antepartum nor intra Two-drug ARV prophylaxis Perinatal HIV partum Antiretroviral (ARV) drugs (with 6 weeks zidovudine Transmission and three doses of Never- 2. Mothers who received only intrapartum ARV drugs apine) 3. Mothers who received antepartum and intrapartum Neverapine doses: (see doses below) ARV drugs but who have detectable viral loads near 1st dose within 48 hours delivery, particularly when delivery was vagina of birth, 4. Mothers with acute or primary HIV infection during 2nd dose 48 hours after pregnancy or breastfeeding (in which case, the moth first dose, er should discontinue breastfeeding) 3rd 96 hours after second dose Mothers with unconfirmed HIV status who have at least Same as in high risk one positive HIV test at delivery or postpartum Infant ARV drugs should be discontinued imme- Presumed Newborn Or diately if supplemental HIV Exposure whose newborns have a positive HIV antibody test testing confirms that the mother does not have HIV Newborn with HIV Positive newborn HIV virologic test/NAT Three-drug ARV regimen using treatment doses based on Pediatric Infec- tious Diseases’ recommen- dations. • All newborns who were perinatally-exposed to HIV should receive postpartum antiretroviral (ARV) drugs to reduce the risk of perinatal transmission of HIV • Newborn ARV regimens administered at doses that are appropriate for the infant’s gestational age should be initiated as close to the time of birth as possible, preferably within 6 to 12 hours of delivery. The prophylaxis regimen for ZIDOVUDINE is: Level of HIV Description Neonatal Management Transmission Risk Oral For the newborn infant 4 mg/kg/dose, twice daily, for the first 4–6 weeks ≥35 weeks’ gestation, as Intravenous of life soon as possible after 3 mg/kg/dose, twice daily, for the first 4-6 weeks of birth life (or until oral is tolerated). 160 | Management Guidelines of Neonates with HIV-Positive Mother

For the newborn infant Oral 2 mg/kg/dose, twice daily for 14 days, then increase ≥30 to <35 weeks’ Intravenous to 3 mg/kg/dose, twice daily for 4 weeks (to com- gestation, as soon as plete a total of 6 weeks of treatment) possible after birth Oral 1.5 mg/kg/dose, twice daily (maximum of 6 For the newborn infant Intravenous weeks). When able to tolerate oral medications, the <30 weeks’ gestation, as twice-daily dose is 2 mg/kg/dose until 14 days of soon as possible after life and then 3 mg/kg/dose to complete 6 weeks of birth treatment 2 mg/kg/dose, twice daily for 28 days, then increase to 3 mg/kg/dose, twice daily, to complete a total of 6 weeks of treatment 1.5 mg/kg/dose, twice daily (maximum of 6 weeks). When able to tolerate oral medications, the twice-daily dose is 2 mg/kg/dose until 28 days of life and then 3 mg/kg/dose to complete a total of 6 weeks of treatment Note: For newborns who are unable to tolerate oral agents, the IV dose is 75% of the oral dose while maintaining the same dosing interval. I. ZIDOVUDINE Weight-directed dosing for infants >35 weeks gestation: Oral suspension of ZIDOVUDINE Fixed weight-band dosing: 4 mg/kg/dose every 12 hours 2 to <3 kg: 10 mg every 12 hours For 4-6 weeks 3 to <4 kg: 15 mg every 12 hours 4 to <5 kg: 20 mg every 12 hours Side effects: Anemia and neutropenia, Bone marrow toxicity may be increased by concomitant administration of acyclovir, ganciclovir, sulfamethoxazole / trimethoprim. Transient lactic acidemia II. The dose for NEVIRAPINE is: Birth weight >2Kg: 12 mg per dose po Birth weight 1.5-‐2 Kg: 8 mg per dose po Side effects: Limited data on toxicity and Non-reported in neonates III. LAMIVUDINE • Only used for treatment • Must be ordered by the Pediatric Infectious Diseases Consultant ***References: 1. Red Book (2018) 2. AIDSinfo and Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV: Guidelines for the use of antiretroviral agents in pediatric HIV infection. AIDSinfo. Rockville, MD. 2019. 3. Nielsen-Saines K, Watts DH, Veloso VG, et al: Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. N Engl J Med 2012; 366(25):2368-2379. 4. AIDSinfo: Recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States. AIDSinfo. Rockville, MD. 2017. Management Guidelines of Neonates with HIV -Positive Mother | 161

2021 NEOMED BOOK Appendix I CARDIOVASCULAR DRUG COMPATIBILITY CHART 162

Amiodarone Bicarbonate Calcim Chlo- ride Calcium Glu- conate Chlorothiazide Digoxin Dobutamine Dopamine Epinephrine Esmolol Fentanyl Furosemide Heparin Indomethacin Insulin Lidocaine Liothyronine Milrinone Amiodarone I CC CI C Bicarbonate I IIC I I I I CC CC C C C Calcium Chloride I C CCC CC Calcium Gluconate I CC C CI CC Chlorothiazide C C IC C Digoxin I CC CCCC Dobutamine CI C C I CC CC I I C C C C Dopamine CI C C C C CC CI I C C C Epinephrine IC C CC CC C I CC Esmolol IC C CI C C Fentanyl C C CCC CC CCC Fluconazole C C CCC IC C C Furosemide CC C CC CC I C IC CI Heparin IC C C CI CC C CI CC C Indomethacin CI II C CC Insulin C I CC I CC CC Lidocaine C C C C C CC CI CC C C C Liothyronine CC CC C C Milrinone C C C C CC CC CI CC C C Morphine CC I CC CC C CI CC C C C Nitroglycerine C C C CC CC CC Nitroprusside C C C C C C CC CCC Phenylephrine CC C C Potassium Chloride C C C C CC CC C CC CC C C C Procainamide CI C C C CI I C CC I Prostaglandin E1 C CC CC CC Vecuronium C CC C CI C 5% Dextrose C C C C C CC CC C CC CC C C C C 10% Dextrose C C C C C CC CC CC CI C C C C Normal Saline C C C C C CC CC C CC CC C C C C Dextrose/Amino I C C I CC CC CC CI C C Acids Cardiovascular Drug Compatibility Chart | 163

2021 NEOMED BOOK Morphine NitroglycerinE Nitroprusside Phenyleph- rine Potassium Chloride Procainamide Prostaglandin E1 Vecuronium 5% Dextrose 10% Dextrose Normal Saline Dextrose/ Amino Acids Amiodarone C CC CC CC C C CI Bicarbonate C C CC CC C I C C CC Calcium Chloride C C C CC C C C CC C Calcium Gluconate C CC CC C C C CC Chlorothiazide I C C CI CC C I CI Digoxin C C C C C CC C C C C Dobutamine C C C C CCC C C C C CC Dopamine C C C C CCC C C C CC CC Epinephrine C C CC C CCC C C C C Esmolol C C C CI CC C C C Fentanyl C CCC C C CC CC Fluconazole C C C CC C C Furosemide I C C C I CC C C CC C Heparin C CC C C CCC C C CC C Indomethacin C CC CC CI CI C Insulin C CC CC C C C Lidocaine C CC C C Liothyronine CC C Milrinone C CC C Morphine C CCC C C Nitroglycerine CCC C Nitroprusside C CCC C C Phenylephrine CC C C Potassium Chloride C C CCC C C Procainamide CC Prostaglandin E1 C CC C Vecuronium C CC C 5% Dextrose C CC 10% Dextrose C CC Normal Saline C CC Dextrose/Amino C Acids 164

