RANOLAZINE: 9,522 Adverse Event Reports & Safety Profile
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Drug Class: Anti-anginal [EPC] · Route: ORAL · Manufacturer: AvKARE · FDA Application: 021526 · HUMAN PRESCRIPTION DRUG · FDA Label: Available
Patent Expires: Jan 24, 2038 · First Report: 1985 · Latest Report: 20250918
What Are the Most Common RANOLAZINE Side Effects?
All RANOLAZINE Side Effects by Frequency
| Side Effect | Reports | % of Total | Deaths | Hosp. |
|---|---|---|---|---|
| Death | 692 | 7.3% | 687 | 45 |
| Myocardial infarction | 610 | 6.4% | 40 | 352 |
| Stent placement | 593 | 6.2% | 1 | 325 |
| Chest pain | 592 | 6.2% | 8 | 361 |
| Angina pectoris | 583 | 6.1% | 3 | 163 |
| Dizziness | 517 | 5.4% | 14 | 141 |
| Dyspnoea | 348 | 3.7% | 12 | 172 |
| Cerebrovascular accident | 334 | 3.5% | 15 | 162 |
| Fall | 299 | 3.1% | 20 | 197 |
| Off label use | 270 | 2.8% | 9 | 67 |
| Nausea | 266 | 2.8% | 5 | 63 |
| Cardiac disorder | 261 | 2.7% | 20 | 144 |
| Intentional product use issue | 261 | 2.7% | 0 | 105 |
| Diabetes mellitus | 257 | 2.7% | 4 | 41 |
| Malaise | 240 | 2.5% | 5 | 105 |
| Constipation | 236 | 2.5% | 1 | 34 |
| Headache | 212 | 2.2% | 3 | 48 |
| Hypoacusis | 199 | 2.1% | 1 | 45 |
| Product use issue | 197 | 2.1% | 3 | 81 |
| Cardiac operation | 191 | 2.0% | 0 | 111 |
Who Reports RANOLAZINE Side Effects? Age & Gender Data
Gender: 42.0% female, 58.0% male. Average age: 70.4 years. Most reports from: US. View detailed demographics →
Is RANOLAZINE Getting Safer? Reports by Year
| Year | Reports | Deaths | Hosp. |
|---|---|---|---|
| 2000 | 2 | 0 | 2 |
| 2001 | 3 | 0 | 2 |
| 2002 | 3 | 0 | 1 |
| 2003 | 1 | 0 | 0 |
| 2004 | 4 | 0 | 1 |
| 2006 | 10 | 0 | 3 |
| 2007 | 7 | 0 | 6 |
| 2008 | 11 | 0 | 5 |
| 2009 | 92 | 0 | 9 |
| 2010 | 35 | 0 | 13 |
| 2011 | 80 | 0 | 19 |
| 2012 | 77 | 8 | 21 |
| 2013 | 160 | 10 | 52 |
| 2014 | 307 | 36 | 113 |
| 2015 | 461 | 81 | 215 |
| 2016 | 520 | 104 | 247 |
| 2017 | 591 | 100 | 264 |
| 2018 | 800 | 103 | 402 |
| 2019 | 448 | 78 | 196 |
| 2020 | 92 | 10 | 31 |
| 2021 | 47 | 1 | 19 |
| 2022 | 64 | 1 | 18 |
| 2023 | 73 | 5 | 12 |
| 2024 | 66 | 7 | 20 |
| 2025 | 17 | 4 | 3 |
What Is RANOLAZINE Used For?
| Indication | Reports |
|---|---|
| Angina pectoris | 6,036 |
| Product used for unknown indication | 2,643 |
| Coronary artery disease | 128 |
| Chest pain | 80 |
| Myocardial ischaemia | 61 |
| Ventricular arrhythmia | 54 |
| Angina unstable | 44 |
| Cardiac disorder | 44 |
| Prinzmetal angina | 27 |
| Atrial fibrillation | 25 |
RANOLAZINE vs Alternatives: Which Is Safer?
Official FDA Label for RANOLAZINE
Official prescribing information from the FDA-approved drug label.
