ATAZANAVIR

ATAZANAVIR (a-ta-zan'a-vir) Reyataz Classifications: antiviral agent; antiretroviral agent; protease inhibitor; Therapeutic: antiretroviral; protease inhibitor Prototype: Saquinavir Pregnancy Category: B

Availability

100 mg, 150 mg, 200 mg capsules

Action

Atazanavir is an HIV-1 protease inhibitor that selectively inhibits the replication of HIV. Protease plays a major role in the virus-specific processing of gene products used in the replication enzymes of HIV-1 infected cells. Thus, protease is necessary for the production of mature viruses. Atazanavir reduces the viral load and increases CD4+ cell count.

Therapeutic Effect

Protease inhibition renders the virus noninfectious. Because HIV protease inhibitors inhibit the HIV replication cycle midway in the process, they are active in acutely and chronically infected cells.

Uses

Treatment of HIV infection in combination with other antiretroviral agents.

Contraindications

Hypersensitivity to atazanavir; severe hepatic insufficiency; lactation; infants <3 mo old; lactation; lactase deficiency.

Cautious Use

Moderate hepatic impairment, hepatitis B or C; pregnancy (category B); infants >3 mo old, children; elderly, females, diabetes mellitus, diabetic ketoacidosis; hemophilia, hepatic disease; hepatitis; jaundice, hypercholesterolemia, hypertriglyceridemia; lactic acidosis, obesity.

Route & Dosage

HIV Infection (treatment-na?ve) Adult: PO 400 mg once/d with a light meal HIV Infection (treatment-experienced) Adult: PO 300 mg once/d plus 100 mg ritonavir with food Hepatic Impairment Reduce dose to 300 mg once/d in moderate hepatic insufficiency; not recommended for use in severe hepatic insufficiency.

Administration

Oral

• Give with a light meal, not on an empty stomach.
• When coadministered with efavirenz, give atazanavir 300 mg and ritonavir 100 mg with efavirenz 600 mg (all as a single daily dose with food). Atazanavir without ritonavir should not be coadministered with efavirenz.
• When coadministered with didanosine buffered formulations, give atazanavir (with food) 2 h before or 1 h after didanosine.
• Give 2 h before/1 h after antacids or buffered drugs.
• Store at 15°–30° C (59°–86° F).

Adverse Effects (≥1%)

Body as a Whole: Peripheral neuropathy, fever, pain, fatigue, allergic reaction, angioedema, asthenia, burning sensation, chest pain, edema, facial atrophy, generalized edema, heat sensitivity, infection, malaise, pallor, peripheral edema, photosensitivity, substernal chest pain, sweating. CNS: Headache, depression, insomnia, dizziness, abnormal dream, abnormal gait, agitation, amnesia, anxiety, confusion, convulsion, decreased libido, emotional lability, hallucination, hostility, hyperkinesia, hypesthesia, increased reflexes, nervousness, psychosis, sleep disorder, somnolence, suicide attempt, twitch. CV: Cardiac arrest, heart block (PR prolongation), hypertension, myocarditis, palpitation, syncope, vasodilatation. GI: Hyperbilirubinemia, jaundice, nausea, vomiting, diarrhea, abdominal pain, anorexia, aphthous stomatitis, colitis, constipation, dental pain, dyspepsia, enlarged abdomen, esophageal ulcer, esophagitis, flatulence, gastritis, gastroenteritis, gastrointestinal disorder, hepatitis, hepatomegaly, hepatosplenomegaly, increased appetite, liver damage, liver fatty deposit, mouth ulcer, pancreatitis, peptic ulcer. Endocrine: Decreased male fertility. Hematologic: Ecchymosis, purpura. Metabolic: Lipodystrophy syndrome, hypercholesterolemia, hypertriglyceridemia. Musculoskeletal: Myalgia, arthralgia. Respiratory: Cough, dyspnea, hiccup. Skin: Rash, alopecia, cellulitis, dermatophytosis, dry skin, eczema, nail disorder, pruritus, seborrhea, urticaria, vesiculobullous rash. Special Senses: Otitis, taste perversion, tinnitus. Urogenital: Abnormal urine, amenorrhea, crystalluria, gynecomastia, hematuria, impotence, kidney calculus, kidney failure, kidney pain, menstrual disorder, oliguria, pelvic pain, polyuria, proteinuria, urinary frequency, urinary tract infection.

Interactions

Drug: May increase levels and toxicity of cyclosporine, systemic lidocaine, sirolimus, tacrolimus; increase risk of myopathy and rhabdomyolysis with atorvastatin, lovastatin, simvastatin; may increase risk of heart block with diltiazem; antacids, h₂-receptor antagonists, proton pump inhibitors may decrease absorption of atazanavir; ritonavir may increase atazanavir levels; may increase toxicity of irinotecan; increased risk of prolonged sedations with benzodiazepines; indinavir may increase risk of hyperbilirubinemia; didanosine, efavirenz, rifampin may decrease atazanavir levels; ergotamine, ergonovine dihydroergotamine, bepridil, pimozide may cause serious adverse reactions; may increase risk of hypotension, visual changes, and priapism with sildenafil, tadalafil, vardenafil. Herbal: St. John's wort may decrease atazanavir levels.

Pharmacokinetics

Absorption: 68% into systemic circulation; taking with food enhances bioavailability. Peak: 2–2.5 h. Metabolism: In liver by CYP3A4. Elimination: 70% in feces, 13% in urine. Half-Life: 7 h.

Nursing Implications

Assessment & Drug Effects

• Monitor CV status and ECG closely, especially with concurrent treatment with other drugs known to prolong the PR interval.
• Lab tests: Baseline and periodic LFTs; total bilirubin if jaundiced; periodic PT/INR with concurrent warfarin therapy; monitor blood glucose closely, especially if diabetic.

Patient & Family Education

• Do not alter the dose or discontinue therapy without consulting physician.
• Inform physician of all prescription, nonprescription, or herbal meds being used.
• Report promptly any of the following: dizziness or lightheadedness; muscle pain (especially with concurrent statin therapy); severe nausea, vomiting (especially if red or "coffee-ground" in appearance), stomach pain, black tarry stools; yellowing of skin or whites of eyes; skin rash or itchy skin; sore throat, fever, or other S&S of infection; unexplained tiredness or weakness.
• If taking both sildenafil and atazanavir, promptly report any of the following sildenafil-associated adverse effects: hypotension, visual changes, or prolonged penile erection.

---

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug