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Ranolazine: Drug information

Ranolazine: Drug information
(For additional information see "Ranolazine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Aspruzyo Sprinkle;
  • Ranexa [DSC]
Brand Names: Canada
  • Corzyna
Pharmacologic Category
  • Antianginal Agent;
  • Cardiovascular Agent, Miscellaneous
Dosing: Adult
Chronic angina

Chronic angina:

Note: May be used in combination with beta-blockers, nitrates, or calcium channel blockers, or may serve as a substitute for these routine antianginal therapies if they are not tolerated due to side effects (Ref).

Oral: Initial: 500 mg twice daily; may increase to 1,000 mg twice daily as needed (based on symptoms); maximum recommended dose: 1,000 mg twice daily.

Ventricular tachycardia

Ventricular tachycardia (off-label use): Oral: 500 to 1,000 mg every 12 hours (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: Oral:

CrCl >80 mL/minute: No dosage adjustment necessary (Ref).

CrCl >30 to 80 mL/minute: No dosage adjustment necessary; however, there is significant interpatient variability in pharmacokinetics and almost doubling of AUC compared to patients with normal renal function. Use with caution, especially in patients with CrCl <50 mL/minute (Ref).

CrCl ≤30 mL/minute:

Note: Use with extreme caution; acute kidney injury and other adverse effects (eg, neurologic) have been observed in some patients with severe kidney impairment.

Initial: 500 mg once daily; maximum: 500 mg twice daily (Ref).

Hemodialysis, intermittent (thrice weekly): Not likely to be significantly dialyzed (moderate plasma protein binding and large Vd): Avoid use (preferred) or dose as for CrCl ≤30 mL/minute with extreme caution and close monitoring for adverse effects (Ref); variable absorption was observed in a small pharmacokinetic study of patients on hemodialysis, limiting the ability to recommend a safe and effective dose (Ref).

Peritoneal dialysis: Has not been studied; avoid use (preferred) or dose as for CrCl ≤30 mL/minute with extreme caution and close monitoring for adverse effects (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. Use is contraindicated with hepatic cirrhosis.

Dosing: Older Adult

Refer to adult dosing. Select dose cautiously, starting at the lower end of the dosing range.

Adverse Reactions (Significant): Considerations
QT prolongation

Use of ranolazine has been associated with prolonged QT interval on ECG. The increase in the mean duration of the QTc interval at therapeutic doses is generally modest (~5 to 10 msec) (Ref); a greater increase (~15 msec) may be seen at higher doses and/or concentrations (Ref). Rare cases of ranolazine-associated torsades de pointes (TdP) have been reported in the presence of other risk factors (Ref). When compared to pure KCNH2 channel inhibitors (formerly called hERG channel) (eg, dofetilide), drugs with combined KCNH2 channel and inward current blockers (calcium or late sodium) (eg, ranolazine) may have a lower risk of TdP (Ref).

Mechanism: Dose-dependent (Ref); related to the pharmacologic action. Ranolazine exhibits multichannel effect including blockade of inward depolarizing currents (ie, late sodium, late L-type calcium, inward sodium-calcium exchanger, and peak L-type calcium currents) and outward repolarizing currents (ie, slow and rapid component of the delayed rectifier potassium currents); as a result, there is a minimal prolongation in the action potential duration and the resulting potential for QT interval prolongation is modest (Ref).

Onset: Varied. The effect of ranolazine on the QT segment is concentration-dependent; therefore, the timing of QT prolongation may be impacted by the presence of risk factors that result in increased concentrations (eg, hepatic impairment, drug interactions) (Ref).

Risk factors:

Ranolazine-induced QTc prolongation:

• Higher doses (eg, >2,000 mg/day)

• Moderate hepatic impairment (Ref)

• Genetic predisposition to or preexisting long QT syndrome (Ref)

• Concomitant administration of drugs known to prolong the QT interval (Ref)

• Concomitant administration of drugs that inhibit CYP3A4 (Ref)

Drug-induced QTc prolongation/torsades de pointes (TdP) (in general):

• Females (Ref)

• Age >65 years (Ref)

• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)

• Genetic defects of cardiac ion channels (Ref)

• History of drug-induced TdP (Ref)

• Congenital long QT syndrome (LQTS) (Ref)

• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 milliseconds (Ref)

• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, or hypomagnesemia) (Ref)

• Bradycardia (Ref)

• Hepatic impairment (Ref)

• Kidney impairment (Ref)

• Loop diuretic use (Ref)

• Sepsis (Ref)

• Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

1% to 10%:

