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| Cardiovascular and Cerebrovascular |
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| Youshu |
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| Brand Name: Youshu |
| Generic Name: Sumatriptan Succinate Tablets |
| Indication: |
the acute treatment of migraine attacks with or without aura in adults
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| Detailed introduction: |
Mechanism of Action
Sumatriptan is a highly selective 5-HT1D receptor agonist that can contract intracranial artery and redistribute blood and improve cerebral blood flow.
The vascular 5-HT1 receptor subtype that sumatriptan activates is present on cranial arteries in both dog and primate, on the human basilar artery, and in the vasculature of human dura mater and mediates vasoconstriction. This action in humans correlates with the relief of migraine headache and neurogenic inflammation in dura mater. Pharmacokinetics
The mean maximum concentration following oral dosing with 25 mg is 18 ng/ml (range: 7
to 47 ng/ml) and 51 ng/ml (range: 28 to 100 ng/ml) following oral dosing with 100 mg of sumatriptan. This bioavailability is primarily due to first pass effect and partly due to incomplete absorption. The bioavailability of this product is 15%. The Cmax is similar during a migraine attack and during a migraine-free period, but the tmax is slightly later during the attack, approximately 2.5 hours compared to 2.0 hours. When given as a single dose, sumatriptan displays dose proportionality in its extent of absorption (area under the curve [AUC]) over the dose range of 25 to 200 mg, but the Cmax after 100 mg is approximately 25% less than expected (based on the 25-mg dose). Food has no significant effect on the bioavailability of sumatriptan, but delays the tmax slightly (by about 0.5 hours).
Plasma protein binding is low (14% to 21%). The effect of sumatriptan on the protein binding of other drugs has not been evaluated, but would be expected to be minor, given the low rate of protein binding. The apparent volume of distribution is 2.4 L/kg.
The elimination half-life of sumatriptan is approximately 2.5 hours. Radiolabeled
14C-sumatriptan administered orally is largely renally excreted (about 60%) with about
40% found in the feces. Most of the radiolabeled compound excreted in the urine is the major metabolite, indole acetic acid (IAA), which is inactive, or the IAA glucuronide. Only
3% of the dose can be recovered as unchanged sumatriptan.
In vitro studies with human microsomes suggest that sumatriptan is metabolized by monoamine oxidase (MAO), predominantly the A isoenzyme, and inhibitors of that enzyme may alter sumatriptan pharmacokinetics to increase systemic exposure. No significant effect was seen with an MAO-B inhibitor.
Indications
Sumatriptan succinate tablets are indicated for the acute treatment of migraine attacks with or without aura in adults.
Safety
Drugs containing ergotamine may exacerbate vascular spasm reaction. Theoretically speaking, combined administration of drugs containing ergotamine and sumatriptan succinate tablets within 24 hours would exacerbate this reaction all the more. It is advisable to avoid the combined use of sumatriptan succinate tablets and drugs containing ergotamine. If patients take sumatriptan succinate tablets at a recommended
dose in combination with monoamine oxidase, plasma drug concentration will reach 7 times higher than the plasma drug concentration when they take sumatriptan succinate tablets at the same dose separately. Therefore, it is advisable to avoid the combined use of sumatriptan succinate tablets and monoamine oxidase.
Reports have shown that combined use of sumatriptan succinate tablets and selective serotonin reuptake inhibitors (such as fluoxetine, PLUVOXAMNE, paroxetine and sertraline) may lead to weakness, hyperreflexia and ataxia. If it is necessary to use sumatriptan succinate tablets in combination with these inhibitors, it is advisable to closely observe these patients.
Adverse Reactions
Serious cardiac events, including some that have been fatal, have occurred following the use of sumatriptan succinate injection or tablets. These events are extremely rare and most have been reported in patients with risk factors predictive of CAD. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation.
Significant hypertensive episodes, including hypertensive crises, have been reported on rare occasions in patients with or without a history of hypertension.
Published literatures reported that:
1. Adverse reactions with 2% incidence in controlled clinical study include:
1) Nontypical sensation: abnormal sensation (various kinds); fever or algidity
2) Ache and sense of pressure
3) Neural system: vertigo
4) Others: ennui and fatigue
Other events that occurred in more than 1% of patients receiving sumatriptan succinate tablets and at least as often on placebo included nausea and/or vomiting, migraine, headache, hyposalivation, dizziness, and drowsiness/sleepiness.
Sumatriptan succinate tablets are generally well tolerated. Across all doses, most adverse reactions were mild and transient and did not lead to long-lasting effects. The incidence of adverse events in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse events.
