saquinavir mesylate

Action

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

Availability

Capsules: 200 mg

Tablets: 500 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

• Clinically significant hypersensitivity (for example, anaphylactic reaction, Stevens-Johnson syndrome) to drug or its components and ritonavir

• When administered with ritonavir in patients with severe hepatic impairment

• Congenital or documented acquired QT-interval prolongation, refractory hypokalemia or hypomagnesemia, or concurrent therapy with other drugs that prolong QT interval

• Complete atrioventricular (AV) block without implanted pacemaker, or patient at high risk for complete AV block

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.

See Know that drug is given only in combination with ritonavir, which inhibits its metabolism. Give both drugs at same time.

See Don't give concurrently with CYP3A substrates (such as alfuzosin, amiodarone, bepridil, cisapride, dofetilide, dihydroergotamine, ergonovine, ergotamine, flecainide, lovastatin, methylergonovine, oral midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, sildenafil when used for pulmonary arterial hypertension, systemic lidocaine, trazodone, triazolam). Life-threatening reactions may occur.

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, allergic reactions, immune reconstitution syndrome

Interactions

Drug-drug. Alfuzosin, digoxin, sildenafil when used for pulmonary arterial hypertension, tadalafil, tricyclic antidepressants, vardenafil: increased blood levels of these drugs

Antiarrhythmics (amiodarone, bepridil, dofetilide, flecainide, propafenone, quinidine), astemizole, cisapride, pimozide, propafenone, systemic lidocaine, 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)

HIV-1 protease inhibitors (atazanavir): possible additive effects on PR interval prolongation

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

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

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

Rifampin: increased risk of severe hepatocellular toxicity

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

See Be aware that immune reconstitution syndrome may occur in patients receiving combination antiretroviral therapy. During initial phase of therapy, patient whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, P. jiroveci pneumonia, and tuberculosis), which may necessitate further evaluation and treatment.

• 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.

See 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.

See 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.