Appendix II SUMMARY OF MEDICATIONS FOR VARIOUS INBORN ERRORS OF METABOLISM 165

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT 1mg/mL solution 0.2 mg /kg every 2 Headache, tingling, Agalsidase-alpha Fabry disease for infusion weeks as IV infusion numbness, tremors, (Replagal®) over 40 minutes.(1, 2) fatigue, change in temperature sensation, increased blood pressure, upset stomach, diarrhea, coughing, sore throat, dif- ficulty sleeping, change in the taste of food, change in smell, difficulty speaking, acne, dry skin and eye problems. About 1 out of 10 patients may have a reaction during or shortly after infusion of Replagal®. These effects include chills & facial flushing (warmth & redness). However, some effects may be serious and may need treatment. Agalsidase-beta Fabry disease 5 mg and 35 mg 1mg/kg every 2 Infusion reactions (Fabrazyme®) single-use vials for weeks as IV infusion consisted of one or more reconstitution to over 2 - 4 hours.(1, 3) of the following: chills, yield (5mg/mL) fever, feeling hot or cold, dyspnea, nausea, flushing, headache, vomiting, paresthesia, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tight- ness, abdominal pain, dizziness, tachycardia, nasal congestion, diar- rhea, edema peripheral, myalgia, back pain, pallor, bradycardia, urticaria, hypotension, face edema, rash, and somnolence Alanine Maple Syrup 300 mg and 500 150 - 400 mg/kg/ None Urine disease mg capsules day adjusted ac- (MSUD) 300 mg, 500 mg, cording to plasma & 1000 mg tabs / amino acids.(4) Powder 166 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Pneumonia, respirato- Alglucosidase-al- Pompe disease 50 mg single-use 20mg/kg every 2 ry failure, respiratory pha (Myozyme®) (GSD II) vials for recon- weeks IV infusion distress, catheter- related stitution to yield over 4 hours.(5-7) infection, respiratory (5mg/mL) syncytial virus infection, gastroenteritis, fever and infusion reactions. Allopurinol - Disorders 100 and 300 mg Children: 2 - 20 mg/ Dermatologic (less than causing hyper- tablets kg/day. 1% ): Rash, Stevens-John- uricemia 20mg/mL suspen- Adults: 100 - 600 son syndrome, Toxic - As a challenge sion (extempora- mg/day. epidermal necrolysis drug to induce neous prepara- The dosage range Hematologic: Agranulo- orotic aciduria tion) is wide. cytosis, Aplastic anemia, Generally, the rec- Eosinophilia, Myelosup- ommended dose is pression, Thrombocyto- what is required to penia (0.6% ) keep the serum uric Hepatic: Granulomatous acid level < 6 mg/dl hepatitis (less than 1%), and avoid xanthine Hepatic necrosis (less calculi (the side ef- than 1%), Hepatotoxicity fect of allopurinol). Immunologic: Immune The dose should hypersensitivity reaction be reduced in renal Renal: Renal failure (less failure.(8-17) than 1%) Alpha-lipoic acid Inborn errors 50 mg, 100 mg, & 25 - 50mg/kg/ Muscle cramps, pares- of pyruvate 250 mg capsules day, dose adjusted thesia and neuropathy dehydrogenase 100 mg, 200 mg, & according to symptoms may worsen complex 300 mg tablets biochemical and at first, platelet disorders, Oral liquid clinical response. purpura, shortness of breath, tension head- (18, 19) ache, urticaria, eczema Ammonium tetra- Neurological 120 mg/day as thiomolybdate presentation of 20 mg capsules below: Nausea and cytopenia (Coprexa®) Wilson disease • 20 mg three times daily with meals and 20 mg 3 times daily between meals for 2 weeks, and then 60 mg/day as below: 10 mg three times daily with meals and 10 mg three times daily between meals.(20, 21) Summary of medications for various Inborn Errors of Metabolism | 1| 67

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Arginine (oral) Chronic man- For argininosuccin- Hyperchloremic meta- agement of hy- 250 mg tablets ic acid synthetase bolic acidosis, hypokel- perammonemia 600 mg and 700 deficiency (ASS) emia, diarrhea, elevated secondary mg capsules and argininosuc- BUN, creatinine levels, to urea cycle Powder cinic acid lyase flushing, nausea, vomit- disorders (e.g. deficiency (ASL); ing, abdominal cramps, Argininosuccinic dose is: bloating, numbness, acid synthetase 400 - 700 mg/kg/ headache deficiency and day div. Q8 hr or 8.8 Arginino suc- –15.4 g/m2/day div. cinic acid lyase Q8 hr deficiency and N-Acetylglu- - For N-Acetylglu- tamate synthe- tamate synthetase tase deficiency) deficiency (NAGS deficiency); dose is: 170 mg/kg/day div. Q8 hr.(22) Arginine h Acute man- 10% solution for - For suspected Hyperchloremic meta- ydrochloride agement of injection (100 mg/ urea cycle or bolic acidosis, hypokel- hyperammone- mL) ASS or ASL, give: emia, diarrhea, elevated (R-Gene®) mic crises in 600mg/kg if (< BUN, creatinine levels, suspected or 20kg) or 12 gram/ flushing, nausea, vomit- confirmed urea m2 if (> 20kg) as ing, abdominal cramps, cycle disorders, a loading dose bloating, numbness, except arginase over 90 minutes headache, phlebitis deficiency followed by 600 mg/kg if (< 20kg) or 12 gram/m2 if (> 20kg) as mainte- nance infusion over 24 hours. -For OTC & CPS: 200mg/kg if (< 20kg) or 4 gram/ m2 if (> 20kg) as a loading dose over 90 minutes followed by 200 mg/kg if (< 20kg) or 4 gram/ m2 if (> 20kg) as mainte- nance infusion over 24 hours. Aspirin As an antithrom- 81, 100, 325 mg 50-100 mg daily. (23) Gastrointestinal ulcer, botic agent used tablets bleeding, tinnitus, bron- in homocystin- chospasm angioedema, uria Reye’s syndrome 168 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Baclofen Dosage is by age: < 2 years: 10 - 20 mg/day div. Q8 hr; titrate dose every 3 days in increments of 5 - 15 mg/day to a maximum of 40 mg daily. 2 - 7 years: 20 - 30 Cardiovascular: mg/day div. Q8 hr; Hypotension (0% to 9% ) titrate dose every 3 Gastrointestinal: days in increments Constipation) of 5 - 15 mg/day Musculoskeletal: to a maximum of Poor muscle tone 60 mg daily. Neurologic: Asthenia (0.7% to 15% ), Dizziness Musculoskeletal 10 mg, 20 mg and ≥ 8 years: 30 - 40 Headache, Somnolence relaxant 25 mg tablets; mg/day div. Q8 Other: Fatigue (2% to 5mg/5mL suspen- hr; titrate dosage 4% ), Shivering (0.5% to sion as above to a 1.3% ) 10 mg/mL suspen- maximum of 120 sion (extempora- mg daily. neous prepara- Alternatively: tion) start at 0.3 mg/kg/ day div. Q8 hr and increase every 1 - 2 week(s) until reach- ing maintenance dose of: 0.75 - 2 mg/kg/day. For > 10 years of age you can reach up to 2.5mg/kg/day Adults: 5 mg three times daily; may increase by 5 mg/ dose every 3 days to a maximum of 80 mg/day. 30 – 75 mg/day is considered the standard dosage range.(24, 25) Summary of medications for various Inborn Errors of Metabolism | |169

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Betaine The aim is to nor- malize homocyste- ine level. For classical ho- mocystinuria and MTHFR deficiency: Classical Ho- Capsules Tablets Children: 100-150 Diarrhea, Drug-induced mocystinuria Powder mg/kg/day ÷ BID gastrointestinal distur- Remethylation Increase weekly bance, Nausea defects by 50 mg/kg incre- ments, as needed. Maximum: 9 grams/ day. Adults:3 grams twice daily, up to 20 grams/day have been used to con- trol high homocys- teine levels. (26-29) - Cbl C, D, E, F, G defects: < 6 months: 250- 500mg twice daily. > 6 months: 75mg/ kg/day ÷ BID.(9) Biotin - Co-factor for 10 and 50 mg tab- Biotinidase defi- Administration of carboxylases lets / capsules ciency, co-factor for anticonvulsant medica- Biotinidase 1 mg capsule carboxylases and tions may impair Biotin deficiency IV (available as Multiple carboxy- absorption Biotin Re- part of a multivita- lase deficiency: Gastrointestinal upset sponsive Basal min complex) 5 - 20 mg/day. (8, 9, Ganglia disease 30, 31) (BRBGD) BRBGD: 5 - 10 mg/ Multiple carbox- kg/day.(32-34) ylase deficiency Chenodeoxycholic 3β-dehydroge- 250 mg tablets 3Bd: 12 - 18 mg/ Cholesterol accumula- acid (Chenodiol®) nase deficiency kg/day for first 2 tion, GI upset, elevated (3Βd) months then 9 - 12 liver enzymes, lipid Delta 4-3-ox- mg/kg/day or 7 mg/ abnormalities, phlebitis, osteroid 5 kg/day with cholic leucopenia beta-reductase acid. deficiency (3- 3-ORD: 8 mg/kg/ ORD) day. Cerebrotendi- CTX: 750 mg/day nous xanthoma- in 3 divided doses. tosis (CTX) (8, 9, 35-38) 170 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Cholesterol Smith-Lemli- 150 mg tablets Children: 100 mg/ Unknown Opitz (SLO) kg/day in 3 divided doses (doses up to 150mg/kg/day have been used). Adults: 40mg/kg/ day or 500 mg /day in 3 divided doses. (9), (39-41) Children ≤10 years: Initial: 2 g/day; titrate dose based on efficacy and toler- ance; Range: 1- 4 g/day. Cholestyramine Familial Hyper- 4 g resin in packets Children >10 years Abdominal discomfort, cholesterolemia and Adolescents: constipation, flatulence, Initial: 2 g/day; nausea and vomiting titrate dose based on efficacy and tolerance, up to 8 g/day. Adults: 3 - 4 grams, three to four times/ day to maximum of 16 - 32 g in 2 - 4 divided doses.(42-45) With chendeoxy- cholic acid: Cholic acid 3-ORD Powder 3Bd: 7 mg/kg/day. Heartburn, acid reflux; 3Βd deficiency 50 mg and 250 (9, 35) nausea, diarrhea, stom- mg Tab 3-ORD: 8 mg/kg/ ach pain; general ill feel- day.(8, 9, 35) ing; jaundice; skin sores; Alone: 6 - 15 mg/ or. numbness, tingling, or kg/day in 2 divided burning pain doses (don’t exceed total dose of 500 mg/day).(35, 46) Neonates: 500 mcg/mL solu- 50 - 150 mcg/kg tion for injection daily injection. Copper histidine Menkes diseases (prepared extem- Infants and chil- Unknown poraneously) dren:1mg/day.(8, 9, 47, 48) Summary of medications for various Inborn Errors of Metabolism | |171

