ADVERSE REACTIONS
Of the patients treated with Ranexa, 1,026 were enrolled in three double-blind, placebo-controlled, randomized studies of up to 12 weeks duration. In addition, upon study completion, 746 patients received continued treatment with Ranexa in open-label, long-term studies; 639 patients were exposed to Ranexa for more than 1 year, 578 patients for more than 2 years and 372 for more than 3 years. Subgroup evaluations in patients with reactive airway disease, CHF, and diabetes were also conducted. These conditions did not alter the general nature or frequency of treatment-emergent adverse events observed in the broader ranolazine-treated population.
In controlled clinical trials of angina patients, the most frequently reported treatment-emergent adverse events (> 4%), occurring more often with ranolazine than placebo, were dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%). In open-label, long-term treatment studies, a similar adverse event profile was observed in patients treated with ranolazine.
About 6% of patients discontinued treatment with Ranexa due to 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%), and nausea (1% versus 0%), asthenia, constipation and headache (each about 0.5% versus 0%).
Small, reversible elevations in serum creatinine and BUN levels have been observed in clinical studies with ranolazine. These elevations were observed without evidence of renal toxicity (see PRECAUTIONS and Laboratory Tests).
Adverse Events Occurring at an Incidence of ≥ 2% Among Ranexa - treated Angina Patients in the CARISA and ERICA Trials
The most commonly observed treatment-emergent adverse events for chronic angina patients from CARISA and ERICA that occurred more frequently with ranolazine than placebo are shown in Table 4.
Table 4: Treatment-Emergent Adverse Events in CARISA and ERICA (≥ 2% in Ranexa-treated Patients) | Number (%) of Angina Patients |
| Placebo
(N = 552) | Ranexa*
(N = 835) |
| *Doses include 500 mg b.i.d., 750 mg b.i.d., and 1000 mg b.i.d. |
| Gastrointestinal Disorders |
| Constipation | 9 (2) | 63 (8) |
| Nausea | 5 (1) | 33 (4) |
| Nervous System Disorders |
| Dizziness | 12 (2) | 41 (5) |
| Headache | 11 (2) | 22 (3) |
The dose-related adverse events of dizziness and syncope are shown in Table 5.
Table 5: Incidence of Dizziness and Syncope in CARISA and ERICA | Number (%) of Angina Patients |
| Placebo
(N = 552) | Ranexa 750 mg b.i.d.
(N = 279) | Ranexa 1000 mg b.i.d.
(N = 556) |
| Dizziness | 12 (2) | 10 (4) | 31 (6) |
| Syncope | 0 | 0 | 4 (0.7) |
Adverse Events Occurring Among All Ranolazine - treated Patients with Chronic Angina
A total of 2,018 patients with chronic angina were treated with ranolazine in controlled clinical trials.
The following additional adverse events 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 – 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
Other more rare (≤ 0.5%) but potentially medically important adverse events observed more frequently with ranolazine than placebo treatment in controlled studies included: bradycardia, hematuria, hypoesthesia, hypotension, orthostatic hypotension, paresthesia, tremor, and blurred vision.
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