Ranolazine is used for the management of stable ischemic heart disease patients with chronic angina, particularly those who fall into the following categories:

• Patients intolerant to Beta Blockers,
• When Beta Blockers are less effective
• Contraindication to a Beta Blocker as in asthma
• when the response to beta-blockers is insufficient, in conjunction with a beta blocker for symptomatic relief.
• in ventricular arrhythmia patients (off-label use)

Ranolazine Dose in Adults

Beta-blockers, nitrates, calcium channel blockers, statins, ace inhibitors, ARBs, and antiplatelets are all possible combinations with ranolazine.

Ranolazine Dose in patients with chronic angina:

• Initial dose: 500 mg twice daily. If the patient is symptomatic, increase the dose to 1000 mg twice daily (maximum dose: 1000 mg twice daily). In case of a missed dose, do not double the dose, give the drug at the next scheduled time.

Ranolazine Dose in ventricular arrhythmias:

• 500 mg to 1000 mg twice daily (Al-khatib)

Dose adjustment with concomitant medications:

• The concomitant use of ranolazine is contraindicated in patients with CYP3A inducers and strong CYP 3A inhibitors.
• Ranolazine dose should not exceed 500 mg twice daily in patients taking diltiazim, fluconazole, erythromycin, verapamil, and other moderate CYP3A inhibitors.

Ranolazine Dose in Childrens

Not recommended for use in children (Not studied)

Pregnancy Category D

• Adverse effects have been observed in animal studies.

Ranolazine during breastfeeding:

• Ranolazine excretion into breast milk is not known.
• The manufaturer recommends weighing benefits and risks in the mother and neonate.

Ranolazine Dose in Renal Disease:

• The manufacturer does not recommend any dose adjustment in patients with renal disease.
• However, the drug should be stopped in patients with acute renal failure.
• It has not been studied in patients with ESRD and those on dialysis.

Ranolazine Dose in Liver Disease:

• The manufacturer does not recommend any dose adjustment in liver disease.
• Ranolazine is contrainidcated in patients with decompensated cirrhosis.

Common side effects of Ranolazine include:

• Cardiovascular:
  • Bradycardia, palpitation, hypotension, edema, and prolonged QT interval.
• Central nervous system:
  • Dizziness, headache, confusion, vertigo, and syncope.
• Skin-related adverse effects:
  • hyperhidrosis
• Gastrointestinal effects:
  • Constipation, anorexia, abdominal pain, xerostomia, nausea, and dyspepsia.
• Genitourinary:
  • Hematuria
• Neuromuscular:
  • Weakness
• Respiratory:
  • Shortness of breath
• Ophthalmic:
  • blurred vision
• ENT-related effects:
  • Tinnitus

Contraindications to Ranolazine:

Decompensated cirrhosis, concurrent use of strong CYP3A inhbitors, and CYP3A inducers.

Warnings & Precautions:

• There is a risk of QT interval prolongation.
• The risk is increased in patients with liver disease.
• Ranolazine should not be advised to patients who are on other drugs that cause QT interval prolongation, Known cardiac patients with QT interval prolongation including both acquired and congenital forms.
• It should not be used in patients with acute Myocardial infarction or angina.
• It should not be used in Liver disease and can also result in acute renal failure. A sudden rise in BUN and creatinine may occur with ranolazine. The drug should be stopped in such cases.
• Potential drug interactions may occur and adverse effects may be more common and serious in elderly patients.

Monitoring Parameters:

• ECG should be ordered at baseline and periodically for QT prolongation.
• Renal functions and electrolytes should be monitored periodically.
• The drug should be stopped in cases of an acute rise in BUN and creatinine.

How to Administer Ranolazine?

• Ranolazine may be taken with or without meals.
• The tablets should not be chewed, crushed or broken.

Mechanism of action of Ranolazine:

• Ranolzine inhibits the inward influx of Sodium channels in the late phase in ischemic cardiac myocytes during cardiac repolarization.
• The resulting reduced intracelluar calcium reduces myocardial oxygen consumption and produces myocardial relaxation.
• This results in an anti-anginal effect without a significant effect on the hemodynamic parameters like pulse rate and blood pressure.
• At higher doses, ranolazine results in QT prolongation via the prolongation of action potential

Absorption is highly variable

Metabolism is via the liver (extensive hepatic metabolism via CYP3A)

Bioavailability is 76%

Half-life elimination of ranolazine is 7 hours and the metabolites is 6 - 22 hours.

Time to peak plasma concentration is 2 - 5 hours

Excretion is primarily via the urine

International Brands of Ranolazine:

• Cartinex
• Cartinex-OD
• Ralozine
• Ranasafe
• Ranev
• Ranexa
• Ranola ER
• Ranolin XR
• Ranosin
• Ranx
• Razine

Ranolazine Brands in Pakistan:

• Rancard XR (searle pharma)
• Ranola (Highnoon pharma)
• Razin Er (Getz Pharma)
• Ranzol SR (Maple Pharma)