Active ingredients: Eletriptan
RELPAX® 20 mg film-coated tablets
RELPAX® 40 mg film-coated tablets
Why is Relpax used? What is it for?
Relpax contains the active substance eletriptan. Relpax belongs to a class of medicines called serotonin receptor agonists. Serotonin is a natural substance found in the brain that promotes the narrowing of blood vessels.
Relpax can be used to treat migraines with or without aura in adult patients. Before the migraine attack, it may go through a phase called the "aura" which involves visual disturbances, numbness and speech disturbances.
Contraindications When Relpax should not be used
Do not take RELPAX
- If you are allergic (hypersensitive) to eletriptan or any of the other ingredients of this medicine (listed in section 6).
- If you have severe liver or kidney disease
- If you have moderate to severe hypertension or mild untreated hypertension.
- If you suffer or have ever suffered from heart problems [eg. heart attack, angina, heart failure or major abnormal heart rhythm (arrhythmia), sudden, temporary narrowing of one of the coronaries].
- If you suffer from circulatory failure (peripheral vascular disease).
- If you have had a stroke (even a mild one that lasted only a few minutes or hours).
- If you have taken ergotamine or ergotamine derivatives (including methysergide) in the 24 hours before or after taking Relpax.
- If you are taking other medicines ending in 'triptan' (eg sumatriptan, rizatriptan, naratriptan, zolmitriptan, almotriptan and frovatriptan).
Talk to your doctor and do not take Relpax if you have ever experienced any of the conditions listed above.
Precautions for use What you need to know before taking Relpax
Talk to your doctor or pharmacist before taking Relpax if:
- have diabetes
- smoke or are on nicotine replacement therapy
- is male and over 40 years old
- is female and postmenopausal
- you or a family member have coronary heart disease
- you have been told that you are at risk of heart disease, before taking Relpax, talk to your doctor
Repeated use of migraine medicines
Repeated use of Relpax or other migraine medicines for several days or weeks can cause chronic daily headache. Tell your doctor if this occurs, as you may need to stop treatment.
Interactions Which drugs or foods may change the effect of Relpax
Other medicines and Relpax
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Taking Relpax with other medicines can cause serious side effects. Do not use Relpax if:
- took ergotamine or ergotamine derivatives (including methysergide) in the 24 hours before or after taking Relpax
- if you are taking other medicines ending in 'triptan' (eg sumatriptan, rizatriptan, naratriptan, zolmitriptan, almotriptan and frovatriptan).
Some medicines can affect the way Relpax works, or Relpax can reduce the effectiveness of other medicines taken at the same time, including:
- Medicines used to treat fungal infections (e.g. ketoconazole and itraconazole)
- Medicines used to treat bacterial infections (e.g. erythromycin, clarithromycin and josamycin).
- Medicines used to treat AIDS and HIV (e.g. ritonavir, indinavir and nelfinavir).
St. John's wort (Hypericum perforatum) should not be taken concomitantly with this medicine. If you are already taking St. John's wort (Hypericum perforatum), consult your doctor before stopping it.
Before taking Relpax, tell your doctor if you are taking certain medicines (commonly called SSRIs * or SNRIs **) for depression or other mental disorders. These medicines may increase the risk of developing serotonin syndrome when used together with some medicines for migraine. See section 4 'Possible Side Effects' for more information on symptoms of serotonin syndrome.
* SSRIs - selective serotonin reuptake inhibitors
** SNRI - serotonin and noradrenaline reuptake inhibitors
RELPAX with food and drink
Relpax can be taken before or after food and drink.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
It is recommended that you avoid breastfeeding for 24 hours after taking this medicine.
Driving and using machines
Relpax or migraines can cause drowsiness. This medicine can also make you dizzy. It is therefore recommended that you avoid driving or operating machinery during a migraine crisis or after taking this medicine.
Relpax contains lactose and the dye sunset yellow aluminum lake (E 110)
Lactose is a type of sugar. If you have been told that you have an "intolerance to some sugars, contact your doctor before taking this medicine. Sunset yellow aluminum lake (E 110) can cause allergic reactions.
Dose, Method and Time of Administration How to use Relpax: Posology
Always take this medicine always exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Adults
This medicine can be taken any time after the migraine attack starts, but it is best to take it as soon as possible. However, only take Relpax during the migraine phase, do not take it to prevent migraine attacks.
- The usual starting dose is one 40 mg tablet
- The tablet should be swallowed whole with a glass of water
- If the first tablet does not make the migraine go away, do not take a second dose for the same migraine attack.
- If after the first tablet the migraine disappears and then comes back, you can take a second dose. However, after taking the first tablet you must wait at least 2 hours before taking the second one.
- You should not take more than 80mg of Relpax in 24 hours (2 tablets x 40mg).
