Dosing and uses of Ranexa (ranolazine)
Adult dosage forms and strengths
tablet, extended-release
- 500mg
- 1,000mg
Angina
Chronic angina
500 mg PO BID initially; may increase to 1,000 mg PO BID, if needed
Dosage considerations
May be used concomitantly with beta blockers, nitrates, calcium channel blockers, antiplatelet therapy, lipid-lowering therapy, ACE inhibitors, and ARBs
Strong CYP3A4 inhibitors of inducers: Contraindicated
Coadministration with moderate CYP3A4 inhibitors: Not to exceed 500 mg PO BId
Coadministration with P-gp inhibitors (eg, cyclosporine): May require downward titration
Dosing Modifications
Renal impairment: Cmax increases between 40-50% in patients with mild, moderate, or severe renal impairment
Hepatic impairment
- Contraindicated for all degrees of hepatic impairment, due to 3-fold increased risk of QT prolongation
- Mild (Child-Pugh A): Cmax increases 30%
- Moderate (Child Pugh B): Cmax increases 80%
Administration
Swallow tablets whole; do not crush, chew, or split
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Ranexa (ranolazine) adverse (side) effects
>10%
Dizziness (5-13%)
1-10%
Nausea (4-9%)
Constipation (5-8%)
Headache (3-6%)
Syncope (3%)
Frequency not defined
Palpitations
Bradycardia
Peripheral edema
Prolonged QT intervaL
Abdominal pain
Dry mouth
Dyspepsia
Anorexia
Vomiting
Hematuria
Dyspnea
Tinnitus
Vertigo
Blurred vision
Vasovagal syncope
Confusional state
Hematuria
Hyperhidrosis
Postmarketing Reports
Neurologic: Tremor, paresthesia, hypoesthesia
Psychiatric: Hallucination
Angioedema
Rash
Pruritus
Orthostatic hypotension
Hypoglycemia (in diabetic patients on antidiabetic medication)
Warnings
Contraindications
Hepatic cirrhosis, including Child-Pugh class A (mild), B (moderate), and C (severe)
Strong CYP3A inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir)
CYP3A inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, rifabutin, rifapentine, St. John’s wort)
Cautions
Not for acute anginal episodes
While ACS patients appear not to be at increased risk for proarrhythmia or sudden death, ranolazine has been shown to block I-Kr and cause dose-related QTc-interval prolongation
Little data available on high doses (ie, >1000 mg BID), long exposure, concomitant use with QT interval-prolonging drugs, or potassium channel variants causing prolonged QT intervaL
Increased risk of QTc prolongation in patients with mild or moderate hepatic impairment
Acute renal failure reported in some patients with severe renal impairment (CrCl <30 mL/min); discontinue if marked increase in creatinine occurs with increased BUn
Individuals >75 years have higher incidence of adverse effects
Causes small reductions in HbA1c in patients with diabetes; must not be considered a treatment for diabetes
Avoid grapefruit products
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if excreted in breast milk; discontinue or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ranexa (ranolazine)
Mechanism of action
Antianginal effects not determined, but does not depend on HR or BP reduction; no effect on rate-pressure product at maximal exercise; shown to inhibit cardiac late sodium current (INA) at therapeutic levels
Absorption
Bioavailability: 76%; absorption is highly variable but is unaffected by food
Peak plasma time: 2-5 hr
Distribution
Protein bound: 62%
Metabolism
Intestine and liver (CYP3A4 and CYP2D6)
Enzymes inhibited: CYP3A4 (weak); CYP2D6 (moderate); both in vitro
Elimination
Half-life: 7 hr
Excretion: Urine (75%), feces (25%)
