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.