Drug interactions

Saquinavir (Invirase) inhibits both the P450 cytochrome CYP3A4 and poly-glycoprotein, so can interact with a wide range of other medications. Any other drugs also metabolised in similar ways should be co-administered with saquinavir with caution.

Dosing recommendations with LPV/r are SQV 1000mg with LPV 400mg/r 100mg, both given twice daily. With maraviroc, SQV is dosed at 1000mg with RTV 100mg and maraviroc 150mg, all twice daily.

Patients taking saquinavir should not take the following drugs:

  • Alfuzosin
  • Amiodarone (Cordarone X), due to heart problems
  • Astemizole, due to heart problems
  • Bepridil, due to heart problems
  • Cisapride, due to heart problems
  • Colchicine in patients with renal or hepatic impairment
  • Ergotamine tartrate (Cafergot / Migril), due to heart problems
  • Flecainide, due to heart problems
  • Halofantrine
  • Hypericin (St John’s wort), due to decreased saquinavir levels
  • Lovastatin, due to the risk of lovastatin-associated side-effects
  • Lumefantrine
  • Midazolam (Hypnovel), due to the risk of sedation or breathing problems
  • Quinidine (Kinidin Dureles), due to heart problems
  • Pimozide (Orap), due to heart problems
  • Propafenone, due to heart problems
  • Rifampicin (Rifadin / Rimactane), due to decreased levels of saquinavir and risks of liver toxicity1,2
  • Simvastatin (Zocor), due to simvastatin-associated side-effects
  • Terfenadine, due to heart problems
  • Triazolam, due to the risk of sedation or breathing problems.

The combination of saquinavir and indinavir (Crixivan) is not recommended, since the drugs appear to interfere with each other’s anti-HIV effects.

Adding fosamprenavir (Telzir) to ritonavir-boosted saquinavir reduces saquinavir levels. This can be restored by increasing the dose of ritonavir from 100 to 200mg twice daily.3

Atazanavir (Reyataz) also enhances the concentrations of once- and twice-daily saquinavir by decreasing the rate of saquinavir elimination.4 This raises the possibility that this triple protease inhibitor combination can be used as salvage therapy, particularly in patients who have experienced failure of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and cannot tolerate nucleoside reverse transcriptase inhibitors (NRTIs).5 6

Tipranavir (Aptivus) reduces the levels of saquinavir when both drugs are boosted with ritonavir.7 Studies still need to be done to ascertain how doses of the protease inhibitors should be adjusted to counteract this effect.

The NNRTIs nevirapine (Viramune) and efavirenz (Sustiva) both lower blood concentrations of saquinavir, even when boosted with ritonavir.8 A higher dose of saquinavir may be required.

Tenofovir (Viread) causes an increase in the blood levels of saquinavir and ritonavir, which may be of benefit in patients who have developed resistance to the drug.9 Conversely, the similar drug adefovir (Hepsera), which is used to treat hepatitis B, enhances the clearance of saquinavir by 49%.10

Rifabutin (Mycobutin) may undermine the efficacy of saquinavir. If taking ritonavir-boosted saquinavir, the dosage of rifabutin should be 150mg three times weekly.

Atorvastatin (Lipitor) should be administered with caution.

Garlic supplements may also substantially reduce saquinavir levels although small amounts of cooked garlic are thought unlikely to affect drug levels.11

Caution is advised when taking any protease inhibitor or NNRTI with the impotence drug sildenafil (Viagra). Levels of sildenafil in the body may be increased if taken with saquinavir, so it should be started at a reduced dose of 25mg.12 Sildenafil does not affect the level of saquinavir in the blood. A similar warning applies to the similar drugs tadalafil (Cialis) and vardenafil (Levitra). Sildenafil is contraindicated if used for treatment of pulmonary arterial hypertension (due to dose required).

One study has found that the anti-diarrhoea drug loperamide (Imodium) can reduce blood levels of unboosted saquinavir by 54%.13 There are no data available on the drug’s impact on saquinavir when boosted with ritonavir, but a similar effect may be of concern.

Omeprazole (Losec), which is a stomach acid-reducing agent, increases blood levels of saquinavir when it is boosted with ritonavir, but without increasing side-effects.14 Further studies are needed to determine the significance of this finding.

References

  1. Rolla V et al. Phase IV clinical trial to access the efficacy and safety of antiretroviral treatment with ritonavir and saquinavir (400 mg-400 mg) concomitant with rifampicin in tuberculosis and AIDS patients. Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 882, 2003
  2. Ribera E et al. A randomized study comparing the efficacy and tolerability of low-dose versus standard-dose stavudine in antiretroviral-naive patients (ETOX Study). Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, abstract TuPe2.4C10, 2005
  3. Boffito M et al. Steady-state pharmacokinetics of saquinavir hard-gel / ritonavir / fosamprenavir in HIV-1-infected patients. J Acquir Immune Defic Syndr 37: 1376-1384, 2004
  4. Boffito M et al. Pharmacokinetics of saquinavir hard-gel / ritonavir and atazanavir when combined once daily in HIV type 1-infected individuals administered different atazanavir doses. AIDS Res Hum Retroviruses 22: 749-756, 2006
  5. Boffito M et al. Atazanavir enhances saquinavir hard gel concentrations in a ritonavir-boosted once daily regimen. AIDS 18: 1291-1297, 2004
  6. von Hentig NH et al. The ATSAQ-1 cohort study: pharmacokinetic interactions of atazanavir (AZV) and saquinavir (SQV) in a ritonavir (RTV) boosted protease inhibitor therapy regimen. 15th International AIDS Conference, Bangkok, abstract WeOrB1235, 2004
  7. Curry K et al. Pharmacokinetics and safety of tipranavir / ritonavir (TPV / r) alone or in combination with saquinavir (SQV), amprenavir (APV), or lopinavir (LPV): interim analysis of BI1181.51. Fifth International Workshop on Clinical Pharmacology of HIV Therapy, Rome, abstract 5.1, 2004
  8. Baril JG et al. Concomitant use of non-nucleoside reverse transcriptase inhibitors (NNRTI) decreases exposure to saquinavir when used with a once-daily saquinavir and low-dose ritonavir dosing regimen. 14th International AIDS Conference, Barcelona, abstract TuPeB4559, 2002
  9. Zong J et al. Pharmacokinetic assessment of tenofovir DF and ritonavir-boosted saquinavir in healthy subjects. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract A-444, 2004
  10. Fletcher C et al. Sex-based differences in saquinavir pharmacology and virologic response in AIDS Clinical Trials Group study 359. J Infect Dis 189: 1176-1187, 2004
  11. Piscitelli SC et al. The effects of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 34: 234-238, 2002
  12. Muirhead GJ et al. Pharmacokinetic interactions between sildenafil and saquinavir / ritonavir. Br J Clin Pharmacol 50: 99-107, 2000
  13. Mikus G et al. Reduction of saquinavir exposure by coadministration of loperamide. Clin Pharmacokinet 43: 1015-1024, 2004
  14. Winston A et al. Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers. AIDS 20: 1401-1406, 2006
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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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.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.