(ra noe' la zeen)
|| See TERMINOLOGY & ABBREVIATIONS ||
|Content & Description||
Tablet, Film Coated, Extended Release ranolazine 500mg & 1000mg.
Ranolazine is available as a film-coated, non-scored, extended-release tablet for oral administration.
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.
|Indication(s) & Dosage||
Ranolazine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies (such as beta-blockers and/or calcium antagonists).
Initiate Ranolazine dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms. Take Ranolazine with or without meals. Swallow Ranolazine tablets whole; do not crush, break, or chew.
In an oral high-dose tolerability study in angina patients, the incidence of dizziness, nausea, and vomiting increased in a dose-dependent manner. In addition to these adverse events, diplopia, lethargy, and syncope were observed in an intravenous overdose study in healthy volunteers. In the event of overdose, the patient should be closely monitored and the treatment should be symptomatic and supportive.
Approximately 62% of ranolazine is bound to plasma proteins, and therefore, complete clearance by haemodialysis is unlikely.
|Contraindications||Ranolazine is contraindicated in patients:
|Warnings & Precautions||
â€¢ 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.
|Pregnancy Category (FDA) and use in Specific Population||
USE IN SPECIFIC POPULATIONS
|Adverse Drug Reaction(s)
||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 2,018 patients with chronic angina were treated with ranolazine in controlled clinical trials. Of the patients treated with Ranolazine, 1,026 were enrolled in three double-blind, placebo-controlled, randomized studies (CARISA, ERICA, MARISA) of up to 12 weeks duration. In addition, upon study completion, 1,251 patients received treatment with Ranolazine in open-label, long-term studies; 1,227 patients were exposed to Ranolazine 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 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 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 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 2.0% in patients treated with Ranolazine and were more frequent than the incidence observed in placebo-treated patients:
Cardiac Disorders â€“ bradycardia, palpitations
Ear and Labyrinth Disorders â€“ tinnitus, vertigo
Gastrointestinal Disorders â€“ abdominal pain, dry mouth, vomiting
General Disorders and Administrative Site Adverse Events â€“ peripheral edema
Respiratory, Thoracic, and Mediastinal Disorders â€“ dyspnea
Vascular Disorders â€“ hypotension, orthostatic hypotension
Other (< 0.5%) but potentially medically important adverse reactions observed more frequently with Ranolazine than placebo treatment in all controlled studies included: angioedema, renal failure, eosinophilia, blurred vision, confusional state, hematuria, 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, but there was no apparent proarrhythmic effect in these high-risk patients.
Ranolazine produces small reductions in hemoglobin A1c. Ranolazine is not a treatment for diabetes.
Ranolazine produces elevations of serum creatinine by 0.1 mg/dL, regardless of previous renal function. The elevation has a rapid onset, shows no signs of progression during long-term therapy, is reversible after discontinuation of Ranolazine, and is not accompanied by changes in BUN. In healthy volunteers, Ranolazine 1000 mg twice daily had no effect upon the glomerular filtration rate. The elevated creatinine levels are likely due to a blockage of creatinine's tubular secretion by ranolazine or one of its metabolites.
Effects of Other Drugs on Ranolazine
CYP3A and P-gp Inducers
|Storage||Store Ranolazine tablets at 25Â°C (77Â°F) with excursion permitted to 15Â° to 30Â°C (59Â° to 86Â°F).|
Chronic Stable Angina
Tolerance to Ranolazine did not develop after 12 weeks of therapy. Rebound increases in angina, as measured by exercise duration, have not been observed following abrupt discontinuation of Ranolazine.
Ranolazine has been evaluated in patients with chronic angina who remained symptomatic despite treatment with the maximum dose of an antianginal agent. In the ERICA (Efficacy of Ranolazine In Chronic Angina) trial, 565 patients were randomized to receive an initial dose of Ranolazine 500 mg twice daily or placebo for 1 week, followed by 6 weeks of treatment with Ranolazine 1000 mg twice daily or placebo, in addition to concomitant treatment with amlodipine 10 mg once daily. In addition, 45% of the study population also received long-acting nitrates. Sublingual nitrates were used as needed to treat angina episodes. Results are shown in Table 3. Statistically significant decreases in angina attack frequency (p = 0.028) and nitroglycerin use (p = 0.014) were observed with Ranolazine compared to placebo. These treatment effects appeared consistent across age and use of long-acting nitrates.
Effects on angina frequency and exercise tolerance were considerably smaller in women than in men. In CARISA, the improvement in Exercise Tolerance Test (ETT) in females was about 33% of that in males at the 1000 mg twice-daily dose level. In ERICA, where the primary endpoint was angina attack frequency, the mean reduction in weekly angina attacks was 0.3 for females and 1.3 for males.
