pharmachologic effect
Serotonin 5-HT1 receptor agonist. A drug with antimigraine activity.
Pharmacokinetics
After oral administration, it is quickly absorbed. 70% of the maximum plasma concentration is achieved after 45 minutes. Cmax in blood plasma is 54 ng/ml. Bioavailability - 14% (due to first-pass metabolism and incomplete absorption). Plasma protein binding is 14-21%.
Metabolized by oxidation with the participation of monoaminoxylase (mainly isoenzyme A) with the formation of metabolites, the main of which are the indoleacetic analogue of sumatriptan, which does not have pharmacological activity against 5-HT1-serotonin receptors, and its glucuronide. It is excreted by the kidneys, mainly in the form of metabolites.
Pharmacodynamics
Sumatriptan is a specific selective agonist of 5-HT1-serotonin receptors, localized primarily in the blood vessels of the brain and their stimulation leads to a narrowing of these vessels. Does not affect other subtypes of 5-HT-serotonin receptors (5-HT2-7). Activates the sensitivity of trigeminal nerve receptors. The therapeutic effect usually occurs 30 minutes after administration.
"Aimovig" and competitors
It must be said that Novartis and Amgen already have serious competitors in the field of targeted anti-migraine therapy: Eli Lilly released Emgality, and Teva Pharmaceutical released Ajovy. These drugs are humanized monoclonal antibodies that target the ligand rather than the CGRP receptor, and in this way they differ from Aimovig, being inferior to the latter at least in tolerability. When using Ajovy, 43–45% of patients experienced pain, redness and itching at the injection site, when using Emgality, 18% of patients experienced such symptoms, and Aimovig caused such reactions only in 5–6% of cases. At the same time, Aimovig is also more convenient to use, since of the three listed drugs, only it comes in the form of an auto-injector - a device that resembles an insulin syringe pen - which needs to be used only once a month. The listed advantages, coupled with the fact that Aimovig became the first targeted drug for the treatment of migraine and immediately filled an empty niche in the market, will most likely provide it with a bright financial future: according to experts, its market share in 2024 will be $2 billion, while the predicted shares of competitors are approximately half as much [20].
The success of Aimovig, apparently, cannot be hampered even by the extremely high price ($575 per month according to the Amgen price list - however, in the United States, the drug is covered by insurance for many patients), which, by the way, some experts consider unreasonable [11]. The company is conducting research on Aimovig in Russia, but when the drug will appear on the market, how much it will cost and who will pay for it is still unknown.
Contraindications to the use of Sumatriptan
- hemiplegic, basilar or ophthalmoplegic forms of migraine;
- IHD or the presence of symptoms suggesting its presence;
- history of myocardial infarction;
- pharmacologically uncontrolled arterial hypertension;
- occlusive diseases of peripheral vessels;
- stroke or transient cerebrovascular accident (including history);
- severe dysfunction of the liver and kidneys;
- simultaneous use with ergotamine or its derivatives and within 24 hours after their administration;
- use while taking monoamine oxidase inhibitors or earlier than 2 weeks after discontinuation of these drugs;
- age under 18 and over 65 years (efficacy and safety have not been established);
- pregnancy;
- breastfeeding (breastfeeding is possible no earlier than 24 hours after taking the drug;
- congenital galactosemia, glucose/galactose malabsorption syndrome, congenital lactose deficiency;
- hypersensitivity to any of the components of the drug.
With caution: epilepsy (including any conditions with a reduced epileptic threshold), pharmacologically controlled arterial hypertension, impaired liver or kidney function, hypersensitivity to sulfonamides (administration of sumatriptan can cause allergic reactions, the severity of which varies from skin manifestations to anaphylaxis) .
Sumatriptan-OBL 50 mg, 2 film-coated tablets
Registration Certificate Holder
FP OBOLENSKOE (Russia)
Dosage form
Medicine - Sumatriptan-OBL (Sumatriptan-OBL)
Description
Film-coated tablets
pink, round, biconvex; on the fracture, the inner layer is white.