- If you feel that one 40 mg tablet does not make the migraine go away, please inform your doctor who may decide to increase the dose to two 40 mg tablets for future episodes.
Use in children and adolescents under the age of 18
Relpax tablets are not recommended for children and adolescents under the age of 18.
Senior citizens
Relpax tablets are not recommended for patients over 65 years of age.
Kidney failure
This medicine can be used in patients with mild to moderate kidney problems. An initial dose of 20 mg and a total daily dose of no more than 40 mg is recommended in these patients. Your doctor will advise you which dose to take.
Hepatic insufficiency
This medicine can be used in patients with mild to moderate liver problems. No dose adjustment is required for mild to moderate hepatic insufficiency.
Overdose What to do if you have taken too much Relpax
If you take more Relpax than you should:
If you accidentally take too many Relpax tablets, contact your doctor right away or go to the nearest emergency department. Always take the medicine pack with you whether you have any tablets left or not. Side effects from taking too many Relpax tablets include high blood pressure and heart problems.
If you forget to take Relpax:
If you forget to take a tablet, take it as soon as you remember unless it is time for the next one. Do not take a double dose to make up for a forgotten one.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Relpax
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if, after taking this medicine, you happen to have any of the symptoms listed below
- Sudden wheezing, difficulty in breathing, swollen eyelids, face or lips, rash or itching (particularly all over the body) as this may be a symptom of an allergic reaction.
- Chest pain and tightness which may be intense and affect the throat. These may be symptoms of heart circulatory problems (cardiac ischaemia).
- Signs and symptoms of serotonin syndrome which may include agitation, hallucinations, loss of coordination, increased heart rate, increased body temperature, sudden changes in blood pressure and overactive reflexes.
Other side effects that may occur:
Common (may affect up to 1 in 10 people)
- Chest pain or tightness or pressure, palpitations, increased heart rate
- Dizziness, spinning sensation of one's body or objects (vertigo), headache, sleepiness, reduced sensitivity to touch and pain
- Sore throat, throat tightness, dry mouth
- Abdominal and stomach pain, indigestion (stomach upset), nausea (feeling of discomfort and discomfort in the stomach or abdomen with an urge to vomit)
- Stiffness (increased muscle tone), muscle weakness, back pain, muscle pain
- General feeling of weakness, hot feeling, chills, runny nose, sweating, tingling or abnormal sensations, flushing, pain.
Uncommon (may affect up to 1 in 100 people)
- Difficulty breathing, yawning
- Swelling of the face, hands or feet, inflammation or infection of the tongue, skin rash, itching
- Increased sensitivity to touch or pain (hyperesthesia), loss of coordination, reduced or slow movements, tremor, slurred speech
- not feeling like yourself (depersonalization), depression, altered thoughts, agitation, confusion, mood swings (euphoria), periods of unresponsiveness (stupor), general feeling of discomfort, illness or lack of well-being (malaise), lack of sleep (insomnia)
- loss of appetite and weight (anorexia), taste disturbance, feeling of thirst
- joint degeneration (arthrosis), bone pain, joint pain
- Increased need to urinate, urination problems, excessive urination, diarrhea
- Change in vision, eye pain, intolerance to light, dry or watery eyes
- Ear pain, ringing in the ears (tinnitus)
- Decreased circulation (peripheral circulation disorders)
Rare (may affect up to 1 in 1,000 people)
- Shock, asthma, hives, skin disorders, tongue edema
- Throat or chest infection, swollen lymph glands
- Slow heartbeat
- Emotional instability (mood swings)
- Joint degeneration (arthritis), muscle disorders, muscle contractions
- Constipation, inflammation of the esophagus, belching
- Chest pain, intense or prolonged menstrual periods
- Eye infections (conjunctivitis)
- Alteration of the voice
Other reported side effects include fainting, high blood pressure, inflammation of the colon and vomiting, brain and blood vessel related accidents, insufficient blood supply to the heart, heart attack, spasms of the arteries or heart muscle.
Your doctor may ask you for regular blood tests to check for increased liver enzymes or other blood problems.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) which is stated on the carton. The expiry date refers to the last day of that month.
PVC Aclar / Al and PVC / Al blisters: This medicinal product does not require any special storage conditions. HDPE bottles: Store the tablets in the original container. Once opened, keep the container tightly closed and away from humidity.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Relpax contains
The active substance in Relpax is eletriptan (as eletriptan hydrobromide).
Each Relpax 20mg film-coated tablet contains 20mg of eletriptan (as eletriptan hydrobromide).
Each Relpax 40mg film-coated tablet contains 40mg of eletriptan (as eletriptan hydrobromide).
The tablets also contain the following ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, titanium dioxide (E171), hypromellose, glycerol triacetate, sunset yellow FCF aluminum lake (E110).
