Naratriptan

Registered South African indications:

• Acute migraine attacks

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe renal impairment (South African recommendations)
• Severe renal impairment (CrCl<15ml/min) (Recommendations in other jurisdictions)
• Severe hepatic impairment (South African recommendations)
• Severe hepatic impairment (Child-Pugh class C) (Recommendations in other jurisdictions)
• Patients who have had a myocardial infarction
• Ischaemic heart disease
• Prinzmetal's angina/coronary vasospasm
• Peripheral vascular disease
• Patients with symptoms or signs consistent with ischaemic heart disease
• History of cerebrovascular accident (CVA) 
• History of transient ischaemic attack (TIA)
• Moderate or severe hypertension, and mild uncontrolled hypertension (Recommendations in other jurisdictions)
• Uncontrolled hypertension (South African recommendations)
• Coadministration with ergotamine or ergotamine derivatives (including methysergide)​​​​​​​
• Coadministration with other triptans/ 5-hydroxytryptamine₁ (5-HT₁) agonists

Cautions

South African recommendations

• Hypersensitivity to sulphonamides
• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly

• Unclear diagnosis of migraine
• Patients not previously diagnosed as migraineurs
• Migraineurs who present with atypical symptoms
• Management of hemiplegic, basilar or ophthalmoplegic migraine
• Patients in whom unrecognised cardiac disease is likely without a prior evaluation for underlying cardiovascular disease
  - Postmenopausal women
  - Males older than 40 years
  - Patients with risk factors for coronary artery disease
• High dosages 
• Prolonged use of acute migraine treatments
• Galactose intolerance e.g. galactosaemia
• Lapp lactase deficiency 
• Glucose-galactose malabsorption 
• May impair ability to drive and operate machinery

Recommendations in other jurisdictions

• Hypersensitivity to sulphonamides
• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment (CrCl≥15ml/min)
• Mild to moderate hepatic impairment (Child-Pugh class A and B)
• Elderly
• Unclear diagnosis of migraine
• Management of hemiplegic, basilar or ophthalmoplegic migraine
• Patients not previously diagnosed as migraineurs
• Migraineurs who present with atypical symptoms
• Administration during the aura phase (prior to the onset of migraine headache)
• Risk factors for ischaemic heart disease 
  - Heavy smokers
  - Users of nicotine substitution therapy without prior cardiovascular evaluation
  - Postmenopausal women
  - Males older than 40 years
• High dosages 
• Prolonged use of any type of painkiller for headaches
• Coadministration with herbal preparations containing St John's wort (Hypericum perforatum)
• Galactose intolerance
• Total lactase deficiency 
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Acute migraine attacks
- With or without aura

• Oral (tab): 2.5mg; Repeat dose after ≥4hrs if needed; Max: 5mg/24hrs 

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Naratriptan should not be used prophylactically

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 Naratriptan tablets should be taken as early as possible after the onset of a migraine headache but may be effective if taken at a later stage

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The tablets should be swallowed whole with water

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If a patient does not respond to the first dose of naratriptan tablets it is unlikely that a second dose will be of benefit in the same attack

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Indications and dosages registered in other jurisdictions

Acute migraine attacks
- With or without aura

• Oral (tab): 2.5mg; Repeat dose after ≥4hrs if needed; Max: 5mg/24hrs

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Naratriptan tablets should be taken as early as possible after the onset of a migraine headache but they are effective if taken at a later stage

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 Naratriptan is recommended as monotherapy for the acute treatment of a migraine attack

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Naratriptan should not be used prophylactically

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If symptoms of migraine should recur, following an initial response, a second dose may be taken provided that there is a minimum interval of four hours between the two doses

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If a patient does not respond to a first dose of naratriptan a second dose should not be taken for the same attack, as it is unlikely to be of benefit. However, naratriptan may be used for subsequent migraine attacks

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Method of administration: Naratriptan should be swallowed whole with water

Not recommended for use

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Naratriptan is not recommended for use in children (under 12 years of age) or adolescents (12-17 years of age) (South African recommendations)

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Adolescents (12-17 years of age): Efficacy of naratriptan at single doses of 0.25, 1.0 and 2.5mg was not demonstrated to be greater than placebo in a placebo-controlled study in adolescents (12 to 17 years). Therefore, the use of naratriptan in patients under 18 years of age is not recommended (Recommendations in other jurisdictions)

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Children (under 12 years of age): There are no data available on the use of naratriptan in children under 12 years of age therefore its use in this age group is not recommended (Recommendations in other jurisdictions)

Pregnancy

South African recommendations

• Caution
• The safe use of naratriptan in pregnant women has not been established