1 tab.
sumatriptan succinate 70 mg, which corresponds to the content of sumatriptan 50 mg
Excipients
: lactose (milk sugar) - 192 mg, calcium hydrogen phosphate (disubstituted calcium phosphate) - 30 mg, magnesium stearate - 3 mg, povidone - 5 mg.
Shell composition:
hypromellose (hydroxypropyl methylcellulose) - 7 mg, copovidone (copolyvidone) - 1 mg, polyethylene glycol 6000 (macrogol 6000) - 1 mg, talc - 0.5 mg, titanium dtoxide - 0.45 mg, crimson dye (Ponceau 4R) - 0.05 mg.
2 pcs. — cellular contour packages (1) — cardboard packs. 2 pcs. — contour cell packaging (2) — cardboard packs. 4 things. — cellular contour packages (1) — cardboard packs. 4 things. — contour cell packaging (2) — cardboard packs. 6 pcs. — cellular contour packages (1) — cardboard packs. 6 pcs. — contour cell packaging (2) — cardboard packs. 7 pcs. — cellular contour packages (1) — cardboard packs. 7 pcs. — contour cell packaging (2) — cardboard packs. 10 pieces. — cellular contour packages (1) — cardboard packs. 10 pieces. — contour cell packaging (2) — cardboard packs.
Indications
Relief of migraine attacks and Horton's syndrome (histamine cephalgia).
Contraindications for use
IHD, arterial hypertension; simultaneous use of drugs containing ergot alkaloids or compounds close to them, lithium preparations, neuronal serotonin reuptake inhibitors; simultaneous use of MAO inhibitors and a period of up to 14 days after their discontinuation; hypersensitivity to sumatriptan.
pharmachologic effect
Migraine treatment; serotonin 5-HT1 receptor agonist. The therapeutic effect of sumatriptan is apparently due to two mechanisms: the substance excites serotonin 5-HT1 receptors in the smooth muscles of the vessels of the carotid artery system and causes their narrowing. The carotid arteries supply blood to the tissues of the head, incl. meninges; The occurrence of migraine attacks is associated with the expansion of blood vessels in the meninges. In addition, sumatriptan activates the receptors of the endings of the afferent fibers of the trigeminal nerve in the dura mater, as a result of which the release of sensory neuropeptides decreases. Sumatriptan does not penetrate the blood-brain barrier well and, according to experimental data, does not have actual analgesic properties.
The effect of sumatriptan usually occurs 30 minutes after oral administration and 10-15 minutes after subcutaneous administration.
Drug interactions
When used simultaneously with lithium salts, cases of the development of serotonin syndrome have been described.
When used simultaneously with moclobemide, the bioavailability of moclobemide increases in the absence of clinical manifestations.
When used concomitantly with rizatriptan, there is a risk of additive hyperstimulation of serotonin 5-HT1 receptors; with ergotamine - vasospasm may develop.
With the simultaneous use of St. John's wort herb preparations, it is possible to enhance the serotonergic effects and develop side effects.
Dosage regimen
To relieve a migraine attack, the oral dose is 100 mg once; sometimes a dose of less than 100 mg may be effective; in case of resumption of the attack, repeated administration is possible, and the daily dose should not exceed 300 mg. S/C is administered at a dose of 6 mg; if necessary, a second injection in the same dose can be performed no earlier than 1 hour after the first injection; maximum daily dose
s/c - 12 mg.
For Horton's syndrome, a dose of 6 mg is administered subcutaneously during an attack; maximum daily dose
- 12 mg; the interval between injections is at least 1 hour.
Side effect
From the side of the central nervous system:
dizziness, weakness, drowsiness.
From the cardiovascular system:
arterial hypotension or short-term increase in blood pressure, bradycardia or tachycardia.
From the digestive system:
nausea, vomiting.
Dermatological reactions:
skin rashes, erythema, itching.
Local reactions:
with subcutaneous injection - short-term pain at the injection site.
Other:
a feeling of warmth, tingling, pain, pressure or constriction in different parts of the body.
special instructions
Sumatriptan is not used to prevent migraine attacks.
Use with caution in cases of impaired liver and kidney function, as well as in patients with epilepsy or other disorders of brain function.
When stopping attacks, it is advisable to start treatment as early as possible, however, the administration of sumatriptan during the aura period, before the appearance of other symptoms, may not prevent the occurrence of headache.
When treated with sumatriptan, symptoms sometimes occur that resemble angina attacks - pain, a feeling of tightness in the chest. In this regard, sumatriptan should not be used if undiagnosed heart and vascular diseases are suspected, until an appropriate examination has been carried out.
If there is no effect on the first dose of sumatriptan, it is necessary to verify the diagnosis.
Safety and effectiveness of use in children and adolescents under 18 years of age have not been established.
Effect on the ability to drive vehicles and operate machinery
During migraine, as well as during sumatriptan therapy, drowsiness may develop. Therefore, during the period of use, patients should be especially careful when driving and engaging in other potentially hazardous activities that require a high speed of psychomotor reactions.
Use during pregnancy and breastfeeding
Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - With caution.
Clinical experience with the use of sumatriptan during pregnancy is limited, and therefore its use is contraindicated.
Should be used with caution during lactation. It is not recommended to breastfeed your baby within 24 hours after taking sumatriptan.
Use for renal impairment
Restrictions in case of impaired renal function - Use with caution. Use with caution in case of impaired renal function.
Use for liver dysfunction
Restrictions for liver dysfunction - With caution.
Use with caution in case of liver dysfunction.
Use in children
Restrictions for children - Contraindicated. Safety and effectiveness of use in children and adolescents under 18 years of age have not been established.
Side effects
The frequency of adverse reactions listed below was determined according to the following: very often - more than 1/10; often - from more than 1/100 to less than 1/10; sometimes - from more than 1/1000 to less than 1/100; rarely - from more than 1/10,000 to less than 1/1000; very rarely - from less than 1/10,000, including isolated cases.
From the nervous system: often - dizziness, drowsiness, sensory disturbances, including parasthesia and decreased sensitivity.
From the cardiovascular system: often - a transient increase in blood pressure (observed soon after taking the drug), "hot flashes".
From the respiratory system and organs of the cell group: often - dyspnea, mild, transient irritation of the mucous membrane or a burning sensation in the nasal cavity or throat, nosebleeds.
From the gastrointestinal tract: often - nausea, vomiting.
From the musculoskeletal system and connective tissue: often - a feeling of heaviness (usually transient, can be intense and occur in any part of the body, including the chest and throat).
General and local reactions: often - pain, a feeling of cold or heat, a feeling of pressure or tightness (usually transient, can be intense and occur in any part of the body, including the chest and throat), weakness, fatigue (usually mild or moderate, transitory).
Laboratory indicators: very rarely - minor deviations in liver test results.
Post-marketing surveillance
From the immune system: very rarely - hypersensitivity reactions, including skin manifestations, as well as anaphylaxis.
From the nervous system: very rarely - seizures (in some cases observed in patients with a history of seizures or with concomitant conditions predisposing to seizures; in some patients no risk factors were identified), tremor, dystonia, nystagmus, scotoma.
On the part of the visual organs: very rarely - flickering, diplopia, decreased visual acuity, blindness (usually transient). However, visual disturbances can be caused by the migraine attack itself.
From the cardiovascular system: very rarely - bradycardia, tachycardia, flutter, arrhythmias, transient changes on the ECG, coronary vasospasm, angina pectoris, myocardial infarction, hypotension, Raynaud's syndrome.
From the gastrointestinal tract: very rarely - ischemic colitis, dysphagia, feeling of discomfort in the abdomen.
