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cabotegravir–rilpivirine 207

injection-site reaction. Other: hypersensi tivity reaction. INTERACTIONS Drug-drug. Anticonvulsants (carba mazepine, oxcarbazepine, phenobarbital, phenytoin): May decrease cabotegravir and rilpivirine levels and decrease antiviral effect. Use together is contraindicated. Antimycobacterials (rifabutin, rifampin, ri fapentine): May decrease cabotegravir and rilpivirine levels and decrease antiviral effect. Use together is contraindicated. Drugs that prolong the QT interval and in crease risk of torsades de pointes (amio darone, ciprofloxacin, haloperidol, SSRIs): May increase risk of prolonged QTc interval. Use together cautiously. Macrolide or ketolide antibiotics (azithromycin, clarithromycin, erythromycin): May increase rilpivirine level and risk of tor sades de pointes. Consider alternatives or use other macrolides with less effect on rilpivirine level (azithromycin). Methadone: May decrease methadone level. Monitor patient closely and adjust methadone maintenance dosage as needed. Other antiretrovirals: May increase risk of adverse effects. Avoid use together. Systemic glucocorticoids (dexamethasone): May decrease rilpivirine level and decrease antiviral effect if more than one dose is given. Use together is contraindicated. Drug-herb. St. John’s wort: May decrease rilpivirine level and decrease antiviral effect. Use together is contraindicated. EFFECTS ON LAB TEST RESULTS • May increase ALT, AST, CK, and lipase levels. CONTRAINDICATIONS & CAUTIONS • Contraindicated in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine. • Hypersensitivity reactions to rilpivirine, including DRESS syndrome, have been re ported. Skin reactions may be accompanied by constitutional symptoms (fever, organ dys function). • Drug may increase risk of liver toxicity in patients with preexisting liver disease or iden tifiable risk factors. • Use in patients with CrCl of less than 30 mL/minute or Child-Pugh class C liver

• Give as soon as possible; suspension may remain in syringe for up to 2 hours. After 2 hours, discard drug and syringe. • Give each injection at separate gluteal sites on opposite sides or at least 2 cm apart us ing the Z-track technique. Ventrogluteal site is preferred. Don’t give by other routes or in other anatomic sites. May need longer needle lengths to reach the gluteus muscle in patients with high BMI. • May give dose up to 7 days before or after the date patient is scheduled to receive main tenance injections. • If patient plans to miss a scheduled injec tion by more than 7 days, give oral therapy to replace up to two consecutive months of injections. Recommended dose is cabote gravir 30 mg PO daily and rilpivirine 25 mg PO daily, with the first dose starting when the next injection is due and continued until the day injection dosing is restarted. If oral ther apy lasts for more than 2 months, an alterna tive regimen is recommended. • Refer to manufacturer’s instructions for un planned missed injections. • Store vials at 36 ◦ to46 ◦ F(2 ◦ to8 ◦ C) in original carton. Don’t freeze. Vials may remain in original carton at room temper ature for up to 6 hours; discard vials after 6hours. ACTION Cabotegravir inhibits the integrase strand transfer step of retroviral DNA integration essential for HIV-1 replication. Rilpivirine in hibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase. Route Onset Peak Duration IM (caboteg ravir) Unknown 7 days Unknown IM (rilpivirine) Unknown 3–4 days Unknown Half-life: Cabotegravir, 5.6 to 11.5 weeks; rilpivirine, 13 to 28 weeks. ADVERSE REACTIONS CNS: abnormal dreams, anxiety, depressive disorders, dizziness, fatigue, fever, headache, sleep disorder. GI: abdominal pain, diarrhea, dyspepsia, flatulence, gastritis, nausea, vom iting. Hepatic: increased transaminases, hepatotoxicity. Metabolic: weight gain, in creased CK and lipase levels. Musculoskele tal: bone and muscle pain. Skin: rash,

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