saquinavir mesylate

saquinavir mesylate (skwin´vir mes´ilāt´),

n brand name: Invirase;
drug class: antiviral;
action: inhibits human immunodeficiency virus (HIV) protease important for viral replication;
use: used in combination with nucleoside analogues, zidovudine, or zalcitabine in the treatment of acquired immunodeficiency syndrome (AIDS).

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saquinavir mesylate

Invirase

Pharmacologic class: Protease inhibitor

Therapeutic class: Antiretroviral

Pregnancy risk category B

Action

Inhibits human immunodeficiency virus (HIV) protease, preventing cleavage of HIV polyproteins and blocking virus replication and maturation

Availability

saquinavir mesylate

Capsules: 200 mg

⊘Indications and dosages

➣ Advanced HIV infection in selected patients

Adults older than age 16: 1,000 mg P.O. b.i.d. given only in combination with ritonavir b.i.d.

Contraindications

• Hypersensitivity to drug or its components
• Concurrent use of antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine); astemizole, cisapride, or terfenadine (not available in United States); ergot derivatives; midazolam; pimozide; rifampin; or triazolam
• Severe hepatic impairment
• Monotherapy

Precautions

Use cautiously in:
• hepatic disease, hemophilia types A and B, diabetes mellitus
• pregnant or breastfeeding patients
• children younger than age 16.

Administration

• Give around the clock without missing doses, within 2 hours of a full meal.
• If prescribed in combination with ritonavir, give both drugs at same time.
• Know that drug is given only in combination with ritonavir, which inhibits its metabolism.
☞ Don't give concurrently with antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine); astemizole, cisapride, terfenadine, ergot derivatives, midazolam, pimozide, rifampin, or triazolam. Life-threatening reactions may occur.

Route	Onset	Peak	Duration
P.O.	Unknown	Unknown	Unknown

Adverse reactions

CNS: headache, dizziness, paresthesia, asthenia, depression, insomnia, anxiety, confusion, ataxia, seizures, suicidal ideation, intracranial hemorrhage

CV: chest pain, peripheral vasoconstriction, thrombophlebitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, flatulence, dyspepsia, buccal mucosal ulcers, pancreatitis

GU: urinary retention, nephrolithiasis, oliguria, acute renal insufficiency

Hematologic: hemolytic anemia, pancytopenia, thrombocytopenia, acute myeloblastic leukemia

Hepatic: jaundice, portal hypertension , exacerbation of chronic hepatic disease (with grade 4 elevated liver function test results)

Metabolic: hyperglycemia, diabetes mellitus (exacerbation or new onset), hypercalcemia, hyperkalemia, hypoglycemia

Musculoskeletal: musculoskeletal pain

Respiratory: bronchitis, cough

Skin: rash, Stevens-Johnson syndrome

Other: altered taste, drug fever

Interactions

Drug-drug. Antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), astemizole, cisapride, pimozide, terfenadine: increased blood levels of these drugs, life-threatening arrhythmias

Benzodiazepines, calcium channel blockers: increased blood levels of these drugs

Carbamazepine, dexamethasone, nevirapine, phenobarbital, phenytoin, rifabutin, rifampin: reduced saquinavir steady-state level

Clarithromycin, indinavir, ketoconazole, nelfinavir, ritonavir: increased saquinavir blood level

Ergot derivatives: elevated blood level of these drugs, life-threatening reactions such as acute ergot toxicity (peripheral vasospasm and ischemia of extremities and other tissues)

HMG-CoA reductase inhibitors: increased risk of myopathy (including rhabdomyolysis)

Midazolam, triazolam: increased risk of life-threatening prolonged or increased sedation or respiratory depression

Nonnucleoside reverse transcriptase inhibitors (delavirdine, nevirapine): increased saquinavir blood level

Sildenafil, tadalafil, tricyclic antidepressants, vardenafil: increased blood levels of these drugs

Warfarin: altered International Normalized Ratio

Drug-diagnostic tests. Alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), bilirubin, calcium, creatinine phosphokinase, potassium: increased levels

Blood glucose: increased or decreased level

Phosphate: decreased level

Platelets, red blood cells, white blood cells: decreased counts

Drug-food. Any food: increased drug absorption

Grapefruit juice: elevated drug blood level, increased pharmacologic and adverse effects

Drug-herbs. Garlic capsules: decreased saquinavir blood level

St. John's wort: 50% reduction in saquinavir blood level

Patient monitoring

• Monitor platelet count, CBC, liver function tests, electrolytes, and uric acid and bilirubin levels. Watch for evidence of life-threatening blood dyscrasias and portal hypertension.
• Assess nutritional status and hydration.
• Monitor neurologic status. Stay alert for depression, suicidal ideation, seizures, and signs or symptoms of intracranial hemorrhage.

Patient teaching

• Tell patient to take with food (but not grapefruit juice) or within 2 hours of a full meal. Stress importance of taking doses around the clock on a regular schedule.
☞ Inform patient (and significant other as appropriate) that drug may cause depression and suicidal thoughts, which should be reported immediately.
• Advise patient to notify prescriber if rash occurs.
☞ Teach patient to recognize and immediately report signs and symptoms of liver disorder or bleeding tendency.
• Tell patient drug interacts with many other drugs, causing serious reactions. Advise him to discuss all drug use with prescriber before therapy starts.
• Caution patient to avoid St. John's wort and garlic capsules during therapy.
• Instruct female patient not to breastfeed, because she may transmit drug effects and HIV to infant.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

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saquinavir mesylate

Fortovase, Invirase^® AIDS An anti-HIV protease inhibitor Adverse effects Nausea, diarrhea, stomach upset, ↑ LFTs, lipodystrophy–characterized by ↑glucose, ↑ lipids, ↑ waist size, ↓ fat in face, arms, legs. See AIDS, AIDS wasting syndrome, Antiretroviral, HIV, Protease inhibitor; Cf Nucleoside analogues.