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Creatine Guanidi- monohydrate noacetate Tablet Powder 300 - 400 mg/kg/ Dehydration methyltrans- day up to 2 g/kg / gastrointestinal distress, Cysteamine ferase (GAMT) day in three to six diarrhea muscle bitartrate deficiency divided doses.(49) cramping (Cystagon®) Arginine:glycine renal dysfunction amidinotrans- weight gain, water ferase (AGAT) retention deficiency Creatine trans- 50 mg and 150 mg Begin with 10 Dermatologic: Rash (7% ) porter defect capsules mg/kg/day and Gastrointestinal: Diarrhea increase weekly (16% ), Loss of appetite Cystinosis until reaching the (31% ), Vomiting (35% ) maintenance dose Neurologic: Lethargy (60 to 90 mg of free (11% ), Somnolence base/kg/day) or (1.3 Other: Fever (22% ) to 1.95 g/m2 per day). The recommended adult dose is 500 mg free base q6 hours; however, for both children and adults, the dose is titrated to reduce, if possible, leukocyte cystine concentra- tion (measured 5-6 hours after a dose) to below 1 nmol half-cystine/ mg protein (50-52) Cysteamine Cystinosis Ophthalmic drops 0.55% solution Neurologic: Headache hydrochloride with benzalkonium (greater than or equal to chloride 0.01% as a 10% ) Ophthalmic: Eye (Cystoran®) preservative: irritation, Pain in eye, 10 - 12 times/day in Photophobia (greater each eye (53, 54) than or equal to 10% ), Red eye (greater than or equal to 10% ), Visual field defect (greater than or equal to 10% ) 172 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Dextrome- thorphan Non-Ketotic 15 mg tablets 5 - 35 mg/kg/ Dizziness, Somnolence, Dichloroacetate Hyperglycinemia 15 mg/ 5mL syrup day in 4 divided fatigue Diazoxide doses. Blood Primary lactic Powder concentration can Peripheral neuropathy; acidosis be monitored; the Sleepiness, mental foggi- therapeutic level ness, confusion is not defined, but Cardiovascular: Hypo- should be greater tension (7% ) than zero (0) and Endocrine metabolic: lower than 100 Hyperglycemia Gastro- nmol/L (55-59) intestinal: 50 mg/kg/day ÷ Nausea and vomiting q12 hr IV (4%) 25 mg/kg/day ÷ Neurologic: Asthenia, q12 hr PO (60) Dizziness (2% ) Hyperinsulin- 50 mg 5 to 15 mg/kg/day ism hyperam- capsules oral in 3 divided doses. monemia (HIHA) Suspension (5 & 50 The dose should be mg/mL) adjusted to achieve adequate control of both fasting hypoglycemia and protein-induced hypoglycemia.(61, 62) Elosulfase alfa Morquio Must be diluted 2 mg/kg weekly Hypersensitivity reac- (VIMIZIM®) syndrome (MPS with sodium over 3-4 hours tions, fever, chills, fatigue, Entacapone IV) chloride 9 mg/mL nausea, vomiting and (0.9%) solution for headache injection to a final volume of 100 mL or 250 mL (based on the patient’s weight, ≥25 kg diluted in 250 mL while <25 kg diluted in 100 mL) prior to infu- sion and delivered intravenously. 5 mL, single-use vials Endocrine metabolic: Hyperpyrexia Musculoskeletal: 15 mg/kg/day: Rhabdomyolysis Disorders of in 2 - 3 divided Neurologic: Dyskinesia BH4 synthesis 200 mg tablet doses.(8, 63) (25% ), Hyperactive be- havior (10% ), Neurolep- tic malignant syndrome Psychiatric: Hallucina- tions (4% ) Summary of medications for various Inborn Errors of Metabolism | |173

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Ezetimibe Familial 10 mg tablet 10 mg/day (64, 65) Hepatitis, increase liver hypercholestro- enzymes, Folic acid laemia 1 mg and 5 mg Variable, 5 - 30mg/ Rhabdomyolysis Long term tablets day (66, 67) supplemen- Bad taste in mouth, large tation to doses: loss of appetite, compensate for nausea, irritability, sleep the so- called pattern disturbance and methylfolate confusion trap in remethyl- ation defect Folinic acid - DHPR defi- 5 mg, 10 mg, 15 Hereditary folate Allergy ciency mg, 25 mg tablets malabsorption: - UMP synthase 10mg/mL injec- Adult: 150-200 deficiency (he- tion solution mg/day PO once reditary orotic 50 mg, 100 mg, daily Infants and aciduria) 200 mg, 350 children: 50 mg or - Methylene syn- mg powder for 10 - 15 mg/kg PO thase deficiency reconstitution once daily.(68, 69) - Methionine (injection) Or 1.5 - 7.5 mg IM synthase defi- once daily (69-71). ciency However, The dose - Hereditary should be adjusted folate malab- in the individual to sorption achieve a normal - Cerebral folate CSF folate level that Transporter is normal for age. defect (72) - Folinic Acid Responsive Other indications: Seizure 5 - 15mg/day PO or - Remethylation IV BID.(8, 73) defect Galsulfase Mucopolysac- 5 mg/mL solution 1 mg/kg/week (74-77) Fever, headache, arthral- (Neglazyme®) charidosis for injection gia, abdominal pain, ear Gemfibrozil VI 300 mg and 600 1.2 grams daily, pain, diarrhea, vomiting Mixed or com- mg tablets usually in 2 divided and infusion reaction G-CSF = bined hyperlip- 300 mg capsules doses; range: 0.9 - Abdominal pain (9.8%), Filgrastim idemia 1.5 grams daily.(78, 79) Acute appendicitis 300 mcg/mL vial, 2.5 mcg/kg once (1.2%), Indigestion Neutropenia in 600 mcg/mL pre- daily. If the mean (19.6%) GSD 1b filled-syringe absolute neutrophil count (ANC) in the Nausea and vomiting subsequent 2-week (57%) and bone pain period was less (24% to 33%) than 1 × 109 cells/L, 174 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT G-CSF = Neutropenia in 300 mcg/mL vial, 2.5 mcg/kg once Nausea and vomiting Filgrastim GSD 1b 600 mcg/mL pre- daily. If the mean (57%) and bone pain (cont’d) filled-syringe absolute neutrophil (24% to 33%) count (ANC) in the Glutamine subsequent 2-week Glycine period was less than 1 × 109 cells/L, the dose should be escalated to 5 mcg/kg/day for the next 2 weeks. Subsequent dose escalations to 10, 20, and 30 mcg/kg/ day after 2 weeks of therapy if the mean ANC remained at less than 1 × 109 cells/L . Maximum dose: 30 mcg/kg/day MSUD Powder Therapy could Peripheral edema, nau- be continued for sea, vomiting, insomnia, - Isovaleric Powder up to depression, fever and acidemia 6 weeks in patients rigor with an ANC re- Blurred vision, temporary - HMG-CoA lyase maining at less than blindness deficiency. 0.5 × 109 cells/L. Chest pain, hypotension, If after 6 weeks bradycardia, EKG Chang- - May be used in of therapy at the es coma, confusion, 3 - Methylcroto highest dose level, seizures, dyspnea nyl glycinuria the ANC failed to in- Electrolyte disturbance: crease more than hyponatremia, Hyperka- 0.5×109 cells/L; then lemia, hemolytic anemia, G-CSF should be nausea, vomiting, throm- discontinued (8, 80) bocytopenia 150 - 400 mg/kg/ day according to plasma amino acids results.(4) 250 mg/kg/day (150 - 300 mg/kg/ day) in 4 divided doses.(8, 9, 81, 82) Summary of medications for various Inborn Errors of Metabolism | |175