There were insufficient numbers of non-Caucasian patients to allow for analyses of efficacy or safety by racial subgroup.
Lack of Benefit in Acute Coronary Syndrome
In a large (n = 6,560) placebo-controlled trial (MERLIN-TIMI 36) in patients with acute coronary syndrome, there was no benefit shown on outcome measures. However, the study is somewhat reassuring regarding proarrhythmic risks, as ventricular arrhythmias were less common on ranolazine, and there was no difference between Ranolazine and placebo in the risk of all-cause mortality (relative risk ranolazine:placebo 0.99 with an upper 95% confidence limit of 1.22).
|Brand Name||Manufacturer/Marketer||Composition||Dosage Form||Pack Size & Price|
|Ralozine SR||Incepta Pharmaceuticals Limited||Ranolazine INN 500 mg||Film Coated Tablet||20's:MRP 320 Tk|
|RANOLA ER||General Pharmaceuticals Ltd||Ranolazine INN 500mg||Tablet (extended release)||500mg x 20's: 280.00 MRP|
|RANOLIN XR||Square Pharmaceuticals Ltd.||Ranolazine 500mg||Tablet||2x10's: 321.00 MRP|
|RANOLIN XR 500mg||Square Pharmaceuticals Ltd.||Ranolazine 500mg||Tablet||20's: 320.00 MRP|
Why is this medication prescribed?
Ranolazine is used alone or with other medications to treat ongoing angina (chest pain or pressure that is felt when the heart does not get enough oxygen). Ranolazine is in a class of medications called anti-anginals. The exact way that ranolazine works is not known at this time.
How should this medicine be used?
Ranolazine comes as an extended-release (long-acting) tablet to take by mouth. It is usually taken with or without food two times a day. Take ranolazine at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor to explain any part you do not understand. Take ranolazine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the tablets whole; do not break, chew, or crush them.
Your doctor will probably start you on a low dose of ranolazine and gradually increase your dose.
Do not take ranolazine to treat a sudden attack of angina. Your doctor will tell you what you should do if you experience an attack of angina. Make sure that you understand these directions.
Ranolazine may help control your condition but will not cure it. Continue to take ranolazine even if you feel well. Do not stop taking ranolazine without talking to your doctor.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor for more information.
What special precautions should I follow?
Before taking ranolazine,
- tell your doctor if you are allergic to ranolazine or any other medications.
- tell your doctor if you are taking any of the following medications: clarithromycin; certain antifungals such as itraconazole and ketoconazole (Nizoral); certain medications to treat human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) such as indinavir, nelfinavir, ritonavir, and saquinavir; nefazodone; certain medications for seizures such as carbamazepine, phenobarbital, and phenytoin; rifabutin; rifampin; and rifapentin . Also tell your doctor if you are taking St. John's wort. Your doctor may tell you not to take ranolazine if you are taking one or more of these medications or herbal products.
- tell your doctor what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: amiodarone; certain antidepressants such as amitriptyline, clomipramine, desipramine, and imipramine; aprepitant; cisapride ; cyclosporine; digoxin; diltiazem; disopyramide; dofetilide; erythromycin; fluconazole; certain medications for mental illness such as haloperidol, risperidone, thioridazine, and ziprasidone; moxifloxacin; pimozide; procainamide; quinidine; sotalol; sparfloxacin ; and verapamil . Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with ranolazine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list or the list above.
- tell your doctor if you have or have ever had liver disease. Your doctor may tell you that you should not take ranolazine.
- tell your doctor if you or anyone in your family has or has ever had a prolonged QT interval (a rare heart problem that may cause fainting or irregular heartbeat) or a fast, slow, or irregular heartbeat. Also tell your doctor if you have or have ever had an abnormal electrocardiogram (EKG: heart rhythm test), low levels of potassium in the blood, or kidney disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking ranolazine, call your doctor.
- you should know that ranolazine may make you dizzy and lightheaded. Do not drive a car, operate machinery, or participate in activities requiring mental alertness and coordination until you know how this medication affects you.
What special dietary instructions should I follow?
Do not drink grapefruit juice or eat grapefruit products while taking this medication.
What should I do if I forget a dose?
Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Ranolazine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
fast, pounding, or irregular heartbeat
Ranolazine may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.
Symptoms of overdose may include:
pain, burning, numbness, or tingling in any part of the body
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to this medicine.
Do not let anyone else use your medication. If you still have symptoms and need further treatment, consult your doctor.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Ref: U.S. National Library of Medicine.
This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.
|| See Brand Manufacturer's Prescribing Information |||| RANOLAZINE ||