Usage
- Naratriptan is prescribed for the acute treatment of migraine attacks, with or without aura. It is not intended for preventative use.
- Pharmacological classification: Naratriptan is a 5-HT1B/1D receptor agonist, belonging to the triptan class of antimigraine medications.
- Mechanism of action: Naratriptan selectively binds to 5-HT1B and 5-HT1D receptors, primarily located on intracranial blood vessels and sensory nerves. This binding leads to vasoconstriction of cranial blood vessels and inhibition of the release of pro-inflammatory neuropeptides, thus relieving migraine pain.
Alternate Names
- International or regional variations: Naratriptanum (Latin).
- Brand names: Amerge, Naramig.
How It Works
- Pharmacodynamics: Naratriptan’s primary effect is the constriction of cranial blood vessels, reducing vasodilation believed to contribute to migraine pain. It also inhibits the release of vasoactive and pro-inflammatory neuropeptides like calcitonin gene-related peptide (CGRP), further mitigating the migraine process.
- Pharmacokinetics:
- Absorption: Naratriptan is well-absorbed orally, with a bioavailability of approximately 70%. Food does not significantly affect absorption.
- Metabolism: Primarily metabolized in the liver, with a small contribution from CYP450 enzymes, making significant metabolic drug interactions unlikely.
- Elimination: Mainly eliminated via renal excretion (approximately 60%), with about 30% as unchanged drug and 30% as inactive metabolites. The elimination half-life is approximately 6 hours.
- Mode of action: Naratriptan acts by selectively agonizing 5-HT1B and 5-HT1D receptors. This leads to:
- Vasoconstriction: Decreasing the dilation of cranial blood vessels, a key factor in migraine pain.
- Inhibition of trigeminal nerve activation: Blocking the release of CGRP and other pro-inflammatory neuropeptides that mediate pain transmission.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Primarily 5-HT1B/1D receptor agonism. Minimal CYP450 enzyme involvement.
- Elimination pathways: Primarily renal excretion, with some hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Initial dose: 1 mg or 2.5 mg orally as a single dose.
- Repeat dose: If migraine returns, a second dose may be taken after 4 hours.
- Maximum dose: 5 mg in any 24-hour period.
Children:
- Naratriptan is not recommended for use in patients under 18 years of age. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients (over 65 years): Not recommended. Elderly patients are more likely to have decreased renal and hepatic function and are at higher risk for cardiovascular disease, thus increasing the risk of adverse events.
- Patients with Renal Impairment:
- Mild to moderate impairment: Initial dose of 1 mg, maximum daily dose of 2.5 mg.
- Severe impairment (creatinine clearance <15 mL/min): Contraindicated.
- Patients with Hepatic Dysfunction:
- Mild to moderate impairment (Child-Pugh A or B): Initial dose of 1 mg, maximum daily dose of 2.5 mg.
- Severe impairment (Child-Pugh C): Contraindicated.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, uncontrolled hypertension, or other significant cardiovascular risk factors. Pre-treatment cardiovascular evaluation is recommended.
Clinical Use Cases
Naratriptan is specifically indicated for the acute treatment of migraine headaches. It is not indicated or recommended for the following:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
Dosage Adjustments
- Dose adjustments are necessary for patients with renal or hepatic impairment as described above.
- In elderly patients, careful dose selection is recommended, usually starting at the low end of the dosing range, due to the higher likelihood of reduced organ function and concomitant diseases.
Side Effects
Common Side Effects:
- Dizziness, drowsiness, fatigue
- Paresthesia (numbness, tingling)
- Flushing
- Nausea
- Jaw, neck, or throat pain/tightness
Rare but Serious Side Effects:
- Allergic reactions (angioedema, anaphylaxis)
- Myocardial infarction, stroke, coronary vasospasm
- Serotonin syndrome
- Peripheral vascular ischemia
- Ischemic bowel disease
Long-Term Effects:
- Medication overuse headache can occur with frequent or excessive use of triptans.
Adverse Drug Reactions (ADR):
- Severe allergic reactions (requiring immediate medical attention)
- Chest pain, shortness of breath, irregular heartbeat (possible cardiac ischemia)
- Neurological symptoms (confusion, seizures, visual disturbances)
Contraindications
- Hypersensitivity to naratriptan
- Severe hepatic impairment (Child-Pugh C)
- Severe renal impairment (creatinine clearance <15 mL/min)
- Ischemic heart disease, coronary vasospasm (Prinzmetal’s angina)
- History of stroke, TIA, hemiplegic or basilar migraine
- Peripheral vascular disease, ischemic bowel disease
- Uncontrolled hypertension
- Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
- Concomitant use of ergot-containing drugs or other 5-HT1B/1D agonists (within 24 hours)
Drug Interactions
- Ergot-containing drugs: Contraindicated due to increased risk of vasospasm.
