Pr
phl-SUMATRIPTAN
(Sumatriptan Succinate Tablets) 25 mg, 50 mg, 100 mg Sumatriptan
. Date of Preparation:
8699, 8th Avenue August 22, 2005 Montreal, Quebec H1Z 2X4
SUMMARY PRODUCT INFORMATION 3 INDICATIONS AND CLINICAL USE 3 CONTRAINDICATIONS 4 WARNINGS AND PRECAUTIONS 4 ADVERSE REACTIONS 10 DRUG INTERACTIONS 13 DOSAGE AND ADMINISTRATION 14 OVERDOSAGE 15 ACTION AND CLINICAL PHARMACOLOGY 15 STORAGE AND STABILITY 17 DOSAGE FORMS, COMPOSITION AND PACKAGING 17
PHARMACEUTICAL INFORMATION 19 CLINICAL TRIALS 20 DETAILED PHARMACOLOGY 22 TOXICOLOGY 26 REFERENCES 33
Pr
phl-SUMATRIPTAN
(Sumatriptan Succinate Tablets) 25 mg, 50 mg, 100 mg Sumatriptan 5-HT1 Receptor Agonist Migraine Therapy
| Route of Administration | Dosage Form/ Strength | Clinically Relevant Nonmedicinal Ingredients |
| Oral | tablet 25 mg, 50 mg, 100 mg | Lactose For a complete listing see Dosage Forms, Composition and Packaging section. |
phl-SUMATRIPTAN (sumatriptan succinate) is indicated for the acute treatment of migraine attacks with or without aura. phl-SUMATRIPTAN is not for use in the management of hemiplegic, basilar, or ophthalmoplegic migraine (see CONTRAINDICATIONS). Safety and efficacy have not been established for cluster headache which is present in an older, predominantly male population.
Geriatrics: WARNINGS AND PRECAUTIONS, Special Population, Geriatrics
Experience of the use of sumatriptan succinate in patients aged over 65 years is limited. Therefore the use of sumatriptan in patients over 65 years is not recommended. (see
)
Pediatrics: WARNINGS AND PRECAUTIONS, Special Population, Pediatrics
The safety and efficacy of sumatriptan succinate in children has not been established and its use in this age group is not recommended. (see
)
General
Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events
: Sumatriptan succinate has been associated with transient chest and/or neck pain and tightness which may resemble angina pectoris. In rare cases, the symptoms have been
The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to phl- SUMATRIPTAN
Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with oral sumatriptan succinate and some have resulted in fatalities. The relationship of sumatriptan succinate to these events is uncertain. In a number of cases, it appears possible that the cerebrovascular events were primary, sumatriptan succinate having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Sumatriptan succinate should not be administered if the headache
being experienced is atypical for the patient. It should also be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). If a patient does not respond to the first dose, the opportunity should be taken to review the diagnosis before a second dose is given.
Patients should be cautioned that drowsiness may occur as a result of treatment with sumatriptan. They should be advised not to perform skilled tasks (e.g. driving or operating machinery) if drowsiness occurs.
Cardiovascular
Cardiac Events and Fatalities Associated with 5-HT1-Agonists: Sumatriptan can cause coronary artery vasospasm. Serious adverse cardiac events, including acute myocardial infarction, life threatening disturbances of cardiac rhythm, and death have been reported within a few hours following the administration of 5-HT1 agonists. Considering the extent of use of 5-HT1 agonists in patients with migraine, the incidence of these events is extremely low. The fact that some of these events have occurred in patients with no prior cardiac disease history and with documented absence of CAD, and the close proximity of the events to sumatriptan succinate use support the conclusion that some of these cases were caused by the drug. In many cases, however, where there has been known underlying coronary artery disease, the relationship is uncertain.
Serious cardiovascular events, some resulting in death, have been reported in association with the use of sumatriptan succinate tablets. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine definitively the proportion of the reported cases that were actually caused by sumatriptan succinate or to reliably assess causation in individual cases. On clinical grounds, the longer the latency between the administration of sumatriptan succinate and the onset of the clinical event, the less likely the association is to be causative. Accordingly, interest has focused on events beginning within 1 hour of the administration of sumatriptan succinate.
