Names and pronunciation
(low-pin′ah-veer/ri-toe′na-veer) Kaletra
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Drug reference
(low-pin′ah-veer/ri-toe′na-veer) Kaletra
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Func. class.: Antiretroviral
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Chem. class.: Protease inhibitor
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Do not confuse: Kaletra/Keppra
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ACTION: Inhibits human immunode- ficiency virus (HIV-1) protease and pre- vents maturation of the infectious virus
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USES: HIV-1 in combination with or without other antiretrovirals
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CONTRAINDICATIONS: Hyper- sensitivity to this product or polyoxyethyl- ated castor oil (oral solution), CYP3A4 metabolized products Precautions: Pregnancy, breastfeed- ing, hepatic disease, pancreatitis, dia- betes, hemophilia, AV block, hypercho- lesterolemia, immune reconstitution syndrome, neonates, cardiomyopathy, congenital long-QT prolongation, hypokalemia, elderly patients, Graves’ disease, polymyositis, Guillain-Barré syndrome, children, HBV/HCV coinfection
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SIDE EFFECTS CNS: Paresthesia, headache, seizures, fever, dizziness, insomnia, asthenia, intracranial bleeding, encephalopathy CV: QT, PR interval prolongation, deep vein thrombosis EENT: Blurred vision, otitis media, tinnitus GI: Diarrhea, buccal mucosa ulceration, abdominal pain, nausea, taste perver- sion, dry mouth, vomiting, anorexia INTEG: Rash MISC: Asthenia, angioedema, anaphylaxis, Stevens-Johnson syndrome, increased lip- ids, lipodystrophy MS: Pain, rhabdomyolysis, myalgias
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INTERACTIONS Increase: toxicity—amiodarone, avanafil, azole antifungals, benzodiazepines, buPRO Pion, cloZAPine, desipramine, dihydroergot amine, encainide, ergotamine, flecainide, HMG-CoA reductase inhibitors, interleukins, meperidine, midazolam, pimozide, piroxi cam, propafenone, quiNIDine, ranolazine, rivaroxaban, saquinavir, triazolam, zolpidem Increase: QT prolongation—class IA/III antidysrhythmics, some phenothiazines, β-agonists, local anesthetics, tricyclics, haloperidol, chloroquine, droperidol, pent amidine, CYP3A4 inhibitors (amiodarone, clarithromycin, erythromycin, telithromy cin, troleandomycin), arsenic trioxide, levomethadyl, CYP3A4 substrates (metha done, pimozide, QUEtiapine, quiNIDine, risperiDONE, ziprasidone) Increase: ritonavir levels—fluconazole Increase: level of both products—cla rithromycin, ddI Increase: levels of bosentan Decrease: ritonavir levels—rifamycins, nevirapine, barbiturates, phenytoin, budesonide, predniSONE Decrease: levels of anticoagulants, atova- quone, divalproex, ethinyl estradiol, lamoTRIgine, phenytoin, sulfamethoxazole, theophylline, voriconazole, zidovudine Drug/Lab Test Increase: AST, ALT, CPK, cholesterol, GGT, triglycerides, uric acid, glucose Decrease: Hct, HB, RBC, neutrophils, WBC Drug/Herb Decrease: ritonavir levels—St. John’s wort; avoid concurrent use • Avoid use with red yeast rice, evening primrose oil
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DOSAGE AND ROUTES HIV-1 infection, treatment without efavirenz, nelfinavir, or nevirapine Adult: PO Twice-daily dosing: Therapy-naive or therapy-experi- enced: Lopinavir 400 mg/ritonavir 100 mg bid; once-daily dosing: Therapy-naive or experienced patients with <3 lopinavir resis- tance-associated substitutions: Lopinavir 800 mg/ritonavir 200 mg daily; once-daily dosing is not recom- mended in those receiving efavirenz, fosamprenavir, nevirapine, nelfinavir, carbamazepine, phenobarbital, or phenytoin. Pregnant women (with no lopinavir resistance–associated amino acid substitutions): PO Lopinavir 400 mg/ ritonavir 100 mg bid; once-daily dos- ing is not recommended. Tablets are recommended; avoid use of the oral solution Child >6 mo/adolescents: PO (solutions) 230 mg/57.5 mg per m2/dose bid HIV-1 infection with combination therapy with efavirenz, nelfinavir, or nevirapine. Adult: PO Twice-daily dosing: Therapy-naive and therapy- experienced patients: Solution: Lopi- navir 520 mg/ritonavir 130 mg (6.5 mL) bid; Tablet: Lopinavir 500 mg/ritonavir 125 mg bid; once-daily dosing: not recommended Children >6 mo/adolescents: PO (solution) 300 mg/75 mg per m2/dose bid HIV-1 infection not receiving concomi- tant efavirenz, nelfinavir, or nevirapine
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Available forms: Oral solution 400 mg lopinavir/100 mg ritonavir/5 mL; tablets 100 mg lopinavir/25 mg ritonavir, 200 mg lopinavir/50 mg ritonavir
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Administer: PO route • TAB: take without regard to food; swallow whole; do not crush, break, chew • ORAL SOL: shake well, use calibrated measuring device • Drug resistance testing should be done before beginning therapy in antiretrovi- ral-naive patients and before changing therapy for treatment failure
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Assess: • HIV: viral load, CD4 at baseline, throughout therapy; blood glucose, plasma HIV RNA, serum cholesterol/lipid profile; resistance testing before starting therapy and after treatment failure • Signs of infection, anemia • Hepatic studies: ALT, AST baseline and periodically • Bowel pattern before, during treat- ment; if severe abdominal pain with bleeding occurs, discontinue product; monitor hydration • Skin eruptions; rash L • Rhabdomyolysis: muscle pain, in creased CPK, weakness, swelling of af fected muscles, tea-colored dark urine; if these occur and if confirmed by CPK, product should be discontinued • QT prolongation: ECG for QT prolonga tion, ejection fraction; assess for chest pain, palpitations, dyspnea • Serious skin disorders: Stevens-John son syndrome, angioedema, anaphylaxis • Pregnancy/breastfeeding: all preg- nant women who experience adverse re- actions should have provider report the reactions to Antiretroviral Pregnancy Registry, 800-258-4263; avoid breast- feeding
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Evaluate: • Therapeutic response: improvement in HIV symptoms; improving viral load, CD4+ T cells
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To take as prescribed; if dose is missed, to take as soon as remembered up to 1 hr before next dose; not to double dose • That product is not a cure for HIV; that opportunistic infections can continue to be acquired • That redistribution of body fat or ac- cumulation of body fat may occur • That others can continue to contract HIV from patient • To avoid OTC, prescription medica- tions, herbs, supplements unless ap- proved by prescriber; not to use St. John’s wort because it decreases prod- uct’s effect; that taking this product with ED drugs may increase adverse reactions • That regular follow-up exams and blood work will be required • To report a change in heart rhythm or abnormal heartbeats • Pregnancy/breastfeeding: to use a nonhormonal contraceptive, to notify provider if pregnancy is planned or sus- pected, avoid breastfeeding
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PHARMACOKINETICS Well absorbed, 98% protein binding, hepatic metabolism, peak 4 hr, terminal half-life 6 hr
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