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Heme arginate Acute porphyria 25 mg/mL solution 3 - 4 mg/kg once Increase blood pressure, (Normosang®) Disorders of for injection daily for 4 days.(8,83) Erythema, nausea, de- Hydroxocobala- cobalamin 1 mg/mL injection 1mg IM daily or crease lymphocyte count, min (vitamin B12) metabolism for solution Oral dose: 10 mg Headache, red color urine 50000 mcg Tablets once or twice daily. Increase blood pressure, 5-Hydroxytryp- Disorders of (8, 9, 84-86) Erythema, nausea, de- tophan neurotransmit- 25 mg, 50 mg, 100 crease lymphocyte count, ter synthesis mg, and 200 mg Start at low dose Headache, red color urine Idursulfase capsules (1 - 2 mg/kg/day) Ataxia, headache, (Elaprase®) Hunter syn- increasing gradually insomnia, mania, mental Imiglucerase drome (mucopo- IV solution must to 8 - 10 mg/kg/day stimulation/agitation (Cerezyme®) lysaccharidosis be diluted in 100 in 4 divided doses. coryza, diaphoresis, II) mL of 0.9 sodium The dose is adjust- tremulousness, halluci- Gaucher disease chloride injection, ed according to nations dermatomyositis, each vial contains clinical response, scleroderma (2 patients), 2mg/mL solution monitoring CSF drowsiness; dyspnea, of idursulfase neurotransmitters hyperventilation protein (6mg) in and prolactin level. eosinophilia, eosinophil- an extractable ia-myalgia syndrome, volume of 3 mL (8, 87) dysarthria, hyperreflexia, and for single use increased motor activity, only 0.5 mg/kg weekly paresthesia, psychosis, 200 units and 400 over 1-3 hour(s). sedation; nausea, vom- units powder for iting, diarrhea, anorexia, reconstitution (88- 90) stomach pain palpita- tions, bradycardia, hy- Various regimens: potension, hypertension Non-neuropathic transient blurred vision, Gaucher’s disease, pupillary dilatation, spon- chronic, symptom- taneous nystagmus atic: a) Children: limited Hypertention, pruritic data available for rash, headache, fever, those younger than urticaria and infusion 2 years of age reaction Hypotension, tachyar- rhythmia, cyanosis, flushing, pruritus, rash, urticaria, shivering, abdominal pain, diarrhea, nausea, backache, an- gioedema, fatigue, fever, chest discomfort 176 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Imiglucerase b) Children (2 (Cerezyme®) years and older): usual dosage, 60 (cont’d) units/kg IV over 1 to 2 hr every 2 weeks; may range from 2.5 units/kg 3 times weekly to 60 units/ kg once every 2 weeks.(91-93) c) Adults: Usual dosage, 60 units/ kg IV over 1 to 2 hr every 2 weeks; may range from 2.5 units/kg 3 times weekly to 60 units/ kg once every 2 weeks. The absence of an improvement in the visceral, haematological and biochemical mark- ers within 6 months may indicate that a higher dose is required. If bone crises continue, the dose should be in- creased by at least 50%.(92, 93) For type III gauch- er disease some cli- nicians recommend higher dosage: 120 U/kg/2 weeks.(8) 10 mg/mL,50 mg/ 1 mg/kg/day in 4 mL, and 100 mg/ divided doses. mL solution for in- Ketamine NKH jection (maybe be Titrate it up to Hypertension, used orally after 30 mg/kg/day tachycardia mixing the dose according to clinical with 0.2– 0.3 mL/ and biochemical kg of cola or other response.(94- 97) beverages Summary of medications for various Inborn Errors of Metabolism | |177

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Laronidase Flushing, injection site (Aldurazyme®) Mucopolysac- 2.9 mg/ 5 mL (500 100 U/kg/week.(98) reaction (18% ), Rash charidosis type 1 units/5mL) solu- (36% ) tion for injection antibody development (91% ), complication of infusion (32% headache; upper respiratory infec- tion (32% ) and fever L-carnitine Primary and sec- 300 mg/mL Oral Acute crises (carni- Diarrhea, nausea, stom- L-citrulline ondary carnitine liquid tine boluses): ach cramps, vomiting deficiency 300 mg capsules Loading Dose: 250 Stomach upset, heart- 500 mg Tablets mg/kg IV over 3 burn, cough, changes in 200 mg/mL Solu- minutes, or urination tion for injection PO: 100 mg/kg/ dose three to - Carbamoyl 500 mg capsules four times daily phosphate syn Powder i.e.(300–400 mg/ thetase (CPS) Sachets kg/day) should be Deficiency given. Urine output should be appropri- - Ornithine ate prior to dosing transcarba (or hemofiltration mylase (OTC) be ongoing). deficiency Chronic: 100 - 300 mg/kg/day ÷ q8 hr. - Lysinuric protein (8, 99-101) intolerance (LPI) CPS and OTC defi- ciency: 170 mg/kg/day or 3.8 g/m2/day. (102-105) LPI: 100 mg/kg/day, however, the aim is to keep the citrulline at normal ranges. In some patients 400 mg/kg/day were used.(106-108) Different dosages are suggested; L-dopa Neurotransmit- 250 mg and 500 generally start at Nausea (5.5% to 5.7% ) ters replacement mg capsules OR low dose: Combined 1-2 mg/kg/day PO preparation with increasing by: carbidopa 1-2 mg/kg/day every few days or weeks up to main- tenance dose of 10 - 12 mg/kg/day. 178 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT L-dopa Dosage can be (cont’d) Maple syrup Powder monitored by mea- Fatigue and loss of coor- L- isoleucine urine disease Sachets suring CSF levels of dination. L-Lysine-HCL LPI Powder neurotransmitter Fanconi’s syndrome, renal - 3-phospho- metabolites or veri- failure L-serine glycerate Powder fying normalization L-tryptophan dehydrogenase 500mg tablets / of serum prolactin Nausea, vomiting, and deficiency (3- capsules levels.(8, 63, 87, stomach upset L-valine** PGDH) Powder 109, 110) Heartburn, stomach pain, -Phosphoserine 600 mg capsules With the help of belching and gas, nausea, aminotrans- Powder metabolic dietitian: vomiting, diarrhea, and ferase (PSAT) Sachets 20 -120 mg/kg/day loss of appetite deficiency orally. Dose adjust- Nausea, vomiting, - Phosphoserine ed as necessary diarrhea, and stomach phosphatase to achieve normal bloating (PSPH) defi- plasma aminoacids ciency levels.(4) NKH Oral: 10 - 40 mg/ Maple syrup kg/day in 3 divided urine disease doses.(8, 107, 111, (MSUD) 112) or 0.05-0.5 mmol/kg, three times per day. Monitor plasma lysine level.(113) • 3-PGDH: Infantile form: 500 - 600 mg/kg/day in 3 divided doses Juvenile form: 100- 150 mg /kg/day in 3 divided doses. • PSAT: 500mg/ kg/day PSPH: 200-300mg/ kg/day However, the doses are varied aiming to normalize CSF serine.(114) 100 mg/kg/day in 3 divided doses. (8, 115) With the help of metabolic dietitian: PO 20-120 mg/kg/ day. Dose adjusted as necessary to achieve normal plasma aminoacids levels.(4) Summary of medications for various Inborn Errors of Metabolism | |179

