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Protease inhibitors (PIs)

Most protease inhibitors are prescribed with another drug (also a protease inhibitor) called ritonavir. Ritonavir is used to boost the effects of the other protease inhibitor in your body. Without ritonavir, your body would metabolise (break down) the protease inhibitor too quickly and it would not work effectively against the virus.

Drug interactions

Protease inhibitors, including ritonavir, have multiple drug interactions. Most of these are caused by the boosting effect of ritonavir, which increases the levels of many drugs, including other protease inhibitors.

Do not take any protease inhibitors with the following medication:

  • drugs for certain heart conditions, such as amiodarone, astemizole, flecainide, lercanidipine, quinidine and dabigatran
  • alfuzosin (used to treat urinary problems)
  • the anti-TB drug rifampicin
  • the lipid-lowering drug simvastatin. Other statins such as rosuvastatin and atorvastatin can be used, but at lower doses
  • the anticoagulant (a drug that prevents blood clotting) rivaroxaban
  • midazolam, a benzodiazepine used to help you sleep, if taken orally. Midazolam can be used at reduced dose when injected as a sedative for certain procedures
  • erectile dysfunction drugs, such as sildenafil (Viagra), tadalafil (Cialis) or vardenafil (Levitra) used at full dose. Get advice from your HIV doctor or pharmacist before taking any drugs for erectile dysfunction
  • ergot derivatives (used to treat cluster headaches and migraines and to manage labour)
  • the antimalarial halofantrine
  • St John’s wort, the herbal antidepressant.

Some drugs can interact with protease inhibitors and change blood levels of one or both drugs, so dose adjustments may be needed. This is the case for:

  • calcium channel blockers (for example, diltiazem and verapamil)
  • the heart drug digoxin
  • the anticoagulant warfarin
  • the asthma and allergy drugs fluticasone, salmeterol, budesonide, mometasone (including inhalers or nasal sprays)
  • dexamethasone eye drops
  • some steroid creams, especially if applied to large areas of skin
  • treatments for acid reflux and ulcers called proton pump inhibitors and H2 receptor antagonists
  • indigestion remedies
  • some anti-fungal treatments (although not shampoos)
  • anticonvulsants (drugs used to treat epilepsy; for example, phenytoin, carbamazepine). Some anticonvulsants should never be used with some PIs (see individual entries)
  • the anti-TB drugs rifabutin and rifapentine
  • immunosuppressants
  • injectable steroids such as triamcinolone (Kenalog)
  • some chemotherapy drugs.

Methadone levels may be reduced by protease inhibitors, and require an increase in dose to achieve the same effect.

Protease inhibitors may reduce the effectiveness of some hormonal contraceptives (such as the ‘pill’, patches or an implant). If you are using this type of contraceptive to prevent pregnancy you may need to use an additional or different type of contraception.

Atazanavir

Names: Atazanavir, Reyataz 

Approved dosage: One red and blue 300mg capsule plus one white 100mg ritonavir tablet taken together once a day. 

Tips on taking it: Take with food to improve absorption. 

Common side-effects: Nausea, diarrhoea, rash, stomach ache, headache, insomnia, vomiting, heartburn, hyperbilirubinaemia (raised bilirubin levels, sometimes leading to jaundice).

Developing some yellow of the skin and/or eyes (jaundice) is fairly common, especially when you first start the drug. Although this can look alarming, it is harmless and does not mean that your liver is damaged, or not working in any way.

Rare side-effects: Kidney stones, abnormal liver function, changes in heart rhythm, lipodystrophy, liver toxicity, diabetes.

Key drug interactions: See the start of this section on protease inhibitors for more information on possible interactions.

Drugs that affect the acidity of your stomach and gastrointestinal tract can stop atazanavir being absorbed, meaning it may not be effective at suppressing HIV:

  • Proton pump inhibitors (indigestion remedies that reduce gastric acid, such as lansoprazole or omeprazole) should not be taken with atazanavir, unless they have been prescribed by your HIV doctor and the dose of atazanavir is increased.
  • H2-receptor antagonists (treatments for ulcers, such as ranitidine [Zantac]) should be taken only once a day, 4 to 12 hours after atazanavir. If atazanavir is taken with tenofovir, you should never take H2-receptor antagonists without speaking to your doctor or pharmacist first.
  • Indigestion remedies or calcium supplements should be taken at least two hours before or one hour after atazanavir.
  • ‘Buffered’ medicines (drugs that have been prepared so they are released slowly into the body) should be taken at least two hours before or one hour after atazanavir.

Talk to your HIV doctor or pharmacist before taking any of these drugs with atazanavir, even if you only take them occasionally.

Atazanavir should not be taken with the anti-HIV drug nevirapine or the chemotherapy drug irinotecan.

Taking NNRTI drugs with atazanavir is not recommended, but if it is required efavirenz could be taken with an increased dose of atazanavir and ritonavir (400mg and 200mg) and you should be monitored closely.

Darunavir

Names: Darunavir, Prezista 

Approved dosage: One dark-red 800mg tablet plus one white 100mg ritonavir tablet taken together once a day. For more resistant HIV, your doctor may prescribe one 600mg tablet plus one 100mg ritonavir tablet taken together twice a day.  

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

Common side-effects: Diarrhoea, nausea, rash, stomach pain, vomiting, headache, fever, lipodystrophy, liver toxicity, diabetes.

Rare side-effects: Abnormal liver function, changes in heart rhythm.  