Drug Description
Ranolazine Extended-Release Tablets is available as a film-coated, non-scored, extended-release tablet for oral administration. Ranolazine is a racemic mixture, chemically described as 1-piperazineacetamide, N (2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-, (±)-. It has an empirical formula of C24H33N3O4, a molecular weight of 427.54 g/mole, and the following structural formula: Ranolazine is a white to off-white solid. Ranolazine is soluble in dichloromethane and methanol; sparingly soluble in tetrahydrofuran, ethanol, acetonitrile, and acetone; slightly soluble in ethyl acetate, isopropanol, toluene, and ethyl ether; and very slightly soluble in water.
Ranolazine
Extended-Release Tablets contain 500 mg or 1000 mg of ranolazine and the following inactive ingredients: microcrystalline cellulose, hydroxypropyl methylcellulose, methacrylic acid and ethyl acrylate copolymer, sodium lauryl sulfate, polysorbate 80, sodium hydroxide and magnesium stearate. Additional inactive ingredients for the 500 mg tablet include polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, iron oxide yellow and iron oxide red; additional inactive ingredients for the 1000 mg tablet include hypromellose, polydextrose, titanium dioxide, talc, maltodextrin, medium chain triglycerides and iron oxide yellow. chemicalstructure
FDA Approved Uses (Indications)
AND USAGE Ranolazine Extended-Release Tablets are indicated for the treatment of chronic angina.
Ranolazine
Extended-Release Tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti- platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers.
Ranolazine
Extended-Release Tablets is an antianginal indicated for the treatment of chronic angina. ( 1 )
Dosage & Administration
AND ADMINISTRATION 500 mg twice daily and increase to 1000 mg twice daily, based on clinical symptoms ( 2.1 )
2.1 Dosing Information Initiate Ranolazine Extended-Release Tablets dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms.
Take Ranolazine
Extended-Release Tablets with or without meals.
Swallow Ranolazine
Extended-Release Tablets whole; do not crush, break, or chew. The maximum recommended daily dose of Ranolazine Extended-Release Tablets is 1000 mg twice daily. If a dose of Ranolazine Extended-Release Tablets is missed, take the prescribed dose at the next scheduled time; do not double the next dose.
2.2 Dose Modification Dose adjustments may be needed when Ranolazine Extended-Release Tablets is taken in combination with certain other drugs <span class="opacity-50 text-xs">[see Drug Interactions (7.1) ]</span>. Limit the maximum dose of Ranolazine Extended-Release Tablets to 500 mg twice daily in patients on moderate CYP3A inhibitors such as diltiazem, verapamil, and erythromycin. Use of Ranolazine Extended-Release Tablets with strong CYP3A inhibitors is contraindicated <span class="opacity-50 text-xs">[see Contraindications (4) , Drug Interactions (7.1) ]</span>. Use of P-gp inhibitors, such as cyclosporine, may increase exposure to Ranolazine Extended-Release Tablets.
Titrate Ranolazine
Extended-Release Tablets based on clinical response [see Drug Interactions (7.1) ].
2.1 Dosing Information Initiate Ranolazine Extended-Release Tablets dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms.
Take Ranolazine
Extended-Release Tablets with or without meals.
Swallow Ranolazine
Extended-Release Tablets whole; do not crush, break, or chew. The maximum recommended daily dose of Ranolazine Extended-Release Tablets is 1000 mg twice daily. If a dose of Ranolazine Extended-Release Tablets is missed, take the prescribed dose at the next scheduled time; do not double the next dose.
2.2 Dose Modification Dose adjustments may be needed when Ranolazine Extended-Release Tablets is taken in combination with certain other drugs <span class="opacity-50 text-xs">[see Drug Interactions (7.1) ]</span>. Limit the maximum dose of Ranolazine Extended-Release Tablets to 500 mg twice daily in patients on moderate CYP3A inhibitors such as diltiazem, verapamil, and erythromycin. Use of Ranolazine Extended-Release Tablets with strong CYP3A inhibitors is contraindicated <span class="opacity-50 text-xs">[see Contraindications (4) , Drug Interactions (7.1) ]</span>. Use of P-gp inhibitors, such as cyclosporine, may increase exposure to Ranolazine Extended-Release Tablets.
Titrate Ranolazine
Extended-Release Tablets based on clinical response [see Drug Interactions (7.1) ].
