RANEXA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RANEXA (RANEXA).
Ranolazine, an antianginal agent, inhibits the late phase of the sodium inward current (late INa) in cardiac myocytes, reducing intracellular sodium and calcium overload, thereby improving diastolic tension and oxygen consumption.
| Metabolism | Extensively metabolized in the liver primarily by CYP3A4, also by CYP2D6. Undergoes oxidation, O-demethylation, and N-dealkylation. |
| Excretion | Primarily metabolized in the liver via CYP3A4 and CYP2D6; less than 5% excreted unchanged in urine. Renal excretion accounts for approximately 75% of total clearance (metabolites and unchanged drug). Fecal excretion accounts for about 25%. |
| Half-life | Terminal elimination half-life is approximately 7 hours (range 6–10 hours) after oral administration. In patients with renal impairment, half-life may be prolonged; no clinically significant accumulation with twice-daily dosing. |
| Protein binding | Approximately 62% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1 L/kg, indicating extensive tissue distribution. This large Vd reflects penetration into tissues including the myocardium. |
| Bioavailability | Oral bioavailability is approximately 76% (extended-release formulation). Food does not significantly affect bioavailability. |
| Onset of Action | Oral: Onset of anti-anginal effect occurs within 2–4 hours after a single dose. Peak effect may be seen after several days of regular dosing due to gradual metabolic modulation. |
| Duration of Action | Duration of anti-anginal effect is approximately 12 hours, supporting twice-daily dosing. Clinical improvement in exercise tolerance is sustained over the dosing interval. |
500 mg orally twice daily; may increase to 1000 mg twice daily based on clinical response.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | CKD-EPI eGFR 30-50 mL/min/1.73m²: 500 mg twice daily; eGFR <30 mL/min/1.73m²: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: use with caution, maximum 500 mg twice daily; Child-Pugh Class C: contraindicated. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | Start at 500 mg twice daily; monitor renal function and adjust per renal dosing; increased risk of adverse effects due to age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RANEXA (RANEXA).
| Breastfeeding | No data on human milk excretion; M/P ratio unknown. Use with caution; consider risk to infant. |
| Teratogenic Risk | Pregnancy Category C. Animal studies show fetal toxicity at high doses; no adequate human studies. Risk not ruled out; use only if benefit outweighs risk. First trimester: potential for harm unknown. Second and third trimesters: limited data, avoid unless necessary. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Severe renal impairment (CrCl <30 mL/min)","Severe hepatic impairment","Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) or inducers (e.g., rifampin)","Pre-existing QT prolongation or concurrent use of other QT-prolonging drugs"]
| Precautions | ["QT prolongation (dose-dependent; avoid in patients with pre-existing QT prolongation or with other QT-prolonging drugs)","Renal impairment (adjust dose for moderate impairment; contraindicated in severe impairment)","Hepatic impairment (contraindicated in severe impairment)","Concomitant use with strong CYP3A4 inhibitors (reduce dose) or inducers (avoid)"] |
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| Monitor maternal ECG for QT prolongation, renal function, and signs of hepatic toxicity. Fetal monitoring per standard obstetric care. |
| Fertility Effects | No specific human data; animal studies show no significant impact on fertility. |