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Protease inhibitors (PIs)
Names: amprenavir, Agenerase™, fosamprenavir, Telzir ™
Approved dosage: eight cream 150mg capsules twice a day. Dose reductions may be recommended due to liver impairment or drug interactions. Approved for use in people over four years of age who have failed previous protease inhibitor-containing therapy. Note: production of amprenavir 150mg capsules ceased in late 2004 and hospitals in the UK are currently using their remaining stock.
A new version of amprenavir called fosamprenavir (Telzir™) has been developed. Its chief advantage is that it requires fewer capsules each day, and there will be more of the drug available in the blood to suppress HIV. This version of amprenavir can also be boosted with the other protease inhibitor ritonavir (Norvir™). The dose of the drug is one mauve 700mg tablet with one cream 100mg capsule of ritonavir twice daily.
Children: liquid formulation available for children over four years.
Tips on taking it: take with or without food. Liquid formulation not recommended for children under four years, pregnant women or individuals with liver damage, due to severe side-effects. Use with caution in people with kidney impairment.
Common side-effects: headache, nausea, vomiting, diarrhoea, rash, fatigue, tingling around the mouth, lipodystrophy and metabolic abnormalities. Oral solution may also cause seizure, stupor, fast heart beat, blood disorders.
Resistance to amprenavir: likely to cause resistance to ritonavir, and possibly also to saquinavir, indinavir and nelfinavir.
Key drug interactions: don't take with rifampicin, terfenadine, astemizole, cisapride, triazolam, midazolam, ergot medications, bepridil and St John’s wort. Dose adjustments may be required when amprenavir is taken with erythromycin, rifabutin, efavirenz, indinavir, ritonavir, nelfinavir, amiodarone, phenobarbitonel, phenytoin, lidocain, warfarin, quinidine, nortriptyline, imipramine, Viagra™, Cialis™, Zyban™, Levitra™, amitryptyline and desipramine. Amprenavir contains high levels of vitamin E, so supplements containing vitamin E should not be taken at the same time as amprenavir. However, you can take supplements containing vitamin E if you are taking fosamprenavir.
atazanavir
Names: atazanavir, Reyataz™
Approved dosage: 300mg (two light and dark blue 150mg capsules) plus one cream 100mg ritonavir capsule taken together once a day. If the combination also contains efavirenz or nevirapine the dose is 400mg (two turquoise 200mg capsules) plus one 100mg ritonavir capsule taken together once a day.
Tips on taking it: take with food.
Common side-effects: diarrhoea.
Rare side-effects: abnormal liver function, jaundice.
Resistance to atazanavir: there is conflicting evidence. Early studies suggested that atazanavir would be effective in people resistant to other protease inhibitors. However, more recent evidence shows that as many as 40% of people who had previously used a protease inhibitor would have reduced sensitivity to the drug. This is why it is recommended to boost atazanavir levels with ritonavir.
Key drug interactions: when taken with efavirenz or tenofovir, levels of atazanavir drop. However, adding 100mg of ritonavir counters this. Take ddI tablets at least two hours before or one hour after atazanavir (not necessary if taking Videx EC). Doses of the anti-TB drug rifabutin should be reduced by 75%. Reduce doses of clarithromycin by half if taken at the same time as atazanavir. Reduce doses of Cialis™, Viagra™, or LevitraTM by half. Don't take with St John's wort. Don't take antacids within four hours of atazanavir. Don't t take lansoprazole, omeprazole, rifampicin, phenytoin, carbamazepine, or simvastatin with atazanavir.
indinavir
Names: indinavir, Crixivan™
Approved dosage: 800mg (two cream 400mg capsules) every eight hours.
Experimental dosage: with ritonavir: 400mg of both drugs twice daily. Alternatively, two 400mg capsules of indinavir and 100mg of ritonavir twice a day, or two 400mg capsules of indinavir and 200mg of ritonavir (other doses have been used in conjunction with drug level monitoring studies).
Tips on taking it: when indinavir is taken without ritonavir it should ideally be taken on an empty stomach (avoiding food for two hours before and one hour after each dose). Alternatively it can be taken with a light, low-fat snack, eg 30g cereal with 100g skimmed milk or a tea or coffee with sugar and skimmed milk plus one biscuit, or two small slices of toast with low-fat spread and 15g of jam per slice. For more suggestions, see NAM's Nutrition booklet, or discuss your options with an HIV dietitian. If indinavir is taken with ritonavir, there are no food restrictions. Drink 1.5 litres of water or a non-caffeinated drink in addition to your usual fluid intake, to reduce the risk of kidney stones. Indinavir must be stored with a desiccant to keep the capsules dry. Can be kept in a dosette box without a desiccant for up to three days.
Common side-effects: kidney stones, pain when urinating, tiny stones in urine, dry lips and skin, liver abnormalities, nausea, lipodystrophy and metabolic abnormalities. Low fluid intake will increase your risk of developing kidney problems.
Rare side-effects: diabetes.
Resistance to indinavir: causes resistance to ritonavir, and is likely to cause resistance to saquinavir, nelfinavir and amprenavir.
Key drug interactions: do not take indinavir with St John's wort, terfenadine, astemizole, cisapride, alprazolam, pimozide, rifampicin, amiodarone, quinidine and ergot alkaloids. Careful monitoring and dose adjustments may be needed if indinavir is taken with drugs including: rifabutin, ketoconazole, the NNRTIs, Viagra™, Cialis™, Levitra™ and simvastatin. Large doses of vitamin C have been shown to reduce indinavir concentrations in the blood.
lopinavir/ritonavir (KaletraTM)
Names: lopinavir/ritonavir, ABT-378/r, Kaletra™
Approved dosage: 400mg lopinavir plus 100mg ritonavir (three orange 133.3mg/33.3mg capsules) twice daily. The dose is increased to four capsules when taken with efavirenz or nevirapine.
Children: approved for children over two years. Liquid formulation available.
Tips on taking it: take with food. KaletraTM should be kept in the fridge. However it can be stored at room temperature (below 25 degrees C) for up to six weeks.
Common side-effects: diarrhoea and loose stools, headache, nausea, vomiting, stomach pain, fatigue, rash, metabolic abnormalities and raised liver enzymes. It is possible that lipodystrophy, a side-effect of other protease inhibitors, will also affect lopinavir/ritonavir users.
Resistance to lopinavir/ritonavir: likely cross-resistance with indinavir and ritonavir and, to some extent, amprenavir. High level resistance to other protease inhibitors may reduce the effectiveness of lopinavir/ritonavir, but lopinavir/ritonavir appears effective against virus resistant to other protease inhibitors.
Key drug interactions: due to the presence of ritonavir, avoid all drugs which negatively interact with ritonavir (see ritonavir entry). Efavirenz and nevirapine reduce levels of lopinavir/ritonavir and dose adjustments are recommended. Lopinavir/ritonavir reduces levels of amprenavir. Do not take with St John’s wort. Monitoring and dose adjustment may be necessary when lopinavir/ritonavir is taken in conjunction with amiodarone, bepredil, quinidine, systemic lidocaine, warfarin, calcium channel blockers, Viagra™, Cialis™, LevitraTM, Zyban™, tacrolimus, cyclosporin, methadone, rifabutin, rifampicin, oral contraceptives, ketoconazole and itraconazole.
nelfinavir
Names: nelfinavir, Viracept™
Approved dosage: five blue 250mg tablets twice a day, or three blue 250mg tablets three times a day.
Children: nelfinavir is approved for use in children. Available in powder form.
Tips on taking it: it is very important that you take nelfinavir with food to increase absorption.
Common side-effects: diarrhoea, nausea, lipodystrophy and metabolic abnormalities.
Resistance to nelfinavir: is likely to cause resistance to saquinavir and may cause resistance to ritonavir and indinavir.
Key drug interactions: careful monitoring and dose adjustments may be needed if nelfinavir is taken with drugs including: oral contraceptives, rifabutin, methadone, carbamazapine, phenytoin, Viagra™, Cialis™, Zyban™, LevitraTM and some lipid-lowering drugs. Do not take nelfinavir with terfenadine, rifampicin, astemizole, cisapride, pimozide, amiodarone, quinidine, midazole, triazolam, simvastin, ergot alkaloids or St John’s wort.
ritonavir
Names: ritonavir, Norvir™
Approved dosage: six 100mg cream capsules twice a day. Alternatively, 7.5ml of ritonavir liquid twice daily. Start on a low dose and increase over 14 days to minimise side-effects.
Ritonavir is also used in small doses (usually 100mg or 200mg once or twice daily) to 'boost' other protease inhibitors. It has been approved for use in this way in the following doses: ritonavir/amprenavir 100/600mg twice daily; ritonavir/fosamprenavir 100/700mg twice daily; ritonavir/atazanavir 100/300mg once daily; ritonavir/saquinavir 100mg/1000mg twice daily.
Experimental dosage: ritonavir/saquinavir 400/400mg twice daily; ritonavir/indinavir 400/400mg or 200/800mg or 100/800mg twice daily.
