BNF for Children 2011-2012

BNFC 2011–2012 5.3.1 HIV infection 311lin resistance and hyperglycaemia occur only rarely inchildren.Fat redistribution (with loss of subcutaneous fat,increased abdominal fat, ‘buffalo hump’ and breastenlargement) is associated with regimens containingprotease inhibitors and nucleoside reverse transcriptaseinhibitors. Stavudine, and to a lesser extent zidovudine,are associated with a higher risk of lipoatrophy andshould be used only if alternative regimens are notsuitable.Dyslipidaemia is associated with antiretroviral treatment,particularly with protease inhibitors; in children,hypercholesterolaemia appears to be more commonthan hypertriglyceridaemia. Protease inhibitors andsome nucleoside reverse transciptase inhibitors areassociated with insulin resistance and hyperglycaemia,but they occur rarely in children. Of the protease inhibitors,atazanavir and darunavir are less likely to causedyslipidaemia, while saquinavir and atazanavir are lesslikely to impair glucose tolerance.Osteonecrosis Osteonecrosis has been reported inchildren with advanced HIV disease or following longtermexposure to combination antiretroviral therapy.Nucleoside reverse transcriptaseinhibitorsCautionsLactic acidosis Life-threatening lactic acidosis associatedwith hepatomegaly and hepatic steatosis hasbeen reported with nucleoside reverse transcriptaseinhibitors. They should be used with caution in childrenwith hepatomegaly, hepatitis (especially hepatitis Ctreated with interferon alfa and ribavirin), liver-enzymeabnormalities and with other risk factors for liver diseaseand hepatic steatosis. Treatment with the nucleosidereverse transcriptase inhibitor should be discontinuedin case of symptomatic hyperlactataemia, lacticacidosis, progressive hepatomegaly or rapid deteriorationof liver function. Stavudine, especially with didanosine,is associated with a higher risk of lactic acidosisand should be used only if alternative regimens are notsuitable.Hepatic impairment Nucleoside reverse transcriptaseinhibitors should be used with caution in childrenwith hepatic impairment (greater risk of hepatic sideeffects,see also Lactic Acidosis above). However, somenucleoside reverse transcriptase inhibitors are used inchildren who also have chronic hepatitis B.Pregnancy See p. 310Breast-feeding See p. 310Side-effects Side-effects of the nucleoside reversetranscriptase inhibitors include gastro-intestinal disturbances(such as nausea, vomiting, abdominal pain,flatulence and diarrhoea), anorexia, pancreatitis, liverdamage (see also Lactic Acidosis, above), dyspnoea,cough, headache, insomnia, dizziness, fatigue, blooddisorders (including anaemia, neutropenia, and thrombocytopenia),myalgia, arthralgia, rash, urticaria, andfever. See notes above for Lipodystrophy Syndrome(p. 310) and Osteonecrosis (above).ABACAVIRCautions see notes above; also test for HLA-B*5701allele before treatment (or if re-starting treatment andHLA-B*5701 status not known)—increased risk ofhypersensitivity reaction in presence of HLA-B*5701allele; interactions: Appendix 1 (abacavir)Hypersensitivity reactions Life-threatening hypersensitivityreactions reported—characterised by fever or rash andpossibly nausea, vomiting, diarrhoea, abdominal pain, dyspnoea,cough, lethargy, malaise, headache, and myalgia; lessfrequently mouth ulceration, oedema, hypotension, sorethroat, acute respiratory distress syndrome, anaphylaxis,paraesthesia, arthralgia, conjunctivitis, lymphadenopathy,lymphocytopenia and renal failure; rarely myolysis; laboratoryabnormalities may include raised liver function tests(see Lactic Acidosis above) and creatine kinase; symptomsusually appear in the first 6 weeks, but may occur at anytime; monitor for symptoms every 2 weeks for 2 months;discontinue immediately if any symptom of hypersensitivitydevelops and do not rechallenge (risk of more severehypersensitivity reaction); discontinue if hypersensitivitycannot be ruled out, even when other diagnoses possible—ifrechallenge necessary it must be carried out in hospitalsetting; if abacavir is stopped for any reason other thanhypersensitivity, exclude hypersensitivity reaction as thecause and rechallenge only if medical assistance is readilyavailable; care needed with concomitant use of drugs whichcause skin toxicityCounselling Children and carers should be told the importanceof regular dosing (intermittent therapy may increasethe risk of sensitisation), how to recognise signs of hypersensitivity,and advised to seek immediate medical attentionif symptoms develop or before re-starting treatment; childrenor their carers should be advised to keep Alert Cardwith them at all timesHepatic impairment see notes above; also avoid inmoderate impairment unless essential; avoid in severeimpairmentRenal impairment manufacturer advises avoid inend-stage renal disease; avoid Kivexa c or Trizivir c ifestimated glomerular filtration rate less than 50 mL/minute/1.73 m 2Pregnancy manufacturer advises avoid (toxicity inanimal studies); see also Pregnancy, p. 310Breast-feeding see p. 310Side-effects see notes above; also hypersensitivityreactions (see above); very rarely Stevens-Johnsonsyndrome and toxic epidermal necrolysis; rash andgastro-intestinal disturbances more common in childrenLicensed use Trizivir c not licensed for use inchildrenIndication and doseHIV infection in combination with other antiretroviraldrugs. By mouthChild 3 months–12 years 8 mg/kg (max. 300 mg)twice daily or 16 mg/kg (max. 600 mg) once dailyorBody-weight 14–21 kg 150 mg twice daily or300 mg once dailyBody-weight 21–30 kg 150 mg in the morningand 300 mg in the evening or 450 mg once dailyBody-weight over 30 kg 300 mg twice daily or600 mg once dailyChild 12–18 years 300 mg twice daily or 600 mgonce daily5 Infections