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Drug Details

RELPAX 20mg and 40mg Film-Coated Tablets

• Drug Class Description
  Selective Serotonin (5HT1) receptor agonists - ATC code: NO2CC06
• Generic Name
  eletriptan hydrobromide
• Presentation
  Film-coated tablet.
  
  Round, convex orange tablets debossed with 'REP 20' and 'REP 40' on one side and 'Pfizer' on the other.
• Description
  Each film-coated tablet contains 20mg, and 40mg eletriptan (as hydrobromide).
  
  Excipients: 23.000 mg Lactose / 0.036 mg Sunset yellow
  
  Excipients: 46.000 mg Lactose / 0.072 mg Sunset yellow
• Indications
  

  Acute treatment of the headache phase of migraine attacks, with or without aura.

• Adult Dosage
  

  RELPAX tablets should be taken as early as possible after the onset of migraine headache but they are also effective if taken at a later stage during a migraine attack.

  RELPAX, if taken during the aura phase, has not been demonstrated to prevent migraine headache and therefore RELPAX should only be taken during the headache phase of migraine.

  RELPAX tablets should not be used prophylactically.

  The tablets should be swallowed whole with water.

  Adults (18-65 years of age):

  The recommended initial dose is 40mg.

  If headache returns within 24 hours: If the migraine headache recurs within 24 hours of an initial response, a second dose of the same strength of RELPAX has been shown to be effective in treating the recurrence. If a second dose is required, it should not be taken within 2 hours of the initial dose.

  If no response is obtained: If a patient does not achieve a headache response to the first dose of RELPAX within 2 hours, a second dose should not be taken for the same attack as clinical trials have not adequately established efficacy with the second dose. Clinical trials show that patients who do not respond to the treatment of an attack are still likely to respond to the treatment of a subsequent attack.

  Patients who do not obtain satisfactory efficacy after an appropriate trial of 40mg, (e.g. good tolerability and failure to respond in 2 out of 3 attacks), may be effectively treated with 80mg (2 x 40mg) in subsequent migraine attacks. A second dose of 80mg should not be taken within 24 hours.

  The maximum daily dose should not exceed 80mg.

  Elderly (over 65 years of age)

  The safety and effectiveness of eletriptan in patients over 65 years of age have not been systematically evaluated due to the small number of such patients in clinical trials. Use of RELPAX in the elderly is therefore not recommended.

  Adolescents (12-17 years of age)

  The efficacy of RELPAX has not been established in this population and its use is therefore not recommended in this age group.

  Children (6-11 years of age)

  The safety and efficacy of RELPAX in children have not been evaluated. Therefore the use of RELPAX is not recommended in this age group.

  Hepatic Impairment

  No dose adjustment is required in patients with mild or moderate hepatic impairment. As RELPAX has not been studied in patients with severe hepatic impairment, it is contra-indicated in these patients.

  Renal Impairment

  As the blood pressure effects of RELPAX are amplified in renal impairment, a 20mg initial dose, is recommended in patients with mild or moderate renal impairment. The maximum daily dose should not exceed 40mg. RELPAX is contra-indicated, in patients with severe renal impairment.

• Child Dosage
  Under 17 years, not recommended
• Elderly Dosage
  Over 65 years, not recommended
• Contra Indications
  

  Hypersensitivity to eletriptan hydrobromide or to any of the excipients.

  Patients with severe hepatic or severe renal impairment.

  Moderately severe or severe hypertension, or untreated mild hypertension.

  Patients with confirmed coronary heart disease, including ischaemic heart disease (angina pectoris, previous myocardial infarction or confirmed silent ischaemia), objective or subjective symptoms of ischaemic heart disease or Prinzmetal's angina.

  Patients with significant arrhythmias or heart failure.

  Patients with peripheral vascular disease.

  Patients with a history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA).

  Administration of ergotamine, or derivatives of ergotamine (including methysergide), within 24hr before or after treatment with eletriptan. Concomitant administration of other 5-HT₁ receptor agonists with eletriptan.

• Special Precautions
  

  This medicinal product contains lactose . Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

  This medicinal product also contains sunset yellow which may cause allergic reactions.

  RELPAX should not be used together with potent CYP3A4 inhibitors eg. ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and protease inhibitors (ritonavir, indinavir and nelfinavir).

  RELPAX should only be used where a clear diagnosis of migraine has been established. RELPAX is not indicated for the management of hemiplegic, ophthalmoplegic, or basilar migraine.