Description of what Relpax looks like and contents of the packs
Relpax tablets are orange in color and round in shape.
Relpax 20mg film-coated tablets are marked "PFIZER" on one side and "REP 20" on the other.
Relpax 40mg film-coated tablets are marked "PFIZER" on one side and "REP 40" on the other.
Relpax is available in opaque PVC Aclar / Al and opaque PVC / Al blisters in packs of 2, 3, 4, 6, 10, 18, 30 and 100 tablets or in HDPE bottles with child resistant HDPE / PP closure of 30 and 100 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
RELPAX
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
RELPAX 20 mg:
each film-coated tablet contains 20 mg of eletriptan (as eletriptan hydrobromide).
Excipients: lactose 23,000 mg; sunset yellow (E110) 0.036 mg
RELPAX 40 mg:
each film-coated tablet contains 40 mg of eletriptan (as eletriptan hydrobromide).
Excipients: lactose 46,000 mg; sunset yellow (E110) 0.072 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
Orange, round shaped, convex tablets marked "REP 20" or "REP 40" on one side and "Pfizer" on the other.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Acute treatment of the headache phase of migraine attacks with or without aura.
04.2 Posology and method of administration
RELPAX tablets should be taken as soon as possible after the onset of the migraine attack, but they are also effective when taken at a later stage.
RELPAX, taken during the aura phase, has not been shown to prevent migraine attacks and therefore should only be taken during the headache phase of migraine attacks.
RELPAX tablets should not be used for prophylaxis.
The tablets should be swallowed whole with water.
Adults (age 18-65 years)
The recommended starting dose is 40 mg.
If the headache returns within 24 hours: If the migraine attack recurs within 24 hours after an initial response, a second dose of RELPAX of the same strength has been shown to be effective in treating relapses. If a second dose is required, it should not be taken within 2 hours of taking the initial dose.
In case of no reply: If a patient does not experience improvement in headache within 2 hours of taking the first dose of RELPAX, they should not take a second dose for the same attack because clinical trials have not adequately established the effectiveness of a second one. dose in these cases Clinical studies show that patients who do not respond to treatment for a migraine attack are likely to still respond to treatment for a subsequent attack.
Patients who do not achieve a satisfactory response after taking 40 mg (e.g. good tolerability and failure in 2 out of 3 attacks) can be treated satisfactorily with the 80 mg dose (2 x 40 mg tablets) in the treatment of subsequent attacks (see section 5.1 Pharmacodynamic properties - Further information on clinical studies). A second dose of 80 mg should not be taken within 24 hours.
The maximum daily dose should not exceed 80 mg (see section 4.8 Undesirable Effects).
Elderly (over 65 years of age)
The safety and efficacy of eletriptan in patients over 65 years of age have not been systematically evaluated due to the small number of these patients enrolled in clinical trials. Therefore, the use of RELPAX in elderly patients is not recommended.
Teenagers (ages 12-17)
The efficacy of RELPAX has not been established in this patient population and therefore the use of the product is not recommended in this age group.
Pediatric patients (ages 6-11 years)
The safety and efficacy of RELPAX in pediatric patients have not been evaluated. Therefore the use of RELPAX is not recommended in patients in this age group (see 5.2 Pharmacokinetic properties).
Hepatic insufficiency
No dosage adjustment is required in patients with mild or moderate hepatic impairment. As RELPAX has not been studied in patients with severe hepatic impairment, the product is contraindicated in these patients.
Kidney failure
Since the effects of RELPAX on blood pressure are increased in the presence of renal insufficiency (see 4.4. Special warnings and special precautions for use), the use of a starting dose of 20 mg is recommended in patients with mild or moderate renal insufficiency. The maximum daily dose should not exceed 40 mg RELPAX is contraindicated in patients with severe renal insufficiency.
04.3 Contraindications
Hypersensitivity to eletriptan hydrobromide or to any of the excipients.
Patients with severe hepatic or renal insufficiency.
Moderate to severe hypertension or untreated mild hypertension.
Patients with documented coronary artery disease, including ischemic heart disease (angina pectoris, previous myocardial infarction or documented silent ischemia), objective or subjective symptoms of ischemic heart disease or Prinzmetal's angina.
Patients with significant arrhythmias or heart failure.
Patients with peripheral vasculopathy.
Patients with a previous episode of cerebrovascular accident (CVA) or transient ischemic attack (TIA).
Administration of ergotamine or ergotamine derivatives (including methysergide) within 24 hours before or after treatment with eletriptan (see section 4.5 Interactions with other medicinal products and other forms of interaction). Concomitant administration of other 5-HT1 receptor agonists and eletriptan.
