MARAVIROC

MARAVIROC (mar-a-vir'ok) Selzentry Classifications: antiviral; antiretroviral; cellular chemokine co-receptor-5 (ccr-5) antagonist; Therapeutic: antiviral; antiretroviral Pregnancy Category: B

Availability

150 mg and 300 mg tablets

Action

Selectively binds to human chemokine coreceptor-5 (CCR-5) on cell membranes of helper T cell lymphocytes preventing interaction with the HIV-1 gp120 envelope protein necessary for the HIV virus to enter helper T cells.

Therapeutic Effect

Prevents infection of helper T cells by HIV-1 viruses with CCR-5 tropism.

Uses

Treatment of human immunodeficiency virus (HIV-1) infection in combination with other antiretroviral agents in treatment-experienced patients who express CCR-5 and who have evidence of HIV-1 replication and HIV-1 strains resistant to multiple antiretroviral agents.

Contraindications

Patients with dual/mixed, or chemokine-related receptor (CCR-4)-tropic HIV-1 virus; treatment na?ve adults or children with HIV-1; lactation; children <16 y.

Cautious Use

Hepatic impairment, hepatitis B or C; renal impairment, especially with co-administration of CYP3A inhibitors; Cl_cr <50 mL/min; co-administration of antihypertensive agents; patients with cardiac disease or increased risk for cardiovascular events; older adults; pregnancy (category B).

Route & Dosage

Regimen without CYP3A Inducers or Inhibitors Adult: PO 300 mg b.i.d. Regimen with CYP3A Inhibitor with/without CYP3A Inducer Adult: PO 150 mg b.i.d. Regimen with CYP3A Inducers without a Strong CYP3A Inhibitor Adult: PO 600 mg b.i.d.

Administration

• Must be given in combination with other antiretroviral drugs.
• Store at 15°–30 °C (59°–86°F).

Adverse Effects (≥1%)

Body as a Whole: Appetite disorders, herpes infection, pain and discomfort, pyrexia. CNS: Depression, disturbances in consciousness, sleep disorders, dizziness, paresthesias and dysesthesias, peripheral neuropathies, sensory abnormalities. CV: Vascular hypertension disorders. GI: Abdominal pain, constipation, dyspepsia, stomatitis, ulceration. Hematologic: Neutropenia. Metabolic: Elevated AST levels. Musculoskeletal: Joint-related signs and symptoms, muscle pains, musculoskeletal symptoms. Respiratory: Breathing abnormalities, bronchitis, bronchospasm, cough, influenza, paranasal sinus disorder, pneumonia, respiratory tract disorders, sinusitis, upper respiratory tract infection. Skin: Apocrine and eccrine gland disorders, benign neoplasms, dermatitis, eczema, folliculitis, lipodystrophies, pruritis, rash. Urogenital: Bladder and urethral symptoms, condyloma acuminatum, urinary tract signs and symptoms.

Interactions

Drug: strong cyp3a4 inhibitors (hiv protease inhibitors with the exception of tipranavir/ritonavir, delavirdine, ketoconazole, itrazonazole, clarithromycin) increase maraviroc plasma level. cyp3a4 inducers (efavirenz, rifampin, carbamazepine, phenobarbital, phenytoin) decrease maraviroc plasma level. Food: Coadministration with a high-fat meal decreases the plasma levels of maraviroc. Herbal: St. John's wort may decrease the plasma levels of maraviroc.

Pharmacokinetics

Absorption: Bioavailability is 23–33%. Peak: 0.5–4 h (dose-dependent). Distribution: 75% protein bound. Metabolism: In liver via CYP3A4. Elimination: Primarily in stool. Half-Life: 14–18 h.

Nursing Implications

Assessment & Drug Effects

• Monitor for and report promptly S&S of hepatotoxicity, hepatitis or infection.
• Monitor for and report S&S of immune reconstitution syndrome (inflammatory response to residual opportunistic infections such as MAC, CMV, PCP, or reactivation of varicella zoster).
• Monitor BP especially in those on antihypertensive drugs and with a history of postural hypotension.
• Monitor CV status especially in those with preexisting conditions that cause myocardial ischemia.
• Lab tests: Baseline and periodic CD4+ cell count and HIV RNA viral load; periodic LFTs, WBC with differential.

Patient & Family Education

• Exercise caution when arising from a lying or sitting positing. Dizziness is a common adverse effect.
• Do not engage in dangerous activities until response to drug is known.
• Report promptly any of the following: itchy rash, yellow skin or eyes, nausea or vomiting, upper abdominal pain, flu-like symptoms, unexplained fatigue.

---

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