Trade Names:Invirase- Capsules 200 mg (as mesylate)- Tablets 500 mg (as mesylate)Fortovase Roche (Canada)
Inhibits HIV protease, the enzyme required to form functional proteins in HIV-infected cells.
Bioavailability averaged 4%.
Saquinavir is approximately 98% protein bound and Vd is 700 L.
Saquinavir undergoes extensive first-pass metabolism. Metabolism is CYP-450–mediated with the specific isoenzyme CYP3A4 responsible for more than 90% of the hepatic metabolism.
Systemic Cl is rapid (1.14 L/h/kg after IV doses of 6, 36, and 72 mg).
Approximately 1% is excreted via urine. Impact of renal function impairment on elimination should be minimal.Hepatic Function Impairment
Pharmacokinetics have not been studied in patients with hepatic function impairment.Elderly
Pharmacokinetics have not been sufficiently studied in patients older than 65 yr of age.Gender
Exposure is higher in women than in men (mean increases in AUC and C max are 56% and 26%, respectively).
Treatment of HIV infection in combination with ritonavir and other antiretroviral agents.
Coadministration of amiodarone, bepridil, cisapride, ergot derivatives, flecainide, midazolam, pimozide, propafenone, quinidine, rifampin, or triazolam; hypersensitivity to saquinavir or any component of the product; when administered with ritonavir, in patients with severe hepatic function impairment.
PO 1,000 mg twice daily.
Store at 59° to 86°F. Store in tightly closed bottle.
Saquinavir plasma levels may be elevated, increasing the risk of adverse reactions.Cimetidine, NNRTI (ie, delavirdine), ranitidine
Saquinavir plasma levels may be elevated; however, appropriate dose when coadministered with saquinavir/ritonavir has not been established.Clarithromycin
Saquinavir and clarithromycin plasma levels may be increased; clarithromycin dosage adjustment may be necessary in patients with renal function impairment.Coadministration with drugs that are highly dependent on CYP3A for Cl that have a narrow therapeutic index or that may result in a potentially serious adverse reaction because of the expected magnitude of an interaction (eg, amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, methylergonovine, midazolam, pimozide, propafenone, quinidine, rifampin, terfenadine, triazolam)
Coadministration with saquinavir/ritonavir is contraindicated.Digoxin
Digoxin plasma concentrations may be elevated. Use with caution.Drugs primarily metabolized by CYP3A4 (eg, benzodiazepines [ie, alprazolam, clorazepate, diazepam, flurazepam], calcium channel blockers [ie, amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil], cyclosporine, lidocaine [systemic], tacrolimus, trazodone, tricyclic antidepressants [eg, amitriptyline, imipramine])
Plasma levels may be increased by saquinavir; monitor patient and/or therapeutic concentration. Adjust dose as needed.Fluticasone inhalation
Plasma levels may be elevated by saquinavir; coadministration is not recommended.Garlic capsules, loperamide
Saquinavir plasma concentrations may be decreased.Grapefruit
Saquinavir plasma concentrations may be elevated; avoid coadministration of saquinavir and grapefruit products.HMG-CoA reductase inhibitors (ie, atorvastatin, lovastatin, rosuvastatin, simvastatin)
Plasma levels may be elevated by saquinavir, increasing the risk of myopathy, including rhabdomyolysis. Coadministration of lovastatin or simvastatin is not recommended. Give the lowest possible dose of atorvastatin or rosuvastatin.Hormonal contraceptives (eg, ethinyl estradiol)
Estrogen concentrations may be reduced; alternative or additional contraceptive measures should be used.Lopinavir/Ritonavir
Ritonavir plasma levels may be reduced.Methadone
Methadone plasma concentration may be reduced; methadone dosage adjustments may be needed.NNRTIs (ie, efavirenz, nevirapine)
Efavirenz and saquinavir plasma concentrations may be reduced; however, appropriate dose when coadministered with saquinavir/ritonavir has not been established.Phosphodiesterase type 5 inhibitors (ie, sildenafil, tadalafil, vardenafil)
Plasma concentrations may be elevated by saquinavir. Monitor for adverse reactions when administered with saquinavir/ritonavir. Use with caution and at dosages not exceeding: sildenafil 25 mg every 48 h, tadalafil 10 mg every 72 h, or vardenafil 2.5 mg every 72 h.Potent inducers of CYP3A4 (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin)
Saquinavir plasma concentrations may be reduced, decreasing the efficacy.Protease inhibitors (eg, atazanavir, indinavir, nelfinavir, ritonavir)
Saquinavir plasma concentrations may be increased; however, appropriate dose when coadministered with saquinavir and/or ritonavir has not been established. Nelfinavir plasma concentrations may be increased.Rifabutin
Saquinavir plasma levels may be reduced, while rifabutin levels may be elevated; however, appropriate dose adjustments have not been established.St. John's wort
Possible loss of virologic activity, including resistance to saquinavir or the class of protease inhibitors.Tipranavir/Ritonavir
Saquinavir plasma levels may be reduced; coadministration with saquinavir is not recommended.Warfarin
Warfarin plasma levels may be altered; INR monitoring is recommended.
None well documented.
The following adverse reactions were reported with saquinavir monotherapy or in combination with ritonavir.
Cyanosis, distended vein, heart murmur, heart rate disorder, heart valve disorder, hypertension, hypotension, peripheral vasoconstriction, syncope, thrombophlebitis.
