Lopinavir/Ritonavir

A to Z Drug Facts

 Action Inhibits HIV protease, the enzyme required to form functional proteins in HIV-infected patients. Ritonavir inhibits the cytochrome P450 (CYP) 3A-mediated metabolism of lopinavir, increasing lopinavir plasma concentrations.

 Indications Treatment of HIV infections in combination with other antiviral agents.

 Contraindications Concurrent administration with drugs that are highly dependent on CYP3A or CYP2D6 for clearance and for which elevated plasma levels are associated with serious or life-threatening reactions.

 Route/Dosage

ADULTS: PO 400/100 mg of lopinavir/ritonavir bid. When combined with efavirenz or nevirapine, a dose of 533/133 mg of lopinavir/ritonavir bid should be considered. CHILDREN (6 MO to 12 YR) Dose based on lopinavir component of combination.

Without efavirenz or nevirapine

7 to < 15 KG CHILD: PO 12 mg/kg bid. 15 to 40 KG CHILD: PO 10 mg/kg bid. > 40 kg CHILD: PO Adult dose.

With efavirenz or nevirapine

7 to < 15 KG CHILD: PO 13 mg/kg bid. 15 to 50 KG CHILD: PO 11 mg/kg bid. > 50 KG CHILD: PO Adult dose.

 Interactions

Anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), corticosteroids (eg, dexamethasone), efavirenz, rifampin, St. John's wort, nevirapine: Effects of lopinavir/ritonavir may be decreased. Antiarrhythmic agents (eg, amiodarone, bepridil, flecainide, lidocaine [systemic], propafenone, quinidine), ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), midazolam, pimozide, triazolam: Contraindicated because of potentially serious or life-threatening reactions. Clarithromycin, dihydropyridine calcium channel blockers (eg, felodipine, nifedipine, nicardipine), HMG-CoA reductase inhibitors (eg, atorvastatin, cerivastatin, lovastatin, simvastatin), immunosuppressants (eg, cyclosporine, sirolimus, tacrolimus, rapamycin), itraconazole, ketoconazole, rifabutin, sildenafil: Lopinavir/ritonavir may increase the effects of these agents. Atovaquone, methadone, oral contraceptives (eg, ethinyl estradiol): Lopinavir/ritonavir may decrease the efficacy of these agents. Disulfiram, metronidazole: Disulfiram-like reaction may occur due to alcohol present in lopinavir/ritonavir oral solution.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Deep vein thrombosis; hypertension; palpitation; thrombophlebitis; vasculitis. CNS: Headache; insomnia; abnormal dreams; agitation; amnesia; anxiety; ataxia; confusion; depression; dizziness; dyskinesia; emotional lability; encephalopathy; hypertonia; decreased libido; nervousness; neuropathy; paresthesia; peripheral neuritis; somnolence; abnormal thinking; tremor. DERM: Rash; acne; alopecia; dry skin; exfoliative dermatitis; furunculosis; maculopapular rash; nail disorder; pruritus; benign neoplasm; skin discoloration; sweating. EENT: Dry mouth; sinusitis; abnormal vision; otitis media; taste perversion; tinnitus. GI: Abdominal pain; abnormal stools; diarrhea; nausea; vomiting; anorexia; constipation; dyspepsia; dysphagia; enterocolitis; eructation; esophagitis; fecal incontinence; flatulence; gastritis; gastroenteritis; GI hemorrhage; colitis; increased appetite; pancreatitis; sialadenitis; stomatitis; ulcerative stomatitis. GU: Abnormal ejaculation; gynecomastia; hypogonadism; kidney calculus; urine abnormalities. HEMA: Anemia; leukopenia. HEPA: Cholecystitis. META: Hypothyroidism; Cushing syndrome; avitaminosis; dehydration; edema; decreased glucose tolerance; lactic acidosis; weight loss. RESP: Bronchitis; dyspnea; pulmonary edema. OTHER: Asthenia; pain; lymphadenopathy; arthralgia; arthrosis; myalgia; back pain; chest pain; substernal pain; chills; facial edema; fever; flu-like symptoms; malaise; viral infection.

