ANTIRETROVIRAL MEDICINES A summary of antiretroviral drugs by approved label, prepared for the WHO paediatric ARV work group by: Dr Diana CLARKE Pediatric Pharmacotherapy Specialist Pediatric HIV Programme Boston Medical Center Dept. of Pediatric Infectious Diseases Max.Finland Lab. of Infectious Diseases 774 Albany Street, Boston, MA 02118 USA
NUCLEOSIDE/NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS DRUG NAME: Zidovudine (ZDV, AZT) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is 3’-azido-3’deoxythymidine CLASS: Pyrimidine nucleoside analog INDICATION: Treatment or prevention of HIV infection MECHANISM OF ACTION: Nucleoside reverse transcriptase inhibitor DOSE: Neonatal (age< 6 wks): 2 mg/kg every 6 hrs Pediatric (6 wks-12 yrs): 180-240 mg/m² BSA twice daily* Adolescent/Adult: 300 mg twice daily BSA=body surface area *FDA approved dosing is three times a day but twice daily dosing is commonly used DRUG NAME: Lamivudine (3TC) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is (2R, cis)-4amino-1-(2-hydroxymethyl-1, 3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one CLASS: Synthetic nucleoside analog INDICATIONS: Treatment of HIV infection or HBV infection MECHANISM OF ACTION: Nucleoside reverse transcriptase inhibitor DOSE: Neonatal (age< 30 days): 2 mg/kg twice daily Pediatric: 4 mg/kg (max 150 mg) twice daily Adolescent (age≥16 years)/Adult dose(wt≥50kg): 150mg twice daily or 300mg once daily (Only dosing information for the HIV indication is included here) HBV=hepatitis B virus DRUG NAME: Stavudine (d4T)
ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is 2’,3’didehydro-3’-deoxythymidine CLASS: Synthetic thymidine nucleoside analog INDICATION: Treatment of HIV infection MECHANISM OF ACTION: Nucleoside reverse transcriptase inhibitor DOSE: Neonatal (age<14 days): 0.5mg/kg twice daily Pediatric (age≥14 days to wt<30 kg): 1 mg/kg (max 30 mg) twice daily Adolescent/Adult (wt≥30 kg): 30 mg twice daily
DRUG NAME: Abacavir (ABC) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is (1 S, cis)-4[2-amino-6-(cyclopropylamino)-9- H- purin-9-yl]-2-cyclopentene-1-methanol sulfate CLASS: Synthetic carbocyclic nucleoside analog INDICATION: Treatment of HIV infection MECHANISM OF ACTION: Nucleoside reverse transcriptase inhibitor DOSE: Pediatric (age 3 mos-16 yrs): 8mg/kg (max 300 mg) twice daily Adult: 300 mg twice daily or 600 mg once daily
DRUG NAME: Didanosine (ddI) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is 2’,3’dideoxyinosine CLASS: Synthetic purine nucleoside analog INDICATION: Treatment of HIV infection MECHANISM OF ACTION: Nucleoside reverse transcriptase inhibitor DOSE: Neonatal/Infant (2 wks-4mos): 50 mg/m² BSA twice daily* Infant (>4mos-<8mos): 100 mg/m² BSA twice daily Pediatric (age>8mos): 120 mg/m² BSA twice daily (range 90-150 mg/m² twice daily) Extended release capsules: Adolescent/Adult: (wt<60 kg): 250 mg once daily. (wt≥60kg):400 mg once daily
BSA=body surface area *Differs from FDA approved dose in younger age group DRUG NAME: Emtricitabine (FTC) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is 5-fluoro-1(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine CLASS: Synthetic nucleoside analog INDICATION: Treatment of HIV infection MECHANISM OF ACTION: Nucleoside reverse transcriptase inhibitor DOSE: Pediatric (3 mos-17yrs): Oral solution: 6 mg/kg (max 240 mg) once daily. Capsules (wt>33kg): 200 mg once daily
Adolescent (age≥18yrs)/Adult: 200 mg once daily
DRUG NAME: Tenofovir disoproxil fumarate (TDF) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): TDF (prodrug of tenofovir) is a fumaric acid salt of bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir CLASS: Acyclic nucleoside phosphonate (nucleotide) analog INDICATION: Treatment of HIV infection MECHANISM OF ACTION: Nucleoside reverse transcriptase inhibitor DOSE: Adult (age≥18yrs): 300 mg once daily
NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
DRUG NAME: Nevirapine (NVP) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is 11cyclopropyl-5, 11-dihydro-4-mehtyl-6H-dipyrido[3,2-b:2’,3’-e][1,4]diazepin-6-one CLASS/MECHANISM OF ACTION: Non-nucleoside reverse transcriptase inhibitor INDICATION: Treatment and prevention of HIV infection DOSE: * Neonatal/Infant Dose (up to 2 months): 5 mg/kg or 120 mg/m² BSA once daily for 14 days, followed by 120 mg/m² BSA twice daily for 14 days, followed by 200 mg/m² BSA twice daily Pediatric Dose: 120-200 mg/m² BSA twice daily (use lead-in once daily dose for 14 days to initiate therapy) Adolescent/Adult dose: 200 mg BSA twice daily (use lead-in once daily dose for 14 days to initiate therapy) BSA=body surface area *Only treatment doses (not PMTCT doses) are included here
DRUG NAME: Efavirenz (EFV) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is (S)-6-chloro4-(cyclopropylethynl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one CLASS/MECHANISM OF ACTION: Non-nucleoside reverse transcriptase inhibitor INDICATION: Treatment of HIV infection DOSE: Pediatric Dose (age≥3 years of age and wt≥10 kg): Administer once daily using weight-based table
Body Weight 10 to < 15 kg 15 to < 20 kg 20 to < 25 kg 25 to < 32.5 kg 32.5 to < 40 kg ≥ 40 kg
EFV Dose (mg) 200 mg 250 mg 300 mg 350 mg 400 mg 600 mg
PROTEASE INHIBITORS DRUG NAME: Lopinavir/Ritonavir (LPV/r, LPV/RTV) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): LPV/r is co-formulation of LPV and RTV. RTV inhibits the CYP3A-mediated metabolism of LPV, thereby increasing plasma concentrations of LPV. The chemical name of LPV is [1S-[1R*,(R*), 3R*,4R*]]-N-[[2,6-dimethylphenoxy)acetyl]amino]-3-hydroxy-5-alpha-(1-methylethyl)2-oxo-1(2H)-pyrimidineacetamide. The chemical name of RTV is 10-Hydroxy-2methyl-5-(1-methylethyl)-1-[2-(1-methylethyl)-4-thiszolyl]-3,6-dioxo-8,11bis(phenylmethyl)-2,4,7,12-tetraazatridecan-13-oic acid, 5-thiazolymethyl ester, [5S(5R*,8R*,10R*,11R*)]. CLASS/MECHANISM OF ACTION: Protease inhibitor INDICATION: Treatment of HIV infection DOSE: Pediatric- 6 mos-12 yrs (w/o NVP, EFV, APV): 7 to < 15 kg: 12 mg/kg LPV/3mg/kg RTV twice daily 15 to 40 kg: 10 mg/kg LPV/2.5 mg/kg RTV twice daily > 40 kg (adult/adolescent): 400 mg LPV/100 mg RTV (2 tabs) twice daily Pediatric- 6 mos-12 yrs (w/ NVP, EFV, APV): 7 to < 15 kg: 13 mg/kg LPV/3.25 mg/kg RTV twice daily 15 to 40 kg: 11 mg/kg LPV/2.75 mg/kg RTV twice daily > 40 kg (adolescent/adult): 600 mg LPV/150 mg RTV (3 tabs) twice daily
DRUG NAME: Nelfinavir (NFV) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is [3S-[2(2S*, 3S*), 3α,4aβ,8aβ]]-N-(1,1-dimethylethyl)decahydro-2-[2-hydroxy-3-[(3-hydroxy-2-
methylbenzoyl)amino]-4-(phenylthio)butyl]-3-isoquinoline carboxamide monomethanesulfonate (salt) CLASS/MECHANISM OF ACTION: Protease inhibitor INDICATION: Treatment of HIV infection DOSE: Pediatric (2 to 13 years): 45-55 mg/kg (may exceed adult dose) twice daily Adolescent/Adult: 1,250 mg twice daily
DRUG NAME: Ritonavir (RTV) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name is 10-Hydroxy2-methyl-5-(1-methylethyl)-1-[2-(1-methylethyl)-4-thiszolyl]-3,6-dioxo-8,11bis(phenylmethyl)-2,4,7,12-tetraazatridecan-13-oic acid, 5-thiazolymethyl ester, [5S(5R*,8R*,10R*,11R*)]. CLASS/MECHANISM OF ACTION: Protease inhibitor INDICATION: Treatment of HIV infection DOSE: Use primarily as a pharmacokinetic enhancer with other PIs. Dose and frequency varies with PI that it is used with.
DRUG NAME: Saquinavir (SQV) ACTIVE PHARMACEUTICAL INGREDIENTS (APIs): chemical name of saquinavir mesylate is N-tert-butyl-decahydro-2-[2®-hydroxy-4-phenyl-3(S)-[[N-(2quinoylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinolone-3(S)-caroxamide methanesulfonate. CLASS/MECHANISM OF ACTION: Protease inhibitor INDICATION: Treatment of HIV infection DOSE: Adolescent (age > 16)/adult: Invirase™ 1000mg + RTV 100 mg twice daily