2. Adverse reactions with incidence of less than 1% in open non-control clinical study include:
Main adverse reactions include: sense of cauterization and numbness, heart throb, cardiac syncope, fall or rise of blood pressure, rhinosinusitis, tinnitus, allergic rhinitis, upper respiratory tract infection, diarrhea, gastralgia, myalgia, photophobia, dyspnea, perspiration and allergy.
Precaution
General:
Chest discomfort and wjaw or neck tightness have been reported following use of sumatriptan succinate tablets and have also been reported infrequently following administration of sumatriptan nasal spray. Chest, jaw, or neck tightness is relatively common after administration of sumatriptan succinate injection. Only rarely have these symptoms been associated with ischemic ECG changes. However, because sumatriptan
may cause coronary artery vasospasm, patients who experience signs or symptoms suggestive of angina following sumatriptan should be evaluated for the presence of CAD or a predisposition to Prinzmetal's variant angina before receiving additional doses of sumatriptan, and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur. Similarly, patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud's syndrome following sumatriptan should be evaluated for atherosclerosis or predisposition to vasospasm.
Sumatriptan succinate should also be administered with caution to patients with diseases that may alter the absorption, metabolism, or excretion of drugs, such as impaired hepatic or renal function.
There have been rare reports of seizure following administration of sumatriptan. Sumatriptan should be used with caution in patients with a history of epilepsy or structural brain lesions that lower their seizure threshold.
Care should be taken to exclude other potentially serious neurologic conditions before treating headache in patients not previously diagnosed with migraine headache or who experience a headache that is atypical for them. There have been rare reports where patients received sumatriptan for severe headaches that were subsequently shown to have been secondary to an evolving neurologic lesion.
For a given attack, if a patient does not respond to the first dose of sumatriptan, the diagnosis of migraine should be reconsidered before administration of a second dose.
1. Sumatriptan succinate tablets should not be used in patients with history, signs and symptoms of ischemic heart disease, ischemic cerebrovascular disease and ischemic peripheral vascular disease. Sumatriptan succinate tablets should not be used in patients with obvious symptoms of cardiovascular disease.
2. Sumatriptan succinate tablets should not be used in patients who are using monoamine oxidase or have used monoamine oxidase within two weeks.
3. Sumatriptan succinate tablets should not be employed in treating migraine caused by hemiplegy and headache caused by vertebral basilar artery disease.
4. Sumatriptan succinate tablets is contraindicated in patients who have used ergotamine drugs or drugs containing ergotamine (such as dihydroergotamine or dihydroergotoxine) within 24 hours. Sumatriptan succinate tablets should not be used in combination with other 5-HT agonists.
5. Sumatriptan succinate tablets should not be given to patients with severe hepatic dysfunction.
6. Sumatriptan succinate tablets should not be used in patients who are allergic to sumatriptan.
7. The use of sumatriptan succinate tablets in patients with uncontrolled hypertension is not recommended.
Administration and Dosage
In controlled clinical trials, single doses of 25, 50, or 100 mg of sumatriptan succinate tablets were effective for the acute treatment of migraine in adults. There is evidence from clinical studies that doses of 50 and 100 mg may provide a greater effect than 25 mg. There is also evidence that doses of 100 mg do not provide a greater effect than 50 mg.
Individuals may vary in response to doses of sumatriptan succinate tablets. The choice of dose should therefore be made on an individual basis, weighing the possible benefit of a higher dose with the potential for a greater risk of adverse events.
If the headache returns or the patient has a partial response to the initial dose, the dose may be repeated after 2 hours, not to exceed a total daily dose of 200 mg. If a headache returns following an initial treatment with sumatriptan succinate injection, additional single sumatriptan succinate tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses. The safety of treating an average of more than 4 headaches in a 30-day period has not been established.
Because of the potential of MAO-A inhibitors to cause unpredictable elevations in the bioavailability of oral sumatriptan, their combined use is contraindicated.
Hepatic disease/functional impairment may also cause unpredictable elevations in the bioavailability of orally administered sumatriptan. Consequently, if treatment is deemed advisable in the presence of liver disease, the maximum single dose should in general not exceed 50 mg.
Description
This product is a white and film-coated tablet.
How Supplied
Youshu tablets, 25 mg of sumatriptan (C14H21N3O2S) as the succinate.
Package
Aluminum plastic package: each box contains two 25 mg tablets.
Price
58 RMB/box |
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