Microsoft word - pediatric dosing guidelines for selected antiretroviral drugs.doc
Notes on paediatric dosing:
• Lamivudine (3TC) is a potent NRTI with an excellent record of efficacy, safety and tolerability in HIV-infected children. It is usually given twice daily in children.
• Zidovudine (AZT) is generally well tolerated in children but has been associated with metabolic complications of therapy, although to a lesser extent than d4T. Initial drug-related side-effects are more frequent with AZT and the drug can cause severe anaemia and neutropenia (haemoglobin monitoring before and during treatment with AZT is thus useful). This is particularly important in areas with stable malaria or where malnutrition is common and anaemia is highly prevalent in young children.
Large volumes of AZT liquid formulation are often poorly tolerated. d4T can be substituted for AZT in the event of intolerance to the latter and vice versa, except in cases of suspected lactic acidosis, where neither drug should be restarted.
Note: AZT should not be administered in combination with d4T.
Although there is less data on ARV drug toxicity in children than in adults, the full spectrum of ARV toxicities observed in adults have also been reported in children. However, some toxicities are less common in children than in adults e.g. Nevirapine-related symptomatic hepatotoxicity is rare in children, while others are more common in children than adults e.g. EFV-related rash or occur only in children e.g. TDF-related loss of bone density.
Drug-related adverse events may be acute, occurring soon after a drug has been administered; they may be subacute, occurring within 1 to 2 days of administration; or they may be late, occurring after prolonged drug administration. Such adverse events may vary in severity from mild to severe and life threatening.
Experience with ARV drugs has led to the recognition of several types of distinct adverse drug effects that may be most common with certain ARV drugs or drug classes. These include:
• haematological adverse events associated with drug-induced bone-marrow suppression, most commonly seen with AZT therapy (anaemia, neutropenia and, more rarely, thrombocytopenia);
• mitochondrial dysfunction, primarily seen with the NRTI drugs, including lactic acidosis, hepatic toxicity, pancreatitis and peripheral neuropathy (the NRTIs differ in their ability to affect mitochondrial function, d4T having greater toxicity than AZT and 3TC, and ABC even less so);
• lipodystrophy and metabolic abnormalities, primarily seen with d4T and the PI class, and to a lesser degree with certain other NRTI drugs (abnormalities include fat misdistribution and body habitus changes, hyperlipidaemia; hyperglycaemia, insulin resistance, diabetes mellitus, osteopaenia, osteoporosis and osteonecrosis);
• allergic reactions such as skin rashes and hypersensitivity reactions, more common with the NNRTI drugs but also seen with certain NRTI drugs, such as ABC.
Efavirenz (EFV) is not currently recommended for use in infants and children under 3 years of age because there is no established dosing. EFV is primarily associated with toxicities related to the central nervous system (CNS), teratogenicity and rash. Rash is more frequent in children than adults, is generally mild, and usually does not require discontinuation of therapy. The CNS symptoms typically abate after 10 to 14 days in the majority of patients; observational studies have revealed transient CNS disturbance in 26% to 36% of children receiving EFV.
• with a history of severe psychiatric illness
• where there is a potential for pregnancy (unless effective contraception can be assured)
• during the first trimester of pregnancy.
In these situations, nevirapine may be the better choice. EFV may be considered as the NNRTI of choice in children with TB/HIV co infection.
Given the limited number of ARV drugs and drug combinations available in resource-limited settings, it is preferable to pursue drug substitutions where feasible so to avoid premature switching to completely new alternative regimens, and to restrict drug substitutions to situations where toxicity is severe or life-threatening.
Toxicity can be monitored clinically on the basis of child/guardian reporting and physical examination, and can also be assessed by means of a limited number of laboratory tests, depending on the specific ARV combination regimen that is utilized and the health care setting. Routine laboratory monitoring, although desirable, is not required and cannot be carried out in many decentralized facilities.
Pediatric Dosing Guidelines for Selected Antiretroviral Drugs
Pediatric dose Maximum dose
Nucleoside reverse transcriptase inhibitors (NRTIs)
Postpartum prophylaxis: 4 mg/kg 2x/day for 1-6 Capsule: 100 mg weeksa Max 300 mg 2x/day
No nucleoside reverse transcriptase inhibitors (NNRTIs)
Induction dose (14 days): 4 mg/kg/day (200
mg/m2) Maintenance dose, <8 years: 7 mg/kg 2x/day Maintenance dose, !8 years: 4 mg/kg 2x/day Postpartum prophylaxis: 4 mg/kg for 6 weeksb Max 200 mg 2x/day
Protease inhibitors (PIs)
<15 kg 12/3 mg/kg 2x/day; !15 kg 10/2.5 mg/kg Capsule:
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