Saquinavir

INVIRASE

What it isThe first HIV protease inhibitor; HIV.

Why this oneIt proved that protease inhibition worked, which made combination antiretroviral therapy possible.

What limits itPoor bioavailability required boosting, and QT and PR prolongation limit it. Effectively obsolete.

FDA-approved for

FDA dosing	Population	Start	Target	Max
HIV-1 infection (with ritonavir + other antiretrovirals)	Adult >16y	1000 mg BID	1000 mg BID	1000 mg BID

Renal Undefined

Hepatic Contraindicated (with ritonavir) in severe hepatic impairment

Doses <1000 mg with ritonavir not recommended (no antiviral activity)

Severe hepatic impairment (when given with ritonavir)
Concurrent rifampin (risk of severe hepatocellular toxicity)
Concurrent CYP3A4-dependent drugs causing serious/life-threatening reactions (ergot derivatives, midazolam, triazolam, pimozide, cisapride, astemizole, terfenadine)

Must be used in combination with ritonavir
Interrupt for serious/severe toxicity until etiology identified or toxicity resolves
Do not use with lovastatin/simvastatin; caution with other CYP3A4-metabolized statins (myopathy incl. rhabdomyolysis)
St. John's wort not recommended (loss of virologic response, resistance)
Fluticasone with INVIRASE/ritonavir not recommended (Cushing's syndrome, adrenal suppression)
Monitor digoxin levels; digoxin dose reduction may be needed
New-onset/exacerbated diabetes mellitus and hyperglycemia (protease-inhibitor class)
Worsening liver disease reported in hepatitis B/C, cirrhosis, chronic alcoholism; caution in hepatic impairment
Hyperlipidemia — monitor cholesterol/triglycerides before and during therapy (marked triglycerides risk pancreatitis)
Spontaneous bleeding in hemophilia A/B (protease-inhibitor class)
Fat redistribution/accumulation; immune reconstitution syndrome
Caution in severe renal impairment (not studied)

Pregnancy Undefined

Lactation Undefined

NO BOXED WARNINGS

Principal riskPoor bioavailability required boosting, and QT and PR prolongation limit it

Direct muscarinic antagonism0 / 4