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT 400 mg tablets Hypermagnesemia, Magnesium oxide Primary hyper- Liquid • 500mg/m2/day. hypokalemia hyponatre- oxaluria type 1 mia nausea ; vomiting Tablet, 250 mg (116) headache Mannose Congenital Bloating, loose stools, disorder of Available in differ- 0.15 mg/kg/dose or and diarrhea glycosylation ent dosage forms, 1 g/kg/day divided type 1b Capsules, powder in 5 doses However, Pharyngitis, oral ulcers, and tablets the mannose gastrointestinal symp- Mercaptopro- Cystinuria Each tablet doses depend on tom, taste sense altered pionylglycine contains all of the plasma mannose immune hypersensitivity (Tiopronin) below ingredients: measurement, and reaction sense of smell L-methylfolate the frequency of altered Methionine Several remeth- Calcium 3 mg, mannose uptakes ylation defects are crucial because headache of the short clear- nausea, diarrhea, Metanx Hyperhomocys- ance half-time of increased salivation, tineimia of vari- mannose.(8, 117-119) urinary frequency ous etiologies The dosage is wide Allergic reactions have 15 - 50 mg/kg/day been reported following in 2 or 3 divided the use of oral L- methyl- doses, maximum folate Calcium. 1000 mg/day. However, the dose depends on mon- itoring free urine cystine level and modify the dose in order to maintain a level below 200 mmol/mmol of cre- atinine. (8, 9, 120, 121 40–50 mg/kg per day adjust the dose to maintain upper normal ranges of plasma and CSF methionine.(67) However, some investigators argue against its usage in such disorders because it may result in sustained hyperhomocysti- naemia.(66) • 1 tablet twice daily.(122) 180 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Acne, skin reactions, aller- Metanx Pyridoxal 5’-phos- gic reactions, photosensi- (cont’d) phate 35 mg, tivity, nausea, Methylcobalamin Vomiting, abdominal 2 mg pain, loss of appetite, increased liver function test results, paresthesia, somnolence, nausea and headaches have been reported with pyridoxal 5’-phosphate. Mild transient diarrhea, polycythemia vera, itch- ing, transitory exanthema and the feeling of swell- ing of the entire body has been associated with methylcobalamin Metronidazole Propionic 250 mg & 500 mg Many regimens Nausea, Jarisch Miglustat acidemia and tablet 125 mg/5 used, the most Herxheimer reaction, (Zavesca) methylmalonic mL suspension common one 10-20 dizziness, headache, can- acidemia 500 mg/ 100 mL mg/kg/day Q8 for 1 dida infection of genital injection week then 3 weeks region, vaginal discharge, off.(101, 123) vaginal irritation - Gaucher 100 mg capsule GD: 100 mg/kg/day Thrombocytopenia, disease (GD) in TID. (124-127) weight loss, abdomi- patients un • NPC: 200 mg TID. nal pain, constipation, able to receive diarrhea, flatulence, intravenous (128, 129) nausea, vomiting, cramp, ERT, leg cramp, asthenia, dizzi- 100-250 mg/kg/ ness, headache, paresthe- - Niemann-Pick day then adjusted sia, tremor disease Type C individually in order visual disturbance (NPC) to maintain normal Gastrointestinal: ammonia plasma Abdominal pain (17% ), N-carbamoylglu- Unknown hy- Tab.:200mg levels and divided Diarrhea (13% ), Vomiting tamate perammonemia, (Dispersible) into 2 to 4 doses. (26% ) NAGS deficiency, Powder for oral (130-137) Hematologic: Anemia (Carbaglu®) CPS- 1 deficien- suspension: 100 Based on limited (13% ), Decreased hemo- cy, propionic mg/mL unpublished data globin (13% ) Immuno- academia or the maintenance logic: Infectious disease methylmalonic dose is less than (13% ) acidemia 100 mg/kg/day. Neurologic: Headache (13% ) Otic: Infection of ear (13% ) Respiratory: Nasophar- yngitis (13%), Tonsillitis (17% ) Other: Fever (17%) Summary of medications for various Inborn Errors of Metabolism | |181

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Nicotinamide Hartnup dis- 50 mg, 100, 250 50-300 mg/day. Dizziness order mg tablet Diarrhea, nausea, vom- 50 mg (8, 138) iting, abdominal pain Nicotinic acid Hyperlipidemia 100 mg flushing, a sensation of (Niacin) 250 mg 100-200 mg 3 warmth in face, neck, and 500 mg tablets times daily, in- ears headache, hepa- Nitisinone, Tyrosinemia and capsules crease totoxicity hypotension, 2-(nitro-4- trifluo- type 1 gradually over 2-4 rash, tingling, itching, Capsules: 2 mg, 5 weeks to 1-2 gram 3 and dry skin restlessness romethyl- mg and 10mg times daily.(8, 139) Hematologic: Leukope- benzoyl) 4mg/mL Suspen- nia, thrombocytopenia 1,3-cyclohe- sion 1mg/kg/day in Hepatic: Liver failure, xanedione (NTBC) 2 divided doses. neoplasm of liver ORFADIN® Ophthalmic: conjunc- (140-142) tivitis, corneal opacity, keratitis, photophobia Pantothenic acid 3-methylglu- Capsules and tab- • 15-150mg, how- Contact dermatitis, Penicillamine taconic aciduria lets 100 mg, 200 ever, 40 times the Diarrhea Cuprimine® type II mg, and 250 mg recommended daily Dermatologic: Rash (5% ) Wilson disease Liquid 200 mg/5 amount for adults Gastrointestinal: Diar- Cystinuria mL (10 mg) was used. rhea, epigastric pain, loss Capsules and of appetite, loss of taste tablets 250 mg (8, 17, 143) (12% ), nausea, ulcer of mouth (7% to 13% ), Wilson disease: vomiting Hematologic: 0.75 and 1.5 g myelosuppression in 2 - 4 divided Renal: Proteinuria (6% ) doses that results in an initial 24-hour cupriuresis of over 2 mg. It should be continued for about three months, by which time the most reliable method of moni- toring maintenance treatment is the determination of free copper in the serum. This equals the difference between quantita- tively determined total copper and ceruloplasmin copper. 182 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Penicillamine Adequately Dermatologic: Rash Cuprimine® treated patients (5% ) will usually have Gastrointestinal: (cont’d) less than 10 mcg Diarrhea, epigastric pain, free copper/dL of loss of appetite, loss of serum. It is seldom taste (12% ), nausea, ulcer necessary to exceed of mouth (7% to 13% ), a dosage of 2g/day. vomiting Hematologic: myelosup- (144-146) pression Renal: Proteinuria (6% ) Cystinuria: 2 g/ day for adults, with a range of 1 to 4 g/ day. For pediatric patients, dosage can be based on 30 mg/kg/day divided in 4 doses.(146) Note: Adjust dose to limit cysteine excretion to 100 - 200 mg/day. Polycitra Chronic treat- Oral solution con- Adult: 15-30 mL Alkalosis, hyperkalemia (Tricitrate ) ment for primary tains: Potassium diluted with water; Pyridoxine hyperoxaluria citrate monohy- taken 4 times a day type 1 and drate 550mg Pediatrics: 5 – 15 primary Sodium citrate mL, diluted in acidosis causes dihydrate water; 4 times/day 500mg and after meals and at Citric acid mono- bed time. hydrate 334 mg per 5 mL The dose is adjust- ed with blood gas monitoring.(147) Pyridoxine tablet 25 mg, 40 CBS: 200 mg/day Decreased folic acid, par- responsive mg, 50 mg, 100 or the lowest dose esthesia, somnolence cystathionine β mg, 250 mg, and that produces synthase defi- 500 mg the maximum ciency (CBS), Liquid oral: 200 biochemical benefit Pyridoxine mg/5 mL (i.e., lowest plasma dependent homocysteine epilepsy (PDE), and methionine Ornithine concentrations), Aminotransfer- as determined by ase Deficiency measurement of (OAT), total homocysteine Primary hyper- and amino acid oxaluria type levels, should be 1(PH1) given.(17, 148) Summary of medications for various Inborn Errors of Metabolism | |183

