sa-KWIN-a-vir

• HIV infection (in combination with ritonavir and other antiretrovirals).

• Inhibits the action of HIV protease and prevents the cleavage of viral polyproteins.

• Slowing of the progression of HIV infection and its sequelae.
• Increased CD4 cell counts and decreased viral load.

Absorption: Incompletely absorbed after oral administration; rapidly undergoes extensive first-pass hepatic metabolism.

Distribution: Distributes into tissues, but CNS penetration is poor.

Protein Binding: 98%.

Metabolism/Excretion: Mostly metabolized by the liver. <1% excreted unchanged in urine.

Half-life: 13 hr.

Contraindicated in:

• Hypersensitivity
• Concurrent alfuzosin, amiodarone, atazanavir, clarithromycin, clozapine, dasatinib, ergot derivatives, disopyramide, dofetilide, erythromycin, flecainide, haloperidol, lidocaine, lovastatin, lurasidone, midazolam (oral), pentamidine, phenothiazines, pimozide, propafenone, quinidine, quinine, rifampin, rilpivirine, sildenafil (Revatio), simvastatin, sunatinib, tacrolimus, trazodone, triazolam, ziprasidone
• Severe hepatic impairment
• QT interval prolongation
• Congenital long QT syndrome
• Refractory hypokalemia or hypomagnesemia
• Complete AV block (in absence of pacemaker)
• Severe hepatic impairment
• Galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (contains lactose)
• Lactation: Breastfeeding not recommended in patients infected with HIV.

Use Cautiously in:

• Diabetes mellitus (may exacerbate hyperglycemia; hyperglycemia may progress to ketoacidosis)
• HF, bradycardia, or electrolyte abnormalities (↑ risk of QT interval prolongation)
• Structural heart disease, conduction system abnormalities, HF, and ischemic heart disease (↑ risk of PR interval prolongation)
• Hemophilia (↑ risk of bleeding)
• OB: Not one of the recommended antiretroviral agents for use during pregnancy
• Pedi: Children <16 yr (safety and effectiveness not established).

CV: TORSADE DE POINTES, heart block, PR interval prolongation, QT interval prolongation, thrombophlebitis.

Derm: STEVENS-JOHNSON SYNDROME, photosensitivity, severe cutaneous reactions.

Endo: fat redistribution, hyperglycemia.

GI: abdominal discomfort, diarrhea, ↑liver enzymes, jaundice, nausea.

Hemat: acute myeloblastic leukemia, hemolytic anemia, thrombocytopenia.

Neuro: ataxia , SEIZURES, confusion, headache, mental depression, psychic disorders, weakness.

Misc: immune reconstitution syndrome.

Drug-Drug:

• Rifampin may ↑ risk of hepatotoxicity; avoid concomitant use.
• ↑blood levels and risk of toxicity from some antiarrhythmics (amiodarone, disopyramide, dofetilide, flecainide, lidocaine, propafenone, quinidine), pimozide, lurasidone, chlorpromazine, clozapine, haloperidol, phenothiazines, thioridazine, ziprasidone, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine), sildenafil (Revatio), alfuzosin, lovastatin, simvastatin, clarithromycin, erythromycin, pentamidine, atazanavir, tacrolimus, dapsone, quinine, trazodone, midazolam (oral), and triazolam; concurrent use contraindicated.
• May significantly ↑ rilpivirine levels; concurrent use contraindicated; when switching to saquinavir/ritonavir, need washout period of 2 wk.
• May significantly ↑ dasatinib and sunatinib levels; concurrent use contraindicated.
• Concurrent therapy with cobicistat is not recommended
• Coadministration with rifabutin significantly ↓ saquinavir levels and ↑ rifabutin levels; ↓ rifabutin dose by at least 75% (max dose of 150 mg every other day or 150 mg 3 times weekly).
• Levels are significantly ↑ by indinavir, nelfinavir, nefazodone, omeprazole, quinupristin/dalfopristin, and ritonavir ; dose adjustments may be necessary.
• Carbamazepine, phenobarbital, phenytoin, nevirapine, efavirenz, and dexamethasone may ↓ levels.
• May ↓ serum cortisol levels with fluticasone.
• May ↑ digoxin, and ketoconazole, calcium channel blockers, cyclosporine, rapamycin, amitriptyline, imipramine, midazolam (IV), fentanyl, alfentanil, and warfarin levels.
• ↑risk of myopathy with atorvastatin; do not exceed atorvastatin dose of 20 mg/day.
• May ↓ the effects of estrogen-containing contraceptives.
• May ↑ concentrations of phosphodiesterase type 5 inhibitors causing hypotension, visual changes, priapism; ↓ starting doses not to exceed 25 mg within 48 hr for sildenafil, 2.5 mg every 72 hr for vardenafil and 10 mg every 72 hr for tadalafil.
• May ↑ risk of adverse effects with salmeterol; concurrent use not recommended.
• May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day; if patient already receiving bosentan, discontinue bosentan at least 36 hr before initiation of tipranavir and then restart bosentan at least 10 days later at 62.5 mg once daily or every other day.
• May ↑ tadalafil (Adcirca) levels; initiate tadalafil (Adcirca) at 20 mg once daily; if patient already receiving tadalafil (Adcirca), discontinue tadalafil (Adcirca) at least 24 hr before initiation of tipranavir and then restart tadalafil (Adcirca) at least 7 days later at 20 mg once daily.
• May ↑ colchicine levels; ↓ dose of colchicine; do not administer colchicine if patients have renal or hepatic impairment.
• May ↑ quetiapine levels; ↓ quetiapine dose to 1/6 of current dose
• Beta-blockers, diltiazem, verapamil, digoxin, clonidine, and ivabradine may ↑ risk of PR interval prolongation and heart block

