Razine Adverse Reactions

375 mg tablet: Undesirable effects in patients receiving Ranolazine are generally mild to moderate in severity and often develop within the first 2 weeks of treatment. The adverse events, considered to be at least possibly related to treatment, are listed below by body system, organ class, and absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), and very rare (<1/10,000).
Metabolism and nutrition disorders: Uncommon: anorexia, decreased appetite, dehydration.
Rare: hyponatremia.
Psychiatric disorders: Uncommon: anxiety, insomnia, confusional state, hallucination.
Rare: disorientation.
Nervous system disorders: Common: dizziness, headache.
Uncommon: lethargy, syncope, hypoesthesia, somnolence, tremor, postural dizziness, paresthesia.
Rare: amnesia, depressed level of consciousness, loss of consciousness, abnormal coordination, gait disturbance, parosmia.
Eye disorders: Uncommon: blurred vision, visual disturbance, and diplopia.
Ear and labyrinth disorders: Uncommon: vertigo, tinnitus.
Rare: impaired hearing.
Vascular disorders: Uncommon: hot flush, hypotension.
Rare: peripheral coldness, orthostatic hypotension.
Respiratory, thoracic, and mediastinal disorders: Uncommon: dyspnea, cough, epistaxis.
Rare: throat tightness.
Gastrointestinal disorders: Common: constipation, vomiting, nausea.
Uncommon: abdominal pain, dry mouth, dyspepsia, flatulence, stomach discomfort.
Rare: pancreatitis, erosive duodenitis, oral hypoesthesia.
Skin and subcutaneous tissue disorders: Uncommon: pruritus, hyperhidrosis.
Rare: angioedema, allergic dermatitis, urticaria, cold sweat, rash.
Musculoskeletal and connective tissue disorders: Uncommon: pain in extremity, muscle cramp, joint swelling, muscular weakness.
Renal and urinary disorders: Uncommon: dysuria, hematuria, chromaturia.
Rare: acute renal failure, urinary retention.
Reproductive system and breast disorders: Rare: erectile dysfunction.
General disorders and administration site conditions: Common: asthenia.
Uncommon: fatigue, peripheral edema.
Laboratory findings: Small, clinically insignificant, reversible elevations in serum creatinine levels have been observed in healthy subjects and patients treated with Ranolazine. There was no renal toxicity related to these findings. A renal function study in healthy volunteers demonstrated a reduction in creatinine clearance with no change in glomerular filtration rate consistent with inhibition of renal tubular secretion of creatinine.
500 mg tablet: 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 1 g 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: bradycardia, palpitations.
Ear and Labyrinth Disorders: tinnitus, vertigo.
Gastrointestinal Disorders: abdominal pain, dry mouth, vomiting.
General Disorders and Administrative Site Adverse Events: peripheral edema.
Respiratory, Thoracic, and Mediastinal Disorders: dyspnea.
Vascular Disorders: 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.
Laboratory Abnormalities: 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 1 g 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.