QuickView for Ranolazine (compound)

Summary
General Info

PubChem

PubChem Compound 56959

Name:	ranolazine
PubChem Compound ID:	56959
Molecular formula:	C₂₄H₃₃N₃O₄
Molecular weight:	427.537 g/mol
Synonyms:	RS-43285; RAN D; KEG-1295; 142387-99-3; 1-Piperazineacetamide, N-(2,6-dimethylphenyl)-4-(2-hydroxy-3-(2-methoxyphenoxy)propyl)-; Ranolazine; ( -)-Ranolazine; Ran4; RS-43285-003; Ranexa. show more » RS-43285; RAN D; KEG-1295; 142387-99-3; 1-Piperazineacetamide, N-(2,6-dimethylphenyl)-4-(2-hydroxy-3-(2-methoxyphenoxy)propyl)-; Ranolazine; ( -)-Ranolazine; Ran4; RS-43285-003; Ranexa; Ranolazine [USAN]; CVT-303; 95635-55-5 show less «

DrugBank

Identification

Name:	ranolazine
Name (isomeric):	DB00243
Drug Type:	small molecule
Synonyms:	Ranolazine 2HCl; Ranolazine Dihydrochloride; (-)-Ranolazine
Brand:	Ranexa
Category:	Enzyme Inhibitors
CAS number:	142387-99-3

Pharmacology

Indication:	For the treatment of chronic angina. It should be used in combination with amlodipine, beta-blockers or nitrates.
Pharmacology:	Ranolazine has antianginal and anti-ischemic effects that do not depend upon reductions in heart rate or blood pressure. It is the first new anti-anginal developed in over 20 years.
Mechanism of Action:	The mechanism of action of ranolazine is unknown. It does not increase the rate-pressure product, a measure of myocardial work, at maximal exercise. In vitro studies suggest that ranolazine is a P-gp inhibitor. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium ... show more » The mechanism of action of ranolazine is unknown. It does not increase the rate-pressure product, a measure of myocardial work, at maximal exercise. In vitro studies suggest that ranolazine is a P-gp inhibitor. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia. show less «
Absorption:	Absorption is highly variable. After oral administration of ranolazine as a solution, 73% of the dose is systemically available as ranolazine or metabolites. The bioavailability of oral ranolazine relative to that from a solution is 76%.
Protein binding:	62%
Biotransformation:	Hepatic, metabolized mainly by CYP3A and to a lesser extent by CYP2D6. The pharmacologic activity of the metabolites has not been well characterized.
Route of elimination:	Ranolazine is metabolized rapidly and extensively in the liver and intestine; less than 5% is excreted unchanged in urine and feces.
Half Life:	7 hours
Toxicity:	In the event of overdose, the expected symptoms would be dizziness, nausea/vomiting, diplopia, paresthesia, and confusion. Syncope with prolonged loss of consciousness may develop.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Grapefruit and grapefruit juice should be avoided throughout treatment.

Take without regard to meals.

Drug interaction:

Tramadol	Ranolazine may decrease the effect of Tramadol by decreasing active metabolite production.
Nelfinavir	Increased levels of ranolazine - risk of toxicity
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ranolazine by decreasing its metabolism. Additive QTc prolongation may also occur. Concomitant therapy is contraindicated.
Amiodarone	Possible additive effect on QT prolongation
Amprenavir	Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentratin of ranolazine by inhibiting its metabolism. Concomitant therapy is contraindicated.

Tramadol	Ranolazine may decrease the effect of Tramadol by decreasing active metabolite production.
Nelfinavir	Increased levels of ranolazine - risk of toxicity
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ranolazine by decreasing its metabolism. Additive QTc prolongation may also occur. Concomitant therapy is contraindicated.
Amiodarone	Possible additive effect on QT prolongation
Amprenavir	Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentratin of ranolazine by inhibiting its metabolism. Concomitant therapy is contraindicated.
Dirithromycin	Increased levels of ranolazine - risk of toxicity
Fluconazole	Increased levels of ranolazine - risk of toxicity
Procainamide	Possible additive effect on QT prolongation
Ritonavir	Increased levels of ranolazine - risk of toxicity
Ketoconazole	Increased levels of ranolazine - risk of toxicity
Digoxin	Ranolazine may increase the serum level of digoxin. Monitor for changes in the serum level and therapeutic and adverse effects of digoxin if ranolazine is initiated, discontinued or dose changed.
Topotecan	The p-glycoprotein inhibitor, Ranolazine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Disopyramide	Possible additive effect on QT prolongation
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tamoxifen	Ranolazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Sotalol	Possible additive effect on QT prolongation
Dofetilide	Possible additive effect on QT prolongation
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Itraconazole	Increased levels of ranolazine - risk of toxicity
Moricizine	Possible additive effect on QT prolongation
Tamsulosin	Ranolazine, 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 Ranolazine is initiated, discontinued, or dose changed.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Indinavir	Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of ranolazine by decreasing its metabolism. Concomitant therapy is contraindicated.
Thioridazine	Possible additive effect on QT prolongation
Quinidine	Possible additive effect on QT prolongation
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Bicalutamide	CYP3A4 inhibitors like ranolazine may increase the serum concentration of ranolazine. Consider therapy modification.
Atazanavir	Atazanavir, a strong CYP3A4 inhibitor, may increase the serum level of ranolazine. Concomitant therapy is contraindicated.
Saquinavir	Increased levels of ranolazine - risk of toxicity
Tipranavir	Increased levels of ranolazine - risk of toxicity
Telithromycin	Telithromycin may reduce clearance of Ranolazine. Concomitant therapy should be avoided.
Tolterodine	Ranolazine may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Conivaptan	CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. The manufacturer contraindicates the use of ranolazine and strong CYP3A4 inhibitors (such as the azole antifungals).1 Monitor for increased effects/toxicity of ranolazine during concomitant use.
Erythromycin	Increased levels of ranolazine - risk of toxicity
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Simvastatin	Ranolazine may increase the serum concentration of simvastatin. Monitor for changes in the therapeutic and adverse effects of simvastatin if ranolazine is initiated, discontinued or dose changed.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Verapamil	Verapamil, a CYP3A4 inhibitor, may increase the serum concentration of Ranolazine. Concomitant therapy is contraindicated.
Clotrimazole	CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of ranolazine. Limit the ranolazine dose to a maximum of 500mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Monitor for increased effects/toxicity of ranolazine during concomitant use.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trimipramine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Ibutilide	Possible additive effect on QT prolongation
Diltiazem	Diltiazem may increase the serum concentration of ranolazine. Consider alternate therapy or limit ranolazine dose to 500 mg twice daily and monitor for changes in the therapeutic and adverse effects if diltiazem is initiated, discontinued or dose changed.
Fosamprenavir	Increased levels of ranolazine - risk of toxicity
Clarithromycin	Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum level of ranolazine. Concomitant therapy is contraindicated.
Bretylium	Possible additive effect on QT prolongation

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Targets

Sodium channel protein type 5 subunit alpha

Sodium channel protein type 9 subunit alpha

Enzymes

Cytochrome P450 3A4

UniProt ID:	P08684
Gene:	CYP3A4
Actions:	substrate

Cytochrome P450 2D6