indication

Used in combination with other antiviral drugs in the treatment of HIV in both adults and children.

pharmacology

Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

mechanism of action

Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

toxicity

Oral LD₅₀ is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.

biotransformation

Primarily hepatic via cytochrome P450 (CYP450) enzymes. CYP3A and CYP2C19 appear to be the predominant enzymes that metabolize nelfinavir in humans. One major and several minor metabolites are found in plasma; the major oxidative metabolite has in vitro antiviral activity comparable to that of the parent drug.

absorption

Well absorbed following oral administration.

half life

3.5 - 5 hours

route of elimination

The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose containing 14C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1–2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.

drug interactions

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

Acenocoumarol: The protease inhibitor, nelfinavir, may increase the anticoagulant effect of acenocoumarol.

Alprazolam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, alprazolam.

Amiodarone: Nelfinavir may increase the effect and toxicity of amiodarone.

Anisindione: The protease inhibitor, nelfinavir, may increase the anticoagulant effect of anisindione.

Aprepitant: This CYP3A4 inhibitor increases the effect and toxicity of aprepitant

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atorvastatin: Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nelfinavir is initiated, discontinued or dose changed.

Bromazepam: Nelfinavir, 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 nelfinavir is initiated, discontinued or dose changed. Dosage adjustments may be required.

Chlordiazepoxide: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, chlordiazepoxide.

Ciclesonide: Increased effects/toxicity of ciclesonide

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Clonazepam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, clonazepam.

Clorazepate: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, clorazepate.

Cyclosporine: The protease inhibitor, nelfinavir, may increase the effect of cyclosporine.

Dantrolene: Nelfinavir 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 nelfinavir is initiated, discontinued or dose changed.

Darifenacin: Nelfinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of darifenacin/solifenacin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of darifenacin if nelfinavir is initiated, discontinued or dose changed.

Diazepam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, diazepam.

Dicumarol: The protease inhibitor, nelfinavir, may increase the anticoagulant effect of dicumarol.

Dihydroergotamine: Nelfinavir increases the effect and toxicity of ergot derivative

Dihydroquinidine barbiturate: Nelfinavir increases the effect and toxicity of quindine

Eletriptan: The protease inhibitor, nelfinavir, may increase the effect and toxicity of eletriptan.

Eplerenone: The protease inhibitor, nelfinavir, may increase the effect and toxicity of eplerenone.

Ergotamine: Nelfinavir increases the effect and toxicity of ergot derivative

Erlotinib: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Estazolam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, estazolam.

Ethinyl Estradiol: Ritonavir could decrease the contraceptive efficacy

Felodipine: Nelfinavir increases the effect and toxicity of felodipine

Fentanyl: The protease inhibitor, nelfinavir, may increase the effect and toxicity of fentanyl.

Flurazepam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, flurazepam.

Fusidic Acid: The protease inhibitor, nelfinavir, may increase the effect and toxicity of fusidic acid.

Halazepam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, halazepam.

Lovastatin: Nelfinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.

Mestranol: Ritonavir could decrease the contraceptive efficacy

Methadone: Nelfinavir decreases the effect of methadone

Midazolam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, midazolam.

Nevirapine: Nevirapine may decrease the effect of nelfinavir.

Pimozide: Nelfinavir increases the effect and toxicity of pimozide

Prazepam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, prazepam.

Quazepam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, quazepam.

Quinidine: Nelfinavir increases the effect and toxicity of quinidine

Quinidine barbiturate: Nelfinavir increases the effect and toxicity of quinidine

Ranolazine: Increased levels of ranolazine - risk of toxicity

Rifampin: Rifampin decreases the effect of nelfinavir

Sildenafil: The protease inhibitor, nelfinavir, may increase the effect and toxicity of sildenafil.

Simvastatin: Nelfinavir may increase the effect and toxicity of simvastatin. Concomitant therapy should be avoided.

Solifenacin: This potent CYP3A4 inhibitor slows darifenacin / solifenacin metabolism

St. John's Wort: St. John's Wort decreases the effect of indinavir

Sunitinib: Possible increase in sunitinib levels

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

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

Tamoxifen: Nelfinavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.

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

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

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

Teniposide: The strong CYP3A4 inhibitor, Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Tiagabine: The strong CYP3A4 inhibitor, Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.

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

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

Tramadol: Nelfinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.

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

Triazolam: The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, triazolam.

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

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

Verapamil: Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.

Vinblastine: Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.

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

Vinorelbine: Nelfinavir, 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 Nelfinavir is initiated, discontinued or dose changed.

Voriconazole: Nelfinavir may decrease the serum concentration of voriconazole likely by increasing its metabolism. Voriconazole may increase the serum concentration of nelfinavir by decreasing its metabolism. Consider alternate therapy or adjust doses and monitor for reduced voriconazole efficacy and increased nelfinavir adverse effects during concomitant therapy.

Warfarin: The protease inhibitor, nelfinavir, may increase the anticoagulant effect of warfarin.

Zolpidem: Nelfinavir, 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 nelfinavir is initiated, discontinued or dose changed.

Zonisamide: Nelfinavir, 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 nelfinavir is initiated, discontinued or dose changed.

Zopiclone: Nelfinavir, 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 nelfinavir is initiated, discontinued or dose changed.