QuickView for Ritonavir (compound)

Summary
General Info

PubChem

PubChem Compound 10395099

Name:	Ritonavir
PubChem Compound ID:	10395099
Description:	An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV.
Molecular formula:	C₃₇H₄₈N₆O₅S₂
Molecular weight:	720.946 g/mol

DrugBank

Identification

Name:	Ritonavir
Name (isomeric):	DB00503
Drug Type:	small molecule
Description:	An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV.
Synonyms:	Abbott 84538
Brand:	Norvir, Norvir Sec
Brand name mixture:	Kaletra(Lopinavir + Ritonavir)
Category:	HIV Protease Inhibitors, Anti-HIV Agents
CAS number:	155213-67-5

Pharmacology

Indication:	Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.
Pharmacology:	Ritonavir 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. Ritonavir binds to th... show more » Ritonavir 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. Ritonavir 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. show less «
Mechanism of Action:	Ritonavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Absorption:	The absolute bioavailability of ritonavir has not been determined.
Protein binding:	98-99%
Biotransformation:	Hepatic. Five metabolites have been identified. The isopropylthiazole oxidation metabolite (M-2) is the major metabolite and has antiviral activity similar to that of ritonavir, however, plasma concentrations are low. The cytochrome P450 enzymes CYP3A and CYP2D6 are primarily involved in the metabolism of ritonavir.
Half Life:	3-5 hours
Toxicity:	Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for two days. The patient reported paresthesias which resolved after the dose was decreased. A post-marketing case of renal failure with eosinophilia has been reported with ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice.
Affected organisms:	Human Immunodeficiency Virus

Interactions

Food interaction:

Avoid St.John's Wort.

Take with food.

Drug interaction:

Amitriptyline	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ritonavir if initiated, discontinued or dose changed.
Temsirolimus	Ritonavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Imipramine	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if ritonavir if initiated, discontinued or dose changed.
Dihydroergotamine	The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, dihydroergotamine.
Alfuzosin	Ritonavir increases the effect/toxicity of alfuzosin

