Saquinavir

Oral
HIV infection

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

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.

Patient w/ haemophilia A and B, pre-existing conduction system abnormalities. Mild to moderate hepatic or severe renal impairment. Pregnancy.

GI disorders (e.g. abdominal pain, nausea, vomiting, flatulence, diarrhoea), fatigue, anaemia, alopecia, anorexia, increased appetite, asthenia, constipation, dizziness; dry lips, mouth and skin; dyspnoea, dyspepsia, eczema, headache, decreased libido, muscle spasm, malaise, peripheral neuropathy, paraesthesia, rash, pruritus, sleep disturbances, taste disorders; increased liver enzyme, blood amylase, bilirubin and creatinine levels; reduced Hb, platelet, lymphocyte and WBC counts; immune reconstitution syndrome, accumulation or redistribution of body fat, metabolic abnormalities (e.g. hypertriglyceridaemia), osteonecrosis. Abscess, angina tonsillaris, candidiasis, cellulitis, herpes simplex, herpes zoster, bacterial or mycotic infections, influenza, moniliasis. Rarely, acute myeloid leukaemia, allergic reactions, ascites, bullous skin eruptions, intestinal obstruction, jaundice, portal HTN, seizures, polyarthritis, attempted suicide.
Potentially Fatal: Hypersensitivity (e.g. anaphylactic reaction, Stevens-Johnson syndrome), thrombocytopenia, haemolytic anaemia, pancreatitis, nephrolithiasis.

PO: B

Monitor ECG, serum K and Mg levels, triglycerides, cholesterol, viral load, CD4 count and glucose.

Symptoms: Fatigue, general weakness, diarrhoea, nausea, vomiting, hair loss, dry mouth, wt loss, hyponatraemia, orthostatic hypotension. Management: Supportive treatment.

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).

Increased absorption w/ high-fat meal. Reduced concentration w/ St John’s wort and garlic. Increased serum levels w/ grapefruit juice.

Description: 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.
Pharmacokinetics:
Absorption: Incompletely absorbed from the GI tract. Increased absorption w/ high-fat meal. Bioavailability: 4%.
Distribution: Extensively distributed into tissues. Volume of distribution: 700 L. Plasma protein binding: Approx 98%.
Metabolism: Rapidly metabolised to several inactive monohydroxylated and dihydroxylated compounds by CYP3A4 isoenzyme. Undergoes extensive first-pass hepatic metabolism.
Excretion: Mainly via faeces. Terminal elimination half-life: 13.2 hr.

Source: National Center for Biotechnology Information. PubChem Database. Saquinavir, CID=441243, https://pubchem.ncbi.nlm.nih.gov/compound/Saquinavir (accessed on Jan. 23, 2020)

Store at 25°C.

Antivirals

J05AE01 - saquinavir ; Belongs to the class of protease inhibitors. Used in the systemic treatment of viral infections.

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