saquinavir (Invirase, Fortovase)
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Introduction
Tradenames: Invirase, Fortovase.
Indications
- treatment of advanced HIV infection in selected patients
- used in combination with nucleoside analogs & other retroviral agents
Contraindications
Caution:
- patients with hepatic insufficiency
- safety & efficacy has not been established for children < 16 years of age
Dosage
600 mg PO TID (with meals or up to 2 hours after full meal)
Capsules: 200 mg.
Pharmacokinetics
- absorption is incomplete; high fats foods may increase absorption 5-fold
- bioavailability: Invirase: 4%; Fortovase: 13%
- widely distributed, CSF penetration is minimal
- protein binding: 98%
- metabolized by cyt P450 3A4
- undergoes extensive 1st pass metabolism
- no known active metabolites
- elimination: 88% in feces, 1% in urine
elimination via liver
protein binding = 98 %
Adverse effects
- not common (1-10%)
- rash, hyperglycemia, elevated serum creatine kinase, diarrhea, abdominal pain/discomfort, nausea, ulceration of buccal mucosa, paresthesia, weakness
- uncommon (< 1%)
- headache, confusion, seizures, ataxia, Stevens-Johnson syndrome, hypoglycemia, hyperkalemia, hypokalemia, low serum amylase, acute myeloblastic leukemia, anemia, hemolytic anemia, thrombocytopenia, jaundice, ascites, exacerbation of chronic liver disease, abnormal liver function tests (AST, ALT, bilirubin), thrombophlebitis
- hyperlipidemia, lipodystrophy syndrome
- arrhythmias
- drug adverse effects of antiretroviral protease inhibitors
- drug adverse effects of antiretroviral agents
Drug interactions
- rifampin may decrease plasma levels of saquinavir (40-80%)
- rifabutin may increase plasma levels of saquinavir
- ketoconazole may increase plasma levels of saquinavir
- saquinavir may decrease metabolism of:
- calcium channel blockers
- clindamycin
- dapsone
- quinidine
- triazolam
- garlic supplements may enhance metabolism & diminish saquinavir levels by 50%[5]
- any drug that inhibits cyt P450 3A4 may increase levels of saquinavir
- any drug that induces cyt P450 3A4 may diminish levels of saquinavir
- saquinavir inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates
- ritonavir in combination with saquinavir may increase risk of torsades de pointes or complete heart block[8]
- drug interaction(s) of fluticasone with HIV1 protease inhibitors
- drug interaction(s) of antiretroviral protease inhibitor in combination with ritonavir
- drug interaction(s) of saquinavir with ritonavir
- drug interaction(s) of statins with antiviral protease inhibitors
- drug interaction(s) of antibiotics with warfarin
Laboratory
Notes
- MUST be used with AZT, or other NRTI (nucleoside reverse transcriptase inhibitor)
- do NOT use suboptimal dose
More general terms
Additional terms
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Physician's Desk Reference (PDR) 56th edition, Medical Economics, 2002
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ 5.0 5.1 Prescriber's Letter 8(3):17 2001
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ 8.0 8.1 8.2 FDA MedWatch 10/21/2010 Invirase (saquinavir): Label Change - Risk of Abnormal Heart Rhythm http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm230449.htm
- ↑ 9.0 9.1 Zuger A Use of Antiretroviral Drugs in Pregnancy. Physician's First Watch, April 22, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. 2014. AIDSinfo. Clinical Guidelines Portal. March 28, 2014. http://aidsinfo.nih.gov/Guidelines/HTML/3/perinatal-guidelines/0 (corresponding NGC guideline withdrawn March 2016) - ↑ Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015