04.4 Special warnings and appropriate precautions for use
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 medicine also contains sunset yellow aluminum lake which can cause allergic reactions.
RELPAX must not be used in conjunction with potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin) and protease inhibitors (ritonavir, indinavir and nelfinavir).
RELPAX should only be used when a clear diagnosis of migraine has been established. RELPAX is not indicated for the treatment of hemiplegic, ophthalmoplegic or basilar migraine.
RELPAX must not be given to treat "atypical" headaches, which are headaches that can be related to potentially serious medical conditions (stroke, ruptured aneurysm) in which cerebral vasoconstriction can be dangerous.
The use of eletriptan may be associated with some transient symptoms, including chest pain and chest tightness, which may be intense and may affect the throat (see section 4.8 Undesirable Effects). When these symptoms are thought to be suggestive of ischemic heart disease, no other doses should be taken and an appropriate assessment should be made.
RELPAX should not be given, without prior investigation, to patients in whom undiagnosed heart disease is likely or in patients at risk for coronary artery disease (CAD) (eg, patients with hypertension, diabetes, smokers, or people who do use of nicotine replacement therapy, men over 40 years of age, postmenopausal women and women with a significant family history of coronary heart disease). Cardiac investigations may not identify all patients with heart disease and, in very rare cases, serious cardiac events have occurred in patients who did not have underlying heart disease when 5-HT1 receptor agonists were administered. RELPAX must not be administered to patients with established coronary artery disease (see section 4.3 Contraindications).
The use of 5-HT1 receptor agonists has been associated with coronary vasospasm. Rare cases of myocardial ischaemia or myocardial infarction have been reported following the use of 5-HT1 receptor agonists.
Side effects may be more common when triptans are taken concomitantly with herbal preparations containing St. John's wort (Hypericum perforatum).
Within the therapeutic dosages used in clinical trials, the use of eletriptan doses of 60 mg or higher resulted in mild and transient increases in blood pressure. However, no clinical evidence of such blood pressure changes was reported in clinical trials. The effect was much more pronounced in subjects with renal insufficiency and in the elderly. In subjects with renal insufficiency, the range of mean maximum increases for systolic blood pressure was 14-17 mmHg (normal 3 mmHg) and for diastolic blood pressure 14-21 mmHg (normal 4 mmHg). In elderly subjects, the mean maximum increase in systolic blood pressure was 23 mmHg compared with 13 mmHg in young adults (placebo 8 mmHg).
In the post-marketing phase of the product, increases in blood pressure have also been reported in patients treated with eletriptan doses of 20 mg and 40 mg and in patients who did not have renal impairment and who were not elderly.
Medication overuse headache (Medication Overuse Headache - MOH)
Prolonged use of any pain reliever to treat headache may make it worse. If this condition is suspected or occurs, the patient should be advised to seek medical advice, and treatment should be discontinued. In the event of attacks occurring. frequent or daily headaches, despite (or due to) the regular use of medications for the treatment of headache, patients should be assumed to have developed medication overuse headache (MOH).
Episodes of serotonin syndrome (including mental altered states, autonomic instability and neuromuscular abnormalities) have been reported following concomitant administration of triptans and selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) medicinal products. . These reactions can be severe. When concomitant use of eletriptan and an SSRI or SNRI is clinically justified, appropriate patient monitoring is advised, particularly at the start of treatment, in case of dose increases or in case of administration of an additional medicinal product with serotonergic activity (see section 4.5).
04.5 Interactions with other medicinal products and other forms of interaction
Effects of other medicinal products on eletriptan
No evidence of interaction with beta-blockers, tricyclic antidepressants, selective serotonin reuptake inhibitors and flunarizine was reported in pivotal clinical trials with eletriptan, but no data from specific interaction studies with these medicinal products are available (except for propranolol, see below).
Population PK analysis based on data collected from clinical trials suggested that the following medicinal products are unlikely to alter the pharmacokinetic properties of eletriptan: beta-blockers, tricyclic antidepressants, selective serotonin reuptake inhibitors, hormone therapy estrogen replacement, estrogen-containing oral contraceptives and calcium channel blockers.
Eletriptan is not a substrate for MAOs. Therefore, no interactions are expected between eletriptan and MAO inhibitors. For this reason, no specific interaction studies have been conducted.
In studies with propranolol (160 mg), verapamil (480 mg) and fluconazole (100 mg) the Cmax of eletriptan increased 1.1-fold, 2.2-fold and 1.4-fold, respectively. The AUC of eletriptan increased 1.3, 2.7 and 2.0-fold, respectively. These effects are not considered clinically significant because there was no increase in blood pressure or adverse events compared with eletriptan alone.