Amitriptyline	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ritonavir if initiated, discontinued or dose changed.
Temsirolimus	Ritonavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Imipramine	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if ritonavir if initiated, discontinued or dose changed.
Dihydroergotamine	The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, dihydroergotamine.
Alfuzosin	Ritonavir increases the effect/toxicity of alfuzosin
Ergotamine	The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, ergotamine.
Diltiazem	Ritonavir increases diltiazem levels
Quinidine	Ritonavir increases the effect and toxicity of quinidine
Vincristine	Ritonavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ritonavir is initiated, discontinued or dose changed.
Divalproex sodium	Possible decrease of valproate levels
Rifampin	Rifampin decreases the effect of ritonavir
Alprazolam	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, alprazolam.
Telithromycin	Ritonavir may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
Topotecan	The p-glycoprotein inhibitor, Ritonavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Rifabutin	Rifabutin decreases the effect of ritonavir
Vinorelbine	Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Erythromycin	Increased toxicity of both agents
Zopiclone	Ritonavir, 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 ritonavir is initiated, discontinued or dose changed.
Aprepitant	This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Rivaroxaban	Use of rivaroxaban with agents that are strong inhibitors of both CYP3A4 like ritonavir and P-glycoproteins are contraindicated.
Meperidine	Ritonavir increases the levels of analgesic
Fluoxetine	Increased risk of serotonin syndrome
Atazanavir	Association with dose adjustment
Trazodone	The protease inhibitor, Ritonavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Ritonavir is initiated, discontinued or dose changed.
Astemizole	Increased risk of cardiotoxicity and arrhythmias
Quinupristin	This combination presents an increased risk of toxicity
Trimipramine	The strong CYP3A4/CYP2D6 inhibitor, Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Ethinyl Estradiol	Ritonavir could decrease the contraceptive efficacy
Oxtriphylline	Ritonavir decreases the effect of theophylline
Doxepin	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if ritonavir if initiated, discontinued or dose changed.
Flecainide	Ritonavir increases the toxicity of the anti-arrhythmic
Methadone	The protease inhibitor, ritonavir, may decrease the effect of methadone.
Eletriptan	The protease inhibitor, ritonavir, may increase the effect and toxicity of eletriptan.
Ketoconazole	Ketoconazole may increase the effect and toxicity of ritonavir.
Nortriptyline	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ritonavir if initiated, discontinued or dose changed.
Propafenone	Ritonavir increases the effect and toxicity of propafenone
Lovastatin	Ritonavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Fusidic Acid	The protease inhibitor, ritonavir, may increase the effect and toxicity of fusidic acid.
Clonazepam	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, clonazepam.
Clozapine	Ritonavir increases the effect and toxicity of clozapine
Delavirdine	Increases the effect of ritonavir
Theophylline	Ritonavir decreases the effect of theophylline
Estazolam	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, estazolam.
Desipramine	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if ritonavir if initiated, discontinued or dose changed.
Eplerenone	This protease inhibitor, ritonavir, may increase the effect and toxicity of eplerenone.
Bromazepam	Ritonavir, 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 ritonavir is initiated, discontinued or dose changed. Dosage adjustments may be required.
Zuclopenthixol	Ritonavir, 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 ritonavir is initiated, discontinued or dose changed.
Dantrolene	Ritonavir 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 ritonavir is initiated, discontinued or dose changed.
Verapamil	Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Tramadol	Ritonavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ritonavir may decrease the effect of Tramadol by decreasing active metabolite production.
Piroxicam	Ritonavir increases the toxicity of piroxicam
Atorvastatin	Ritonavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if ritonavir is initiated, discontinued or dose changed.
Itraconazole	Itraconazole may increase the effect and toxicity of ritonavir.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Zolpidem	Ritonavir, 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 ritonavir is initiated, discontinued or dose changed.
Digoxin	Ritonavir increases levels/effect of digoxin
Erlotinib	This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Vinblastine	Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Fentanyl	Ritonavir increases the effect and toxicity of fentanyl/alfentanyl
Buspirone	Ritonavir increases the effect and toxicity of buspirone
Cyclosporine	The protease inhibitor, ritonavir, may increase the effect of cyclosporine.
Tadalafil	Ritonavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tolterodine	Ritonavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Flurazepam	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, flurazepam.
Tamsulosin	Ritonavir, 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 Ritonavir is initiated, discontinued, or dose changed.
Atomoxetine	The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Amoxapine	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if ritonavir if initiated, discontinued or dose changed.
Chlordiazepoxide	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, chlordiazepoxide.
Tamoxifen	Ritonavir may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
Venlafaxine	Ritonavir, 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 Ritonavir is initiated, discontinued, or dose changed.
Ciclesonide	Increased effects/toxicity of ciclesonide
Tacrolimus	The protease inhibitor, Ritonavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ritonavir therapy is initiated, discontinued or altered.
Clomipramine	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if ritonavir if initiated, discontinued or dose changed.
Pimozide	The protease inhibitor, ritonavir, may increase the effect and toxicity of pimozide.
Teniposide	The strong CYP3A4 inhibitor, Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Olanzapine	Ritonavir decreases the effect of olanzapine
Clorazepate	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, clorazepate.
Midazolam	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, midazolam.
Voriconazole	Ritonavir may decrease the serum concentration of voriconazole by increasing its metabolism. Concomitant therapy with high dose ritonavir is contraindicated. Caution should be used with lower doses as decreased voriconazole efficacy may occur.
Gefitinib	This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Bupropion	Ritonavir increases the effect and toxicity of bupropion
Ranolazine	Increased levels of ranolazine - risk of toxicity
Darifenacin	This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Zonisamide	Ritonavir, 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 ritonavir is initiated, discontinued or dose changed.
Triazolam	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, triazolam.
Diazepam	The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, diazepam.
Aminophylline	Ritonavir decreases the effect of theophylline
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Abacavir	The serum concentration of Abacavir may be decreased by protease inhibitors such as Ritonavir. The antiviral response should be closely monitored.
Bepridil	Ritonavir increases the effect and toxicity of bepridil
Vardenafil	Ritonavir, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Tiagabine	The strong CYP3A4 inhibitor, Ritonavir, 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 Ritonavir is initiated, discontinued or dose changed.
Mefloquine	Mefloquine decreases the effect of ritonavir
Tretinoin	The strong CYP2C8 inhibitor, Ritonavir, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Ritonavir is initiated, discontinued to dose changed.
Carbamazepine	Ritonavir increases the effect of carbamazepine
Amiodarone	Ritonavir increases the effect and toxicity of amiodarone
Propoxyphene	Ritonavir increases the levels of analgesic