Instructions for Rizoptan tablets 10 mg blister No. 3
Composition
active ingredient: rizatriptan;
1 tablet contains 14.53 mg of rizatriptan benzoate equivalent to 10 mg of rizatriptan;
Excipients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: round, flat-cylindrical tablets, with a bevel, with a score on one side, white or almost white in color.
Pharmacotherapeutic group
Drugs used in migraine. Selective serotonin 5-HT1 receptor agonists. Rizatriptan. ATC code N02C C04.
Pharmacological properties
Pharmacodynamics
Rizatriptan binds selectively with high affinity to human 5-HT1B and 5-HT1D receptors and has little or no effect or pharmacological activity at 5-HT2, 5-HT3; adrenergic α1, α2, or β; dopaminergic D1, D2; histamine H1; muscarinic, or benzodiazepine receptors.
The therapeutic activity of rizatriptan in the treatment of migraine headache may be explained by its agonistic effects on 5-HT1B and 5-HT1D receptors on extracerebral intracranial blood vessels, which are thought to dilate during an attack, and on the trigeminal sensory nerves that innervate them. Activation of 5-HT1B and 5-HT1D receptors may result in constriction of the intracranial blood vessels that cause pain and inhibition of neuropeptide release, leading to decreased inflammation of sensory tissues and decreased transmission of the central trigeminal pain signal.
Pharmacokinetics
Absorption.
After oral administration, rizatriptan is rapidly and completely absorbed. The mean oral bioavailability of the tablets is approximately 40–45%, and mean peak plasma concentrations (Cmax) are reached after approximately 1–1.5 hours (Tmax). Oral administration of rizatriptan with a high-fat breakfast did not affect the extent of rizatriptan absorption, but its absorption was delayed by approximately one hour.
Food effect: Tmax is delayed by approximately 1 hour if the tablets are taken in a fed state.
Distribution.
Rizatriptan is minimally (14%) bound to plasma proteins. The volume of distribution is approximately 140 L in men and 110 L in women.
Biotransformation.
The primary route of metabolism of rizatriptan is through oxidative deamination by monoamine oxidase-A (MAO-A) to the indoleacetic acid metabolite, which is not pharmacologically active. A small amount of N-monodesmethyl-rizatriptan is formed, a metabolite that has similar activity to the parent compound at 5-HT1B/1D receptors but has no significant effect on the pharmacodynamic activity of rizatriptan. Plasma concentrations of N-monodesmethyl-rizatriptan are approximately 14% of those of the parent compound, and the compound is excreted at a similar rate. Other minor metabolites include the N-oxide, the 6-hydroxy compound, and the sulfate conjugate of the 6-hydroxy metabolite. None of these minor metabolites is pharmacologically active.
Breeding.
After oral administration of doses above the 2.5–10 mg dose range, the area under the curve increases almost proportionally. The plasma half-life of rizatriptan averages 2–3 hours in men and women. The plasma clearance of rizatriptan averages about 1000–1500 mL/min in men and about 900–1100 mL/min in women; about 20–30% of this is renal clearance. After oral administration of 14C-labeled rizatriptan, approximately 80% of the radioactivity is excreted in the urine and about 10% of the dose is excreted in the feces. This indicates that the metabolites are primarily excreted by the kidneys.
Based on the first-pass metabolism of rizatriptan, approximately 14% of an oral dose is excreted unchanged in the urine, while 51% is excreted as the indoleacetic acid metabolite. Less than 1% is excreted in the urine as the active N-monodesmethyl metabolite.
If rizatriptan is taken in maximum doses, there is no daily accumulation of the drug in plasma.
Characteristics in different patients.
Patients with a migraine attack: A migraine attack does not affect the pharmacokinetics of rizatriptan.
Gender: In males, the AUC of rizatriptan (10 mg orally) was approximately 25% lower than in females, the Cmax was 11% lower, and the Tmax was approximately the same. This apparent pharmacokinetic difference is not clinically significant.
Elderly patients: rizatriptan plasma concentrations are similar to those in young patients.