In clinical studies with erythromycin (1000 mg) and ketoconazole (400 mg), specific and potent inhibitors of CYP3A4, significant increases in eletriptan Cmax (2 and 2.7-fold) and AUC (3.6 and 5.9-fold) were observed. This increase in exposure was associated with an increase in eletriptan t1 / 2 from 4.6 to 7.1 hours after administration with erythromycin and from 4.8 to 8.3 hours after administration with 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 trials with oral caffeine / ergotamine given 1 and 2 hours after eletriptan, small but additive increases in blood pressure were observed; such increases are predictable based on the pharmacology of the two drugs. It is therefore recommended not to take drugs containing ergotamine or ergotamine-like (eg dihydroergotamine) within 24 hours following eletriptan administration. Likewise, at least 24 hours should elapse between the administration of an ergotamine-containing preparation and the administration of eletriptan.
Effects of eletriptan on other medicinal products
There is not in vitro or in vivo no evidence that therapeutic doses of eletriptan (and associated concentrations) could result in "inhibition or induction" of the cytochrome P450 enzymes, including CYP3A4, responsible for drug metabolism. Therefore, eletriptan is considered unlikely to cause clinically significant drug interaction reactions mediated by these enzymes.
Selective Serotonin Reuptake Inhibitors (SSRIs) / Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) and Serotonin Syndrome:
Symptoms consistent with serotonin syndrome (including altered mental states, autonomic instability and neuromuscular abnormalities) have been reported in some patients following the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). ) and triptans (see section 4.4).
04.6 Pregnancy and lactation
Pregnancy:
No clinical data are available on the use of RELPAX in pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development. RELPAX should only be used during pregnancy if clearly necessary.
Feeding time:
Eletriptan is excreted in breast milk. In a study involving 8 women treated with a single 80 mg dose, the mean total amount of eletriptan found in breast milk over 24 hours was 0.02% of the dose. However, caution is required when taking it. Consider administering RELPAX to breastfeeding women. Infant exposure can be minimized by avoiding breastfeeding for 24 hours after taking the drug.
04.7 Effects on ability to drive and use machines
Migraine or RELPAX treatment may cause drowsiness or dizziness in some patients. Patients should be advised to evaluate their ability to perform complex tasks, such as driving cars, during a migraine attack and after taking RELPAX.
04.8 Undesirable effects
RELPAX has been administered in clinical studies to over 5000 subjects who took one or two doses of 20 mg, 40 mg or 80 mg. The most common adverse reactions were asthenia, somnolence, nausea and dizziness. In randomized clinical trials conducted at doses of 20 mg, 40 mg and 80 mg, a correlation was observed between the incidence of adverse events and dose escalation. The following adverse reactions (with an "incidence ≥ 1% and greater than placebo) have been reported in clinical trials in patients treated at therapeutic doses. Events are categorized by frequency: common (≥1 / 100,
Infections and infestations
Common: pharyngitis and rhinitis;
Rare: respiratory tract infections.
Disorders of the blood and lymphatic system
Rare: lymphadenopathy.
Metabolism and nutrition disorders
Uncommon: anorexia.
Psychiatric disorders
Uncommon: Altered thinking, agitation, confusion, depersonalization, euphoria, depression and insomnia;
Rare: emotional instability.
Nervous system disorders
Common: somnolence, headache, dizziness, paraesthesia or dysaesthesia, hypertonia, hypoesthesia and myasthenia;
Uncommon: tremor, hyperesthesia, ataxia, hypokinesia, speech disturbances, stupor and altered taste.
Eye disorders
Uncommon: visual impairment, eye pain, photophobia and lacrimation disturbance;
Rare: conjunctivitis.
Ear and labyrinth disorders
Common: dizziness;
Uncommon: ear pain, tinnitus.
Cardiac pathologies
Common: palpitations and tachycardia;
Rare: bradycardia.
Vascular pathologies
Common: hot flashes;
Uncommon: peripheral vascular disorders;
Rare: shock.
Respiratory, thoracic and mediastinal disorders
Common: throat tightness;
Uncommon: dyspnoea, respiratory distress and yawning;
Rare: asthma and altered voice.
Gastrointestinal disorders
Common: abdominal pain, nausea, dry mouth and dyspepsia;
Uncommon: diarrhea and glossitis;
Rare: constipation, oesophagitis, tongue edema and belching.
Hepatobiliary disorders
Rare: increased bilirubin and AST.
Skin and subcutaneous tissue disorders
Common: sweating;
Uncommon: rash and itching;
Rare: skin changes and urticaria.
Musculoskeletal, connective tissue and bone disorders
Common: back pain, muscle pain;
Uncommon: arthralgia, osteoarthritis and bone pain;
Rare: arthritis, myopathy and muscle spasms.
Renal and urinary disorders
Uncommon: pollakiuria, urinary tract disorders and polyuria.
