Saquinavir

Indications

Saquinavir is used for: HIV infection

Adult Dose

Oral HIV infection Adult: In combination w/ other antiretrovirals: 1,000 mg bid w/ ritonavir 100 mg bid. Treatment-naive patients: 500 mg bid (w/ ritonavir 100 mg bid) for the 1st 7 days of treatment then increase to 1,000 mg bid.

Child Dose

HIV Infection Indicated in combination with ritonavir and other antiretrovirals (ARTs) for treatment of HIV-1 infection <16 years: Safety and efficacy not established >16 years: 1000 mg (plus ritonavir 100 mg) PO q12hr For patients already taking ritonavir 100 mg BID as part of their ART regimen, no additional ritonavir is needed

Renal Dose

Administration

Should be taken with food. Take w/ meals or up to 2 hr after meals

Contra Indications

Hypersensitivity. Congenital or documented acquired QT prolongation, complete AV block (including patients at high risk) w/o implanted pacemakers, electrolyte disturbance (particularly uncorrected hypokalaemia), clinically relevant bradycardia or heart failure w/ reduced left-ventricular ejection fraction, history of symptomatic arrhythmia. Severe hepatic impairment. Lactation. Concomitant admin w/ drugs that prolong QT or PR interval, sedative/hypnotics (triazolam, oral midazolam), HMG-CoA reductase inhibitors (simvastatin, lovastatin), ergot alkaloids, rifampicin, quetiapine, alfuzosin.

Precautions

Patient w/ haemophilia A and B, pre-existing conduction system abnormalities. Mild to moderate hepatic or severe renal impairment. Pregnancy. Monitoring Parameters Monitor ECG, serum K and Mg levels, triglycerides, cholesterol, viral load, CD4 count and glucose.

Pregnancy-Lactation

Pregnancy Prospective pregnancy data from the APR are not sufficient to adequately assess a drug-associated risk of birth defects or fetal outcomes; limited number of reports on use of drug during pregnancy has been submitted to the APR and number of exposures to drug is insufficient to make a risk assessment compared to a reference population Animal data In animal reproduction studies with saquinavir, no evidence of adverse developmental effects were observed at highest achievable plasma exposures (AUC) in both rats and rabbits, resulting in exposures approximately 25% of those obtained in humans at recommended human dose (RHD) combined with drug; therapy should be administered during pregnancy only if potential benefit justifies potential risk to fetus Lactation The Centers for Disease Control and Prevention recommends that HIV-infected mothers in US not breastfeed their infants to avoid risking postnatal transmission of HIV-1 There are no data available regarding presence of drug in human milk, effects on breastfed infant, or on milk production Because of potential for HIV-1 transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants) and adverse reactions in breastfed infants similar to those seen in adults, instruct mothers not to breastfeed if receiving therapy

Interactions

May increase plasma concentration of fusidic acid. Increased risk of bleeding w/ anticoagulants (e.g. rivaroxaban). May alter plasma concentrations of warfarin. Potentially Fatal: Potentially prolonged or increased sedation and resp depression w/ sedative/hypnotics (oral midazolam, triazolam). Increased risk of myopathy including rhabdomyolysis w/ HMG-CoA reductase inhibitors (simvastatin, lovastatin). Increased potential for acute ergot toxicity w/ ergot alkaloids (e.g. ergotamine, dihydroergotamine, ergonovine, methylergonovine). Increased risk of severe hepatotoxicity w/ rifampicin. Risk of coma w/ quetiapine. Risk of hypotension w/ alfuzosin. Additive effect on QT or PR interval prolongation w/ antiarrhythmics (amiodarone, bepridil, dofetilide, flecainide, systemic lidocaine, propafenone, quinidine) neuroleptics (e.g. pimozide, clozapine, haloperidol), sildenafil (if used for pulmonary arterial HTN), antidepressant (trazodone), some anti-infectives (clarithromycin, erythromycin, halofantrine, pentamidine), some antihistamines (terfenadine, astemizole).

Adverse Effects

Side effects of Saquinavir : 1-10% Rash Hyperglycemia Diarrhea Abdominal discomfort Nausea Abdominal pain Buccal mucosa ulceration Paresthesia Weakness Increased CPK <1% Headache Confusion Seizures Ataxia Pain Stevens-Johnson syndrome Hypoglycemia Hyper- & hypokalemia Low serum amylase AML Hemolytic anemia Thrombocytopenia Jaundice Ascites

Mechanism of Action

Saquinavir is a selective, competitive, reversible HIV protease inhibitor that interferes w/ the formation of essential proteins and enzymes. It blocks virus maturation and causes non-functional, immature and non-infectious virions formation.