Cardiovascular: Bradycardia (≤4%), hypotension (≤4%), orthostatic hypotension (≤4%), palpitations (≤4%), peripheral edema (≤4%), syncope (≤4%)

Dermatologic: Hyperhidrosis (≤4%)

Gastrointestinal: Abdominal pain (≤4%), anorexia (≤4%), constipation (5%), dyspepsia (≤4%), nausea (4%), vomiting (≤4%), xerostomia (≤4%)

Genitourinary: Hematuria (≤4%)

Nervous system: Asthenia (≤4%), confusion (≤4%), dizziness (6%; may be dose-related), headache (6%), vertigo (≤4%)

Ophthalmic: Blurred vision (≤4%)

Otic: Tinnitus (≤4%)

Respiratory: Dyspnea (≤4%)

<1%:

Genitourinary: Urine discoloration

Hematologic & oncologic: Eosinophilia, leukopenia, pancytopenia, thrombocytopenia

Hypersensitivity: Angioedema

Nervous system: Hypoesthesia, paresthesia, tremor

Renal: Increased blood urea nitrogen, kidney failure

Respiratory: Pulmonary fibrosis

Postmarketing:

Cardiovascular: Flattened T wave on ECG (Vicente 2015), inversion T wave on ECG (Kumthekar 2015), notching of T wave on ECG (Vicente 2015), prolonged QT interval on ECG (Vadnais 2010), torsades de pointes (Liu 2013; Morrow 2007)

Dermatologic: Acute generalized exanthematous pustulosis (Grelck 2015), pruritus, skin rash

Genitourinary: Dysuria, urinary retention

Nervous system: Ataxia, hallucination, myoclonus (Porhomayon 2013)

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (Dein 2018), myalgia (Dein 2018)

Renal: Increased serum creatinine

Contraindications

Hepatic cirrhosis; concurrent use of strong CYP3A inhibitors; concurrent use of CYP3A inducers.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to ranolazine or any component of the formulation; concurrent use of class Ia antiarrhythmics (eg, quinidine, procainamide, disopyramide) or class III antiarrhythmics (eg, sotalol, ibutilide, amiodarone, dronedarone); severe renal impairment (GFR ≤30 mL/minute/1.73 m2); moderate or severe hepatic impairment.

Warnings/Precautions

Disease-related concerns:

• Acute coronary syndrome: Ranolazine will not relieve acute angina episode and has not demonstrated benefit in acute coronary syndrome.

• Hepatic impairment: Ranolazine plasma levels increase by 30% in patients with mild (Child-Pugh class A) and by 80% in patients with moderate (Child-Pugh class B) hepatic impairment. Use is contraindicated in patients with cirrhosis.

• Renal impairment: Acute renal failure has been observed in some patients with severe renal impairment (CrCl <30 mL/minute); if acute renal failure develops (marked increase in serum creatinine associated with increased BUN), discontinue ranolazine and manage appropriately. Monitor renal function periodically in patients with moderate to severe renal impairment; particularly for increases in serum creatinine accompanied by increased BUN. In a renal impairment study, patients with severe impairment exhibited an initial elevation in diastolic BP (~12 to 17 mm Hg at day 3), however, this diminished to ~4 mm Hg increase by day 5 (Jerling 2005); consider monitoring BP in patients with renal dysfunction.

Concurrent drug therapy issues:

• CYP3A inhibitors: Use is contraindicated with inducers and strong inhibitors of CYP3A.

Special populations:

• Older adult: Use with caution in patients ≥75 years of age; they may experience more adverse events (including serious adverse events) and drug discontinuations due to adverse events.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Packet, Oral:

Aspruzyo Sprinkle: 500 mg (60 ea); 1000 mg (60 ea)

Tablet Extended Release 12 Hour, Oral:

Ranexa: 500 mg [DSC], 1000 mg [DSC]

Generic: 500 mg, 1000 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Pack (Aspruzyo Sprinkle Oral)

500 mg (per each): $6.07

1000 mg (per each): $9.96

Tablet, 12-hour (Ranolazine ER Oral)

500 mg (per each): $6.42 - $7.40

1000 mg (per each): $10.54 - $12.15

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 12 Hour, Oral:

Corzyna: 500 mg, 1000 mg

Administration: Adult

Oral:

Granules: Sprinkle granules on 1 tablespoonful of soft food (eg, applesauce, yogurt) and swallow immediately; do not crush or chew.

Tablet: Administer with or without meals. Swallow tablet whole; do not crush, break, or chew.

Bariatric surgery: Granules, extended release; Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. There are no IR formulations available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, close clinical monitoring is advised in the immediate postoperative phase for the theoretical circumstance of reduced absorption after bariatric surgery.