Patients with renal impairment: It is known that in patients with renal insufficiency (creatinine clearance 10-60 mL/min/1.73 m2), the area under the curve of rizatriptan was not significantly different from that in healthy subjects. In patients on hemodialysis (creatinine clearance < 10 mL/min/1.73 m2), the area under the curve of rizatriptan was approximately 44% greater than in patients with normal renal function. The maximum plasma concentration of rizatriptan in patients with any degree of renal insufficiency was the same as in healthy subjects.
Indication
Emergency treatment of the headache phase of migraine attacks, with or without aura.
Contraindication
Hypersensitivity to rizatriptan or any of the excipients. Concomitant use with monoamine oxidase (MAO) inhibitors or use within two weeks of discontinuing treatment with MAO inhibitors. Severe hepatic or severe renal insufficiency. History of cerebrovascular accident or transient ischemic attack. Moderate or severe hypertension, as well as untreated mild hypertension. Established coronary artery disease, including ischemic heart disease (angina pectoris, history of myocardial infarction or documented asymptomatic ischemia), signs and symptoms of ischemic heart disease or Prinzmetal's angina. Peripheral vascular disease. Concomitant use of rizatriptan and ergotamine, ergot alkaloid derivatives (including methysergide) or other 5-HT1B/1D receptor agonists.
Interaction with other medicinal products and other types of interactions
Ergotamine, ergot derivatives (including methysergide), other 5-HT1B/1D receptor agonists: Due to an additive effect, the concomitant use of rizatriptan and ergotamine, ergot derivatives (including methysergide) or other 5-HT1B/1D receptor agonists (e.g. sumatriptan, zolmitriptan, naratriptan) increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated (see section "Contraindications").
Monoamine oxidase inhibitors: Rizatriptan is primarily metabolized by monoamine oxidase subtype A (MAO-A). Plasma concentrations of rizatriptan and its active N-monodesmethyl metabolite are increased by concomitant use of a selective, reversible inhibitor of monoamine oxidase A. A similar or greater effect is expected with non-selective, reversible monoamine oxidase inhibitors (e.g. linezolid). Due to the risk of coronary spasm and hypertension, rizatriptan is contraindicated in patients taking monoamine oxidase inhibitors (see section 4.3).
Beta-blockers: Plasma concentrations of rizatriptan may be increased by concomitant administration of propranolol. This increase is most likely due to an interaction of the first-pass metabolism of the two drugs, since MAO-A plays a role in the metabolism of both rizatriptan and propranolol. This interaction results in a mean increase in AUC and Cmax of 70-80%. Patients taking propranolol should be given RISOPTAN® at a dose of 5 mg (see section 4.2).
The drugs nadolol and metoprolol do not change the plasma concentrations of rizatriptan.
Selective serotonin reuptake inhibitors/norepinephrine and serotonin reuptake inhibitors and serotonin syndrome: There have been reports of patients with symptoms similar to serotonin syndrome (including altered mental status, autonomic nervous system disorders and neuromuscular disorders) following the use of serotonin reuptake inhibitors/norepinephrine, serotonin reuptake inhibitors and triptans (see section 4.4).
In vitro studies indicate that rizatriptan inhibits cytochrome P450 2D6 (CYP2D6). There are no clinical data on their interaction. When prescribing rizatriptan to patients taking CYP2D6 substrates, the potential for interaction should be considered.
Application features
Rizoptan® cannot be used for prophylaxis.
Food effects: The absorption of rizatriptan is delayed by approximately 1 hour when taken with food. Therefore, the onset of action may be delayed if taken in a fed state (see also section 5.1).
Rizoptan® should only be prescribed to patients who have a clear diagnosis of migraine. Rizoptan® should not be prescribed to patients with basilar or hemiplegic migraine.
Rizoptan® should not be used to treat atypical headaches, i.e. those that may be associated with potentially serious conditions (e.g. stroke, ruptured aneurysm) in which cerebrovascular vasoconstriction may be dangerous.