Drug-Natural Products:

• St. John's wort and garlic may ↓ levels and effectiveness; may promote development of drug resistance.

Drug-Food:

• Grapefruit juice↑ serum levels and effects.
• Food significantly increases ↑ the absorption of saquinavir.Garlic can significantly ↓ levels.

• PO (Adults): 1000 mg twice daily in combination with ritonavir 100 mg twice daily (patients switching from another ritonavir-containing regimen or from an NNRTI-based regimen [not including rilpivirine] should also receive this particular dosing regimen); Treatment-nave patients or patients switching from regimen containing rilpivirine — 500 mg twice daily with ritonavir 100 mg twice daily for 7 days, then ↑ saquinavir dose to 1000 mg twice daily with ritonavir 100 mg twice daily.

• PO: Administer within 2 hr after a full meal to increase effectiveness. Taking without food causes decreased blood concentrations and may result in no antiviral activity.
  • Administer ritonavir at same time as saquinavir.

Invirase

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

• Tablets (contain lactose): 500 mg;

(blood levels)

• Assess for change in severity of symptoms of HIV and for symptoms of opportunistic infections during therapy.
• Monitor ECG prior to starting therapy and periodically in patients with HF, bradyarrhythmias, hepatic impairment and electrolyte abnormalities. May cause QT interval prolongation. Do not begin therapy in patients with QT interval 450 msec. If therapy is started, reevaluate ECG after 10 days of therapy. Discontinue therapy if QT interval prolongation is >20 msec over pre-treatment.
• Assess patient for rash (mild to moderate rash usually occurs in the 2nd wk of therapy and resolves within 1–2 wk of continued therapy). If rash is severe (extensive erythematous or maculopapular rash with moist desquamation or angioedema) or accompanied by systemic symptoms (serum sickness-like reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis), therapy must be discontinued immediately.

• Monitor viral load and CD4 count regularly during therapy.
  • Monitor serum electrolytes prior to and periodically during therapy. Correct hypokalemia and hypomagnesemia prior to starting therapy.
  • May cause hyperglycemia, which may result in diabetic ketoacidosis.
  • Monitor hematologic and hepatic function before and periodically during therapy. May cause anemia, thrombocytopenia, and ↑ liver enzymes. Use with rifampin greatly ↑ risk of hepatitis and ↑ serum transaminases.

• Risk for infection (Indications, Side Effects).

• Instruct patient to take saquinavir as directed at the same time each day, within 2 hr after a full meal. Take missed doses as soon as possible if not almost time for next dose; do not double doses. Do not discontinue without consulting health care professional.
• Advise patient to avoid taking grapefruit and garlic capsules during therapy.
• Instruct patient that saquinavir should not be shared with others.
• Inform patient that saquinavir does not cure HIV or prevent associated or opportunistic infections. Saquinavir may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading HIV to others. Advise patient that the long-term effects of saquinavir are unknown at this time.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort.
• Inform patient that saquinavir may cause hyperglycemia. Advise patient to notify health care professional if increased thirst or hunger; unexplained weight loss; increased urination; fatigue; or dry, itchy skin occurs.
• Instruct patient to notify health care professional immediately if rash occurs. Rare but serious bullous skin eruptions with polyarthritis may also occur.
• Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
• Immune reconstitution syndrome may trigger opportunistic infections or autoimmune disorders. Notify health care professional if symptoms occur.
• Rep: Advise patient taking oral contraceptives to use a nonhormonal method of birth control during saquinavir therapy. If pregnancy is suspected notify health care professional promptly. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise female patient to avoid breastfeeding during therapy.
• Emphasize the importance of regular follow-up exams and blood tests to determine progress and monitor for side effects.

• Slowing of the progression of HIV infection and its sequelae.
• Decrease in viral load and improvement in CD4 cell counts.

NDC Code^*

• 0004- Genentech, Inc.
  • 0004-0244- Invirase
    • 0004-0244-51- 120 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0004-0244-51)