Resistance to darunavir: The drug works well in many people with resistance to other protease inhibitors.

Key drug interactions: See the start of this section on protease inhibitors for more information on possible interactions.

Do not take darunavir with the anti-HIV drug lopinavir/ritonavir (Kaletra). The lipid-lowering drug pravastatin should be taken with caution with darunavir.

Fosamprenavir

Names: Fosamprenavir, Telzir 

Approved dosage: One pink 700mg tablet with one white 100mg ritonavir tablet twice daily. 

Tips on taking it: Take with or without food.  

Common side-effects: Raised lipids, nausea, vomiting, diarrhoea, rash, abdominal pain, headache, dizziness, tiredness, tingling around the mouth, changes in liver and pancreas function, lipodystrophy, liver toxicity, diabetes.

Rare side effects: Severe rash, changes in heart rhythm.

Resistance: Resistance to fosamprenavir is likely to cause resistance to ritonavir. 

Key drug interactions: See the start of this section on protease inhibitors for more information on possible interactions.

Do not take fosamprenavir with the anti-HIV drugs etravirine or tipranavir. Do not take fosamprenavir with the anti-hepatitis drug telaprevir or the antimalarial halofantrine.

Lopinavir/ritonavir (as Kaletra)

Names: Lopinavir/ritonavir, Kaletra 

Note: Lopinavir is only available in combination with ritonavir.

Approved dosage: 400mg lopinavir plus 100mg ritonavir twice a day, in yellow tablets containing 200mg lopinavir and 50mg ritonavir; two tablets are taken twice daily. Once-daily dose of four yellow tablets each containing 200mg of lopinavir and 50mg ritonavir is available for people starting treatment for the first time.

Children: A Kaletra tablet containing 100mg of lopinavir and 25mg of ritonavir is available for use by children who can swallow a tablet. A liquid formulation is also available. 

Tips on taking it: The tablet can be taken with or without food, but must not be broken, chewed or crushed. Taking with food can reduce potential irritation of the stomach.

Common side-effects: Lipodystrophy, raised liver enzymes, nausea, vomiting, diarrhoea, abdominal pain, weakness, headache, heartburn, raised lipids, liver toxicity, diabetes.

Rare side-effects: Changes in heart rhythm.

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

Key drug interactions: See the start of this section on protease inhibitors for more information on possible interactions.

Efavirenz and nevirapine reduce levels of Kaletra and dose adjustments are sometimes recommended when taking twice-daily Kaletra. Once-daily Kaletra should not usually be taken together with either efavirenz or nevirapine. Kaletra should not be taken with tipranavir/ritonavir or with darunavir.

Once-daily Kaletra should not be taken with carbamazepine, phenobarbital or phenytoin (used to treat epilepsy).

Do not take Kaletra with the anti-hepatitis drug telaprevir; fentanyl (for pain relief); trazodone; Zyban; or anti-cancer drugs called tyrosine kinase inhibitors. 

Ritonavir

Names: Ritonavir, Norvir 

Approved dosage: Ritonavir was one of the first protease inhibitors developed, but is no longer used as an anti-HIV drug due to its side-effects.  However, it is given at very low doses (too low for anti-HIV effects) to ‘boost’ the level of other PIs. When used for its boosting effects, the dose of ritonavir is usually 100mg or 200mg once or twice daily (depending on the frequency with which you take the protease inhibitor it is boosting).

Ritonavir is also approved for use as an anti-HIV drug at a dose of 600mg.

Tips on taking it: Take with food to reduce nausea. Do not chew, break or crush tablets. Ritonavir tablets and liquid should always be stored at room temperature. 

Common (at full dose): Raised lipid and liver enzymes, nausea, vomiting, diarrhoea, abdominal pain, headache, weakness, numbness around the mouth, bad taste in mouth, lipodystrophy, liver toxicity, diabetes.

Common (at low dose): Raised lipid levels.

Rare: Changes in heart rhythm.

Resistance to ritonavir: Likely to be some resistance to fosamprenavir. 

Key drug interactions: See the start of this section on protease inhibitors for more information on possible interactions.

Ritonavir interacts with many other medications. Consult your doctor or HIV pharmacist before taking any other drugs with ritonavir or a ritonavir-boosted drug (including inhalers, nasal sprays, medicines bought from a high-street chemist, herbal preparations and recreational drugs).

Tipranavir

Names: Tipranavir, Aptivus 

Approved dosage: Two 250mg pink capsules together with 200mg (two 100mg white tablets) 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: Nausea, diarrhoea, vomiting, abdominal pain, tiredness, headache, fever, lipid increases, flatulence, liver abnormalities, rash, lipodystrophy, diabetes, liver toxicity.

Rare side-effects: Bleeding in brain, changes in heart rhythm.

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: See the start of this section on protease inhibitors for more information on possible interactions.

Tipranavir can reduce the effectiveness of abacavir and zidovudine. It’s recommended that it not be taken with either of these drugs unless no other NRTI is available.

Some drugs can interact with tipranavir and change blood levels of one or both drugs, so dose adjustments may be needed. This is the case for: antidepressants; disulfiram (Antabuse); and the antibiotic metronidazole; anticonvulsants (used to treat epilepsy). Care should be taken with the antifungal treatments itraconazole and ketoconazole, and high doses (more than 200mg a day) of these and fluconazole avoided.

Anti-HIV drugs

Published October 2014

Last reviewed October 2014

Next review October 2017

Contact NAM to find out more about the scientific research and information used to produce this booklet.

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.