  RELPAX should not be given for the treatment of 'atypical' headaches, i.e. headaches, which may be related to a possibly serious condition (stroke, aneurysm rupture) where cerebrovascular vasoconstriction may be harmful.

  Eletriptan can be associated with transient symptoms including chest pain and tightness, which may be intense and involve the throat. Where such symptoms are thought to indicate ischaemic heart disease, no further dose should be taken and appropriate evaluation should be carried out.

  RELPAX should not be given without prior evaluation, to patients in whom unrecognised cardiac disease is likely, or to patients at risk of coronary artery disease (CAD) [e.g. patients with hypertension, diabetes, smokers or users of nicotine substitution therapy, men over 40 years of age, post-menopausal women and those with a strong family history of CAD]. Cardiac evaluations may not identify every patient who has cardiac disease and, in very rare cases, serious cardiac events have occurred, in patients without underlying cardiovascular disease when 5-HT₁ agonists have been administered. Patients in whom CAD is established, should not be given RELPAX.

  5-HT₁ receptor agonists have been associated with coronary vasospasm. In rare cases, myocardial ischaemia or infarction, have been reported with 5-HT₁ receptor agonists.

  Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St. John's wort (Hypericum perforatum)

  Within the clinical dose range, slight and transient increases in blood pressure have been seen with eletriptan doses of 60mg or greater. However, these increases have not been associated with clinical sequelae in the clinical trial programme. The effect was much more pronounced in renally impaired and elderly subjects. In renally impaired subjects, the range of mean maximum increases in systolic blood pressure was 14 -17mmHg (normal 3mmHg) and for diastolic blood pressure was 14 -21mmHg (normal 4mmHg). In elderly subjects, the mean maximum increase in systolic blood pressure was 23mmHg compared with 13mmHg in young adults (placebo 8mmHg). Post-marketing reports of increases in blood pressure have also been received for patients taking 20 and 40 mg doses of eletriptan, and in non-renally impaired and non-elderly patients.

  Excessive use of any anti-migraine medicinal product can lead to daily chronic headaches requiring a therapeutic window. Overuse of all triptans has been reported primarily in patients with chronic daily headache. Overuse of all triptans has been reported primarily in patients with chronic daily headache.

  Serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) has been reported following concomitant treatment with triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs). These reactions can be severe. If concomitant treatment with eletriptan and an SSRI or SNRI is clinically warranted, appropriate observation of the patient is advised, particularly during treatment initiation, with dose increases, or with addition of another serotonergic medication.

• Interactions
  

  Effect of other medicinal products on eletriptan

  In the pivotal clinical trials of eletriptan no evidence of interaction with beta-blockers, tricyclic antidepressants, selective serotonin re-uptake inhibitors and flunarizine was reported but data from formal clinical interaction studies with these medicinal products are not available (other than propranolol, see below).

  Population pharmacokinetic analysis of clinical studies has suggested that the following medicinal products (beta-blockers, tricyclic antidepressants, selective serotonin re-uptake inhibitors, oestrogen based hormone replacement therapy, oestrogen containing oral contraceptives and calcium channel blockers) are unlikely to have an effect on the pharmacokinetic properties of eletriptan.

  Eletriptan is not a substrate for MAO. Therefore there is no expectation of an interaction between eletriptan and MAO inhibitors. Therefore no formal interaction study has been undertaken.

  In clinical studies with propranolol (160mg), verapamil (480mg) and fluconazole (100mg) the C_max of eletriptan was increased 1.1 fold, 2.2 fold and 1.4 fold respectively. The increase in eletriptan's AUC being 1.3 fold, 2.7 fold and 2.0 fold respectively. These effects are not considered clinically significant as there were no associated increases in blood pressure or adverse events compared to administering eletriptan alone.

  In clinical studies with erythromycin (1000mg) and ketoconazole (400mg), specific and potent inhibitors of CYP3A4, significant increases in eletriptan C_max (2 and 2.7- fold) and AUC (3.6 and 5.9- fold) respectively, were observed. This increased exposure was associated with an increase in eletriptan t_1/2 from 4.6 to 7.1 hours for erythromycin and from 4.8 to 8.3 hours for ketoconazole (see 5.2 Pharmacokinetic Properties). Therefore, RELPAX should not be used together with potent CYP3A4 inhibitors eg. ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and protease inhibitors (ritonavir, indinavir and nelfinavir).