Contraindications
Ranolazine extended-release tablets are contraindicated in patients: 1. Taking strong inhibitors of CYP3A [see Drug Interactions (7.1) ] 2. Taking inducers of CYP3A [see Drug Interactions (7.1) ] 3. With liver cirrhosis [see Use in Specific Populations (8.6) ] 4. Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) ( 4 , 7.1 ) 5. CYP3A inducers (e.g., rifampin, phenobarbital, St.John's wort) ( 4 , 7.1 ) 6. Liver cirrhosis ( 4 , 8.6 )
Known Adverse Reactions
REACTIONS Most common adverse reactions (>4% and more common than with placebo) are dizziness, headache, constipation, nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact A2A Integrated Pharmaceuticals at 1-800-380-6709 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 2018 patients with chronic angina were treated with ranolazine in controlled clinical trials. Of the patients treated with Ranolazine Extended-Release Tablets, 1026 were enrolled in three double-blind, placebo-controlled, randomized studies (CARISA, ERICA, MARISA) of up to 12 weeks’ duration. In addition, upon study completion, 1251 patients received treatment with Ranolazine Extended-Release Tablets in open-label, long-term studies; 1227 patients were exposed to Ranolazine Extended-Release Tablets for more than 1 year, 613 patients for more than 2 years, 531 patients for more than 3 years, and 326 patients for more than 4 years. At recommended doses, about 6% of patients discontinued treatment with Ranolazine Extended-Release Tablets because of an adverse event in controlled studies in angina patients compared to about 3% on placebo. The most common adverse events that led to discontinuation more frequently on Ranolazine Extended-Release Tablets than placebo were dizziness (1.3% versus 0.1%), nausea (1% versus 0%), asthenia, constipation, and headache (each about 0.5% versus 0%). Doses above 1000 mg twice daily are poorly tolerated. In controlled clinical trials of angina patients, the most frequently reported treatment- emergent adverse reactions (>4% and more common on Ranolazine Extended-Release Tablets than on placebo) were dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%). Dizziness may be dose-related. In open-label, long-term treatment studies, a similar adverse reaction profile was observed. The following additional adverse reactions occurred at an incidence of 0.5 to 4.0% in patients treated with Ranolazine Extended-Release Tablets and were more frequent than the incidence observed in placebo-treated patients: Cardiac Disorders – bradycardia, palpitations Ear and Labyrinth Disorders – tinnitus, vertigo Eye Disorders – blurred vision Gastrointestinal Disorders – abdominal pain, dry mouth, vomiting, dyspepsia General Disorders and Administrative Site Adverse Events – asthenia, peripheral edema Metabolism and Nutrition Disorders – anorexia Nervous System Disorders – syncope (vasovagal)
Psychiatric
Disorders – confusional state Renal and Urinary Disorders – hematuria Respiratory, Thoracic, and Mediastinal Disorders – dyspnea Skin and Subcutaneous Tissue Disorders – hyperhidrosis Vascular Disorders – hypotension, orthostatic hypotension Other (<0.5%) but potentially medically important adverse reactions observed more frequently with Ranolazine Extended-Release Tablets than placebo treatment in all controlled studies included: angioedema, renal failure, eosinophilia, chromaturia, blood urea increased, hypoesthesia, paresthesia, tremor, pulmonary fibrosis, thrombocytopenia, leukopenia, and pancytopenia. A large clinical trial in acute coronary syndrome patients was unsuccessful in demonstrating a benefit for Ranolazine Extended-Release Tablets, but there was no apparent proarrhythmic effect in these high-risk patients [see Clinical Studies (14.2)].
Laboratory
Abnormalities: Ranolazine Extended-Release Tablets produces elevations of serum creatinine by 0.1 mg/dL, regardless of previous renal function, likely because of inhibition of creatinine’s tubular secretion. In general, the elevation has a rapid onset, shows no signs of progression during long-term therapy, is reversible after discontinuation of Ranolazine Extended-Release Tablets, and is not accompanied by changes in BUN. In healthy volunteers, Ranolazine Extended-Release Tablets 1000 mg twice daily had no effect upon the glomerular filtration rate. More marked and progressive increases in serum creatinine, associated with increases in BUN or potassium, indicating acute renal failure, have been reported after initiation of Ranolazine Extended-Release Tablets in patients with severe renal impairment [see Warnings and Precautions (5.2) , Use in Specific Populations (8.7) ].