Fatigue (6%); agitation, amnesia, anxiety, anxiety attack, appetite disturbance, asthenia, ataxia, confusion, convulsions, decreased appetite, depression, dizziness, excessive dreaming, dysarthria, dysesthesia, euphoria, extremity numbness, facial numbness, facial pain, hallucination, headache, hyperesthesia, hyperreflexia, hyporeflexia, insomnia, irritability, lethargy, libido disorder, light-headed feeling, myelopolyradiculoneuritis, overdose effect, paresis, paresthesia, peripheral neuropathy, poliomyelitis, prickly sensation, progressive multifocal leukoencephalopathy, psychic disorder, psychosis, reduced intellectual ability, seizures, somnolence, spasms, speech disorder, suicide attempt, tremor, unconsciousness, weakness.
Pruritus, rash (3%); dry lips/skin, eczema (2%); acne, alopecia, bullous skin eruption, chalazion, dermatitis, erythema, folliculitis, furunculosis, hair changes, hot flashes, increased sweating, maculopapular rash, nail disorder, night sweats, papillomatosis, photosensitivity, pigment changes, seborrheic dermatitis, severe cutaneous reaction associated with increased LFT, skin disorder, skin nodule, skin ulceration, Stevens-Johnson syndrome, urticaria, verruca, xeroderma.
Blepharitis, decreased hearing, dry eye syndrome, earache, ear pressure, epistaxis, eye irritation, laryngitis, otitis, pharyngitis, rhinitis, taste alteration, tinnitus, visual disturbance, xerophthalmia.
Nausea (11%); diarrhea (8%); vomiting (7%); abdominal pain (6%); constipation (2%); abdominal discomfort, anorexia, ascites, bloodstained feces, buccal mucosa ulceration, cheilitis, colic, discolored feces, dry mouth, dyspepsia, dysphagia, esophagitis, eructation, flatulence, frequent bowel movements, gastralgia, gastritis, GI inflammation, intestinal obstruction, gingivitis, glossitis, hemorrhoids, infectious diarrhea, melena, pelvic pain, painful defecation, pancreatitis, parotid disorder, rectal hemorrhage, right and left quadrant abdominal pain, salivary gland disorder, stomatitis, toothache, tooth disorder, upset stomach.
Enlarged prostate, impotence, micturition disorder, nephrolithiasis, renal calculus, urinary tract bleeding, UTI, vaginal discharge.
Acute myeloblastic leukemia, anemia, dermal bleeding, hemolytic anemia, leucopenia, lymphadenopathy, microhemorrhages, neutropenia, pancytopenia, splenomegaly, thrombocytopenia, thrombocytopenia leading to death.
Exacerbation of chronic liver disease with grade 4 LFT, hepatitis, hepatomegaly, hepatosplenomegaly, hyperbilirubinemia, jaundice, liver enzyme disorder, portal hypertension.
Increased alkaline phosphatase, ALT, amylase, AST, creatine phosphokinase, gamma-glutamyl transferase, LDH, and TSH.
Lipodystrophy (5%); diabetes mellitus/hyperglycemia (3%); decreased weight, dehydration, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hyperphosphatemia, hypertriglyceridemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia, increased weight, redistribution/accumulation of body fat.
Back pain (2%); arthralgia, arthritis, leg cramps, muscle cramps, musculoskeletal disorders, musculoskeletal pain, myalgia, polyarthritis, stiffness, tissue changes, trauma.
Pneumonia (5%); bronchitis, sinusitis (3%); cough, dyspnea, hemoptysis, pulmonary disease, respiratory disorder, upper respiratory tract infection.
Fever, influenza (3%); abscess, allergic reaction, angina tonsillaris, bacterial infection, candidiasis, cellulitis, chest pain, drug fever, edema, external parasites, herpes simplex, herpes zoster, intoxication, lymphadenopathy, moniliasis, mucosa damage, mycotic infection, retrosternal pain, shivering, staphylococcal infection, tumor, wasting syndrome.
Monitor WBC and differential. Note any significant changes. Monitor Hct and Hgb frequently (severe anemia may require blood transfusions). Perform clinical chemistry, viral load, and CD4 count prior to therapy and at appropriate intervals thereafter. Periodically monitor triglyceride levels during therapy.
Category B .
Undetermined. HIV-infected mothers should not breast-feed their infants.
Not recommended for children younger than 16 yr of age.
Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.
Because only 1% is excreted in the urine, the effect of renal function impairment is expected to be minimal.
Exercise caution when administering to patients with hepatic function impairment.
May occur; advise patients to take protective measures against exposure to UV light or sunlight until tolerance is determined.
New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and hyperglycemia have been reported.
Do not reduce dose; lower doses do not exhibit antiviral activity.
Accumulation or redistribution of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, has occurred in patients receiving antiretroviral therapy. A causal relationship has not been established.
Spontaneous bleeding has been reported in patients with hemophilia A and B; however, a causal relationship has not been established.
Worsening of liver disease has been reported in patients with chronic alcoholism, hepatitis B or C, and/or underlying liver abnormalities.
Elevated cholesterol and/or triglyceride levels have been reported. Markedly elevated triglyceride levels are risk factors for pancreatitis.
During initial phase of treatment, patients may develop an inflammatory response to indolent or residual opportunistic infections.
Saquinavir must be used in combination with nucleoside analog (eg, zalcitabine, zidovudine) therapy.
Varying degrees of cross-resistance have been observed among protease inhibitors. Continued administration following loss of viral suppression may increase the likelihood of cross-resistance to other protease inhibitors.
No acute toxicities or sequelae have been reported.
Copyright © 2009 Wolters Kluwer Health.