Literature
- Three generations of drugs;
- Search for drug targets;
- Sanoeva M.Zh. and Saidvaliev F.S. (2016). Migraine - yesterday, today, tomorrow. A modern view of the problem. "International Neurological Journal". 8, 72–78;
- How a migraine happens. Johns Hopkins Medicine;
- Migraine headaches. (2018). WebMD;
- Paul L. Durham. (2006). Calcitonin Gene-Related Peptide (CGRP) and Migraine. Headache
.
46 , S3-S8; - What to know about the new anti CGRP migraine treatment options. (2018). American Migraine Foundation;
- Silberstein S. D. (2016). Migraine. MSD Directory;
- Migraine triggers: your personal checklist. (2019). WebMD;
- Rusakova E. (2018). The FDA has approved the drug to prevent migraines. N+1;
- Kolata G. (2018). The FDA approves the first drug designed to prevent migraines. The New York Times;
- Theo Vos, Amanuel Alemu Abajobir, Kalkidan Hassen Abate, Cristiana Abbafati, Kaja M Abbas, et. al.. (2017). Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet
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390 , 1211-1259; - Francesca Puledda, Kevin Shields. (2018). Non-Pharmacological Approaches for Migraine. Neurotherapeutics
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15 , 336-345; - Doodipala Samba Reddy. (2013). The pathophysiological and pharmacological basis of current drug treatment of migraine headache. Expert Review of Clinical Pharmacology
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6 , 271-288; - Ogbru A. and Ogbru O. Prescription migraine medications. RxList;
- Boyce S., Ali Z., Hill R. G. (2001). New developments in analgesia. Drug Discovery World;
- Azimova Yu.E. (2017). Triptans: an era of specific treatment for migraine. "Nervous diseases". 1, 10–14;
- Ameri M. and Lewis H. (2018). The evolution of transdermal drug delivery and treating migraine. Drug Discovery World;
- Migraine medications. (2013). TMedWeb;
- Dmitriev R. (2019). "Aimovig" will turn chronic migraine into episodic. "Mosmedpreparaty";
- Aimovig (erenumab) for the treatment of episodic migraine. Clinical Trials Arena;
- Khoruzhaya A. (2018). A new anti-migraine drug goes on sale. "Neuronews";
- Targeted therapy is a targeted strike against the disease.
Drug interactions
When administered simultaneously with ergotamine and ergotamine-containing drugs, prolonged vasospasm is possible.
Possible interaction between sumatriptan and MAO inhibitors (decreased metabolism of sumatriptan, increased its concentration).
With the simultaneous use of sumatriptan and drugs from the group of selective serotonin reuptake inhibitors, the development of weakness, hyperreflexia and impaired coordination of movements is possible.
There was no interaction of sumatriptan with propranolol, flunirizine, pizotifen and ethanol.
Modern medicines
A special project about modern medicines, the history of their creation, development methods and development trends.
The special project partner, Cytiva, was formed as a result of the sale of the GE Healthcare Biopharma division to Danaher Corporation. Cytiva is a global provider of technologies and services that advance and accelerate the development and manufacturing of therapeutics. The company has a rich heritage dating back hundreds of years. Cytiva's clients conduct life-saving activities ranging from basic biological research to the development of innovative vaccines, biologics and novel cell and gene therapies. The company's mission is to provide the tools and services they need to do things better, faster and safer, leading to better outcomes for patients.
The first two articles of our special project “Modern Medicines” were devoted to general issues of how the drug industry developed [1] and how scientists search for new drug targets [2]. This article opens a number of news materials about interesting modern medicines.
Sumatriptan dosage
Inside, the tablet should be swallowed whole with water. Treatment should be started as early as possible when a migraine attack occurs. The recommended dose is 50 mg, if necessary - 100 mg.
If migraine symptoms do not disappear or decrease after taking the first dose, then the drug should not be used again to relieve the same attack.
To relieve subsequent attacks (if symptoms decrease or disappear and then recur), you can take a second dose within the next 24 hours, provided that the interval between doses is at least 2 hours.
The maximum daily dose is 300 mg.