  In clinical studies with oral (caffeine/ergotamine) administered 1 and 2 hours after eletriptan, minor though additive increases in blood pressure were observed which are predictable based on the pharmacology of the two drugs. Therefore it is recommended that either ergotamine-containing or ergot-type medications (e.g. dihydroergotamine) should not be taken within 24 hours of eletriptan dosing. Conversely, at least 24 hours should elapse after the administration of an ergotamine-containing preparation before eletriptan is given.

  Effect of eletriptan on other medicinal products

  There is no in vitro or in vivo evidence that clinical doses (and associated concentrations) of eletriptan will inhibit or induce cytochrome P450 enzymes including CYP3A4 drug metabolising enzymes and therefore it is considered that eletriptan is unlikely to cause clinically important drug interactions mediated by these enzymes.

  Selective Serotonin Reuptake Inhibitors (SSRIs) /Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) and Serotonin Syndrome:

  There have been reports describing patients with symptoms compatible with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans.

• Adverse Drug Reactions
  

  RELPAX has been administered in clinical trials to over 5000 subjects, taking one or two doses of RELPAX 20 or 40 or 80mg. The most common adverse reactions noted were asthenia, somnolence, nausea and dizziness. In randomised clinical studies using doses of 20, 40 and 80mg, a trend for a dose-dependency of the incidence of adverse events has been shown. The following adverse reactions (with an incidence >1% and higher than placebo) were reported in patients treated with therapeutic doses in clinical trials. Events are categorized by frequency as common (>1/100 to <1/10), uncommon (>1/1,000 to <1/100), or rare (>1/10,000 to <1/1,000).

  Infections and infestations:

  Common: pharyngitis, and rhinitis

  Rare: respiratory tract infection

  Blood and the lymphatic system disorders:

  Rare: lymphadenopathy

  Metabolism and nutrition disorders:

  Uncommon: anorexia

  Psychiatric disorders:

  Uncommon: thinking abnormal, agitation, confusion, depersonalisation, euphoria, depression, and insomnia

  Rare: emotional lability

  Nervous system disorders:

  Common: somnolence, headache, dizziness, tingling or abnormal sensation, hypertonia, hypoaesthesia, and myasthenia

  Uncommon: tremor, hyperaesthesia, ataxia, hypokinesia, speech disorder, stupor, and taste perversion

  Eye disorders:

  Uncommon: abnormal vision, eye pain, photophobia, and lacrimation disorder

  Rare: conjuntivitis

  Ear and labyrinth disorders:

  Common: vertigo

  Uncommon: ear pain, tinnitus

  Cardiac disorders:

  Common: palpitation, and tachycardia

  Rare: bradycardia

  Vascular disorders:

  Common: flushing

  Uncommon: peripheral vascular disorder

  Rare: shock

  Respiratory, thoracic and mediastinal disorders:

  Common: throat tightness

  Uncommon: dyspnea, respiratory disorder and yawning

  Rare: asthma and voice alteration

  Gastrointestinal disorders:

  Common: abdominal pain, nausea, dry mouth, and dyspepsia

  Uncommon: diarrhoea, and glossitis

  Rare: constipation, oesophagitis, tongue oedema and eructation

  Hepato-biliary disorders:

  Rare: bilirubinaemia, and increased AST

  Skin and subcutaneous tissue disorders:

  Common: sweating

  Uncommon: rash and pruritis

  Rare: skin disorder and urticaria

  Musculoskeletal, connective tissue and bone disorders:

  Common: back pain, myalgia

  Uncommon: arthralgia, arthrosis and bone pain

  Rare: arthritis, myopathy and twitching

  Renal and urinary disorders:

  Uncommon: increased urinary frequency, urinary tract disorder and polyuria

  Reproductive system and breast disorders:

  Rare: breast pain and menorrhagia

  General disorders and administration site conditions:

  Common: feeling hot, asthenia, chest symptoms (pain, tightness, pressure), and chills

  Uncommon: malaise, face oedema, thirst, oedema and peripheral oedema

  The common adverse events seen with eletriptan are typical of adverse events reported with 5-HT1 agonists as a class.

  In post-marketing experience, the following undesirable effects have been reported:

  Immune System Disorders: Allergic reactions, some of which may be serious

  Nervous system disorders: Serotonin syndrome, Rare cases of syncope

  Vascular Disorders: hypertension

  Gastrointestinal disorders: As with some other 5HT 1B/1D agonists, rare reports of ischaemic colitis have been received., vomiting