Recommendations in other jurisdictions

• Caution
• Evaluation of experimental animal studies does not indicate any direct teratogenic effects or harmful effects on peri- and postnatal development. However, delays in foetal ossification and possible effects on embryo viability have been observed in the rabbit
• Post-marketing data from prospective pregnancy registries have documented the pregnancy outcomes in <60 women exposed to naratriptan. Due to a small sample size no definitive conclusion can be drawn regarding the risk of birth defects following exposure to naratriptan
• Because animal reproduction studies are not always predictive of human response, administration of naratriptan should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus

Breastfeeding 

South African recommendations

• Caution 
• Naratriptan and/or related metabolites are secreted into the milk of lactating rats. Caution should be exercised when considering the administration of naratriptan to breastfeeding women

Recommendations in other jurisdictions

• Caution; not recommended
• Naratriptan and/or drug-related metabolites are secreted into the milk of lactating rats
• Transient effects in the pre and post-natal development of neonatal rats were observed only at maternal exposures sufficiently in excess of maximum human exposure. No studies have been conducted to determine the level of transference of naratriptan into breast milk of nursing women. It is recommended that infant exposure be minimised by avoiding breastfeeding for 24 hours after treatment

Fertility 

• No information available

Renal Impairment 

South African recommendations

• Mild to moderate: Caution; dose adjustment recommended 
  Dosage should not exceed 2.5mg daily 
• Severe: Contraindicated 

Recommendations in other jurisdictions

• Mild to moderate (CrCl≥15ml/min): Caution; dose adjustment recommended 
  Dosage should not exceed 2.5mg daily 
• Severe (CrCl<15ml/min): Contraindicated

Hepatic Impairment 

South African recommendations

• Mild to moderate: Caution; dose adjustment recommended 
  Dosage should not exceed 2.5mg daily 
• Severe: Contraindicated

Recommendations in other jurisdictions

• Mild to moderate (Child-Pugh class A and B): Caution; dose adjustment recommended
  The maximum dose in any 24-hour treatment period is a single 2.5mg tablet
• Severe (Child-Pugh class C): Contraindicated

Elderly 

South African recommendations

• Caution; no information available 
  The safety and effectiveness of naratriptan in the elderly (over 65 years of age) have not been evaluated. There is a moderate decrease (26%) in clearance with age

Recommendations in other jurisdictions

• Caution; no information available 
  The safety and effectiveness of naratriptan in individuals over age 65 have not been evaluated and therefore, its use in this age group cannot be recommended. There is a moderate decrease in clearance with age

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Tingling
• Dizziness
• Somnolence
• Fatigue

Cardiovascular Disorders

• Coronary artery vasospasm
• Transient ischaemic electrocardiogram (ECG) changes
• Angina
• Myocardial infarction
• Peripheral vascular ischaemia
• Bradycardia
• Tachycardia
• Palpitations
• Increased blood pressure (approximately 5mmHg (systolic) and 3mmHg (diastolic) up to 12 hours after administration)

Gastrointestinal Disorders

• Nausea and vomiting
• Ischaemic colitis

Musculoskeletal Disorders 

• Sensations of heaviness

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria
• Pruritis
• Facial oedema

Immune System Disorders

• Hypersensitivity reactions
  - Cutaneous hypersensitivity
  - Anaphylaxis

Sensory Disorders

• Visual disturbance

Others

• Pain
• Sensations of heat
• Sensations of pressure or tightness

• Other triptans
• Ergotamine
• Ergotamine-containing preparations
• Methysergide
• Dihydroergotamine (DHE)
• Sumatriptan
• Other 5-HT₁ receptor agonists
• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin noradrenaline reuptake inhibitors (SNRIs)

• Blood pressure

Specific cases may require

• Cardiovascular evaluation (in triptan-naïve patients who have multiple cardiovascular risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease)
• Electrocardiogram (ECG) (in patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation)

Additional observations

• Headache severity
• Signs/symptoms suggestive of angina
• Signs/symptoms of
  - Serotonin syndrome
  - Hypersensitivity reactions

Naratriptan is a selective agonist for the vascular 5-hydroxytryptamine₁ (5-HT₁) receptor. This receptor is found predominantly in intracranial (cerebral and dural) blood vessels. Naratriptan has high affinity for human cloned 5-HT_1B and 5-HT_1D receptors; the human 5-HT_1B receptor is thought to correspond to the vascular 5-HT₁ receptor mediating contraction of intracranial blood vessels. Naratriptan has little effect at other 5-HT receptor (5-HT₂, 5-HT₃, 5-HT₄ and 5-HT₇) subtypes. In animals, naratriptan selectively constricts the carotid arterial circulation which supplies blood to the extracranial and intracranial tissues such as the meninges. In addition, experimental evidence suggests that naratriptan inhibits trigeminal nerve activity. Both these actions may contribute to the anti-migraine action of naratriptan in humans.

Tablet 2.5mg

• Naramig (GSK) originator