Rizatriptan Uses, Dosage, Side Effects, FAQ - MedicinesFAQ (2023)

RizatriptanTablet, oral tablet, disintegration

Rizatriptan binds with high affinity to cloned human 5-HT1B/1D receptors. Rizatriptan benzoate is believed to exert its therapeutic effects in the treatment of migraine by binding to 5-HT1B/1D receptors located on intracranial blood vessels and sensory nerves of the trigeminal system.

Rizatriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) receptors type 1B and 1D. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists and has only weak affinity for 5-HT1A, 5-HT5A and 5-HT7 receptors and no significant affinity or pharmacological activity for 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or in alpha1, alpha2 or beta adrenergic receptors, dopamine1; dopamine2; muscarinic or benzodiazepine receptors. This effect in humans correlates with migraine relief. Experimental data from animal studies indicate that rizatriptan not only causes vasoconstriction but also activates 5-HT1 receptors on peripheral trigeminal nerve terminals that innervate cranial blood vessels, which may also contribute to the antimigraine effect of rizatriptan in humans.

Usos

Rizatriptan benzoate is used for the acute treatment of migraines with or without aura in adults and children and adolescents aged 6 to 17 years.

Rizatriptan is also used for the concomitant treatment of these conditions: Acute migraine with aura, Acute migraine without aura

How rizatriptan works

Three distinct pharmacological actions have been associated with the antimigraine activity of triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nucleus cell excitability by 5-HT1B/1D receptor agonism in the brainstem; and (3) vasoconstriction of meningeal, dural, cerebral, or pial vessels as a result of trigeminal nucleus HT1B vascular receptor agonism.

Rizatriptan

Structure

Dose

Rizatriptan dosage

Dosage information for adults: The recommended starting dose of rizatriptan benzoate is 5 mg or 10 mg for the acute treatment of migraine headaches in adults. The 10 mg dose may have a stronger effect than the 5 mg dose but may have a higher risk of side effects.

Redosing in adults: Although the efficacy of a second or subsequent dose has not been demonstrated in placebo-controlled studies, if migraine recurs, a second dose can be given 2 hours after the first dose. The maximum daily dose should not exceed 30 mg within 24 hours. The safety of treating an average of more than four headaches in a 30-day period has not been established.

Dosing information in pediatric patients (6 to 17 years): Dosing in pediatric patients is based on the patient's body weight. The recommended dose of rizatriptan benzoate is 5 mg in patients weighing less than 40 kg and 10 mg in patients weighing 40 kg or more.

The efficacy and safety of treatment with more than one dose of rizatriptan benzoate within 24 hours in pediatric patients 6 to 17 years of age have not been established.

Dose adjustment for patients on propranolol: Omitted sections or subsections of the full prescribing information are not listed.

• adult patients: For adult patients taking propranolol, only the 5 mg dose of rizatriptan benzoate is recommended, up to a maximum of 3 doses in any 24 hour period (15 mg).
• pediatric patients: For pediatric patients weighing 40 kg or more taking propranolol, only a single dose of 5 mg rizatriptan benzoate (maximum dose of 5 mg in 24 hours) is recommended. Rizatriptan benzoate should not be prescribed to propranolol-treated pediatric patients weighing less than 40 kg.

Administration of Rizatriptan Benzoate tablets, administration with liquid is not required. The orally disintegrating tablets are packaged in a blister in an outer foil pouch and patients should not remove the blister from the outer pouch until just prior to administration. The blister pack should then be opened with dry hands and the tablet, which disintegrates in the mouth, placed on the tongue where it will dissolve and be swallowed with saliva.

side effects

The following side effects are discussed in more detail in other sections of the label:

• Myocardial ischemia, myocardial infarction and Prinzmetal's angina
• Arrhythmias
• Chest, throat, neck and/or jaw pain/tightness/pressure
• Cerebrovascular events
• Other vasospastic reactions
• Medication overuse headache
• Serotonin Syndrome
• Elevated blood pressure

toxicity

Overdose symptoms include dizziness, fainting, heart and blood vessel problems, high blood pressure, loss of bowel and bladder control, slow heartbeat, and vomiting.

Caution

Old man; mild to moderate liver or kidney failure; coronary heart disease; pregnancy, lactation. Can make you tired. history of seizures. Ensure that there is an interval of at least 24 hours after stopping an ergot compound and starting a serotonin (5-HT1) agonist.

interaction

Propranolol: The rizatriptan dose should be adjusted in patients treated with propranolol since propranolol increases the plasma AUC of rizatriptan by 70%.

Drugs containing ergot: Drugs containing ergot have been reported to produce prolonged vasospastic reactions. Because these effects may be additive, the use of ergotamine-containing or ergot-type medicinal products (such as dihydroergotamine or methysergide) and rizatriptan within 24 hours is contraindicated.

Other 5-HT1 agonists: Since their vasospastic effects can be additive, the concomitant use of rizatriptan and other 5-HT1 agonists within 24 hours is contraindicated.

SSRIs/SNRIs and Serotoninergic Syndrome: Cases of serotonin syndrome have been reported with concomitant use of triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs).

monoamine oxidase inhibitors: Rizatriptan is contraindicated in patients taking MAO-A inhibitors and non-selective MAOIs. A specific MAO-A inhibitor increased the systemic exposure of rizatriptan and its metabolite

food interaction

• Take with or without food. However, the onset of action may be delayed by about 1 hour if taken with food.