Diseases of the reproductive system and breast
Rare: breast pain and menorrhagia.
General disorders and administration site conditions
Common: sensation of heat, asthenia, chest symptoms (pain, tightness, pressure) and chills;
Uncommon: malaise, face edema, thirst, edema and peripheral edema.
Adverse events commonly encountered with eletriptan are typical ones already reported for the 5-HT1 receptor agonist class.
In the post-marketing phase of the product, the following undesirable effects have been reported:
Disorders of the immune system: allergic reactions, some of which can be serious, including angioedema.
Nervous system disorders: serotonin syndrome, rare cases of syncope
Vascular pathologies: hypertension
Gastrointestinal disorders: As with other 5-HT1B / 1D receptor agonists, rare cases of ischemic colitis have been reported; He retched.
04.9 Overdose
Some subjects were treated with single 120 mg doses without reporting significant adverse events. However, hypertension or other more severe cardiovascular symptoms may occur in the event of an overdose based on the drug class.
In the event of an overdose, standard supportive measures should be adopted as appropriate. The elimination half-life of eletriptan is approximately 4 hours and therefore, following an overdose of eletriptan, patients should be monitored and general supportive care should be used for at least 20 hours or until signs and symptoms resolve.
The effects of hemodialysis or peritoneal dialysis on serum concentrations of eletriptan are unknown.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Selective Serotonin Receptor Agonists (5HT1). ATC code: N02CC06.
Mechanism of action / pharmacology: Eletriptan is a selective agonist of vascular 5-HT1B receptors and neuronal 5-HT1D receptors. Eletriptan also exhibits a "high affinity for the 5-HT1F receptor and this may contribute to its anti-migraine mechanism of action."Eletriptan possesses modest affinity for human recombinant 5-HT1A, 5-HT2B, 5-HT1E and 5-HT7 receptors.
Learn more about clinical trials
The efficacy of RELPAX in the acute treatment of migraine was evaluated in 10 placebo-controlled clinical trials in approximately 4000 patients treated with RELPAX at doses ranging from 20 mg to 80 mg. Relief of migraine attack occurred as early as 30 minutes after oral administration. Response rates (reduction of moderate or severe migraine pain to no pain or mild pain) 2 hours after administration they were 59-77% for the 80 mg dose, 54-65% for the 40 mg dose, 47-54% for the 20 mg dose, and 19-40% for the placebo. RELPAX has also been shown to be effective in treating symptoms associated with migraine such as vomiting, nausea, photophobia and phonophobia.
The recommendation for a dose increase to 80 mg is based on long-term open-label studies and a short-term double-blind study in which only a trend towards statistical significance was observed.
RELPAX retains its efficacy in the treatment of migraine associated with the menstrual cycle. RELPAX, when taken during the aura phase, has not been shown to prevent migraine headaches and therefore RELPAX should only be taken during the headache phase. of migraine attacks.
In a non-placebo controlled pharmacokinetic study in patients with renal impairment, greater increases in blood pressure were observed following the administration of an 80 mg dose of RELPAX than in healthy volunteers (see section 4.4). This finding cannot be explained on the basis of pharmacokinetic variations and therefore may represent a specific pharmacodynamic effect following the administration of eletriptan in patients with renal insufficiency.
05.2 "Pharmacokinetic properties
Absorption:
Eletriptan is well and rapidly absorbed from the gastrointestinal tract (at least 81%) after oral administration. Absolute oral bioavailability in men and women is approximately 50%. Median Tmax is 1.5 hours after oral administration. A pharmacokinetics. linear has been demonstrated with the use of the drug in the therapeutic dosage range (20-80 mg).
The AUC and Cmax of eletriptan increased by approximately 20-30% following oral administration with a high-fat meal. Following oral administration during a migraine attack, an approximately 30% reduction in AUC was observed, while Tmax increased to 2.8 hours.
After repeated dosing (20 mg 3 times / day) for 5-7 days, the pharmacokinetics of eletriptan remained linear and the percentage of accumulation remained within expected values. With multiple dosing of higher doses (40 mg 3 times / day and 80 mg 2 times / day), the accumulation of eletriptan over 7 days was greater than expected (approximately 40%).
Distribution:
The volume of distribution of eletriptan following intravenous administration is 138 liters indicating tissue distribution. Eletriptan binds to plasma proteins only in a moderate percentage (approximately 85%).
Metabolism:
Studies in vitro indicate that eletriptan is primarily metabolised by the hepatic cytochrome P450 enzyme, CYP3A4. This is demonstrated by the increased plasma concentrations of eletriptan following concomitant administration of erythromycin and ketoconazole, known potent and selective inhibitors of CYP3A4. Studies in vitro they also show a modest involvement of CYP2D6, although clinical studies do not indicate any evidence of polymorphism with this enzyme.
