Home Drug Guide Cobicistat; Darunavir Ethanolate

Drug Guide

Generic Name

Cobicistat; Darunavir Ethanolate

Brand Names Prezcobix

Classification

Therapeutic: Antiretroviral for HIV infection

Pharmacological: Protease inhibitor (Darunavir) and Pharmacokinetic enhancer (Cobicistat)

FDA Approved Indications

Treatment of human immunodeficiency virus (HIV) type 1 infection in combination with other antiretroviral agents

Mechanism of Action

Darunavir inhibits the HIV-1 protease enzyme, preventing viral maturation. Cobicistat inhibits CYP3A enzymes, boosting the plasma concentration of Darunavir by decreasing its metabolism.

Dosage and Administration

Adult: 600 mg Darunavir with 150 mg Cobicistat once daily, taken with food.

Pediatric: Safety and efficacy not established for pediatric patients.

Geriatric: No specific dosage adjustment necessary, but caution advised due to age-related hepatic, renal, or cardiac impairment.

Renal Impairment: Use with caution; adjustment may be necessary based on renal function.

Hepatic Impairment: Contraindicated in patients with moderate to severe hepatic impairment.

Pharmacokinetics

Absorption: Rapidly absorbed, with peak plasma concentrations reached in about 2 hours.

Distribution: Widely distributed in tissues, plasma protein binding approximately 99%.

Metabolism: Darunavir is primarily metabolized by CYP3A; Cobicistat is metabolized by CYP3A and inhibits CYP3A.

Excretion: Primarily fecal; minimal renal excretion.

Half Life: Approximately 15 hours for Darunavir when boosted with Cobicistat.

Contraindications

Hypersensitivity to any component.
Concurrent use with certain drugs metabolized by CYP3A that can cause serious interactions.

Precautions

Monitor for hepatic toxicity, especially in patients with pre-existing liver disease.
Caution in patients with cardiac arrhythmias, as drugs may prolong QT interval.

Adverse Reactions - Common

Nausea (77%)
Headache (31%)
Fatigue (28%)
Diarrhea (25%)

Adverse Reactions - Serious

Hepatotoxicity (including potentially fatal hepatic failure) (Rare)
Allergic reactions including rash, Stevens-Johnson syndrome (Rare)
QT prolongation and PR interval prolongation (Rare)

Drug-Drug Interactions

Caused by CYP3A inducers/inhibitors; e.g., rifampin, carbamazepine, certain statins.

Drug-Food Interactions

N/A

Drug-Herb Interactions

St. John's Wort, which induces CYP3A and reduces effectiveness.

Nursing Implications

Assessment: Monitor hepatic function, lipid profile, and cardiac status.

Diagnoses:

Risk for hepatotoxicity
Risk for altered pharmacokinetics due to drug interactions.

Implementation: Administer with food, monitor labs, and observe for adverse reactions.

Evaluation: Assess viral load, liver function tests, and for any signs of adverse reactions.

Patient/Family Teaching

Take medication with food to improve absorption.
Do not alter dose or stop without consulting healthcare provider.
Report any signs of allergic reactions, jaundice, or irregular heartbeat.

Special Considerations

Black Box Warnings:

Potential for serious hepatotoxicity, including fatal cases.
Risk of lactic acidosis and severe hepatomegaly with steatosis.

Genetic Factors: Limited data, but consider pharmacogenomics in future research.

Lab Test Interference: May cause increases in serum bilirubin and transaminases.

Overdose Management

Signs/Symptoms: GI symptoms, hypersensitivity reactions, QT prolongation.

Treatment: Supportive care, activated charcoal if early, and symptomatic treatment. No specific antidote.

Storage and Handling

Storage: Store at room temperature, 20°C to 25°C (68°F to 77°F).

Stability: Stable under recommended storage conditions.