 Precautions

Pregnancy: Category C. Lactation: HIV-infected mothers should not breastfeed their infants. Children < 6 mo: Safety and efficacy not established. Elderly: Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity. Hepatic function impairment: Use with caution, decreased lopinavir/ritonavir clearance may occur. Pancreatitis: Fatalities have been associated with use.

 Administration/Storage

• Refrigerate(36° to 46°F; 2° to 8°C); capsules and oral solution remain stable until expiration date. Protect from light. If stored at room temperature (77°F, 25°C), use within 2 months
• Administer with food.
• Administer in combination with other antiviral drugs.
• Do not administer with the following drugs, as serious problems or death have occurred: Dihydroergotamine, ergonovine, ergotamine, methylergonovine, triazolam, astemizole, pimozide, cisapride, propafenone, terfenadine, flecainide, midazolam.
• Do not administer with medications that are highly dependent on CYPE or CYP2D6 for clearance.
• Read “statement to patients and health care providers” on product label.
• If administered with didanosine, give didanosine on an empty stomach 1 hr before or 2 hr after lopinavir/ritonavir.

 Assessment/Interventions

• Obtain a complete drug history; assess for allergies and potential drug interactions.
• Monitor patients for adverse effects including GI problems, signs and symptoms of liver and renal problems, pancreatitis, angina, diabetes, changes in fat distribution, increased bleeding in patients with hemophilia, and other unusual occurrences.
• Monitor lab values (eg, ALT, AST), creatinine clearance, GGT, CPK, uric acid, triglycerides, CD4 count, and CBC.
• Assess patients for signs and symptoms of hyperglycemia. Test blood sugar periodically.
• Monitor patients for signs and symptoms of opportunistic infections.

 Patient/Family Education

• Instruct patients to take lopinavir/ritonavir with food to increase absorption.
• Instruct patients to take lopinavir/ritonavir with antiviral drugs every day as prescribed. Stress the relationship between strict adherence to drug schedule and reduction of viral load.
• Review package insert with patients.
• Caution patients not to alter the dose or discontinue therapy without consulting health care provider. If a dose is missed, take the dose as soon as possible and then return to normal schedule. If a dose is skipped, do not double the next dose.
• Instruct patients that lopinavir/ritonavir is not a cure for HIV infection. Patients may still transmit the disease to others through any aspect of sexual contact; use recommended precautions.
• Teach patients that they may still develop opportunistic infections and other complications associated with the HIV disease. Patients should be aware of signs and symptoms of infection and report symptoms to primary health care provider.
• Stress the importance of periodic examinations and laboratory tests in the control of the disease and prevention of complications.
• Inform patients that sustained decreases in plasma HIV RNA have been associated with a reduced risk of progression to AIDS and death.
• Warn patients that lopinavir/ritonavir may interact with other drugs. Patients should not take any prescription, nonprescription, or herbal medication such as St. John's wort without consulting primary health care provider or physician.
• Review with patients the medications that must not be taken with lopinavir/ritonavir and explain the serious reactions that might occur.
• Instruct patients taking didanosine to take it 1 hr before or 2 hr after lopinavir/ritonavir.
• Warn patients taking sildenafil of an increased risk of adverse effects including hypotension, visual changes, and sustained erection. Have patients promptly report any symptoms to physician.
• Instruct patients receiving estrogen-based hormonal contraceptives that additional or alternative contraceptive measures should be used during therapy with lopinavir/ritonavir.
• Inform patients that redistribution or accumulation of body fat may occur during antiretroviral therapy including protease inhibitors. The cause and long-term health effects of these conditions are not known at this time.
• Instruct patient to maintain weight ³ 15% above standard ideal body weight. Inform pregnant patients of the risks of HIV transmission and that the effects of lopinavir/ritonavir on the fetus are unknown.
• Instruct mothers not to breastfeed if the baby is HIV-negative because of the possibility of transmitting HIV through the breast milk.
• Inform patients that taking protease inhibitors may increase the chance of developing new or worsening diabetic conditions.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts