Relpax Warnings, Precautions, Pregnancy, Nursing, Abuse - Eletriptan hydrobromide

Relpax Warnings, Precautions, Pregnancy, Nursing, Abuse - Eletriptan hydrobromide

WARNINGS

RELPAX Tablets should only be used where a clear diagnosis of migraine has been established. CYP3A4 Inhibitors: Eletriptan should not be used within at least 72 hours of treatment with the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir. Eletriptan should not be used within 72 hours with drugs that have demonstrated potent CYP3A4 inhibition and have this potent effect described in the CONTRAINDICATIONS, WARNINGS or PRECAUTIONS sections of their labeling (see CLINICAL PHARMACOLOGY: Drug Interactions and DOSAGE AND ADMINISTRATION). In a coronary angiographic study of rapidly infused intravenous eletriptan to concentrations exceeding those achieved with 80 mg oral eletriptan in the presence of potent CYP3A4 inhibitors, a small dose-related decrease in coronary artery diameter similar to that seen with a 6 mg subcutaneous dose of sumatriptan was observed. Risk of Myocardial Ischemia and/or Infarction and Other Cardiac Events: Because of the potential of 5-HT₁ agonists to cause coronary vasospasm, eletriptan should not be given to patients with documented ischemic or vasospastic coronary artery disease (CAD) (see CONTRAINDICATIONS). It is strongly recommended that eletriptan not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient’s medical history, electrocardiographic, or other investigations reveal findings indicative of, or consistent with coronary artery vasospasm or myocardial ischemia, eletriptan should not be administered (see CONTRAINDICATIONS).

Cardiac Events and Fatalities Associated With 5-HT₁ Agonists: Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported within a few hours following the administration of other 5-HT₁ agonists. Considering the extent of use of 5-HT1 agonists in patients with migraine, the incidence of these events is extremely low.

Premarketing experience with eletriptan among the 7,143 unique individuals who received eletriptan during pre-marketing clinical trials: In a clinical pharmacology study, in subjects undergoing diagnostic coronary angiography, a subject with a history of angina, hypertension and hypercholesterolemia, receiving intravenous eletriptan (Cmax of 127 ng/mL equivalent to 60 mg oral eletriptan), reported chest tightness and experienced angiographically documented coronary vasospasm with no ECG changes of ischemia. There was also one report of atrial fibrillation in a patient with a past history of atrial fibrillation. Postmarketing experience with eletriptan: There was one report of myocardial infarction and death in a patient with cardiovascular risk factors (hypertension, hyperlipidemia, strong family history of CAD) in association with inappropriate concomitant use of eletriptan and sumatriptan. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine definitively if the case was actually caused by eletriptan or to reliably assess causation in individual cases.

Cerebrovascular Events and Fatalities Associated With 5-HT₁ Agonists: Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with 5-HT₁ agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, and transient ischemic attack).

Other Vasospasm-Related Events: 5-HT₁ agonists may cause vasospastic reactions other than coronary artery vasospasm. Both peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported with 5-HT₁ agonists.

Increase in Blood Pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasion in patients receiving 5-HT₁ agonists with and without a history of hypertension. In clinical pharmacology studies, oral eletriptan (at doses of 60 mg or more) was shown to cause small, transient dose-related increases in blood pressure, predominantly diastolic, consistent with its mechanism of action and with other 5-HT_1B/1D agonists. The effect was more pronounced in renally impaired and elderly subjects. A single patient with hepatic cirrhosis received eletriptan 80 mg and experienced a blood pressure of 220/96 mm Hg five hours after dosing. The treatment related event persisted for seven hours. Eletriptan is contraindicated in patients with uncontrolled hypertension (see CONTRAINDICATIONS).

An 18% increase in mean pulmonary artery pressure was seen following dosing with another 5-HT₁ agonist in a study evaluating subjects undergoing cardiac catheterization.

As with other 5-HT₁ agonists, sensations of tightness, pain, pressure and heaviness have been reported after treatment with eletriptan in the precordium, throat, and jaw. Events that are localized to the chest, throat, neck and jaw have not been associated with arrhythmias or ischemic ECG changes in clinical trials; in a clinical pharmacology study of subjects undergoing diagnostic coronary angiography, one subject with a history of angina, hypertension and hypercholesterolemia, receiving intravenous eletriptan, reported chest tightness and experienced angiographically documented coronary vasospasm with no ECG changes of ischemia. Because 5-HT₁ agonists may cause coronary artery vasospasm, patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of CAD or a predisposition to Prinzmetal’s variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur. Similarly, patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud’s syndrome following the use of any 5-HT₁ agonist are candidates for further evaluation (see CONTRAINDICATIONS and WARNINGS).

Hepatically Impaired Patients: The effects of severe hepatic impairment on eletriptan metabolism was not evaluated. Subjects with mild or moderate hepatic impairment demonstrated an increase in both AUC (34%) and half-life. The C_max was increased by 18%. Eletriptan should not be used in patients with severe hepatic impairment. No dose adjustment is necessary in mild to moderate impairment (see DOSAGE AND ADMINISTRATION).

Binding to Melanin-Containing Tissues: In rats treated with a single intravenous (3 mg/kg) dose of radiolabeled eletriptan, elimination of radioactivity from the retina was prolonged, suggesting that eletriptan and/or its metabolites may bind to the melanin of the eye. Because there could be accumulation in melanin-rich tissues over time, this raises the possibility that eletriptan could cause toxicity in these tissues after extended use. Although no systematic monitoring of ophthalmologic function was undertaken in clinical trials, and no specific recommendations for ophthalmologic monitoring are offered, prescribers should be aware of the possibility of long-term ophthalmologic effects.

Corneal Opacities: Transient corneal opacities were seen in dogs receiving oral eletriptan at 5 mg/kg and above. They were observed during the first week of treatment, but were not present thereafter despite continued treatment. Exposure at the no-effect dose level of 2.5 mg/kg was approximately equal to that achieved in humans at the maximum recommended daily dose.

INFORMATION FOR PATIENTS

See PATIENT INFORMATION at the end of this labeling for the text of the separate leaflet provided for patients.

Laboratory Tests: No specific laboratory tests are recommended.