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Pyridoxine 50 & 100 mg PDE: 100 mg IV, Acne, skin reactions, aller- Pyridoxal phos- tablets additional doses gic reactions, photosen- (cont’d) phate- may be admin- sitivity, nausea, vomiting, dependent istered over the abdominal pain, loss Pyridoxal phos- seizures course of 30 min of appetite, increased phate (PLP) Glutaric aciduria while observing for liver function test results, Riboflavin (GA1), Multi- both a clinical and paresthesia, somnolence, ple acyl Co A possible electro- nausea and headaches dehydrogenase graphic response. deficiency If IV administration (MAD), of pyridoxine is not possible for a first trial, pyridoxine is given orally/ enterally: 30 mg/ kg/day. Long term treatment; there are no clear-cut dosing recommen- dations, generally 15 - 30 mg/kg/day have been used in infants or up to 200 mg/day in neonates and 500 mg/day in adults.(149) OAT deficiency: 300 - 600 mg/day. (8, 17, 150) PH1: 5-10 mg/ kg/day. Moni- tor oxalate and glycolate excretion and titrate the dose accordingly.(151, 152) 30 mg/kg/day divided in three or four doses enterally, for three to five days. 30- 50 mg/kg/ day divided in 4-6 doses.(73, 153) 25 mg, 50 mg, 100 GA1: There is no Urine discoloration mg tablet firm evidence that 400 mg capsule riboflavin improves the neurological outcome of GA. (100) 184 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT However, respon- siveness to 100 - 150 mg/day divided in 2 - 3 doses have been demonstrated in few patients. (154, 155) Riboflavin Short-chain acyl- MAD: 100 - 400mg/ (cont’d) CoA dehydro- day in 2-3 divided genase (SCAD), doses.(156, 157) Mitochondrial SCAD: 10 mg/kg/ complex 1 defi- day, divided into ciency three doses with a maximum of 150 mg/day.(158) Sapropterin hyperphenylala- Powder, for oral Mitochondrial com- Abdominal pain, diar- dihydrochloride ninemia (HPA) solution: plex 1 deficiency: rhea, nausea, vomiting, due to BH4 100 mg/sachet 3 - 20 mg/kg/day headache, nasal dis- (Kuvan®) responsive Tab.:100 MG (Dis- divided in 3 doses. charge, throat pain, URTI Sebelipase alfa Phenylketonuria integrating) Hypersensitivity reac- (PKU). (9, 159) tions, fever, chills, fatigue, (KANUMA) Wolman 20mg/10mL, nausea, vomiting, red disease or single-use vials BH4 loading test: swollen skin, headache, lysosomal Has to be diluted 20 mg/kg/dose tachycardia acid lipase (LAL) with sodium once daily for 2 deficiency. chloride 9 mg/mL consecutive days. (0.9%) solution for infusion using Others: 10 - 20 mg/ aseptic technique. kg/day once daily (160-162), monitor phenylalanine lev- els and adjust the dose accordingly For Infants (under 6 months of age at time of diagno- sis) with rapidly progressive LAL-D, the recommended starting dosage is 1 mg/kg adminis- tered once weekly as an intravenous infusion. For pa- tients who do not achieve an optimal clinical response, consider increasing dosing to 3 mg/kg once weekly. Summary of medications for various Inborn Errors of Metabolism | |185

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Selegiline Disorders of BH4 5 mg capsule and 0.1-0.25 mg/kg/day GI upset, backache, head- (l-deprenyl) synthesis tablet in 3-4 divided dos- ache, insomnia, rhinitis, Sodium benzoate - Hyperam- es. Dosage can dyskinesia monaemia Powder be monitored by Sodium in urea cycle Measuring CSF lev- Endocrine metabolic: bicarbonate disorders and 0.5 mEq/mL solu- els of neurotrans- Hyperammonemia (5%), in undiagnosed tion or dilute the 1 mitter metabolites Hypokalemia (7% ), Meta- patients with mEq/mL solution or bolic acidosis (4% ) hyperammonae- 1:1 with sterile Verifying normal- Hematologic: Anemia mia water ization of serum (4% ), Disseminated - No evidence prolactin levels. intravascular coagulation to support (3% ) use of sodium (163, 164) Neurologic: Cerebral benzoate in edema (5% ), Coma (3%), acute crises of Acute crises: 0.25 Neurotoxicity, Seizure propionic or g/kg (<20 kg) or (6% ) methylmalonic 5.5 g/m2 (>20kg) academia.(101) as a loading dose Metabolic alkalosis followed by same - Persistent met- dose as mainte- abolic acidosis nance dose over 24 hours.(22, 104) In difficult to control chronic hyperammonemia, a dose of 250 mg/ kg PO divided in 3 doses may be considered.(101) In NKH up to 750 mg/kg/day have been used.(57) Adults: HCO3- (mEq) = 0.2 x weight (kg) x base deficit (mEq/L) or HCO3- (mEq) = 0.5 x weight (kg) x [24 - serum HCO3- (mEq/L)] Infants and Children: HCO3- (mEq) = 0.3 x weight (kg) x base deficit (mEq/L) or HCO3-(mEq) = 0.5 x weight (kg) x [24 - serum HCO3- (mEq/L)] 186 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Sodium Comes in com- If acid-base status is bicarbonate Hyperammonae- bination with not available: Dose Endocrine metabolic: (cont’d) mia in urea cycle Sodium Benzoate for older Children Hyperammonemia (5% ), disorders and (Ammonul®) and Adults: 2- 5 Hypokalemia (7% ), Meta- Sodium in undiagnosed mEq/kg I.V. infusion bolic acidosis (4% ) phenylacetate patients with over 4-8 hours; Hematologic: Anemia hyperammonae- subsequent doses (4% ), Disseminated mia should be based on intravascular coagulation - No evidence patient’s acid-base (3% ) to support status.(165) Neurologic: Cerebral use of sodium edema (5% ), Coma (3% benzoate in Acute crises: 0.25 ), Neurotoxicity, Seizure acute crises of g/kg (<20 kg) or (6% ) propionic or 5.5 g/m2 (>20kg) methylmalonic as a loading dose academia.(101) followed by same dose as mainte- nance dose over 24 hours.(22, 104) Sodium Chronic man- 500 mg tablet 0.45 - 0.6 g/kg/day Endocrine metabolic: phenylbutyrate agement of urea Available also as (if <20 kg); or 9.9 Acidosis (14% ), Hypoal- cycle disorders powder -13 g/m2/day in buminemia (11%) larger patients.(22, Hematologic: Anemia (9% ) 104, 105) Reproductive: Amenorrhea (23% ), Irregular periods (23% Statins - Hyperlipidae- Atorvastatin Depends on the • Headache, Difficulty mias. Simvas- (lipitor) Fluvastatin type of statin used sleeping, Flushing of tatin used in (lescol) Lovastatin the skin, Muscle aches, Smith–Lemli– (mevacor) Pravas- (17, 166). tenderness, or weakness Opitz syndrome tatin(pravachol) (myalgia) Simvastatin(zocor) For more details • Drowsiness; Dizziness, Rosuvastatin about the dosage Nausea or vomiting, (crestor) please refer to Abdominal cramping or reference 172. pain. Summary of medications for various Inborn Errors of Metabolism | |187

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Tetrahydrobiop- - BH4 loading 50 mg tablet BH4 loading test: 20 Abdominal pain, diar- test, disorders of THAM acetate mg/kg/dose once rhea, nausea, vomiting, terin (BH4) BH4 synthesis, solution daily for 2 consecu- headache, nasal dis- BH4 responsive Inj.: 36 mg / mL - tive days. charge, throat pain, URTI THAM PKU. Currently, 500 mL Others: 5 - 20 mg/ TROMETHAMINE replaced by kg/day, monitor Hypervolemia, Hypo- Kuvan® phenylalanine lev- glycemia, respiratory els and adjust the depression Refractory se- dose accordingly. vere metabolic acidosis with (160, 167) hypernatremia IV dose based on buffer base deficit of extracellular flu- id: THAM(R) (mL of 0.3 molar solution) = weight (kg) X base deficit (mEq/L) X 1.1.(168, 169) Thiamine re- Various dosage sponsive MSUD, have been used: 100mg/day,(170) Thiamine Thiamine 50 mg, 100 mg, 10mg/kg/day (2), Injection site reaction responsive pyru- 250 mg, 500 mg the dose ranges vate dehydroge- tablet between nase 100 mg/mL 10- 1000 mg/day. deficiency injection (4, 8, 171, 172) Complex I deficiency 500 - 750 mg/ day for pediatric patients and 750 - 1250 mg/day for adults given in divided doses: two, three or four times daily. Triethylene tetra- Wilson disease 250 mg capsules This may be Myasthenia gravis, spas- mine (trientine) in cases of increased to a ticity, dystonia, contact penicillamine maximum of 2000 dermatitis intolerance mg/day for adults or 1500 mg/day for children. Adjust the dose by determina- tion of free copper in the serum, which equals the difference between quantitatively determined total copper and ceru- loplasmin. 188 | Summary of medications for various Inborn Errors of Metabolism

DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Triethylene tetra- Adequately treated mine (trientine) patients will usually have less than 10 (Cont’d) mcg free copper/ dL of serum.(20, 21) Triheptanoin Very long Oral Liquid, 100% To provide 30-35% Most common adverse Ubiquinone chain fatty acid w/w of total calories.(173- reactions are (≥10%): (Coenzyme Q10 ) oxidation defect, abdominal pain, diarrhea, pyruvate carbox- 175) vomiting, and nausea. Uridine ylase deficiency, Velaglucerase alfa Adult-onset 50 mg, 100 mg, The dosages used Diarrhea, nausea, heart- acid maltase de- 120 mg, 200 mg are highly variable. burn, appetite suppres- Vitamin C ficiency (GSD II) soft gel capsule Adult: 200 - 600 mg sion headache, dizziness Primary CoQ10 QID, irritability, agitation deficiency Pediatrics: 2 - 15 mild increase in liver en- UMP synthase mg/kg/day BID. zymes skin rash, pruritus, deficiency (He- (176) Other used: exanthema reditary orotic 30 mg/kg/day.(177) aciduria) As high as 2000 Gaucher disease mg/day have been Glutathione used.(178) Synthetase deficiency (GS) 100 mg cap 100 - 150 mg/ Vomiting; Diarrhea; Hawkinsinuria, 50 units/ mL drops kg/day in divided Nausea Tyrosinemia doses. (179, 180) type III and Transient 200 U/vial and 400 60 U/kg adminis- Gastrointestinal: Abdomi- tyrosinemia of U/vial tered every other nal pain; Nausea newborn Powder for solu- week over 1 hour. Hematologic: Partial tion for injection thromboplastin time (181) increased Musculoskeletal: Arthral- Adjust based upon gia, Backache disease activity. Neurologic: Dizziness, Headache Respiratory: Upper respi- ratory infection Others: Asthenia, Complication of infusion, Fatigue, Fever 100 mg tablet GS deficiency: Nephrolithiasis, diarrhea, 100 mg/mL drops 100mg/kg/day. iron overload 1g effervescent (182- 184) tablet Others: 200 - 1000mg/day. Summary of medications for various Inborn Errors of Metabolism | |189

2021 NEOMED BOOK DRUGS INDICATION/S HOW SUPPLIED** DOSE SIDE EFFECT Vitamin E Glutathione 100 mg capsule Bleeding, hepatotoxicity, Synthetase 50 units/ mL drops GS deficiency:10 retinal hemorrhage, Zinc deficiency (GS) mg/kg/day.(182-184) pulmonary 50 mg (elemental embolism, sepsis Acrodermatitis zinc) capsule and AE: No consensus enteropathica tablet regarding the dos- Nausea, vomiting (AE) 15 mg/ 10mL age but generally Wilson disease suspension the recommended (extemporaneous initial dose is 5 - preparation 10mg/kg/day and maintenance dose: 1-2 mg/kg/day. (185-188) Wilson disease: The adult dose: is 50 mg t.i.d., each dose shall be sepa- rated from food and beverages other than water by at least 1 hour. The paediatric dose: is 25 mg b.i.d. until 5 years of age, 25 mg t.i.d. until 16 years of age, or until 125 lbs body weight, and then 50 mg t.i.d.(189) 190 | Summary of medications for various Inborn Errors of Metabolism

Appendix III MILK COMPOSITION FORMULA PER 100 ML 191

2021 NEOMED BOOK Breast Milk per 100ml & Human Milk Fortifier per Packet Revised 29/03/2021 PR ODU CT S KCAL CHO CHO Sources Protein Protein Source Fat Fat Source OSM Iron Zinc Vit D Mg Gram Gram Gram Mosm/ kg Ca++ PO4 mg mg IU mg SIMILAC HUMAN MILK FORTIFIER NON FAT MILK A PACKET (0.9 Gram) W HEY PROTEIN water mg mg HUMAN MILK MATURE Human milk W hey 4 0.5 Corn Syrup Solid Lactose 0.3 72% Casien 28% 0.1 MCT OIL 380 29 16 0.08 0.3 30 1.7 HUMAN MILK PREMATURE Human milk W hey PRE NAN HUMAN MILK 68 7.2 LACTOSE 100% 1.1 72% Casien 28% 3.9 Human milk fat MCT 2% LCT 290 28 14 0.03 0.1 2.1 3.5 FORTIFIER 98% 290 25 13 0.12 0.3 2 3.1 W hey Protein 67 6.6 LACTOSE 100% 1.4 3.9 Human milk fat MCT 2% LCT 98% 4 0.3 Maltodextrin 0.4 0.2 DHA ; MCT OIL 400 19 11 0.45 0.2 35 1 Preterm Formula PR ODU CT S KCAL CHO CHO Sources Protein Protein Source Fat Fat Source OSM Iron Zinc Vit D Mg Gram Gram Gram Mosm/ kg Ca++ PO4 mg mg IU mg water mg mg PRETERM SIMILAC SP. CARE 81 8.4 Lactose Corn Syrup 2.4 Non Fat W hey Milk 4.4 MCT OIL SOY OIL COCONUT 380 146 81 1.5 1.2 122 9.7 OIL PRE NAN RTF 80 8.6 Maltodextrin 2.9 Cow's Milk 3.9 Oleic Sunflower Coconut Oil 308 116 76 1.9 1.5 116 8 ENFAMIL PREMATURE 81 9.0 Corn Syrup Solid Lactose 2.4 Non Fat W hey 4.1 MCT OIL SOY OIL 300 110 61 2 1 196 7 Protein NURALAC LBW 80 8.4 Corn Syrup Lactose 2.4 W hey Non Fat Milk 4.1 MCT OIL Soy High Oleic Veg 300 108 69 1.4 1.2 196 1.4 APTAMIL PREMATURE Skim Milk Oil BLEMIL PRETERM RONALAC LBW 80 8.4 Lactose 2.6 W hey Protein 3.9 LCP MCT Oil 375 101 63 1.6 1.1 124 8 S26 LBW 85 47 1 0.6 68 8 81 9.0 Maltodextrin Lactose 2.3 Casein W hey 4.1 Linoleic Acid 300 83 54 1 0.6 64 8 73 42 1 0.7 58 7 82 9.0 Maltodextrin 2.4 Milk solids 4.1 Vegetable Oil 300 82 8.0 Maltodextrin 1.9 Casein W hey 3.9 Linoleic Acid 300 Regular Formula PR ODU CT S KCAL CHO CHO Sources Protein Protein Source Fat Fat Source OSM Ca++ PO4 Iron Zinc Vit D Mg Gram Gram Gram Mosm/ kg mg mg IU mg water mg mg BLEMIL PLUS 67 7 Lactose Maltodextrin 1.4 Casein W hey 3.5 Linoleic Acid 270 66 36 1 0.7 40 6 RONALAC 67 8 Maltodextrin 1.5 Milk solids 3.4 Vegetable Oil 270 55 28 1 0.5 41 5 NURALAC 54 40 0.4 1.3 42 6 68 8 Corn Syrup Solid Lactose 3.5 W hey Non Fat Milk 3.5 MCT OIL Soy High Oleic Veg 280 skim milk Oil SIMILAC ADVANCE 68 8 Lactose 1.4 W hey Non Fat Milk 3.7 Soy Oil Saff Oil Coconut Oil 270 52 28 1 0.5 50 4 APTAMIL 65 8 Lactose 1.3 Casein W hey 3 MCT Oil 270 49 28 0.5 0.5 48 5 SIMILAC GOLD HMO 64 7 Lactose Non Fat Milk S26 GOLD 67 7 Lactose Maltodextrin 1.4 W hey Protein Con. 3.5 High Oleic sunflower oil Soy 250 47 28 0.7 0.6 47.4 5 Frutooligosaccharide Oil Coconut Oil 250 46 33 1 0.6 46 6 PR ODU CT S CHO Sources Maltodextrin lactose 1.5 Casein W hey 3.6 Linoleic Acid HIGH CALORIE INFATRINI galactooligosaccharide ELECARE 24 Special Formula ELECARE 20 .69% NEOCATE INFANT 24 KCAL CHO Corn Syrup Solids Protein Protein Source Fat Fat Source OSM Ca++ PO4 Iron Zinc Vit D Mg NEOCATE INFANT 20 Gram Corn Syrup Solids Gram Gram Mosm/ kg mg mg mg mg IU mg NOVALAC ALLERNOVA 27 Corn Syrup Solids 54% NOVALAC ALLERNOVA 24 Corn Syrup Solids 54 % water NOVALAC ALLERNOVA 20 SIMILAC 27 100 10.0 Maltodextrin 2.6 Skimmed milk W hey 5.4 Veg Oil MCT Oil - coconut. 350 100 50 1 0.8 73 9 Maltodextrin protein 80 8.0 Maltodextrin 68 7.2 2.4 100% Free Amino 3.6 MCT High Oleic Safflower Oil 380 84 62 1.2 0.9 47 6.7 80 9.0 Lactose Acids Soy Oil 78 57 1.2 0.8 41 5.7 67 7.2 83 60 1 0.8 52 7.2 90 9.0 2.1 100% Free Amino 3.2 MCT High Oleic Safflower Oil 350 77 55 1 0.7 49 7 80 8.0 Acids Soy Oil 82 51 1 0.8 52 8 67 7.0 76 46 1 0.6 46 7.2 90 10.0 2.3 100% Free Amino 3.9 MCT Oil - 33% LCT 67% 406 70 41 1 0.5 40 6.8 Acid 70 37 2 0.7 66 5 1.9 100% Free Amino 3.4 MCT Oil - 33% LCT 67% 342 Acid 2.2 Hydrolyzed Casein 4.4 Vegetable oil Coconut oil 300 Protein 2.0 Hydrolyzed Casein 3.9 Vegetable oil Coconut oil 270 Protein 1.7 Hydrolyzed Casein 3.5 Vegetable oil Coconut oil 260 Protein 1.9 W hey Non Fat Milk 4.8 Soy Oil Saff Oil Coconut Oil 339 RONALAC LF 66 7.5 Maltodextrin 1.6 Milk Solids 3.3 VEGETABLE OIL 270 55 28 1.0 0.5 40 4.6 NAN HA 24 80 9.0 280 51 36 1 0.8 46 8 NAN HA 20 67 7.6 Lactose 1.8 Pa rt ia lly-H ydrolyz ed 3.9 Corn Oil Coconut Oil 250 44 31 0.7 0.6 40 7.2 Lactose Maltodextrin W hey Protein APTAMIL PEPTI JUNIOR 68 8.0 290 49 27 1 0.5 40 5 NAN 1 24 80 9.0 Maltodextrin 1.5 Pa rt ia lly-H ydrolyz ed 3.4 Pal Olein Sunflwer oil Corn 280 49 28 1 0.91 51 7 NAN 1 67 7.5 Lactose W hey Protein Oil Coconut Oil 250 43 24 0.7 0.7 46 5.7 NAN AR 24 80 10.0 299 48 30 1 0.8 42 7 NAN AR 20 67 8.0 Lactose Maltodextrin Extensively MCT Oil Veg Oil Palm Oil low 250 42 24 0.7 0.7 36 6.5 RENA START 100 13.0 Potato Starch 230 24 19 1 0.9 96 8 Potato Starch 1.7 Hydrolyzed W hey 3.7 erucic acid grapeseed oil PRE NAN 80 9.0 Dried Glucose 250 122 72 2 1 138 8 SIMILAC NEOSURE 74 8.0 Protein soybean oil 290 78 46 1 0.8 52 7 1.7 Cow's Milk W hey 3.8 Corn Oil Coconut Oil 1.2 Cow's Milk W hey 3.6 Palm olein Fish oil Sunflower oil Coconut Oil 1.4 Pa rt ia lly-H ydrolyz ed 4.1 Vegetable oil W hey Protein 1.2 Pa rt ia lly-H ydrolyz ed 3.3 Vegetable oil W hey Protein 1.5 W hey Protein 4.8 Vegetable Oil Post-Discharge Formula (PDF) Maltodextrin 2.2 W hey Protein 4.2 MCT OIL Veg Palm Lactose maltodextrin 1.9 Non Fat W hey 4.1 MCT OIL SOY OIL COCONUT Protein OIL 192