- Other 5-HT1B/1D agonists (triptans): Contraindicated within 24 hours of naratriptan administration.
- SSRIs, SNRIs, TCAs, MAOIs: Increased risk of serotonin syndrome. Close monitoring is required.
- CYP450 interactions: Minimal interaction anticipated due to limited metabolism via CYP450 enzymes.
- Oral contraceptives: May decrease naratriptan clearance.
- Smoking: May increase naratriptan clearance.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (US FDA); B3 (Australian TGA). Animal studies have shown developmental toxicity. No adequate and well-controlled studies in humans. Use only if the potential benefit justifies the potential risk to the fetus.
- Fetal risks: Potential for embryolethality, fetal abnormalities, and growth retardation.
- Breastfeeding: Limited information available. Breastfeeding should be avoided for 24 hours after administration. Consider alternate medications if possible.
Drug Profile Summary
- Mechanism of Action: 5-HT1B/1D receptor agonist, leading to vasoconstriction and inhibition of neuropeptide release.
- Side Effects: Dizziness, drowsiness, paresthesia, flushing, nausea, jaw/neck/throat pain. Rarely: allergic reactions, cardiac events, serotonin syndrome.
- Contraindications: Hypersensitivity, severe hepatic/renal impairment, ischemic heart disease, stroke history, uncontrolled hypertension, concomitant use of ergot drugs or triptans.
- Drug Interactions: Ergot drugs, triptans, SSRIs/SNRIs/TCAs/MAOIs, oral contraceptives, smoking.
- Pregnancy & Breastfeeding: Category C. Use with caution. Avoid breastfeeding for 24 hours post-dose.
- Dosage: Adults: 1-2.5 mg initially, max 5 mg/24 hours. Not for pediatric use.
- Monitoring Parameters: Blood pressure, heart rate, neurological status.
Popular Combinations
- While naratriptan is generally used as monotherapy, it may be combined with analgesics such as NSAIDs or acetaminophen for additive pain relief in some cases. However, combination with other triptans or ergot-containing drugs is contraindicated.
Precautions
- General Precautions: Ensure accurate migraine diagnosis, rule out other neurological conditions. Assess cardiovascular risk factors. Monitor for serotonin syndrome. Avoid overuse.
- Specific Populations: See sections on elderly patients, renal/hepatic impairment, and pregnancy/breastfeeding.
- Lifestyle Considerations: Alcohol may exacerbate drowsiness and dizziness. Alcohol can also trigger migraine attacks in some individuals. Smoking may affect naratriptan clearance.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Naratriptan?
A: Adults: 1 mg or 2.5 mg orally as a single dose. A second dose may be taken after 4 hours if the migraine returns. Maximum dose: 5 mg/24 hours. Not recommended for patients under 18 years.
Q2: Can Naratriptan be used to prevent migraines?
A: No, Naratriptan is intended for acute treatment of migraine attacks, not for prevention.
Q3: What are the common side effects of Naratriptan?
A: Common side effects include dizziness, drowsiness, numbness/tingling, flushing, nausea, and pain or tightness in the jaw, neck, or throat.
Q4: Who should not take Naratriptan?
A: Individuals with a history of heart disease, stroke, uncontrolled hypertension, severe liver or kidney disease, or hypersensitivity to naratriptan should not take this medication. Also, it is contraindicated with concurrent use of ergot-containing drugs or other triptans.
Q5: Can Naratriptan be taken during pregnancy or while breastfeeding?
A: Naratriptan is a Pregnancy Category C drug and should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Breastfeeding should be avoided for 24 hours after taking naratriptan.
Q6: What should I do if I experience chest pain after taking Naratriptan?
A: Chest pain can be a sign of a serious side effect. Stop taking naratriptan and seek immediate medical attention.
Q7: Can Naratriptan interact with other medications?
A: Yes, Naratriptan can interact with certain medications like ergot alkaloids, other triptans, SSRIs, SNRIs, MAOIs, and some antidepressants. Inform your doctor about all medications you are taking.
Q8: How long does it take for Naratriptan to work?
A: Naratriptan typically begins to work within 1-2 hours, but the time to maximum relief can vary.
Q9: What if the first dose of Naratriptan doesn’t work?
A: If the first dose does not provide relief, a second dose can be taken after 4 hours. However, do not exceed the maximum daily dose of 5 mg. If there is no response to the second dose, do not take additional doses for the same attack.
Q10: Can Naratriptan cause serotonin syndrome?
A: Yes, especially when taken with other serotonergic medications such as SSRIs, SNRIs, TCAs, or MAOIs. Watch for symptoms like agitation, confusion, rapid heart rate, fever, and muscle rigidity.
