Invirase® (Hard gel formulation) and Fortovase® (Soft gel formulation)
Invirase Fortovase
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HOW SAQUINAVIR WORKS
Saquinavir is a member of the group of drugs referred to as protease inhibitors (PIs). This class of drug combats viral replication of HIV by blocking HIV's protease protein. This protein or enzyme is used by HIV to break up large viral proteins into smaller particles from which new HIV particles can be formed. Protease inhibitors ensure that these new particles are immature and incapable of infecting new cells, thus inhibiting the HIV replication process.
History
Saquinavir hard gel was first licensed in Europe in 1996, saquinavir soft gel received its license in September 1998. The licences were granted for the use of saquinavir in combination with antiretroviral nucleoside analogues for the treatment of HIV-1 in adults.
Combination therapy
Saquinavir is established as an effective component of combination antiretroviral therapy against an optimal antiretroviral background, it should not be used as monotherapy as resistant viruses rapidly emerge. When boosted with ritonavir, saquinavir soft gel and hard gel are equally potent. Careful consideration needs to be applied when incorporating saquinavir into anti-HIV combination therapy, as several interactions with other antiretrovirals have been observed.
If saquinavir is used alongside other protease inhibitors, interactions should be carefully considered. These interactions may indicate the necessity for dose modifications.
Dosing
Saquinavir is produced in two formulations - a 200mg, beige-opaque, soft gelatin capsule or a 200mg, green and yellow hard gel tablet. The recommended adult daily dose of boosted saquinavir soft gel and hard gel is five 200mg capsule or tablet swallowed whole and taken with 100mg ritonavir capsule twice daily, and within two hours of consuming a meal.
Dosing restrictions
Saquinavir soft and hard gel formulations should be taken with a full meal or within two hours of a consuming a meal in order to ensure adequate absorption. Saquinavir is metabolised by the CYP3A4 enzyme. Any drug that inhibits or accelerates this process is likely to impact on the levels of saquinavir in the blood. Sub-optimal levels of saquinavir in the blood increase the risk of resistance developing. Similarly any drug that shares this metabolic pathway is likely to be affected by the co-administration of saquinavir, for this reason there are a number of dosing restrictions or recommended dose modifications.
Drug interactions with saquinavir include
St. John's Wort should not be taken alongside saquinavir as it reduces plasma levels of saquinavir and can therefore potentially reduce its efficacy
Caution should be taken when administering saquinavir alongside other PIs and NNRTIs, drug interactions should be considered
If saquinavir is co-administered with didanosine (ddI) then saquinavir should be taken with food an hour after or at least two hours before ddI
Levels of sildenafil (Viagra(r)) in the body are increased in the presence of saquinavir, a reduced dose of 25mg sildenafil is recommended
Co-administration of saquinavir with rifabutin and rifampicin (TB medication) results in decreased levels of saquinavir, alternatives should be sought
Saquinavir should not be administered alongside triazolam, cisapride, astemizole, terfenadine, midazolam or pimozide
HMG-CoA reductase inhibitors (cholesterol lowering drugs), which are highly dependent on CYP3A4 metabolism, are expected to have increased plasma concentrations when co-administered with saquinavir: this may cause myopathy (muscle disorder), so the combination of these drugs (e.g. lovastatin or simvastatin) with saquinavir is not recommended. Atorvastatin is less dependent on CYP3A4 for metabolism, but caution must be exercised
Treatment with the antibiotic clarithromycin or the antifungal ketoconazole increases the plasma levels of saquinavir
The efficacy of the oral contraceptive pill may be reduced if used alongside saquinavir
Side effects
The most common side effects of saquinavir are those related to gastro-intestinal disturbance. These are likely to occur in the first few weeks after commencing treatment. The most common side effects include:
Diarrhoea
Flatulence
Nausea
Vomiting
Abdominal pain/distension
Dyspepsia
Fatigue
Headache
Dizziness
Fever
Rash
Muscle/joint pain
Depression
Other side effects associated with saquinavir and common to all the protease inhibitors include
Lipodystrophy (although incidence and degree varies between all PIs)
Myopathy (muscle disease)
Increased bleeding in those with bleeding disorders
Increase in blood fats
Diabetes
Pancreatitis
Storage
Saquinavir soft gel and hard gel capsules stored at room temperature should be used within 3 months. Stocks stored in the refrigerator should be used by the expiry date.
Pre-existing conditions
Saquinavir soft gel and hard gel should be used with caution in patients with hepatic impairment. All protease inhibitors, including saquinavir, have been associated with increased bleeding in patients with bleeding disorders, these patients may require additional clotting agents if protease inhibitors are included in their antiretroviral combination therapy.
Use during pregnancy
There are no adequate and well-controlled studies of saquinavir in pregnant women. For this reason saquinavir should only be used during pregnancy if the benefits justify any potential risks. In addition, as it is not known whether saquinavir is excreted into breast-milk, mothers should be advised not to breastfeed their infants if receiving saquinavir.
Paediatric use
Saquinavir is not licensed for use in children under 16 years of age.
Saquinavir-resistant HIV
It is widely accepted that all protease inhibitors experience an element of cross-resistance within the group.
Fortovase 