Gastric tube: Granules: Add contents of 1 sachet to a plastic catheter tip syringe and add 30 mL of water; gently shake for ~15 seconds and immediately administer through a 12 French or larger NG tube. Rinse with 20 mL of water. Rinse with an additional water (~15 mL) if needed to ensure granules are not left in the syringe.

NG tube: Granules: Add contents of 1 sachet to a plastic catheter tip syringe and add 50 mL of water; gently shake for ~15 seconds and immediately administer through a 12 French or larger NG tube. Rinse with additional water (~15 mL) if needed to ensure granules are not left in the syringe.

Use: Labeled Indications

Chronic angina: Treatment of chronic angina.

Use: Off-Label: Adult

Ventricular tachycardia

Medication Safety Issues
Sound-alike/look-alike issues:

Ranexa [DSC] may be confused with CeleXA, PreNexa Premier

Metabolism/Transport Effects

Substrate of CYP2D6 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak), CYP3A4 (weak), OCT2, P-glycoprotein/ABCB1

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification

Alcohol (Ethyl): May increase the serum concentration of Ranolazine. Risk X: Avoid combination

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: Ranolazine may enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Ranolazine may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy

Clofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Ranolazine. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Ranolazine. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ranolazine. Risk X: Avoid combination

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy

Dalfampridine: OCT2 Inhibitors may increase the serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider therapy modification

Digoxin: Ranolazine may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with ranolazine. Reduce digoxin concentrations by either reducing the digoxin dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

Dofetilide: OCT2 Inhibitors may increase the serum concentration of Dofetilide. Risk X: Avoid combination

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy

Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider therapy modification

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lovastatin: Ranolazine may increase the serum concentration of Lovastatin. Ranolazine may also enhance the distribution of lovastatin to specific cells/tissues/organs where P-glycoprotein is present in large amounts (eg, brain, T-lymphocytes, testes, etc.). Management: Consider a lovastatin dose reduction if combined with ranolazine. An American Heart Association scientific statement recommends limiting lovastatin doses to 20 mg daily when used with ranolazine. Monitor closely for lovastatin toxicity. Risk D: Consider therapy modification

Mavacamten: Ranolazine may enhance the adverse/toxic effect of Mavacamten. Risk X: Avoid combination

MetFORMIN: Ranolazine may increase the serum concentration of MetFORMIN. Management: Limit the metformin dose to a maximum of 1,700 mg per day when used together with ranolazine 1,000 mg twice daily. Monitor patients for metformin toxicities, including lactic acidosis and carefully weigh the risks and benefits of this combination. Risk D: Consider therapy modification

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Ranolazine. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Red Yeast Rice: Ranolazine may increase the serum concentration of Red Yeast Rice. Ranolazine may also enhance the distribution of lovastatin, a component of red yeast rice, to specific cells/tissues/organs where P-glycoprotein is present in large amounts (eg, brain, T-lymphocytes, testes, etc.). Management: Consider reducing the dose of red yeast rice if combined with ranolazine. An American Heart Association scientific statement recommends limiting lovastatin doses to 20 mg daily when used with ranolazine. Red yeast rice interacts similarly. Risk D: Consider therapy modification

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification

Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification

RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy

Simvastatin: Ranolazine may increase the serum concentration of Simvastatin. Management: Carefully consider the potential benefits and risks of this combination. Limit simvastatin to 20 mg daily if coadministered, and monitor closely for signs and symptoms of myopathy or rhabdomyolysis. Risk D: Consider therapy modification

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification

Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

Food Interactions

Grapefruit, grapefruit juice, or grapefruit-containing products may increase the serum concentration of ranolazine. Management: Limit ranolazine dose to a maximum of 500 mg twice daily in patients concurrently consuming grapefruit juice; monitor for increased effects/toxicity.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Breastfeeding Considerations

It is not known if ranolazine is excreted into breast milk. According to the manufacturer, the decision to breastfeed during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.

Dietary Considerations

Limit the use of grapefruit juice; the ranolazine dose should not exceed 500 mg twice daily when taken with grapefruit juice or grapefruit-containing products.

Monitoring Parameters

Baseline and follow up ECG to evaluate QT interval; monitor renal function periodically in patients with moderate to severe renal impairment, particularly for increases in serum creatinine accompanied by increased BUN; consider monitoring blood pressure in patients with renal dysfunction; correct and maintain serum potassium in normal limits

Mechanism of Action

Ranolazine exerts antianginal and anti-ischemic effects without changing hemodynamic parameters (heart rate or blood pressure). At therapeutic levels, ranolazine inhibits the late phase of the inward sodium channel (late INa) in ischemic cardiac myocytes during cardiac repolarization reducing intracellular sodium concentrations and thereby reducing calcium influx via Na+-Ca2+ exchange. Decreased intracellular calcium reduces ventricular tension and myocardial oxygen consumption. It is thought that ranolazine produces myocardial relaxation and reduces anginal symptoms through this mechanism although this is uncertain. At higher concentrations, ranolazine inhibits the rapid delayed rectifier potassium current (IKr) thus prolonging the ventricular action potential duration and subsequent prolongation of the QT interval.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Highly variable.

Protein binding: ~62%.

Metabolism: Extensive; Hepatic via CYP3A (major) and 2D6 (minor); intestines.

Bioavailability: 76% (compared to solution).

Half-life elimination: Ranolazine: Terminal: 7 hours; Metabolites (active and inactive [Yao 2009]): 6 to 22 hours.

Time to peak, plasma: 2 to 5 hours.

Excretion: Primarily urine (75% mostly as active and inactive metabolites; <5% as unchanged drug); feces (25% mostly as active and inactive metabolites; <5% as unchanged drug).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: AUC0-12 geometric mean ratio values 1.72, 1.8, and 1.97 in patients with CrCl >50 to 80 mL/minute, 30 to 50 mL/minute, and <30 mL/minute, respectively, versus patients with normal kidney function. CVT-2738 (active metabolite) AUC0-12 increased 81%, 276%, and 375% in patients with CrCl >50 to 80 mL/minute, 30 to 50 mL/minute, and <30 mL/minute, respectively, versus patients with normal kidney function (Jerling 2005).

Hepatic function impairment: Cmax is increased by 30% in cirrhotic patients with mild (Child-Pugh class A) hepatic impairment and 80% in cirrhotic patients with moderate (Child-Pugh class B) hepatic impairment.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Ranexa;
  • (AT) Austria: Ranexa;
  • (BD) Bangladesh: Ralozine | Ranola | Ranolin | Ranozex;
  • (BG) Bulgaria: Ranexa;
  • (BR) Brazil: Riscard;
  • (CH) Switzerland: Ranexa;
  • (CO) Colombia: Civenistu | Ranexicor;
  • (DE) Germany: Ranexa;
  • (DO) Dominican Republic: Ranexa | Ranolazina;
  • (EE) Estonia: Ranexa;
  • (ES) Spain: Ranexa;
  • (ET) Ethiopia: Rancv;
  • (GB) United Kingdom: Ranexa;
  • (GR) Greece: Ranexa;
  • (HK) Hong Kong: Ranexa;
  • (HR) Croatia: Ranexa;
  • (IE) Ireland: Ranexa;
  • (IN) India: Angicorn | Angidil sr | Angiotec | Caroza | Cartinex | Corvela | Nefazor.xr | Ran CV | Rancad | Randear | Rangil | Ranogard | Ranolaz | Ranopill | Ranozex | Ranx | Ranz | Razine | Razona | Razonin | Revulant | Rolazin | Rozo | Synx;
  • (IT) Italy: Ranexa;
  • (JO) Jordan: Ranexa;
  • (KE) Kenya: Cartinex | Rancv | Ranexa;
  • (KR) Korea, Republic of: Ranexa sr;
  • (LB) Lebanon: Ranexa;
  • (LT) Lithuania: Ranexa;
  • (LV) Latvia: Ranexa;
  • (MY) Malaysia: Ranexa;
  • (NG) Nigeria: Rancv;
  • (NO) Norway: Ranexa;
  • (PE) Peru: Rancv;
  • (PH) Philippines: Ranexa | Razine;
  • (PK) Pakistan: Angibar xr | Angiwell xr | Cardazin xr | Ranagin xr | Rancard xr | Ranogen er | Ranogin er | Ranola | Ranx | Ranzol xr | Rolazin er | Valazor;
  • (PL) Poland: Ranexa;
  • (PR) Puerto Rico: Aspruzyo sprinkle | Ranolazine extended release;
  • (PT) Portugal: Ranexa;
  • (QA) Qatar: Ranexa;
  • (RO) Romania: Ranexa;
  • (RU) Russian Federation: Ranexa;
  • (SG) Singapore: Ranexa;
  • (SI) Slovenia: Ranexa;
  • (TH) Thailand: Ranexa;
  • (TR) Turkey: Latixa | Razina;
  • (TW) Taiwan: Rancad;
  • (UA) Ukraine: Ranexa;
  • (UG) Uganda: Rancv
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