Appendix IV SAMPLE OF TPN SHEET 193

2021 NEOMED BOOK 194

Appendix V LIST OF TOPICAL MEDICATIONS 195

2021 NEOMED BOOK MEDICATION DOSE SPECIAL CONSIDERATION Fusidic acid 2% Skin infection : If a gauze dressing is used , frequen- cream/ ointment Apply small amount to affected area 2-3 times cy may be reduced to one or twice daily for 7-14 days daily Fusidic acid plus Dermatitis with secondary bacterial infec- A single treatment course should not hydrocortisone tions: normally exceed 2 weeks. cream / ointment A small quantity should be applied to the affected area twice daily until a satisfactory (Fucidin H ) response is obtained. Hydrocortisone1% Corticosteroid-responsive dermatosis: Treatment courses of less than 2 cream/ ointment Apply a thin film to affected area 2 to 4 times weeks are common for certain chron- daily depending on the severity of the condi- ic skin conditions; however, longer tion. or repeated intermittent courses can be appropriate, particularly when prescribed under the guidance of a dermatologist. Increased risk for corticosteroid-in- duced skin atrophy (eg, face, inter- triginous areas) Miconazole 2 % Dermatological superficial fungal infec- Off label use for infant younger than cream / ointment tion: 2 years Apply to affected area twice daily for 7 days Mupirocin MRSA decolonization: 2 % ointment Nasal & umbilical site: Apply small amount to both anterior nares 2 to 3 times / day for 5-10 days in conjunction with umbilical application of topical ointment MRSA or impetigo, minor skin infection: Ap- ply small amount 3 times daily for 5 to 10 days Nystatin 100,000 Diaper dermatitis, Candidal & Mucocutane- unit/ gram cream ous candida infection: Apply to affected area 2 to 4 times daily Mucocutaneous candida infection: Apply to affected area 2-4 times per day Zinc oxide 7.5-15 Skin protectant : % cream Apply liberally to affected area as needed , especially with each diaper change 196

MEDICATION DOSE SPECIAL CONSIDERATION The combination of phenylephrine Cyclopentolate 1% Mydriasis , cycloplegia: & Cyclopentolate is the preferred eye drops 1 drop in combination with phenylephrine agent due to lower Cyclopentolate 2.5% eye drop for 3 doses 5-15 minutes a part concentration and reduced risk for systemic reaction Erythromycin 0.5% Ophthalmia neonatorum prophylaxis : eye ointment Instill 1 cm ribbon into each conjunctival sac Gentamycin 0.3 Ophthalmic infections : Note : % eye drops/oint- Ointment : Use should be reserved for treatment Apply to affected eye 2-3 times daily of susceptible infection and not ment Drop: Instill 1 to 2 drops into affected eye routine prophylaxis for ophthalmia every 4 hours. Up to 2 drops every hour for neonatorum severe infection Off label use for infant younger than Neomycin / poly- Inflammatory ocular conditions : 2 years. mixin / dexameth- Drops : Instill 1 to 2 drops in affected eyes As per Pediatric Ophthalmologist’ (into conjunctival sac) every 4-6 hour (Not to order only. asone exceed 5 days) eye drops / oint- Ointment: Apply to conjunctival sac every 8 hr (Not to exceed 5 days) ment Ofloxacin 0.3 % Bacterial conjunctivitis : Initial : Off label use for infant younger than eye drops instill 1 to 2 drops in affected eyes every 4 hour 1 year. for the first 2 days then 1 to 2 drops 4 times daily for additional 5 days. Phenylephrine Mydriasis , cycloplegia : 2.5% eye drop 1 drop in combination with Cyclopentolate 1% eye drops for 2-3 doses 5-15 minutes a part Prednisolone 1 % eye drops Ophthalmic inflammation: Initiate with more frequent dosing Instill 1 to 2 drops into conjunctival sac 2 to 4 and decrease as clinically indicat- Tetracaine 1% times daily. ed. Do not discontinue therapy eye drops Ophthalmic anesthesia: prematurely, with draw therapy with 1 Drops in each eye 5 minute before eye exam gradual tapering of dose in chronic Tropicamide conditions 0.5 % or 1% eye drops Mydriasis : Instill 1 drop in each eye 15 minutes apart for 2-4 doses List of Topical Medications | 1| 97

About the Book The Neonatal Medication Book (NEOMEDBOOK) is a project spear-headed by the Neonatal Intensive Care Department at King Abdulaziz Medical City - Riyadh, Ministry of National Guard Health Affairs. The creation of this reference book was made possible through the collaborative efforts of the Department of Neonatology in all MNGHA hospitals, Nursing Services, Pharmaceutical Care Services, Quality Management and other Pediatric subspecialties such as Infectious Diseases, Endocrinology and Metabolic Disorders. This book was created in our effort to provide an evidence-based, accessible, and standardized medication reference for Neonatal healthcare providers all over the kingdom, to guide them in providing the best standard of clinical care for our sick, vulnerable patients. Ministry of National Guard Health A airs King Abdulaziz Medical City, Ar Rimayah, Riyadh 14815 Kingdom of Saudi Arabia [email protected]