As with other 5-HT1B/1D receptor agonists, rizatriptan should not be prescribed without prior evaluation in patients with suspected cardiac disease or in patients at risk of developing coronary artery disease (e.g., patients with hypertension, diabetes mellitus, smokers or those taking nicotine replacement therapy; men over 40 years of age, postmenopausal women, patients with ventricular septal defect, and those with a family history of serious coronary artery disease). Cardiac evaluation may not detect all patients with cardiac disease, and in very rare cases, serious cardiac complications have been observed in patients without pre-existing cardiovascular disease when taking 5-HT1 receptor agonists. Rizatriptan should not be prescribed to patients with established coronary artery disease (see section 4.3).
5-HT1B/1D receptor agonists are associated with coronary spasm. In some cases, myocardial ischemia or infarction has been reported with the use of 5-HT1B/1D receptor agonists.
Other 5-HT1B/1D receptor agonists (e.g. sumatriptan) should not be administered concomitantly with rizatriptan.
It is recommended to wait at least six hours after taking rizatriptan before taking ergotamine-containing medications (e.g. ergotamine, dihydroergotamine, or methysergide). Before taking rizatriptan, you should ensure that at least 24 hours have passed since the last dose of ergotamine-containing medications.
Serotonin syndrome (including altered mental status, autonomic nervous system disorders, and neuromuscular disorders) has been reported following concomitant use of triptans and selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors. These reactions can be serious. If concomitant use of rizatriptan and selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors is clinically indicated, appropriate monitoring of the patient is recommended, especially at the start of treatment, during dose increases, or when another serotonergic agent is added.
Undesirable effects are more likely to occur with the simultaneous use of triptans (5-HT1B/1D agonists) and herbal preparations containing St. John's wort (Hypericum perforatum).
Angioedema (e.g. swelling of the face, tongue and larynx) may occur in patients taking triptans, including rizatriptan. If angioedema of the tongue or pharynx occurs, the patient should be monitored closely until symptoms resolve. Triptans should be discontinued immediately and replaced with a drug from a different class of drug.
The drug contains lactose, so patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take it.
When prescribing rizatriptan to patients taking CYP2D6 substrates, the potential for interaction should be considered.
Headache caused by excessive use of the drug.
Prolonged use of any painkiller for headaches may worsen headaches. If this occurs (or is suspected), consult a doctor and discontinue treatment. Headache caused by excessive use of the drug may be suspected in patients who experience frequent or daily headaches despite regular use of headache medications.
Ability to influence reaction speed when driving vehicles or other mechanisms
In some patients, migraine or taking Rizoptan® may cause drowsiness. Dizziness has also been reported in some patients taking rizatriptan. Therefore, patients should assess their ability to perform complex tasks during migraine attacks and after taking Rizoptan®.
Use during pregnancy or breastfeeding
Reproductive function.
The effect on human reproductive function has not been studied. Animal studies are known to have shown minimal effects on reproductive function at plasma concentrations that far exceed therapeutic concentrations in humans (more than 500 times).
Use during pregnancy.
The safety of rizatriptan for use in pregnant women has not been established. Animal studies that address embryonal/fetal development or the course of pregnancy, parturition, and postnatal development have not shown harmful effects at exposure levels in excess of the human therapeutic exposure level.
Because animal reproductive and in utero studies are not always predictive of human response, RISOPTAN® should be used during pregnancy only if clearly needed.
Use during lactation.
Therefore, caution should be exercised when prescribing rizatriptan to breastfeeding women. Exposure to the infant should be minimized by not breastfeeding for 24 hours after administration of the drug.
Method of administration and doses
For internal use. Do not use Rizoptan® for prophylactic purposes.
The tablets should be swallowed whole with liquid.
Absorption time is delayed by approximately 1 hour if the drug is taken in a fed state.
The recommended dose is 10 mg.
Repeated administration: the next dose can be taken no earlier than 2 hours later; no more than two doses can be taken within a 24-hour period.
