No

Antiretroviral Agent, Protease Inhibitor

Treatment of HIV infection in selected patients; used in combination with at least two other antiretroviral agents

B

Clinical effects on the fetus: Administer saquinavir during pregnancy only if benefits to the mother outweigh the risk to the fetus

Breast-feeding/lactation: HIV-infected mothers are discouraged from breast-feeding to decrease postnatal transmission of HIV

Hypersensitivity to saquinavir or any components; exposure to direct sunlight without sunscreen or protective clothing; coadministration with terfenadine, cisapride, astemizole, triazolam, midazolam, or ergot derivatives

The indication for saquinavir for the treatment of HIV infection is based on changes in surrogate markers. At present, there are no results from controlled clinical trials evaluating its effect on patient survival or the clinical progression of HIV infection (ie, occurrence of opportunistic infections or malignancies); use caution in patients with hepatic insufficiency; safety and efficacy have not been established in children <16 years of age. May exacerbate pre-existing hepatic dysfunction; use with caution in patients with hepatitis B or C and in cirrhosis

Protease inhibitors cause dyslipidemia which includes elevated cholesterol and triglycerides and a redistribution of body fat centrally to cause "protease paunch", buffalo hump, facial atrophy, and breast enlargement. These agents also cause hyperglycemia.

Dermatologic: Rash

Endocrine & metabolic: Hyperglycemia

Gastrointestinal: Diarrhea, abdominal discomfort, nausea, abdominal pain, buccal mucosa ulceration

Neuromuscular & skeletal: Paresthesia, weakness, increased CPK

<1%: Headache, confusion, seizures, ataxia, pain, Stevens-Johnson syndrome, hypoglycemia, hyper- and hypokalemia, low serum amylase, upper quadrant abdominal pain, acute myeloblastic leukemia, hemolytic anemia, thrombocytopenia, jaundice, ascites, bullous skin eruption, polyarthritis, portal hypertension, exacerbation of chronic liver disease, elevated LFTs, altered AST/ALT, bilirubin, Hgb, thrombophlebitis

CYP3A3/4 enzyme substrate; CYP3A3/4 enzyme inhibitor

Increased effect: Ketoconazole significantly increases plasma levels and AUC of saquinavir; as a known, although not potent inhibitor of the cytochrome P-450 system, saquinavir may decrease the metabolism of terfenadine and astemizole, as well as cisapride, ergot derivatives, midazolam, and triazolam (and result in rare but serious effects including cardiac arrhythmias); other drugs which may have increased adverse effects if coadministered with saquinavir include calcium channel blockers, clindamycin, dapsone, and quinidine. Both clarithromycin and saquinavir levels/effects may be increased with coadministration. Delavirdine may increase concentration; ritonavir may increase AUC >17-fold; concurrent administration of nelfinavir results in increase in nelfinavir (18%) and saquinavir (mean: 392%).

Saquinavir increased serum concentrations of simvastatin and atorvastatin. Use cautiously with HMG-CoA reductase inhibitors. Avoid use with simvastatin.

As an inhibitor of HIV protease, saquinavir prevents the cleavage of viral polyprotein precursors which are needed to generate functional proteins in and maturation of HIV-infected cells

Absorption: Poor, increased with high fat meal. Fortovase® has improved absorption over Invirase®

Distribution: V_d: 700 L; does not distribute into CSF

Protein binding: ~98% bound to plasma proteins

Metabolism: Widely metabolized undergoing extensive first pass metabolism

Bioavailability: ~4% (Invirase®); 12% to 15% (Fortovase®)

Adults: Oral:

Invirase®: Three 200 mg capsules (600 mg) 3 times/day within 2 hours after a full meal in combination with a nucleoside analog

Dose of either Fortovase® or Invirase® in combination with ritonavir: 400 mg twice daily

Monitor viral load, CD4 count, triglycerides, cholesterol, glucose

May rarely cause confusion or ataxia; report of acute paranoia reaction to saquinavir

Contraindicated with triazolam and midazolam; barbiturates and carbamazepine may increase the metabolism of saquinavir

No information available to require special precautions

No effects or complications reported

Saquinavir is is not a cure for HIV nor has it been found to reduce transmission of HIV. Take as directed, with food. Diabetics will need to monitor glucose levels frequently while taking this medication; this medication may exacerbate diabetes and hyperglycemia. You may experience headache or confusion; if these persist notify prescriber. You may develop sensitivity to sunlight (wear protective clothing, use sunblock, or avoid direct sunlight); mouth sores (frequent oral care is necessary). Report persistent nausea, vomiting, abdominal pain, or diarrhea; skin rash or irritation; muscles weakness or tremors; easy bruising or bleeding; fever or chills; yellowing of eyes or skin; or dark urine or pale stools. Breast-feeding precautions: Do not breast-feed.

Observe for signs of opportunistic infections and other illnesses associated with HIV; administer on a full stomach, if possible

Capsule (hard) as mesylate (Invirase®): 200 mg

Capsule (soft) (Fortovase®): 200 mg

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