Rizatriptan-cholesterol interaction

[Major] The class of drugs known as 5-hydroxytryptamine1 (5-HT1) receptor agonists can produce vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia.

In rare cases, serious adverse cardiac events, including acute myocardial infarction, arrhythmia, cardiac arrest and death, have been reported within hours of 5-HT1 agonist administration, in some cases even in patients with no history or evidence of coronary artery disease. (VILLAIN).

Significant increases in blood pressure, including hypertensive crisis, transient increases in blood pressure and peripheral vascular resistance have also been reported rarely in patients with and without a history of hypertension.

Generally, patients with potentially unrecognized CAD as predicted by the presence of risk factors (e.g., hypertension, hypercholesterolaemia, smoking, obesity, diabetes, family history of severe CAD, women with surgical or physiological menopause, or men over 40 years of age). should not receive 5-HT1 agonists unless cardiovascular assessment provides satisfactory clinical evidence in the absence of CAD, ischemic heart disease, or other significant underlying cardiovascular disease.

As a precaution, the manufacturers recommend that the first dose be administered in such patients under medical supervision and that electrocardiographic monitoring be considered during the interval immediately following dosing to detect any asymptomatic cardiac ischemia that may occur.

Regular cardiovascular assessments should be performed during long-term intermittent use.

Rizatriptan-drug interaction

Main ingredients: duloxetine, ondansetron

Moderat: Paracetamol/Hydrocodon

Not known: amphetamine/dextroamphetamine, erenumab, diphenhydramine, galcanezumab, omega-3 polyunsaturated fatty acids, nasal fluticasone, pregabalin, albuterol, montelukast, topiramate, paracetamol, cyanocobalamin, ascorbic acid, cholecalciferol, lisdexamfetamine, alprazolam, cetirizine

Rizatriptan disease interaction

Major: CHD risk factors, cardiovascular disease, liver disease, migraine

Moderate: PKU, renal impairment

volume of distribution

• 140L [small]
• 110 liters [female]

Eliminationsweg

Rapidly after oral administration. Bioavailability is 45%. Food does not affect the bioavailability of rizatriptan. However, administration of rizatriptan with food delays the time to peak plasma concentration by 1 hour. The rate of absorption is not affected by the presence of a migraine attack.

half-life

2-3 hours

Eliminationsweg

Approximately 14% of an oral dose is excreted in the urine as unchanged rizatriptan, while 51% is excreted as the indoleacetic acid metabolite, indicating extensive first-pass metabolism.

Use during pregnancy and lactation

The pregnancy: Inform patients that rizatriptan benzoate should not be used during pregnancy unless the potential benefit justifies the potential risk to the foetus.

breastfeeding mothers: It is not known if this medicine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when administering rizatriptan benzoate to breastfeeding women. Rizatriptan is extensively excreted in rat milk, with concentrations in milk being at least 5-fold higher than concentrations in maternal plasma.

contraindication

Rizatriptan benzoate is contraindicated in patients with:

• Coronary ischemic disease (angina, history of myocardial infarction, or documented silent ischemia) or other significant underlying cardiovascular disease
• Coronary artery vasospasm, including Prinzmetal hemorrhage
• History of stroke or transient ischemic attack (TIA).
• peripheral vascular disease (PVD)
• Ischemic Bowel Disease
• uncontrolled high blood pressure
• Recent use (i.e. within 24 hours) of another 5-HT1 agonist, ergot-containing drug, orergot-type drug (such as dihydroergotamine or methysergide)
• Hemiplegicorbasilarmigrana
• Concomitant administration or recent discontinuation (i.e. within 2 weeks) of an MAO-A inhibitor
• Hypersensitivity to rizatriptan benzoate (angioedema and anaphylaxis observed)

special warning

pediatric use: Safety and efficacy in pediatric patients less than 6 years of age have not been established. The efficacy and safety of rizatriptan in the acute treatment of migraine in patients 6 to 17 years of age has been demonstrated in an adequate and well-controlled study. The incidence of adverse reactions reported in pediatric patients in the acute clinical study was similar in patients receiving rizatriptan to patients receiving placebo. The pattern of adverse reactions in pediatric patients is expected to be similar to that in adults.

geriatric use: Clinical trials of rizatriptan did not enroll a sufficient number of subjects 65 years of age or older to determine whether they responded differently than younger subjects. Other reported clinical experiences have not identified differences in response between elderly and younger patients.

Although the pharmacokinetics of rizatriptan were similar in elderly (≥ 65 years) and younger adults (n = 17), in general the dose for an elderly patient should be chosen cautiously and start at the lower end of the dose range. This reflects the higher frequency of decreased liver, kidney, or heart function and concomitant disease or other drug therapy.

Geriatric patients with other cardiovascular risk factors (eg, diabetes, hypertension, smoking, obesity, family history of severe coronary artery disease) should undergo a cardiovascular evaluation before receiving rizatriptan.

renal insufficiency: For mild to moderate deterioration, start with 5 mg. An additional dose of 5 mg can be taken after an interval of at least 2 hours. Maximum: 10 mg/24 hrs. Avoid in case of severe deterioration.

hepatic dysfunction: For mild to moderate deterioration, start with 5 mg. An additional dose of 5 mg can be taken after an interval of at least 2 hours. Maximum: 10 mg/24 hrs. Avoid in case of severe deterioration.

acute overdose

May cause high blood pressure and cardiovascular symptoms. Gastric lavage with activated charcoal may be considered. Monitor the patient's ECG and clinical condition.

storage condition

Store at 15-30°C.

Innovators monograph