Ranexa Information
Ranexa (Ranolazine) Dosage And Administration
Initiate Ranexa (Ranolazine) dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms. Take Ranexa (Ranolazine) with or without meals. Swallow Ranexa (Ranolazine) tablets whole; do not crush, break, or chew.
The maximum recommended daily dose of Ranexa (Ranolazine) is 1000 mg twice daily.
If a dose of Ranexa (Ranolazine) is missed, take the prescribed dose at the next scheduled time; do not double the next dose.
Ranexa (Ranolazine) Dosage Forms And Strengths
Ranexa (Ranolazine) is supplied as film-coated, oblong-shaped, extended-release tablets in the following strengths:
Ranexa (Ranolazine) Contraindications
Ranexa (Ranolazine) is contraindicated in patients:
Ranexa (Ranolazine) Use In Specific Populations
A population pharmacokinetic evaluation of data from angina patients and healthy subjects showed no effect of diabetes on ranolazine pharmacokinetics. No dose adjustment is required in patients with diabetes.
Ranexa (Ranolazine) produces small reductions in HbA1c in patients with diabetes, the clinical significance of which is unknown. Ranexa (Ranolazine) should not be considered a treatment for diabetes.
Ranexa (Ranolazine) Overdosage
High oral doses of ranolazine produce dose-related increases in dizziness, nausea, and vomiting. High intravenous exposure also produces diplopia, paresthesia, confusion, and syncope. In addition to general supportive measures, continuous ECG monitoring may be warranted in the event of overdose.
Since ranolazine is about 62% bound to plasma proteins, hemodialysis is unlikely to be effective in clearing ranolazine.
Ranexa (Ranolazine) Description
Ranexa (Ranolazine) is available as a film-coated, non-scored, extended-release tablet for oral administration.
Ranolazine is a racemic mixture, chemically described as 1-piperazineacetamide, -(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-, (±)-. It has an empirical formula of CHNO, 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.
Ranexa (Ranolazine) tablets contain 500 mg or 1000 mg of ranolazine and the following inactive ingredients: carnauba wax, hypromellose, magnesium stearate, methacrylic acid copolymer (Type C), microcrystalline cellulose, polyethylene glycol, sodium hydroxide, and titanium dioxide. Additional inactive ingredients for the 500 mg tablet include polysorbate 80 and FD&C Yellow No. 6 Lake; additional inactive ingredients for the 1000 mg tablet include lactose monohydrate, triacetin, and Iron Oxide Yellow.
Ranexa (Ranolazine) Clinical Pharmacology
The mechanism of action of ranolazine's antianginal effects has not been determined. Ranolazine has anti-ischemic and antianginal effects that do not depend upon reductions in heart rate or blood pressure. It does not affect the rate-pressure product, a measure of myocardial work, at maximal exercise. Ranolazine at therapeutic levels can inhibit the cardiac late sodium current (I). However, the relationship of this inhibition to angina symptoms is uncertain.
The QT prolongation effect of ranolazine on the surface electrocardiogram is the result of inhibition of I, which prolongs the ventricular action potential.
Ranexa (Ranolazine) Nonclinical Toxicology
Ranolazine tested negative for genotoxic potential in the following assays: Ames bacterial mutation assay, Saccharomyces assay for mitotic gene conversion, chromosomal aberrations assay in Chinese hamster ovary (CHO) cells, mammalian CHO/HGPRT gene mutation assay, and mouse and rat bone marrow micronucleus assays.
There was no evidence of carcinogenic potential in mice or rats. The highest oral doses used in the carcinogenicity studies were 150 mg/kg/day for 21 months in rats (900 mg/m/day) and 50 mg/kg/day for 24 months in mice (150 mg/m/day). These maximally tolerated doses are 0.8 and 0.1 times, respectively, the maximum recommended human dose (MRHD) of 2 grams on a surface area basis. A published study reported that ranolazine promoted tumor formation and progression to malignancy when given to transgenic APC (min/+) mice at a dose of 30 mg/kg twice daily . The clinical significance of this finding is unclear.
Animal reproduction studies with ranolazine were conducted in rats and rabbits.
There was an increased incidence of misshapen sternebrae and reduced ossification of pelvic and cranial bones in fetuses of pregnant rats dosed at 400 mg/kg/day (2 times the MRHD on a surface area basis). Reduced ossification of sternebrae was observed in fetuses of pregnant rabbits dosed at 150 mg/kg/day (1.5 times the MRHD on a surface area basis). These doses in rats and rabbits were associated with an increased maternal mortality rate.
Ranexa (Ranolazine) Clinical Studies
CARISA (Combination Assessment of Ranolazine In Stable Angina) was a study in 823 chronic angina patients randomized to receive 12 weeks of treatment with twice-daily Ranexa (Ranolazine) 750 mg, 1000 mg, or placebo, who also continued on daily doses of atenolol 50 mg, amlodipine 5 mg, or diltiazem CD 180 mg. Sublingual nitrates were used in this study as needed.
In this trial, statistically significant (p
The effects of Ranexa (Ranolazine) on angina frequency and nitroglycerin use are shown in Table 2.
Tolerance to Ranexa (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 Ranexa (Ranolazine) .
Ranexa (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 Ranexa (Ranolazine) 500 mg twice daily or placebo for 1 week, followed by 6 weeks of treatment with Ranexa (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 Ranexa (Ranolazine) compared to placebo. These treatment effects appeared consistent across age and use of long-acting nitrates.
Ranexa (Ranolazine) References
M.A. Suckow et al. The anti-ischemia agent ranolazine promotes the development of intestinal tumors in APC (min/+) mice. Cancer Letters 209(2004):165−9.
Ranexa (Ranolazine) How Supplied/storage And Handling
Ranexa (Ranolazine) is supplied as film-coated, oblong-shaped, extended-release tablets in the following strengths:
Ranexa (Ranolazine) extended-release tablets are available in:
Ranexa (Ranolazine) Patient Counseling Information
To ensure safe and effective use of Ranexa (Ranolazine) , the following information and instructions should be communicated to the patient when appropriate.
Patients should be advised:
Ranexa (Ranolazine)
Ranexa (Ranolazine)
Ranexa (Ranolazine)
