Drug Detail

Lopinavir/ritonavir

Last Updated June 10, 2016

Trade Names

Aluvia, Kaletra

Drug Classification

HIV protease inhibitor antiretroviral

Formulations

100/25 mg, 200/50 mg tablets; 80/20 mg/mL oral solution (42% alcohol)

Indications and Pharmacology

Indication: treatment of HIV infection in combination with other antiretrovirals. Postexposure prophylaxis in combination with other antiretrovirals.

Mechanism of action*: Inhibits cleavage of viral gag-pol polyproteins precursors into functional proteins by binding to the HIV protease enzyme.

Pharmacokinetics*: metabolized in the liver CYP 450 3A4. Inhibits CYP 450 3A enzyme. Half life: 5-6 hours. Bioavailability enhanced by food.

Dosage

Adult Dose:

  • 400/100 mg twice daily with food.
  • With efavirenz or nevirapine: 500/125 mg twice daily with food.*
  • With rifampicin: preferred - lopinavir/ritonavir 800/200 mg twice daily; alternative - lopinavir 400 mg + ritonavir 400 mg twice daily with food (dose adjustments can be made gradually over 1-2 weeks).
  • With rifabutin: dose of rifabutin should be adjusted (see Drug–Drug Interactions).

Use in Renal or Hepatic Insufficiency: Use with caution in patients with liver disease or preexisting diabetes.

Lopinavir/ritonavir is highly metabolised in the liver and concentrations may be increased in patients with hepatic impairment. Therapeutic drug monitoring should be done if available.

Use in Pregnancy and Breastfeeding: Excreted into breast milk.

Use in Children:

  • 7-14 kg: 12/3 mg/kg lopinavir/ritonavir twice daily.
  • 15-40 kg: 10/2.5 mg/kg lopinavir/ritonavir twice daily.
  • > 40 kg: up to 400/100 mg lopinavir/ritonavir twice daily.

Dose adjustment for children taking efavirenz, or nevirapine if PI experienced:

  • 7-14 kg: 13/3.25 mg/kg lopinavir/ritonavir twice daily.
  • 15-45 kg: 11/2.75 mg/kg lopinavir/ritonavir twice daily.
  • > 45 kg: up to 500/125 mg lopinavir/ritonavir twice daily.

Warnings

See Drug–Drug Interactions.

Contraindicated with porphyria.

Fasting lipid profile and blood glucose measurements should be taken before initiation and repeated at 6 months and then annually.

Drug–Drug Interactions

Contraindicated: lovastatin, simvastatin, cisapride, pimozide, oral midazolam, triazolam, dihydroergotamine, ergotamine, methylergonovine, St John’s wort, alfuzosin, sildenafil for pulmonary arterial hypertension.*

Increased concentrations of concomitant medication: antiarrhythmics, warfarin, rivaroxaban, trazodone, ketoconazole, itraconazole, clarithromycin, rifabutin (dose rifabutin 150 mg every other day),
bosentan, fluticasone, glucocorticoids, atorvastatin, lovastatin, rosuvastatin, simvastatin, avanafil, sildenafil, tadalafil, vardenafil, dihydropyridine, midazolam, colchicine, bedaquiline, quetiapine, vincristine, vinblastine, dasatinib, nilotinib, simeprevir, cyclosporine, tacrolimus, sirolimus, budesonide, salmeterol, fentanyl.*

Decreased concentrations of concomitant medication: methadone, warfarin, lamotrigine, phenytoin, valproic acid, bupropion, voriconazole, ethinyl estradiol, norethindrone, atovaquone, boceprevir.*

Decreased concentrations of lopinavir/ritonavir with concomitant medication: boceprevir, carbamazepine, phenobarbital, phenytoin, dexamethasone, budesonide, prednisone, rifampin.*

Drug interactions between lopinavir/ritonavir and other antiretrovirals*:

Considerations for Special Populations

See above for pregnancy and lactation.

Use with caution in patients with liver disease or preexisting diabetes.

Do not use in patients with porphyria.

Adverse Effects

Gastrointestinal symptoms (nausea, vomiting, diarrhoea, flatulence), pancreatitis, hyperlipidaemia, increased liver enzymes, hyperglycaemia/insulin resistance/diabetes, fat maldistribution, potential increased bleeding in patients with haemophilia, PR and QT prolongation possible, elevated serum transaminases.*

*Information from US prescribing information.
Recommendation from Southern African HIV Clinician Society Guidelines.