Children: ritonavir is not formally approved for use in children, although it can be made available.
Tips on taking it: take with food to reduce nausea. If taking the liquid, try mixing it with a milk-based nutritional supplement. Do not mix with water, fizzy drinks or fruit juice. To disguise the taste, suck ice cubes or icy fruit juice before and after your dose. Alternatively, follow ritonavir with chocolate, mango, peanut butter, salty crisps or other food with strong flavour. Norvir™ capsules should be stored in a fridge, but can be kept at room temperature (below 25 degrees C) for up to 30 days. Ritonavir liquid should always be stored at room temperature.
Common side-effects: diarrhoea, stomach pain, nausea, vomiting, weakness, taste abnormalities, loss of appetite, numbness around the mouth, lipodystrophy and metabolic abnormalities.
Rare side-effects: kidney problems, diabetes.
Resistance to ritonavir: causes resistance to indinavir and is likely to mean some resistance to nelfinavir, saquinavir and amprenavir.
Key drug interactions: ritonavir interacts with many other medications. Consult your doctor or HIV pharmacist before taking any other drugs with ritonavir (including inhalers, medicines bought from a high street chemist, herbal preparations and recreational drugs). Do not take ritonavir with piroxicam, dextropropoxyphene, pethidine; amiodarone, encainide, flecainide, propafenone, quinidine, bupropion (ZybanTM, astemizole, terfenadine, clozapine, pimozide, alprazolam, clorazepate, diazepam, estazolam, bepridil, cisapride; fluorazepam, midazolam, triazolam, zolpidem, Viagra™, Cialis™ LevitraTM or St John’s wort.
saquinavir (Invirase™)
Saquinavir is available in two formulations: as a hard gel capsule called Invirase™, or a soft gel capsule called Fortovase™. Advice on taking saquinavir differs depending upon which formulation you are taking.
Names: saquinavir (hard gel), Invirase™
Approved dosage: two orange 500mg tablets (or five yellow and green 200mg capsules) together with one 100mg capsule of ritonavir twice a day.
Children: Invirase™ is not approved for use by children.
Tips on taking it: take Invirase™ within two hours of a full meal to increase absorption.
Common side-effects: diarrhoea, stomach pain, nausea, lipodystrophy and metabolic disorders.
Rare side-effects: diabetes.
Resistance to saquinavir: may mean resistance to nelfinavir, indinavir and ritonavir.
Key drug interactions: do not take with rifampicin, rifabutin, astemizole, terfenadine, cisapride or the herbal anti-depressant St John’s wort. Careful monitoring and dose adjustments may be needed if taking saquinavir with many other drugs including: NNRTIs, methadone, anti-arrhythmics, some anti-depressants, some anti-convulsants, some lipid-lowering drugs, dapsone, ergotamine, dihydroergotamine, dexamethasone, Viagra™, Cialis™ and LevitraTM. Do not take with garlic supplements. If combined with ritonavir, drug interactions may change.
saquinavir (Fortovase™)
Names: saquinavir (soft gel), Fortovase™
Approved dosage: six cream 200mg capsules three times a day.
Experimental dosages: if taking Fortovase™ twice daily, take eight capsules twice a day. With 400mg ritonavir, take two 200mg capsules of Fortovase™ twice a day. With nelfinavir, take five nelfinavir 250mg tablets and six 200mg capsules of Fortovase™ twice a day.
Children: Fortovase™ is not available to children.
Tips on taking it: take Fortovase™ within two hours of food. Fortovase™ should be stored in a fridge. But it can be kept at room temperature (below 25 degrees C) for up to three months.
Common side-effects: diarrhoea, stomach pain, nausea, lipodystrophy and metabolic abnormalities.
Rare side-effects: diabetes.
Resistance to saquinavir: may mean resistance to nelfinavir, indinavir and ritonavir.
Key drug interactions: do not take with rifampicin, rifabutin, astemizole, terfenadine, cisapride or the herbal anti-depressant St John’s wort. Careful monitoring and dose adjustments may be needed if taking saquinavir with many other drugs including: NNRTIs, methadone, anti-arrhythmics, some anti-depressants, some anti-convulsants, some lipid-lowering drugs, dapsone, ergotamine, dihydroergotamine, dexamethasone, Viagra™, Cialis™ and LevitraTM. Do not take with garlic supplements. If combined with ritonavir, drug interactions may change.
Note: Roche Pharmaceuticals, the manufacturers of Fortovase™, have announced that they will cease its production in 2006 or soon after.