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of Ranolazine Extended-Release Tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Nervous System Disorders – Abnormal coordination, myoclonus, paresthesia, tremor, and other serious neurologic adverse events have been reported to occur, sometimes concurrently, in patients taking ranolazine. The onset of events was often associated with an increase in ranolazine dose or exposure. Many patients reported symptom resolution following drug discontinuation or dose decrease. Metabolism and Nutrition Disorders – Cases of hypoglycemia have been reported in diabetic patients on antidiabetic medication.
Psychiatric
Disorders – hallucination Renal and Urinary Disorders – dysuria, urinary retention Skin and Subcutaneous Tissue Disorders – angioedema, pruritus, rash
6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 2018 patients with chronic angina were treated with ranolazine in controlled clinical trials. Of the patients treated with Ranolazine Extended-Release Tablets, 1026 were enrolled in three double-blind, placebo-controlled, randomized studies (CARISA, ERICA, MARISA) of up to 12 weeks’ duration. In addition, upon study completion, 1251 patients received treatment with Ranolazine Extended-Release Tablets in open-label, long-term studies; 1227 patients were exposed to Ranolazine Extended-Release Tablets for more than 1 year, 613 patients for more than 2 years, 531 patients for more than 3 years, and 326 patients for more than 4 years. At recommended doses, about 6% of patients discontinued treatment with Ranolazine Extended-Release Tablets because of an adverse event in controlled studies in angina patients compared to about 3% on placebo. The most common adverse events that led to discontinuation more frequently on Ranolazine Extended-Release Tablets than placebo were dizziness (1.3% versus 0.1%), nausea (1% versus 0%), asthenia, constipation, and headache (each about 0.5% versus 0%). Doses above 1000 mg twice daily are poorly tolerated. In controlled clinical trials of angina patients, the most frequently reported treatment- emergent adverse reactions (>4% and more common on Ranolazine Extended-Release Tablets than on placebo) were dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%). Dizziness may be dose-related. In open-label, long-term treatment studies, a similar adverse reaction profile was observed. The following additional adverse reactions occurred at an incidence of 0.5 to 4.0% in patients treated with Ranolazine Extended-Release Tablets and were more frequent than the incidence observed in placebo-treated patients: Cardiac Disorders – bradycardia, palpitations Ear and Labyrinth Disorders – tinnitus, vertigo Eye Disorders – blurred vision Gastrointestinal Disorders – abdominal pain, dry mouth, vomiting, dyspepsia General Disorders and Administrative Site Adverse Events – asthenia, peripheral edema Metabolism and Nutrition Disorders – anorexia Nervous System Disorders – syncope (vasovagal)
Psychiatric
Disorders – confusional state Renal and Urinary Disorders – hematuria Respiratory, Thoracic, and Mediastinal Disorders – dyspnea Skin and Subcutaneous Tissue Disorders – hyperhidrosis Vascular Disorders – hypotension, orthostatic hypotension Other (<0.5%) but potentially medically important adverse reactions observed more frequently with Ranolazine Extended-Release Tablets than placebo treatment in all controlled studies included: angioedema, renal failure, eosinophilia, chromaturia, blood urea increased, hypoesthesia, paresthesia, tremor, pulmonary fibrosis, thrombocytopenia, leukopenia, and pancytopenia. A large clinical trial in acute coronary syndrome patients was unsuccessful in demonstrating a benefit for Ranolazine Extended-Release Tablets, but there was no apparent proarrhythmic effect in these high-risk patients [see Clinical Studies (14.2)].
Laboratory
Abnormalities: Ranolazine Extended-Release Tablets produces elevations of serum creatinine by 0.1 mg/dL, regardless of previous renal function, likely because of inhibition of creatinine’s tubular secretion. In general, the elevation has a rapid onset, shows no signs of progression during long-term therapy, is reversible after discontinuation of Ranolazine Extended-Release Tablets, and is not accompanied by changes in BUN. In healthy volunteers, Ranolazine Extended-Release Tablets 1000 mg twice daily had no effect upon the glomerular filtration rate. More marked and progressive increases in serum creatinine, associated with increases in BUN or potassium, indicating acute renal failure, have been reported after initiation of Ranolazine Extended-Release Tablets in patients with severe renal impairment [see Warnings and Precautions (5.2) , Use in Specific Populations (8.7) ].