Two major circulating metabolites have been identified that contribute significantly to plasma radioactivity following administration of 14-labeled eletriptan. The metabolite formed through N-oxidation has not shown any activity in animal models in vitro. The metabolite formed by N-demethylation has instead shown, in animal models in vitro, an activity similar to that of eletriptan. A third area of radioactivity in plasma has not been formally identified, but most likely it is a combination of hydroxylated metabolites that have also been detected in urine and faeces.
Plasma concentrations of the active N-desmethyl metabolite are only 10-20% of those of parent drug and therefore are not expected to contribute significantly to the therapeutic activity of eletriptan.
Elimination:
The mean total plasma clearance of eletriptan following intravenous administration is 36 l / h with a plasma half-life of approximately 4 hours. The mean renal clearance following oral administration is approximately 3.9 l / h. renal accounts for approximately 90% of the total clearance indicating that eletriptan is eliminated primarily via the metabolic pathway.
Pharmacokinetics in particular groups of patients
Gender of belonging:
A meta-analysis of all clinical pharmacology studies and a population pharmacokinetic analysis performed on data from clinical studies indicate that gender does not significantly affect plasma concentrations of eletriptan.
Elderly (over 65 years of age):
Although not statistically significant, a small (16%) reduction in clearance associated with a statistically significant increase in half-life (from approximately 4.4 hours to 5.7 hours) is observed between elderly patients (65-93 years) and younger adult subjects. in elderly patients.
Teenagers (ages 12-17):
The pharmacokinetics of eletriptan (40 mg and 80 mg) in adolescent migraine patients administered the drug in the intercritical period were similar to that seen in healthy adult subjects.
Children (ages 6-11 years):
There are no differences in clearance of eletriptan in children compared to adolescents. However, the volume of distribution is lower in children, with plasma levels higher than expected following administration of the administered dose in adults.
Hepatic impairment:
Subjects with hepatic impairment (Child-Pugh A and B) showed a statistically significant increase in both AUC (34%) and half-life. A small increase in Cmax (18%) was observed. This modest change in exposure the drug is not considered clinically relevant.
Renal impairment:
Subjects with mild (creatinine clearance 61-89 mL / min), moderate (creatinine clearance 31-60 mL / min) or severe (creatinine clearance plasma protein) renal impairment.
An increase in blood pressure was observed in this group of patients.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans as demonstrated by conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and reproductive toxicity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core: microcrystalline cellulose; lactose monohydrate; croscarmellose sodium; magnesium stearate.
Coating: titanium dioxide (E171); hypromellose; lactose monohydrate; triacetin; sunset yellow (E110).
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Opaque PVC / Aclar or Opaque PVC / Aluminum blisters: the product does not require any special storage precautions.
HDPE bottles: keep the container tightly closed to keep it away from humidity.
06.5 Nature of the immediate packaging and contents of the package
Opaque PVC / Aclar or Opaque PVC / Aluminum blisters in packs of 2, 3, 4, 6, 10, 18, 30 and 100 tablets (20 mg, 40 mg).
HDPE bottles with HDPE / PP child resistant closure of 30 and 100 tablets (20 mg, 40 mg).
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
PFIZER ITALIA S.r.l. - Via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
RELPAX 20 mg film-coated tablets:
Aluminum blister, 2 tablets - AIC: 035307014 / M
Aluminum blister, 3 tablets - AIC: 035307026 / M
Aluminum blister, 4 tablets - AIC: 035307038 / M
Aluminum blister, 6 tablets - AIC: 035307040 / M
Aluminum blisters, 10 tablets in separable units - AIC: 035307053 / M
Aluminum blister, 18 tablets - AIC: 035307065 / M
Aluminum blisters, 30 tablets in separable units - AIC: 035307077 / M
Aluminum blisters, 100 tablets in separable units - AIC: 035307089 / M
Aclar blister, 2 tablets - AIC: 035307091 / M
Aclar blister, 3 tablets - AIC: 035307103 / M
Aclar blister, 4 tablets - AIC: 035307115 / M
Aclar blister, 6 tablets - AIC: 035307127 / M
Aclar blister, 10 tablets in separable units - AIC: 035307139 / M
Aclar blister, 18 tablets - AIC: 035307141 / M
Aclar blister, 30 tablets in separable units - AIC: 035307154 / M
Aclar blister, 100 tablets in separable units - AIC: 035307166 / M
HDPE bottle, 30 tablets - AIC: 035307178 / M
HDPE bottle, 100 tablets - AIC: 035307180 / M
RELPAX 40 mg film-coated tablets:
Aluminum blister, 2 tablets - AIC: 035307192 / M
Aluminum blister, 3 tablets - AIC: 035307204 / M
Aluminum blister, 4 tablets - AIC: 035307216 / M
