SAQUINAVIR MESYLATE

(sa-quin'a-vir mes'y-late)

Invirase
Classifications: antiretroviral agent; protease inhibitor;
Therapeutic: antiretroviral; protease inhibitor
Pregnancy Category: B

Availability

200 mg gelatin capsules; 500 mg tablet

Action

Synthetic peptide that inhibits the activity of HIV protease and prevents the cleavage of viral polyproteins essential for the maturation of HIV.

Therapeutic Effect

Effectiveness indicated by reduced viral load (decreased number of RNA copies), and increased number of T helper CD4 cells.

Uses

Advanced HIV infection, usually in combination with zidovudine or zalcitabine.

Contraindications

Significant hypersensitivity to saquinavir; severe hepatic impairment; concurrent administration with lovastatin, simvastatin, amiodarone, flecainide, propafenone, quinidine, ergot derivatives, rifampin, cisapride, triazolam, midazolam, antimicrobial resistance to other protease inhibitors, monotherapy, lactation.

Cautious Use

Mild to moderate hepatic insufficiency; severe renal impairment; hepatitis B or C; diabetes mellitus, diabetic ketoacidosis; older adults; hemophilia A or B, pregnancy (category B). Safety and efficacy in HIV-infected children <16 y are not established.

Route & Dosage

HIV
Adult: PO Invirase 600 mg (3 x 200 mg) t.i.d. taken 2 h after a full meal; Fortovase 1200 mg (6 x 200 mg) t.i.d. with meals; or 1000 mg b.i.d. with ritonavir 100 mg b.i.d.

Administration

Oral

Give with or up to 2 h after a full meal to ensure adequate absorption and bioavailability.
Do not administer to anyone taking rifampin or rifabutin because these drugs significantly decrease the plasma level of saquinavir.
Store Invirase at 15°–30° C (59°–86° F) in tightly closed bottle. Store Fortovase in refrigerator. Capsules are stable for 3 mo at room temperature ≤25° C (≤77° F).

Adverse Effects (≥1%)

CNS: Headache, paresthesia, numbness, dizziness, peripheral neuropathy, ataxia, confusion, convulsions, hyperreflexia, hyporeflexia, tremor, agitation, amnesia, anxiety, depression, excessive dreaming, hallucinations, euphoria, irritability, lethargy, somnolence. CV: Chest pain, hypertension, hypotension, syncope. Endocrine: Dehydration, hyperglycemia, diabetes, weight changes. Hematologic: Anemia, splenomegaly, thrombocytopenia, pancytopenia. GI: Nausea, diarrhea, abdominal discomfort, dyspepsia, mucosal damage, change in appetite, dry mouth. Skin: Rash, pruritus, acne, erythema, seborrhea, hair changes, photosensitivity, skin ulceration, dry skin. Body as a Whole: Myalgia, allergic reaction. Respiratory: Bronchitis, cough, dyspnea, epistaxis, hemoptysis, laryngitis, rhinitis. Special Senses: Xerophthalmia, earache, taste alterations, tinnitus, visual disturbances.

Interactions

Drug: Rifampin, rifabutin significantly decrease saquinavir levels. Phenobarbital, phenytoin, dexamethasone, carbamazepine may also reduce saquinavir levels. Saquinavir levels may be increased by delavirdine, ketoconazole, ritonavir, clarithromycin, indinavir. May increase serum levels of triazolam, midazolam, ergot derivatives, nelfinavir, sildenafil. May significantly increase simvastatin levels and toxicity; may increase risk of ergotamine toxicity of dihydroergotamine, ergotamine. Herbal: St. John's wort, garlic may decrease antiretroviral activity. Food: Grapefruit juice (>1 qt/d) may increase plasma concentrations and adverse effects.

Pharmacokinetics

Absorption: Rapidly from GI tract; only 4% reaches systemic circulation; food significantly increases bioavailability. Distribution: 98% protein bound. Metabolism: In liver (CYP3A4), first-pass metabolism. Elimination: Primarily in feces (>80%). Half-Life: 13 h.

Nursing Implications

Assessment & Drug Effects

Lab tests: Monitor serum electrolytes, CBC with differential, liver function, blood glucose and HbA_1C, CPK, and serum amylase prior to initiating therapy and periodically thereafter.
Monitor for and report S&S of peripheral neuropathy.
Assess for buccal mucosa ulceration or other distressing GI S&S.
Monitor weight periodically.
Monitor for toxicity if any of the following drugs is used concomitantly: calcium channel blockers, clindamycin, dapsone, quinidine, triazolam, or simvastatin.

Patient & Family Education

Take drug within 2 h of a full meal.
Be aware of all drugs which should not be taken concurrently with saquinavir.
Be aware that saquinavir is not a cure for HIV infection and that its long-term effects are unknown.
Report any distressing adverse effects to physician.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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