Protease inhibitors (PIs)

Atazanavir

Names : Atazanavir, Reyataz 

Approved dosage : 300mg (two light and dark blue 150mg capsules) plus one cream-coloured 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 a snack to improve absorption. 

Common side-effects : Non-dangerous yellowing of the skin caused by increased levels of bilirubin, peripheral neuropathy, headache, insomnia, vomiting, diarrhoea, abdominal pain, nausea, indigestion, rash, tiredness. 

Rare side-effects : Abnormal liver function, kidney stones and pancreatitis. 

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 capsules). 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 treatments for erectile dysfunction by half. Don’t take with St John’s wort. Don’t take antacids within four hours of atazanavir. Don’t take lansoprazole, omeprazole, rifampicin, phenytoin, carbamazepine or simvastatin with atazanavir. Take ranitidine once a day only, twelve hours apart from atazanavir (for example, take atazanavir in the morning and ranitidine at night). 

Darunavir

Names: Darunavir, Prezista 

Approved dosage: 600mg (two orange 300mg tablets) plus one 100mg cream-coloured ritonavir capsule taken together twice a day.  

Tips on taking it: Must be taken with food to improve absorption. 

Common side-effects: Diarrhoea, nausea, rash and headache. 

Resistance to darunavir: The drug works well in many people with resistance to other protease inhibitors. However, resistance to amprenavir/fosamprenavir can reduce the effectiveness of darunavir. 

Key drug interactions: Astemizole; carbamazepine; dihydroergotamine; ergometrine; ergotamine tartrate; St John’s wort; midazolam; phenytoin; pimozide; rifampicin; and simvastatin. Careful monitoring required if taken with methadone, rifabutin, Viagra, Cialis or Levitra. 

Fosamprenavir

Names : Fosamprenavir, Telzir 

Approved dosage : One pink 700mg tablet with one cream-coloured 100mg capsule of ritonavir twice daily. 

Tips on taking it : Take with or without food.  

Common side-effects : Diarrhoea, increased blood fats, nausea, vomiting, pain in the stomach, rash, headache, feeling dizzy, tiredness, changes in liver and pancreas function. 

Rare side-effects include : Changes in cholesterol levels, Stevens-Johnson Syndrome.

Resistance to fosamprenavir : Is likely to cause resistance to ritonavir, and possibly also to saquinavir, indinavir and nelfinavir. 

Key drug interactions: Viagra, Cialis, Levitra, Zyban, simvastatin. 

Indinavir

Names : Indinavir, Crixivan 

Approved dosage : 800mg (two cream-coloured 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 : If indinavir is taken with ritonavir, there are no food restrictions. 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, e.g. 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 or pharmacist. Drink 1.5 litres of water or a non-caffeinated drink throughout the day 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 : Headache, dizziness, nausea, vomiting, diarrhoea, rash, kidney stones, fatigue, strange tastes in the mouth, abdominal pain, sleep disturbance, flatulence, dry mouth, acid regurgitation, in-growing toenails, dry skin and muscle pain. 

Rare side-effects include : Diabetes and liver abnormalities. 

Resistance to indinavir : Causes resistance to ritonavir, and is likely to cause resistance to saquinavir, nelfinavir and fosamprenavir. 

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, NNRTIs, Viagra, Cialis, Levitra and simvastatin. Large doses of vitamin C have been shown to reduce indinavir concentrations in the blood. 

Lopinavir/ritonavir (as Kaletra)

Names : Lopinavir/ritonavir, Kaletra 

Note: Lopinavir is only available in combination with ritonavir.  

Approved dosage : 400mg lopinavir plus 100mg ritonavir in hard tablets containing 200mg lopinavir and 50mg ritonavir so two yellow tablets are required twice daily. There is now also a once-daily dose of Kaletra consisting of four tablets once a day for patients who are starting treatment for the first time.  

Children : A tablet containing 100mg of lopinavir and 25mg of ritonavir is available for use in children. Liquid formulation also available. 

Tips on taking it : The tablet can be taken with or without food, but must not be broken, chewed or crushed.

Common side-effects : Diarrhoea, insomnia, headache, nausea, vomiting, abdominal pain, abnormal stools, indigestion, flatulence, rash, feeling weak and changes in blood fats and sugars.

Rare side-effects include : Abnormal kidney or liver function. 