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of Ranolazine Extended-Release Tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Nervous System Disorders – Abnormal coordination, myoclonus, paresthesia, tremor, and other serious neurologic adverse events have been reported to occur, sometimes concurrently, in patients taking ranolazine. The onset of events was often associated with an increase in ranolazine dose or exposure. Many patients reported symptom resolution following drug discontinuation or dose decrease. Metabolism and Nutrition Disorders – Cases of hypoglycemia have been reported in diabetic patients on antidiabetic medication.
Psychiatric
Disorders – hallucination Renal and Urinary Disorders – dysuria, urinary retention Skin and Subcutaneous Tissue Disorders – angioedema, pruritus, rash
Warnings
AND PRECAUTIONS
- QT interval prolongation: Can occur with ranolazine. Little data available on high doses, long exposure, use with QT interval-prolonging drugs, potassium channel variants causing prolonged QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation. ( 5.1 )
- Renal failure: Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL<60mL/min). If acute renal failure develops, discontinue Ranolazine Extended-Release Tablets. ( 5.2 )
5.1 QT Interval Prolongation Ranolazine blocks I Kr and prolongs the QTc interval in a dose-related manner. Clinical experience in an acute coronary syndrome population did not show an increased risk of proarrhythmia or sudden death <span class="opacity-50 text-xs">[see Clinical Studies (14.2) ]</span>. However, there is little experience with high doses (>1000 mg twice daily) or exposure, other QT-prolonging drugs, potassium channel variants resulting in a long QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation.
5.2 Renal Failure Acute renal failure has been observed in some patients with severe renal impairment (creatinine clearance [CrCL] <30 mL/min) while taking Ranolazine Extended-Release Tablets. If acute renal failure develops (e.g., marked increase in serum creatinine associated with an increase in blood urea nitrogen [BUN]), discontinue Ranolazine Extended-Release Tablets and treat appropriately <span class="opacity-50 text-xs">[see Use in Specific Populations (8.7) ]</span>. Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL <60 mL/min) for increases in serum creatinine accompanied by an increase in BUN.
5.1 QT Interval Prolongation Ranolazine blocks I Kr and prolongs the QTc interval in a dose-related manner. Clinical experience in an acute coronary syndrome population did not show an increased risk of proarrhythmia or sudden death <span class="opacity-50 text-xs">[see Clinical Studies (14.2) ]</span>. However, there is little experience with high doses (>1000 mg twice daily) or exposure, other QT-prolonging drugs, potassium channel variants resulting in a long QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation.
5.2 Renal Failure Acute renal failure has been observed in some patients with severe renal impairment (creatinine clearance [CrCL] <30 mL/min) while taking Ranolazine Extended-Release Tablets. If acute renal failure develops (e.g., marked increase in serum creatinine associated with an increase in blood urea nitrogen [BUN]), discontinue Ranolazine Extended-Release Tablets and treat appropriately <span class="opacity-50 text-xs">[see Use in Specific Populations (8.7) ]</span>. Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL <60 mL/min) for increases in serum creatinine accompanied by an increase in BUN.
Drug Interactions
INTERACTIONS
- Moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin): Limit Ranolazine Extended-Release Tablets to 500 mg twice daily. ( 7.1 )
- P-gp inhibitors (e.g., cyclosporine): Ranolazine exposure increased.
Titrate Ranolazine
Extended-Release Tablets based on clinical response. ( 7.1 )
- CYP3A substrates: Limit simvastatin to 20 mg when used with Ranolazine Extended-Release Tablets. Doses of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may need to be reduced with Ranolazine Extended-Release Tablets. ( 7.2 )
- OCT2 substrates: Limit the dose of metformin to 1700 mg daily when used with Ranolazine Extended-Release Tablets 1000 mg twice daily. Doses of other OCT2 substrates may require adjusted doses. ( 7.2 )
- Drugs transported by P-gp (e.g., digoxin), or drugs metabolized by CYP2D6 (e.g., tricyclic antidepressants) may need reduced doses when used with Ranolazine Extended-Release Tablets. ( 7.2 )
See
17 for PATIENT COUNSELING INFORMATION and FDA-Approved Patient Labeling
7.1 Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Do not use Ranolazine Extended-Release Tablets with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir <span class="opacity-50 text-xs">[see Contraindications (4) , Clinical Pharmacology (12.3) ]</span>. Moderate CYP3A Inhibitors Limit the dose of Ranolazine Extended-Release Tablets to 500 mg twice daily in patients on moderate CYP3A inhibitors, including diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) , Clinical Pharmacology (12.3) ]</span>. P-gp Inhibitors Concomitant use of Ranolazine Extended-Release Tablets and P-gp inhibitors, such as cyclosporine, may result in increases in ranolazine concentrations.