Aluminum blister, 6 tablets - AIC: 035307228 / M
Aluminum blisters, 10 tablets in separable units - AIC: 035307230 / M
Aluminum blister, 18 tablets - AIC: 035307242 / M
Aluminum blisters, 30 tablets in separable units - AIC: 035307255 / M
Aluminum blisters, 100 tablets in separable units - AIC: 035307267 / M
Aclar blister, 2 tablets - AIC: 035307279 / M
Aclar blister, 3 tablets - AIC: 035307281 / M
Aclar blister, 4 tablets - AIC: 035307293 / M
Aclar blister, 6 tablets - AIC: 035307305 / M
Aclar blister, 10 tablets in separable units - AIC: 035307317 / M
Aclar blister, 18 tablets - AIC: 035307329 / M
Aclar blister, 30 tablets in separable units - AIC: 035307331 / M
Aclar blister, 100 tablets in separable units - AIC: 035307343 / M
HDPE bottle, 30 tablets - AIC: 035307356 / M
HDPE bottle, 100 tablets - AIC: 035307368 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
January 22, 2002 / February 12, 2011
10.0 DATE OF REVISION OF THE TEXT
November 15, 2012
11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY
12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL
IMPORTANT INFORMATION NOTE
AGREED WITH THE ITALIAN DRUG AGENCY (AIFA)
April 2013
RELPAX (Eletriptan hydrobromide): Contraindications in the administration of Relpax
Dear Doctor / Dear Doctor,
Pfizer, in agreement with the Italian Medicines Agency (AIFA), wishes to bring to your kind attention some important safety information relating to the use of Relpax.
Relpax contains the active substance Eletriptan hydrobromide, a selective agonist of vascular 5-; HT1B receptors and neuronal 5-; HT1D receptors, and is authorized for the acute treatment of the headache phase of migraine attacks with or without aura.
Analyzing cases of cardiovascular adverse events it was found that Relpax was been on several occasions administered to patients with pre-existing cardiovascular events in whom the medicinal product is contraindicated.
From February 1, 2008 to December 31, 2012, 15 cases, confirmed by healthcare professionals, of cerebrovascular events concomitant with eletriptan use were reported internationally, 14 of which (93%) were serious cases. Of the 15 cases, 4 cases had a history of a contraindicated condition or the use of a contraindicated medicine.
From 1 February 2008 to 31 December 2012, 85 reports of cardiovascular events concomitant with the use of eletriptan were made. Of the 85 cases confirmed internationally by healthcare professionals, 55 (65%) were serious cases. Of the 85 cases, 17 cases had a history of a contraindicated condition and / or use of a contraindicated medicine.
It is therefore considered necessary to draw the attention of prescribers to remember in which situations the use of Relpax is contraindicated:
• Hypersensitivity to eletriptan hydrobromide or to any of the excipients;
• Patients with severe hepatic or renal insufficiency;
• Moderate to severe hypertension or untreated mild hypertension;
• Patients with documented coronary artery disease, including ischemic heart disease (angina pectoris, previous myocardial infarction or documented silent ischemia), objective or subjective symptoms of ischemic heart disease or Prinzmetal's angina;
• Patients with significant arrhythmias or heart failure;
• Patients with peripheral vasculopathy;
• Patients with a previous episode of cerebrovascular accident (CVA) or transient ischemic attack (TIA);
• Administration of ergotamine or ergotamine derivatives (including methysergide) within 24 hours prior to or following treatment with eletriptan.
• Concomitant administration of other 5-; HT1 receptor agonists and eletriptan.
Doctors are recommended to prescribe Relpax only after careful evaluation of the benefit / risk ratio of each individual patient and in any case never in situations where its use is contraindicated.
It should be remembered that the contraindications of Relpax towards patients with a history of cardiovascular diseases are common to those of the other triptans on the market.
It is also advisable to carefully monitor patients, particularly at the start of treatment, in order to stop treatment immediately when the first symptoms of cardiovascular events appear.
Doctors and other healthcare professionals are required to report any suspected adverse reactions
associated with Relpax. Doctors and other healthcare professionals can send reports of suspected adverse reactions, through the appropriate form, promptly, to the Pharmacovigilance Manager of the healthcare facility to which they belong, who will enter them in the database of the National Pharmacovigilance Network.
AIFA takes the opportunity to remind all doctors and pharmacists of the importance of reporting suspected adverse drug reactions, as an indispensable tool for confirming a favorable benefit-risk ratio in real conditions of use.
This Important Information Note is also published on the AIFA website (www.agenziafarmaco.it) whose regular consultation is recommended for the best professional and service information to the citizen.