Resistance to lopinavir/ritonavir : Likely cross-resistance with indinavir and ritonavir and, to some extent, fosamprenavir. High-level resistance to other protease inhibitors may reduce the effectiveness of lopinavir/ritonavir. 

Key drug interactions : Due to the presence of ritonavir, avoid all drugs that negatively interact with ritonavir (see ritonavir entry). Efavirenz and nevirapine reduce levels of lopinavir/ritonavir and dose adjustments are recommended. 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, Levitra, Zyban, tacrolimus, cyclosporin, methadone, rifabutin, rifampicin, oral contraceptives, ketoconazole, intraconazole and simvastatin.  

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, flatulence, rash and metabolic abnormalities. 

Rare side-effects include : Jaundice and diabetes.  

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, Levitra and some lipid-lowering drugs. Do not take nelfinavir with terfenadine, rifampicin, astemizole, cisapride, pimozide, amiodarone, quinidine, midazole, triazolam, simvastatin, ergot alkaloids or St John’s wort. 

Ritonavir

Names : Ritonavir, Norvir 

Approved dosage : Ritonavir is mainly 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/atazanavir 100/300mg once daily; ritonavir/fosamprenavir 100/700mg twice daily; ritonavir/darunavir 100mg/600mg twice daily; ritonavir/lopinavir 100mg/400mg twice daily; ritonavir/saquinavir 100mg/1000mg twice daily; ritonavir/tipranavir 200mg/500mg twice daily. Ritonavir is also approved for use as a single protease inhibitor at a dose of 600mg twice a day (six 100mg cream-coloured capsules). However it is very rarely used in this way.  

Tips on taking it : Take with food to reduce nausea. Ritonavir capsules should be stored in a fridge, but can be kept at room temperature (below 25 degrees C) for up to 30 days. A new heat-stable ritonavir tablet was approved in February 2010. 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, metabolic abnormalities. 

Resistance to ritonavir : Causes resistance to indinavir and is likely to mean some resistance to nelfinavir, saquinavir and fosamprenavir. 

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, Zyban, astemizole, terfenadine, clozapine, pimozide, alprazolam, clorazepate, diazepam, estazolam, bepridil, cisapride; fluorazepam, midazolam, triazolam, zolpidem, Viagra, Cialis, Levitra or St John’s wort. 

Saquinavir

Names : Saquinavir, 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 : Saquinavir is not approved for use in children. 

Tips on taking it : Take saquinavir within two hours of a full meal to increase absorption. 

Common side-effects : Fatigue, anaemia, nausea, vomiting, and metabolic disorders. 

Rare side-effects : Diabetes and Stevens-Johnson Syndrome. 

Resistance to saquinavir : May mean resistance to nelfinavir, indinavir and ritonavir. 

Key drug interactions : Do not take with rifampicin, rifabutin, astemizole, terfenadine, cisapride or 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 antidepressants, some anticonvulsants, some lipid-lowering drugs, dapsone, ergotamine, dihydroergotamine, dexamethasone, Viagra, Cialis and Levitra. Do not take with garlic supplements.  

Tipranavir

Names : Tipranavir, Aptivus 

Approved dosage : Two 250mg pink capsules together with 200mg (two 100mg cream-coloured capsules) ritonavir, twice daily. 

Tips on taking it : To be taken with food. Tipranavir capsules should be stored in the fridge, but can be kept at room temperature (below 25 degrees C) for up to 60 days. 

Common side-effects : Diarrhoea, nausea, vomiting, abdominal pain, flatulence, tiredness, headache, increased blood fats, liver abnormalities and rash.  

Rare side-effects : Diabetes and kidney problems. 

Resistance to tipranavir: Test-tube studies report that resistance to tipranavir is slow to develop, and that there is no clear pattern of cross-resistance to currently available protease inhibitors. 

Key drug interactions : Rifampicin, cisapride pimozide, sertindole, triazolam, ergot derivatives, astemizole, terfenadine, simvastatin, lovastatin, amiodarone, bepridil, flecainide, propafenone, quinidine and St John’s wort. Take special care with Viagra, Cialis and Levitra, disulfiram, fluticasone, atorvastatin and metronidazole.

Tipranavir may also interact with other types of medicines, which may lead to a loss of effectiveness of these medicines. These include the morphine-substitute methadone and oral contraceptives. If you are using oral contraceptives to prevent pregnancy you should use an additional or different type of contraception.

If you are taking ddI EC, it should be taken at least two hours apart from tipranavir.