Zolmitriptan

ZOLMITRIPTAN- zolmitriptan spray
Padagis Israel Pharmaceuticals Ltd

1 INDICATIONS AND USAGE

Zolmitriptan Nasal Spray is indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older.

Limitations of Use:

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Only use zolmitriptan if a clear diagnosis of migraine has been established. If a patient has no response to zolmitriptan treatment for the first migraine attack, reconsider the diagnosis of migraine before zolmitriptan is administered to treat any subsequent attacks.

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Zolmitriptan is not indicated for the prevention of migraine attacks.

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Safety and effectiveness of zolmitriptan have not been established for cluster headache.

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Not recommended in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.2) ].

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Information

The recommended starting dose for zolmitriptan nasal spray in adult and pediatric patients 12 years of age and older is 2.5 mg. As the individual response to zolmitriptan nasal spray may vary, the dose should be adjusted on an individual basis. The maximum recommended single dose of zolmitriptan is 5 mg.

If the migraine has not resolved by 2 hours after taking zolmitriptan, or returns after a transient improvement, another dose may be administered at least 2 hours after the previous dose.

The maximum daily dose should not exceed 10 mg in any 24-hour period.

The safety of zolmitriptan in the treatment of an average of more than four headaches in a 30-day period has not been established.

2.2 Dosing in Patients with Hepatic Impairment

Zolmitriptan nasal spray is not recommended in patients with moderate to severe hepatic impairment because of increased zolmitriptan blood levels in these patients and elevation of blood pressure in some of these patients. The recommended dosage of zolmitriptan nasal spray in patients with mild hepatic impairment is the same as for patients with normal hepatic function [see Dosage and Administration (2.1), Warnings and Precautions (5.8), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.3 Dosing in Patients taking Cimetidine

If zolmitriptan is co-administered with cimetidine, limit the maximum single dose of zolmitriptan to 2.5 mg, not to exceed 5 mg in any 24-hour period [see Drug Interactions (7.4) and Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Nasal Spray 2.5 mg and 5 mg.

4 CONTRAINDICATIONS

Zolmitriptan is contraindicated in patients with:

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Ischemic coronary artery disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), other significant underlying cardiovascular disease, or coronary artery vasospasm including Prinzmetal’s angina [see Warnings and Precautions (5.1) ]

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Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2) ]

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History of stroke, transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at higher risk of stroke [see Warnings and Precautions (5.4) ]

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Peripheral vascular disease (PVD) [see Warnings and Precautions (5.5) ]

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Ischemic bowel disease [see Warnings and Precautions (5.5) ]

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Uncontrolled hypertension [see Warnings and Precautions (5.8) ]

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Recent use (i.e., within 24 hours) of another 5-HT₁ agonist, ergotamine-containing medication, or ergot-type medication (such as dihydroergotamine or methysergide) [see Drug Interactions (7.1, 7.3)]

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Concurrent administration of an MAO-A inhibitor or recent discontinuation of a MAO-A inhibitor (that is within 2 weeks) [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]

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Known hypersensitivity to zolmitriptan (angioedema and anaphylaxis seen) [see Adverse Reactions (6.2) ]

5 WARNINGS AND PRECAUTIONS

5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina

Zolmitriptan is contraindicated in patients with ischemic or vasospastic coronary artery disease (CAD). There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of zolmitriptan. Some of these reactions occurred in patients without known CAD. 5-HT₁ agonists including zolmitriptan may cause coronary artery vasospasm (Prinzmetal’s Angina), even in patients without a history of CAD.

Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving zolmitriptan. Do not administer zolmitriptan if there is evidence of CAD or coronary artery vasospasm [see Contraindications (4) ]. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administrating the first zolmitriptan dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following zolmitriptan administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of zolmitriptan.

5.2 Arrhythmias

Life-threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT₁ agonists. Discontinue zolmitriptan if these disturbances occur. Patients with Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders should not receive zolmitriptan [see Contraindications (4) ].

5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure

As with other 5-HT₁ agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with zolmitriptan and is usually non-cardiac in origin. However, if a cardiac origin is suspected, patients should be evaluated. Patients shown to have CAD and those with Prinzmetal’s variant angina should not receive 5-HT₁ agonists [see Contraindications (4) ].

5.4 Cerebrovascular Events

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred 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 5-HT₁ agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. Discontinue zolmitriptan if a cerebrovascular event occurs.

As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine, other potentially serious neurological conditions should be excluded. Zolmitriptan should not be administered to patients with a history of stroke or transient ischemic attack [see Contraindications (4) ].