Naratriptan Hcl (naratriptan HCl)

Available as naratriptan hydrochloride; dosage is expressed in terms of naratriptan.

Naratriptan is available in a tablet formulation for oral administration. Naratriptan may be administered without regard to meals.

Tablets should be stored at 20-25degreesC.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

5-Ht1d Agonists/Ergot Alkaloids

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The 5-HT1D agonists and ergot alkaloids can produce vasospastic reactions.

CLINICAL EFFECTS: Concurrent therapy may produce additive vasospastic effects.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer states that sumatriptan should not be used within 24 hours of an ergotamine-containing or ergotamine-like medication (such as dihydroergotamine or methysergide).(1,2) The Australian(3) and UK(4,5) manufacturers state that 24 hours should elapse before sumatriptan is administered following an ergotamine-containing preparation and 6 hours should elapse before an ergotamine-containing preparation is administered following sumatriptan. The US manufacturer states that zolmitriptan should not be used within 24 hours of an ergotamine-containing or ergotamine-like medication.(6) The UK manufacturer states that zolmitriptan should not be used within 6 hours of an ergotamine-containing or ergotamine-like medication.(7) The The Australian manufacturer states that 24 hours should elapse before zolmitriptan is administered following an ergotamine-containing preparation and 6 hours should elapse before an ergotamine-containing medication is administered following zolmitriptan.(8) The US manufacturer states that the use of rizatriptan within 24 hours of an ergotamine-containing or ergot-type medication is contraindicated.(9) The US manufacturer states that the use of naratriptan within 24 hours of an ergotamine-containing or ergot-type medication is contraindicated.(10) The Australian manufacturer states that concurrent use of naratriptan and ergotamine or ergotamine derivatives is not recommended.(11) The US manufacturer states that the use of eletriptan within 24 hours of an ergotamine-containing or ergot-type medication is contraindicated.(12) The UK manufacturer states that the use of eletriptan within 24 hours of an ergotamine-containing or ergot-type medication is not recommended.(13)

DISCUSSION: Because of the theoretical risk of additive vasospastic effects, the US manufacturer states that the use of sumatriptan within 24 hours of an ergotamine-containing or ergotamine-like medication is contraindicated.(1,2) The Australian(3) and UK(4,5) manufacturer states that 24 hours should elapse before sumatriptan is administered following an ergotamine-containing preparation and 6 hours should elapse before an ergotamine-containing medication is administered following sumatriptan. Although the pharmacokinetics of zolmitriptan were not affected by ergotamine, the UK manufacturer of zolmitriptan recommends that 6 hours should elapse between the administration of zolmitriptan and an ergotamine preparation.(7) The US manufacturer of zolmitriptan states under contraindications that zolmitriptan should not be used within 24 hours of an ergotamine-containing or ergot-type medication.(6) The Australian manufacturer states that 24 hours should elapse before zolmitriptan is administered following an ergotamine-containing preparation and 6 hours should elapse before an ergotamine-containing medication is administered following zolmitriptan.(8) Because of the additive risk of prolonged vasospastic reactions, the manufacturers of rizatriptan(9) and naratriptan(10) in the US state that the use of ergotamine-containing or ergot-type medications and these agents is contraindicated. The Australian manufacturer states that concurrent use of naratriptan and ergotamine or ergotamine derivatives is not recommended.(11) Administration of oral ergotamine one and two hours after eletriptan resulted in additive increases in blood pressure.(13)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known or suspected ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, documented silent ischemia), coronary artery vasospasm (e.g., Prinzmetal variant angina), and uncontrolled hypertension.

*Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

*Peripheral vascular disease or ischemic bowel disease.

*History of cerebrovascular syndromes (e.g., stroke, transient ischemic attack) or history of hemiplegic or basilar migraine.

*Recent (i.e., 24 hours or less) treatment with another 5-HT1 receptor agonist or an ergotamine-containing or ergot-type drug.

*Known hypersensitivity to naratriptan.

*Severe renal or hepatic impairment.

• Acute myocardial infarction
• Angina
• Cerebral ischemia
• Cerebrovascular accident
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Coronary artery disease
• Hemiplegic migraine
• Ischemic bowel disease
• Myocardial ischemia
• Peripheral vascular disease
• Prinzmetal angina
• Serotonin syndrome
• Severe uncontrolled hypertension

• Chronic kidney disease stage 2 (mild) GFR 60-89 ml/min
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Disease of liver
• Hypertension
• Tachyarrhythmia

There are no moderate contraindications for this drug.

The most common adverse effects (>=2% and greater than placebo) with naratriptan include paresthesia, nausea, dizziness, drowsiness, malaise/fatigue, and throat/neck symptoms.

More Frequent

• Chest tightness

Rare or Very Rare

• Acute myocardial infarction
• Anaphylaxis
• Angioedema
• Cardiac arrhythmia
• Cerebrovascular accident
• Coronary artery spasm
• Hypertension
• Hypertensive crisis
• Intracerebral hemorrhage
• Ischemic bowel disease
• Myocardial ischemia
• Peripheral ischemia
• Prinzmetal angina
• Raynaud's phenomenon
• Serotonin syndrome
• Splenic infarction

More Frequent

• Chest pain
• Malaise
• Nausea

Less Frequent

• Blurred vision
• Dizziness
• Drowsy
• Fever
• Neck pain
• Paresthesia

Rare or Very Rare

• Abdominal pain with cramps
• Anticholinergic toxicity
• Diarrhea
• Jaw pain
• Medication overuse headache

No enhanced messaging available.

Safety and efficacy have not been established in pediatric patients younger than 18 years of age.

Data on the developmental risk associated with use of naratriptan during pregnancy from a prospective pregnancy exposure registry and epidemiological studies are inadequate to draw definitive conclusions regarding the risk of birth defects following naratriptan exposure.

Naratriptan produced developmental toxicity (e.g., embryolethality, fetal abnormalities) when given to pregnant rats and rabbits. The lowest doses that produced evidence of developmental toxicity in animals were associated with plasma exposures 2.5 to 11 times that in humans at the maximum recommended daily dose for rabbits and rats, respectively.

Naratriptan is distributed into milk in rats; it is not known whether naratriptan is distributed into human milk or has any effects on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for naratriptan and any adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Dose selection for geriatric patients should be cautious, usually initiating on the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Clinical trials of naratriptan did not include a sufficient number of patients >=65 years of age to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between geriatric and younger patients.

Dose selection for geriatric patients should be cautious, usually initiating on the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

A cardiovascular evaluation is recommended for geriatric patients with cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) prior to naratriptan administration.