If headache recurs within 24 hours: If headache returns after relief of the initial attack, another dose may be taken. The above dosage guidelines should be followed. In the absence of effect: The efficacy of a second dose to treat the same attack when the first dose has failed has not been tested in rizatriptan studies. Therefore, if the patient has not had a therapeutic effect after taking the first dose, a second dose should not be taken to treat the same attack.
Studies of rizatriptan have shown that even if there is no therapeutic effect during one attack, there is still a possibility of a therapeutic effect in subsequent attacks.
Some patients may require a lower dose of RISOPTAN (5 mg), particularly in the following patient groups:
Patients taking propranolol. Rizatriptan should be taken no earlier than 2 hours after taking propranolol; Patients with mild to moderate renal impairment; Patients with mild to moderate hepatic impairment.
The time interval between two doses should be at least 2 hours; no more than 2 doses can be taken in a 24-hour period.
Patients aged 65 and over.
The efficacy and safety of rizatriptan in patients aged 65 years and older have not been systematically studied.
Children
The efficacy and safety of Rizoptan® in children (under 18 years of age) have not been established.
Overdose
Rizatriptan 40 mg (taken as a single dose or as two doses separated by two hours) was generally well tolerated; the most common adverse effects were dizziness and somnolence.
Hypertension or other more serious cardiovascular symptoms may occur following overdose. Patients suspected of having overdosed with rizatriptan should be given gastric lavage (e.g., gastric lavage followed by administration of activated charcoal). Clinical and electrocardiographic monitoring should be performed for at least 12 hours thereafter, even if clinical symptoms are absent.
The effect of hemodialysis and peritoneal dialysis on serum rizatriptan concentrations is unknown.
Adverse reactions
The most common side effects are dizziness, drowsiness and weakness/fatigue. The frequency of adverse reactions is defined as follows: very common (more than 10%); common (1-10%); uncommon (0.1-1%); rare (0.01-0.1%); frequency unknown (cannot be estimated from the available data).
On the part of the immune system: rare - allergic reactions, anaphylaxis/anaphylactoid reaction.
On the part of the psyche: frequent - insomnia; infrequent - disorientation, irritability.
Nervous system: frequent - dizziness, drowsiness, paresthesia, headache, hypoesthesia, decreased mental activity; infrequent - ataxia, tremor, vertigo, dysgeusia/unpleasant taste, fainting; frequency unknown - convulsions, serotonin syndrome.
On the part of the organs of vision: infrequently - blurred vision.
Cardiovascular system: frequent - palpitations, hot flashes; infrequent - arrhythmia, tachycardia, ECG changes, hypertension; rare - cerebrovascular disorders (according to reports, most of these adverse reactions occurred in patients with risk factors for coronary artery disease), bradycardia; frequency unknown - myocardial ischemia or infarction (according to reports, most of these adverse reactions occurred in patients with risk factors for coronary artery disease), peripheral vascular ischemia.
From the respiratory system, thoracic and mediastinal organs: frequent - discomfort in the throat; infrequent - shortness of breath; rare - wheezing.
From the digestive tract: frequent - nausea, dry mouth, vomiting, diarrhea, dyspepsia; infrequent - feeling of thirst; frequency unknown - ischemic colitis.
Skin and subcutaneous tissue disorders: common: redness; uncommon: itching, urticaria, angioedema (e.g. facial, tongue and throat swelling), rash, increased sweating; frequency unknown: toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders: common: feeling of heaviness; uncommon: neck pain, stiffness, stiffness, muscle weakness, facial pain, myalgia.
General disorders: common - asthenia/fatigue, abdominal or chest pain.
Expiration date
3 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store out of the reach of children, in the original packaging at a temperature not exceeding 25 °C.
Packaging
3 tablets in a blister; 1 blister in a cardboard pack.
Vacation category
According to the recipe.
Producer
"Pharma Start" LLC.
Location of the manufacturer and its business address
Ukraine, 03124, Kyiv, Vaclav Havel Boulevard, 8.
