Antiretroviral drug

Primary toxicities

Monitoring/management

Nucleoside analogue reverse transcriptase inhibitors

See drug class effects for all drugs (text and Table 10)

Discontinue antiretroviral therapy if signs/symptoms of lactic acidosis/ hepatic steatosis. Following resolution of symptoms, ART can be restarted using a PI plus an NNRTI plus possibly either ABC or tenofovir. Other NsRTIs (ZDV, ddI, 3TC, d4T) should not be used.

Abacavir

Hypersensitivity reaction

Monitor for symptoms of hypersensitivity reaction. Hypersensitivity reaction is progressive; drug should be stopped; resolves once drug stopped. Do not rechallenge, as anaphylactic reactions and death reported.

Didanosine

Pancreatitis; painful peripheral neuropathy(dose-related, reversible); abdominal cramps, diarrhoea related to antacid in formulation

Monitor for signs of neuropathy; consider drug discontinuation and change to another NsRTI (not d4T) if severe.

Abdominal pain, nausea, vomiting should trigger evaluation for pancreatitis(serum pancreatic amylase, lipase). Discontinue therapy if confirmed; when resolves, restart and change to another NsRTI (not d4T).

Clinical evaluation for signs of hepatitis (jaundice, hepatomegaly); monitor liver transaminases. Discontinue all therapy if confirmed, do not restart until resolves.

Enteric coated capsules cause less diarrhoea and fewer drug interactions. ddI/d4T should not be given to pregnant women because of increased risk of lactic acidosis.

Lamivudine

Painful peripheral neuropathy; pancreatitis; headache, fatigue, insomnia; muscle aches; rash; rare neutropenia, thrombocytopenia

Abdominal pain, nausea, vomiting should trigger evaluation for pancreatitis(serum pancreatic amylase, lipase). Discontinue therapy if confirmed; when resolves, restart and change to another NsRTI (not ddI or d4T).

Potential efficacy for hepatitis B infection (hepatitis flare-up may occur if3TC is discontinued).

Stavudine

Painful peripheral neuropathy; pancreatitis; anaemia, macrocytosis; insomnia, anxiety, panic attacks

Monitor for signs of neuropathy; consider discontinuation or change to another NRTI (not ddI) if severe.

Abdominal pain, nausea, vomiting should trigger evaluation for pancreatitis(serum pancreatic amylase, lipase). Discontinue therapy if confirmed; when resolves, restart and change to another NRTI (not ddI).

Clinical evaluation for signs of hepatitis (jaundice, hepatomegaly); monitor liver transaminases. Discontinue all therapy if confirmed, do not restart until resolves, change to another NRTI.

ddI/d4T should not be given to pregnant women because of increased risk of lactic acidosis.

Antiretroviral drug

Primary toxicities

Monitoring/management

Zidovudine

Initial headache, nausea common and self-limited; anaemia, granulocytopenia, thrombocytopenia; macrocytosis is expected effect of therapy, requires no intervention; myopathy (elevated creatinine phosphokinase may be seen) with long-term use; blue to black discoloration of nails in pigmented races.

Clinical examination for signs of anaemia.

Monitor complete blood count with differential for haematological toxicity; for severe anaemia or neutropenia (absolute neutrophil count <500/ml), reduce ZDV dose if needed or change to another NsRTI; transfusions can be used for severe anaemia if ZDV therapy required.

Check creatinine phosphokinase if muscle weakness/pain; consider discontinuation of ZDV or change to another NsRTI if severe.

Non-nucleoside reverse transcriptase inhibitors

Efavirenz

Dizziness, anxiety, lightheadedness, dysphoria, nightmares; rash (less than with NVP); hepatitis.

Clinical evaluation for rash; rash from one NNRTI does not predict cross- reaction with other.

Clinical evaluation for signs of hepatitis (jaundice, hepatomegaly); monitor liver transaminases. Discontinue all therapy if confirmed, do not restart until resolves.

Nevirapine

Rash, can be severe, Stevens-Johnson syndrome rare; fulminant hepatotoxicity rare.

Clinical evaluation for rash; rash from one NNRTI does not predict cross- reaction with other. Low-dose lead-in period over first two weeks minimizes rash occurrence.

If rash is mild or moderate, NVP can be continued cautiously while the rash is observed or EFZ can be substituted for NVP. Do not increase dose during lead-in phase if rash; stop drugs and restart NVP at lead-in dosing when resolves. Permanently discontinue NVP if rash severe, and avoid NNRTI class of drugs.

Clinical evaluation for signs of hepatitis (jaundice, hepatomegaly); monitor liver transaminases. Discontinue all therapy if confirmed, do not restart until resolves; permanently discontinue NVP if hepatitis (changing NNRTI to EFZ can be tried).

Antiretroviral drug

Primary toxicities

Monitoring/management

Protease inhibitors

See drug class effects for all drugs (text and Table 10).

Monitor for symptoms of hyperglycaemia (polydipsia/polyuria/polyphagia), urine dipstick for glucose.

Clinical evaluation for signs of hepatitis (jaundice, hepatomegaly); monitor liver transaminases. Discontinue all therapy if confirmed, do not restart until resolves.

Consider avascular necrosis in patients presenting with hip or shoulder pain, limp.

Indinavir

Nephrolithiasis, crystalluria, haematuria, rare interstitial nephritis; asymptomatic hyperbilirubinaemia; nausea, gastrointestinal disturbances; rash; insomnia, dizziness, metallic taste; alopecia, dry skin; thrombocytopenia.

Drink at least 1.5 litres of fluids per day. Monitor urinanalysis for haematuria. Evaluate if flank pain, possibly temporarily discontinue IDV, restart after resolves (recurrent nephrolithiasis in 50%).

Hyperbilirubinaemia clinically insignificant.

Lopinavir/ritonavir

Diarrhoea; skin rash; headache, weakness

Diarrhoea mild.

Nelfinavir

Diarrhoea, gastrointestinal disturbance.

Diarrhoea is self-limited; can be controlled with loperamide, calcium carbonate, psyllium, oat bran.

Saquinavir

Diarrhoea; headache confusion.

Generally well tolerated with low-dose ritonavir boost to provide higher levels.