Rizatriptan

from Wikipedia, the free encyclopedia
Structural formula
Rizatriptan Structural Formula V.1.svg
General
Non-proprietary name Rizatriptan
other names

3- [2- (dimethylamino) ethyl] -5- (1,2,4-triazol-1-ylmethyl) indole

Molecular formula
  • C 15 H 19 N 5 (rizatriptan)
  • C 15 H 19 N 5 · C 6 H 5 COOH (rizatriptan benzoate)
External identifiers / databases
CAS number
  • 144034-80-0 (rizatriptan)
  • 145202-66-0 (rizatriptan benzoate )
PubChem 5078
DrugBank DB00953
Wikidata Q212171
Drug information
ATC code

N02 CC04

Drug class

Triptans

Mechanism of action

Selective 5-HT 1 receptor agonist

properties
Molar mass
  • 269.34 g · mol -1 (Rizatriptan)
  • 391.47 g · mol -1 (Rizatriptan benzoate)
Melting point
  • 120-121 ° C (rizatriptan)
  • 178–180 ° C (rizatriptan benzoate)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Rizatriptan is a selective serotonin agonist from the triptan group and is approved as a medicinal substance for the treatment of migraine headaches . Approval was granted in 1998 in the USA by the FDA and in the same year in Germany by the Federal Institute for Drugs and Medical Devices . Rizatriptan requires a prescription .

pharmacology

Pharmacodynamics

Like the other approved triptans, rizatriptan is a so-called serotonin agonist . It acts agonistically on the 5-HT 1B receptors . This causes vasoconstriction (narrowing) of the intracranial blood vessels. As an additional mechanism of action via a 5-HT are 1D mediated receptors inhibition (inhibition) of the release of vasoactive neuropeptides and the central transmission of pain in the brain stem postulated.

Pharmacokinetics

The absorption of rizatriptan proceeds comparatively quickly (time of the maximum plasma concentration T max approx. 50 minutes), whereby a high bioavailability of approx. 45 percent and a half-life of two to three hours is achieved. With peroral application of 10 milligrams, the onset of action takes place after 30 minutes.

Dosage and application

Rizatriptan is used in doses of five and ten milligrams in the form of tablets and sublingual tablets . Both dosage forms contain it in the form of its benzoic acid salt (7.265 or 14.53 milligrams of rizatriptan benzoate). The standard dose is ten milligrams, a dose of five milligrams should be used in the case of impaired liver or kidney function.

It is generally not preventive, but should be taken at the first sign of a migraine headache. A single dose is usually sufficient; if the effect is insufficient, a second application can be carried out after two hours. The total daily dose should not exceed 20 milligrams. In around a third of patients, headaches recur after the first dose, so that a second application is necessary. About 10 to 20 percent of patients do not respond to treatment with rizatriptan.

Like all triptans, rizatriptan is considered to be the agent of choice for the acute treatment of moderate and severe migraine headaches, but due to its risk profile and the costs it is only a reserve agent for long-term treatment. Frequent use can also increase the frequency of migraine attacks and even drug-induced constant headaches.

Side effects

Rizatriptan is generally considered to be well tolerated. The most common adverse effects include hot flashes, dry mouth and thirst, temporary muscle weakness, dizziness, nausea, weakness and fatigue, palpitations, tachycardia and shortness of breath. Heart attack provocation and the induction of severe cardiac arrhythmias are known to be life-threatening but rare side effects.

Because of the possible side effects, driving and other potentially dangerous activities should be avoided after ingestion.

Risk groups and contraindications

Possible contraindications in which the use of rizatriptan should only be carried out with particular caution relate to the presence of high blood pressure , diabetes mellitus , peripheral vascular disease and mild to moderate impairment of liver or kidney function. The groups of people for whom use is associated with increased risks also include postmenopausal women and smokers.

Rizatriptan should not be used in the presence of heart disease because of the risk of ischemic conditions and vasospasm . In addition, it should not be used in angina pectoris , in patients with previous heart attacks and strokes , in severe impairment of liver and kidney function and in two special forms of migraine, familial hemiplegic migraine (FHM) and basilar migraine.

In the absence of clinical experience, its use in children and adolescents under 18 years of age and in adults over 65 years of age, in pregnant women and in mothers who are breastfeeding is not recommended.

Interactions

A combined intake with other triptans must be avoided because of the increased effect via the same mechanism of action and the resulting increased risk of side effects, as well as the combination with ergotamine derivatives due to an increased risk of vasospasm. The combination with migraine drugs from other substance classes should be agreed with the attending physician.

The American health authority FDA warns of a potentially life-threatening interaction of serotonin syndrome , i.e. an accumulation of too much serotonin in the nervous system, when a triptan and an antidepressant from the group of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and noradrenaline are taken at the same time. Reuptake inhibitors (SNRI). Symptoms of serotonin syndrome can include restlessness, hallucinations, loss of coordination, rapid heartbeat, fluctuations in blood pressure, increased body temperature, increased reflexes, nausea, vomiting, and diarrhea.

literature

Individual evidence

  1. ^ A b The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 1423, ISBN 978-0-911910-00-1 .
  2. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  3. ↑ Limmroth V: mechanism of action of triptans . In: Pharmacy in our time . 31, No. 5, 2002, pp. 458-461. doi : 10.1002 / 1615-1003 (200209) 31: 5 <458 :: AID-PAUZ458> 3.0.CO; 2-G . PMID 12369163 .
  4. ↑ FDA Public Health Advisory: Combined Use of 5-Hydroxytryptamine Receptor Agonists (Triptans), Selective Serotonin Reuptake Inhibitors (SSRIs) or Selective Serotonin / Norepinephrine Reuptake Inhibitors (SNRIs) May Result in Life-threatening Serotonin Syndrome , July 19, 2006 ( English).

Web links