indication

Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.

pharmacology

Lopinavir is an antiretroviral of the protease inhibitor class. Inhibiting HIV-1 protease (responsible for protein cleavage), results in selectively inhibiting the cleavage of HIV gag and gag-pol polyproteins, thereby preventing viral maturation.

mechanism of action

Lopinavir inhibits the HIV viral protease enzyme. This prevents cleavage of the gag-pol polyprotein and, therefore, improper viral assembly results. This subsequently results in non-infectious, immature viral particles.

toxicity

Although human experience of acute overdosage with lopinavir is limited, accidental ingestion of the product by a young child could result in significant alcohol-related toxicity and could approach the potential lethal dose of alcohol.

biotransformation

Hepatic. Lopinavir is extensively metabolized by the hepatic cytochrome P450 system, almost exclusively by the CYP3A isozyme.

absorption

Administered alone, lopinavir has insufficient bioavailability; however, like several HIV protease inhibitors, its blood levels are greatly increased by low doses of ritonavir, a potent inhibitor of cytochrome P450 3A4.

drug interactions

Abacavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Lopinavir. The antiviral response should be closely monitored.

Bromazepam: Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if lopinavir is initiated, discontinued or dose changed. Dosage adjustments may be required.

Dantrolene: Lopinavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if lopinavir is initiated, discontinued or dose changed.

Darunavir: Decreased levels of darunavir

Fosphenytoin: Levels of both drugs are affected

Phenytoin: Levels of both drugs are affected

Tacrolimus: The protease inhibitor, Lopinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Lopinavir therapy is initiated, discontinued or altered.

Tadalafil: Lopinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.

Tamoxifen: Lopinavir may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.

Tamsulosin: Lopinavir, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Lopinavir is initiated, discontinued, or dose changed.

Telithromycin: Lopinavir may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.

Temsirolimus: Lopinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.

Teniposide: The strong CYP3A4 inhibitor, Lopinavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Lopinavir is initiated, discontinued or dose changed.

Tiagabine: The strong CYP3A4 inhibitor, Lopinavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Lopinavir is initiated, discontinued or dose changed.

Tipranavir: Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Lopinavir. Consider alternate therapy.

Tolterodine: Lopinavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.

Topotecan: The p-glycoprotein inhibitor, Lopinavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.

Tramadol: Lopinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Lopinavir may decrease the effect of Tramadol by decreasing active metabolite production.

Trazodone: The protease inhibitor, Lopinavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Lopinavir is initiated, discontinued or dose changed.

Trimipramine: The strong CYP3A4/CYP2D6 inhibitor, Lopinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Lopinavir is initiated, discontinued or dose changed.

Vardenafil: Lopinavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.

Venlafaxine: Lopinavir, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Lopinavir is initiated, discontinued, or dose changed.

Verapamil: Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Lopinavir is initiated, discontinued or dose changed.

Vinblastine: Lopinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Lopinavir is initiated, discontinued or dose changed.

Vincristine: Lopinavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing its efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Lopinavir is initiated, discontinued or dose changed.

Vinorelbine: Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Lopinavir is initiated, discontinued or dose changed.

Voriconazole: Lopinavir may reduce serum concentration and efficacy of voriconazole. This combination should be avoided unless the potential benefits outweigh the risk of reduced voriconazole efficacy.

Zolpidem: Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if lopinavir is initiated, discontinued or dose changed.

Zonisamide: Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if lopinavir is initiated, discontinued or dose changed.

Zopiclone: Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if lopinavir is initiated, discontinued or dose changed.

Zuclopenthixol: Lopinavir, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if lopinavir is initiated, discontinued or dose changed.