Titrate Ranolazine
Extended-Release Tablets based on clinical response in patients concomitantly treated with predominant P-gp inhibitors such as cyclosporine [see Dosage and Administration (2.2) ]. CYP3A Inducers Do not use Ranolazine Extended-Release Tablets with CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John’s wort [see Contraindications (4) , Clinical Pharmacology (12.3) ].
7.2 Effects of Ranolazine on Other Drugs Drugs Metabolized by CYP3A Limit the dose of simvastatin in patients on any dose of Ranolazine Extended-Release Tablets to 20 mg once daily, when ranolazine is co-administered. Dose adjustment of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with a narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may be required as Ranolazine Extended-Release Tablets may increase plasma concentrations of these drugs <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>.
Drugs
Transported by P-gp Concomitant use of ranolazine and digoxin results in increased exposure to digoxin. The dose of digoxin may have to be adjusted [see Clinical Pharmacology (12.3) ].
Drugs
Metabolized by CYP2D6 The exposure to CYP2D6 substrates, such as tricyclic antidepressants and antipsychotics, may be increased during co-administration with Ranolazine Extended-Release Tablets, and lower doses of these drugs may be required.
Drugs
Transported by OCT2 In subjects with type 2 diabetes mellitus, concomitant use of Ranolazine Extended-Release Tablets 1000 mg twice daily and metformin results in increased plasma levels of metformin.
When Ranolazine
Extended-Release Tablets 1000 mg twice daily is co-administered with metformin, metformin dose should not exceed 1700 mg/day. Monitor blood glucose levels and risks associated with high exposures of metformin. Metformin exposure was not significantly increased when given with Ranolazine Extended-Release Tablets 500 mg twice daily [see Clinical Pharmacology (12.3) ].
7.1 Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Do not use Ranolazine Extended-Release Tablets with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir <span class="opacity-50 text-xs">[see Contraindications (4) , Clinical Pharmacology (12.3) ]</span>. Moderate CYP3A Inhibitors Limit the dose of Ranolazine Extended-Release Tablets to 500 mg twice daily in patients on moderate CYP3A inhibitors, including diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) , Clinical Pharmacology (12.3) ]</span>. P-gp Inhibitors Concomitant use of Ranolazine Extended-Release Tablets and P-gp inhibitors, such as cyclosporine, may result in increases in ranolazine concentrations.
Titrate Ranolazine
Extended-Release Tablets based on clinical response in patients concomitantly treated with predominant P-gp inhibitors such as cyclosporine [see Dosage and Administration (2.2) ]. CYP3A Inducers Do not use Ranolazine Extended-Release Tablets with CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John’s wort [see Contraindications (4) , Clinical Pharmacology (12.3) ].
7.2 Effects of Ranolazine on Other Drugs Drugs Metabolized by CYP3A Limit the dose of simvastatin in patients on any dose of Ranolazine Extended-Release Tablets to 20 mg once daily, when ranolazine is co-administered. Dose adjustment of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with a narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may be required as Ranolazine Extended-Release Tablets may increase plasma concentrations of these drugs <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>.
Drugs
Transported by P-gp Concomitant use of ranolazine and digoxin results in increased exposure to digoxin. The dose of digoxin may have to be adjusted [see Clinical Pharmacology (12.3) ].
Drugs
Metabolized by CYP2D6 The exposure to CYP2D6 substrates, such as tricyclic antidepressants and antipsychotics, may be increased during co-administration with Ranolazine Extended-Release Tablets, and lower doses of these drugs may be required.
Drugs
Transported by OCT2 In subjects with type 2 diabetes mellitus, concomitant use of Ranolazine Extended-Release Tablets 1000 mg twice daily and metformin results in increased plasma levels of metformin.
When Ranolazine
Extended-Release Tablets 1000 mg twice daily is co-administered with metformin, metformin dose should not exceed 1700 mg/day. Monitor blood glucose levels and risks associated with high exposures of metformin. Metformin exposure was not significantly increased when given with Ranolazine Extended-Release Tablets 500 mg twice daily [see Clinical Pharmacology (12.3) ].