Drug reference

Ritonavir

Antiretroviral · Antiviral

AntiretroviralAntiviral

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

—

not curated

Top interactionssee all 12 →

CilostazoleContraindicatedTextbookKDT 7e · p555
Ergot DerivativesContraindicatedTextbookG&G 14e · p1245-1266
AlprazolamContraindicatedDatabaseDDInter
ColchicineContraindicatedDatabaseDDInter

Mechanism

Ritonavir is an HIV-1 and HIV-2 protease inhibitor that binds to and inhibits the viral aspartyl protease, preventing cleavage of Gag-Pol polyprotein precursors into functional structural proteins and enzymes needed for mature virion assembly. Its most important clinical role is as a pharmacokinetic booster: ritonavir is the most potent CYP3A4 inhibitor among available drugs, and low-dose ritonavir (100-200 mg) dramatically increases plasma levels and extends half-lives of co-administered protease inhibitors (lopinavir, atazanavir, darunavir) without contributing significant antiviral activity itself.

Indications

Chronic hepatitis C infection of genotype 1 (in combination with dasabuvir, with or without ribavirin, with or without compensated cirrhosis)Chronic hepatitis C infection of genotype 4 (in combination with ribavirin, with or without compensated cirrhosis)used mainly as a pharmacokinetic enhancer (CYP3A4 inhibitor) in combination with other PIsHIV (as an antiretroviral drug or more commonly in low dose as a booster for other PIs like lopinavir, atazanavir, saquinavir, indinavir)

Dosing

Adult: ▶ BY MOUTH ▶ Adult: 40 mg daily, dose to be taken at night ▶ BY MOUTH Adult: Initially 20 mg daily, then increased if necessary up to 40 mg daily, dose to be taken at night, close medical supervision is required if dose is increased to maximum dose DOSE ADJUSTMENTS DUE TO INTERACTIONS ▶ Manufacturer advises reduce dose by half with concurrent use of ombitasvir with paritaprevir and ritonavir.…

Pharmacokinetics

Half-life

3–5

Bioavailability

>60%

Protein binding

98–99%

Metabolism

CYP3A4 > 2D6

Excretion

3.5% (renal, unchanged)

Side effects

Common

nauseavomitingdiarrheaanorexiaabdominal paintaste perversionperipheral paresthesiasperioral paresthesiaselevated serum total cholesterolelevated triglycerideslipodystrophydrug interactionsdiarrhoeaparesthesiasfatiguelipid abnormalities (raised triglycerides and cholesterol)gastrointestinal intoleranceastheniaheadachedizzinesslimb and facial tinglingnumbnessrashes

Serious

Hepatotoxicity
lipodystrophy (abdominal obesity, buffalo hump with wasting of limbs and face)
dyslipidaemia (requiring hypolipidaemic drugs)
insulin resistance
diabetes (may be exacerbated)

Drug interactions

Cilostazole

Contraindicated

Textbook

Increased plasma levels and toxicity of cilostazole.

Should not be administered along with inhibitors of CYP3A4.

Source: KDT 7e · p555

Ergot Derivatives

Contraindicated

Textbook

Increased ergot derivative concentrations, leading to ergotism.

Should not be combined.

Source: G&G 14e · p1245-1266

Alprazolam

Contraindicated

Database

Profoundly increased alprazolam plasma concentrations, leading to severe and prolonged sedation, respiratory depression, and psychomotor impairment.

Concomitant use is contraindicated due to the risk of severe and potentially life-threatening adverse effects. Use an alternative benzodiazepine not metabolized by CYP3A4 or an alternative antiretroviral.

Source: DDInter

Colchicine

Contraindicated

Database

Life-threatening toxicities of colchicine.

The drug is contraindicated in patients with hepatic or renal impairment requiring concomitant therapy with CYP3A4 inhibitors.

Source: DDInter

Domperidone

Contraindicated

Database

Significantly increased domperidone plasma levels, leading to increased risk of QT prolongation and Torsades de Pointes (TdP)

Concomitant use is contraindicated. Avoid co-administration.

Dronedarone

Contraindicated

Database

Markedly increase dronedarone blood levels.

Contraindicated.

Source: DDInter

Ergotamine

Contraindicated

Database

Ergotism: severe peripheral vasospasm, gangrene

Never combine. Use alternative migraine therapy.

Source: DDInter

Methylergometrine

Contraindicated

Database

Ergotism: vasospasm, gangrene

Absolute contraindication in HIV patients on PIs.

Source: DDInter

Silodosin

Contraindicated

Database

Significantly increased plasma concentrations of silodosin, leading to an increased risk of orthostatic hypotension and other dose-dependent adverse effects.

Concomitant use is contraindicated. An alternative alpha-blocker or antiretroviral should be considered.

Source: DDInter

Atorvastatin

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Carbamazepine

Severe

Textbook-cited

Carbamazepine toxicity (diplopia, ataxia, drowsiness).