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[×] Entry inhibitors
 BRAND NAMES
- Europe: Invirase EPAR summary for the public, Prescribing Information
- International: Invirase
- Italy: Invirase
- U.S.: Invirase
 MECHANISM OF ACTION
Saquinavir, is a protease inhibitor. It blocks an enzyme required for the proteolytic cleavage of the viral polyprotein precursors to the individual proteins found in infectious HIV. The cleavage of these viral polyproteins is essential for the maturation of infectious virus.
Saquinavir binds to the active site of HIV protease and prevents cleavage of the polyproteins, resulting in the formation of immature non-infectious viral particles.
Saquinavir, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level.
Saquinavir does not cure HIV infection or AIDS, but it may delay the damage to the immune system and the development of infections and diseases associated with AIDS.
Saquinavir is used with Ritonavir, another protease inhibitor that is used as a ‘booster’. Ritonavir inhibits CYP3A4, that normally metabolizes protease inhibitors, therfore, it slows down the rate at which saquinavir is broken down, increasing its levels in the blood.
Saquinavir is indicated for the treatment of HIV-1 infection in combination with ritonavir and other antiretroviral agents
Saquinavir must be administered in combination with ritonavir:
- Adults (over 16 years of age): 1000 mg twice daily in combination with ritonavir 100 mg twice daily.
Saquinavir and ritonavir should be taken with or within 2 hours after a meal.
- Patients with congenital or documented acquired QT prolongation, patients with refractory hypokalemia or hypomagnesemia, or those on concomitant therapy with other drugs that prolong the QT interval.
- Patients with complete atrioventricular (AV) block without implanted pacemakers, or patients who are at high risk of complete AV block.
- Patients with clinically significant hypersensitivity (e.g., anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir.
- When administered with ritonavir is contraindicated in patients with severe hepatic impairment.
- Coadministration of Saquinavir/ritonavir with rifampin due to the risk of severe hepatotoxicity
- Coadministration of Saquinavir/Ritonavir with CYP3A4 substrates for which increased plasma levels may result in serious or life-threatening reactions:
| Drug Class
|| Drugs Within Class That Are Contraindicated With Saquinavir/Ritonavir
|| Clinical Comment|
|Alpha 1-adrenoreceptor antagonist|| Alfuzosin
|| Potentially increased alfuzosin concentrations can result in hypotension.|
|| Amiodarone, bepridil, dofetilide, flecainide, lidocaine (systemic), propafenone, quinidine
|| Potential for serious and/or life-threatening cardiac arrhythmia.|
|| Increased trazodone concentrations can result in potentially life threatening cardiac arrhythmia..|
| Ergot Derivatives
||Dihydroergotamine, Ergotamine,Methylergonovine|| Potential for serious and/or life threatening reactions such as ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues.|
| GI Motility Agent
|| Potential for serious and/or life threatening reactions such as cardiac arrhythmias.|
| HMG-CoA Reductase Inhibitors
|| Lovastatin, Simvastatin
|| Potential for serious reactions such as myopathy including rhabdomyolysis.|
|| Potential for serious and/or life threatening reactions such as cardiac arrhythmias|
| PDE5 Inhibitors
|| Sildenafil (Revatio®) [for treatment of pulmonary arterial hypertension]
|| A safe and effective dose has not been established when used with Saquinavir/Ritonavir. There is increased potential for sildenafil associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope).|
|| Triazolam, oral Midazolam
|| Potential for serious and/or life threatening reactions such as prolonged or increased sedation or respiratory depression|
 WARNINGS AND PRECAUTIONS
- Certain drugs should not be coadministered with Saquinavir/Ritonavir due to the risk of serious or life-threatening reactions. (See contraindications)
- QT and PR interval prolongations have been observed in a healthy volunteer study. Use with caution in patients with preexisting conduction system abnormalities and certain heart diseases.
- Patients on Saquinavir therapy may develop new onset or exacerbations of diabetes mellitus, hyperglycemia, elevated cholesterol and/or triglyceride concentrations, redistribution/accumulation of body fat, and immune reconstitution syndrome. Monitor cholesterol and triglycerides prior to therapy and periodically thereafter.
- In patients with underlying hepatitis B or C, cirrhosis, chronic alcoholism and/or other underlying liver abnormalities there have been reports of worsening liver disease.
- Hemophilia: Spontaneous bleeding may occur and additional factor VII may be required.
- Various degrees of cross-resistance have been observed.
- Saquinavir/Ritonavir is potent inhibitor of CYP3A4, significantly increasing the exposure of drugs primarily metabolized by CYP3A4.
- Coadministration of Saquinavir/Ritonavir with drugs that induce CYP3A4 may result in decreased plasma concentrations of saquinavir and reduced efficacy.
- Certain drugs or drug classes should not be coadministered with Saquinavir/Ritonavir based on drug interaction studies or predicted drug interactions (See Contraindications)
 PREGNANCY AND LACTATION
- Pregnancy Category B (US). Saquinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. It is not known whether saquinavir is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Saquinavir.
 SIDE EFFECTS
The most common adverse reactions are nausea, vomiting, diarrhea, fatigue, and abdominal pain.