Cardiac events that have been observed to have onset within 1 hour of sumatriptan succinate administration include: coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation, cardiac arrest, and death. Some of these events occurred in patients who had no findings of CAD and appear to represent consequences of coronary artery vasospasm. However, among reports from the USA of serious cardiac events occurring within 1 hour of sumatriptan succinate administration, almost all of the patients had risk factors predictive of CAD and the presence of significant underlying CAD was established in most cases (see CONTRAINDICATIONS). Special Cardiovascular Pharmacology Studies: In subjects (n=10) with suspected coronary artery disease undergoing angiography, a 5-HT1 agonist at a subcutaneous dose of 1.5 mg produced an 8% increase in aortic blood pressure, an 18% increase in pulmonary artery blood pressure, and an 8% increase in systemic vascular resistance. In addition, mild chest pain or tightness was reported by four subjects. Clinically significant increases in blood pressure were experienced by three of the subjects (two of whom also had chest pain/discomfort). Diagnostic angiogram results revealed that 9 subjects had normal coronary arteries and 1 had insignificant coronary artery disease. In an additional study with this same drug, migraine patients (n=35) free of cardiovascular disease were subjected to assessments of myocardial perfusion by positron emission tomography while receiving a subcutaneous 1.5 mg dose in the absence of a migraine attack. Reduced coronary vasodilatory reserve (~10%), increase in coronary resistance (~20%), and decrease in hyperemic myocardial blood flow (~10%) were noted. The relevance of these finding to the use of the recommended oral doses of this 5.-HT1 agonist is not known. Similar studies have not been done with sumatriptan succinate. However, owing to the common pharmacodynamic actions of 5-HT1 agonists, the possibility of cardiovascular effects of the nature described above should be considered for any agent of this pharmacological class. Other Vasospasm Related Events: 5-HT1 agonists may cause vasospastic reactions other than coronary artery vasospasm. Extensive post-market experience has shown the use of sumatriptan succinate to be associated with rare occurrences of peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea.
Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions in patients with and without a history of hypertension. Sumatriptan is contraindicated in patients with uncontrolled or severe hypertension (see
). In patients with controlled hypertension, sumatriptan should be administered with caution, as transient increases in blood pressure and peripheral vascular resistance have been observed in a small portion of patients.
Hepatic/Biliary/Pancreatic
The effect of hepatic impairment on the efficacy and safety of sumatriptan succinate has not been evaluated, however, the pharmacokinetic profile of sumatriptan succinate in patients with moderate1 hepatic impairment shows that these patients, following an oral dose of 50 mg, have much higher plasma sumatriptan succinate concentrations than healthy subjects (Table 1). Therefore, an oral dose of 25 mg may be considered in patients with hepatic impairment.
| Parameter | Mean Ratio (hepatic impaired/healthy) n=8 | 90% Cl | p-value |
| AUC 4 | 181% | 130 to 252% | 0.009 * |
| C max | 176% | 129 to 240% | 0.007 * |
*Statistically significant The pharmacokinetic parameters of 6 mg subcutaneous sumatriptan do not differ statistically between normal volunteers and moderately hepatically impaired subjects. However, sumatriptan should not be administered to patients with severe hepatic impairment (see CONTRAINDICATIONS).
Neurologic
There is insufficient information on the efficacy and safety of sumatriptan succinate in the treatment of cluster headache, which is present in an older, predominantly male population. The need for prolonged use and the demand for repeated medication in this condition renders the dosing information inapplicable for cluster headache.
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 5-HT1 agonists for severe headaches that were subsequently shown to have been secondary to an evolving neurologic lesion. For newly diagnosed patients or patients presenting with atypical symptoms, the diagnosis of migraine should be reconsidered if no response is seen after the first dose of sumatriptan.
Seizures:
Caution should be observed if sumatriptan is to be used in patients with a history of epilepsy or structural brain lesions which lower the convulsion threshold.
Ophthalmologic
Binding to Melanin Containing Tissues:
In rats treated with a single subcutaneous dose (0.5 mg/kg) or oral dose (2 mg/kg) of radiolabeled sumatriptan succinate, the elimination half life of
Assessed by aminopyrine breath test (>0.2-0.4 scaling units).
radioactivity from the eye was 15 and 23 days, respectively, suggesting that sumatriptan succinate and/or its metabolites bind to the melanin of the eye. Because there could be an accumulation in melanin rich tissues over time, this raises the possibility that sumatriptan succinate could cause toxicity in these tissues after extended use. However, no effects on the retina related to treatment with sumatriptan succinate were noted in any of the oral or subcutaneous toxicity studies. Although no systematic monitoring of ophthalmologic function was undertaken in clinical trials, and no specific recommendations for ophthalmologic monitoring are offered, prescribers should be aware of the possibility of long term ophthalmologic effects.
Renal
The effects of renal impairment on the efficacy and safety of sumatriptan succinate have not been evaluated. Therefore sumatriptan is not recommended in this patient population.
Sensitivity/Resistance
Rare hypersensitivity (anaphylaxis/anaphylactoid) reactions may occur in patients receiving 5-HT1 agonists; such as sumatriptan Such reactions can be life threatening or fatal. In general, hypersensitivity reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens (see CONTRAINDICATIONS). Owing to the possibility of cross-reactive hypersensitivity reactions, sumatriptan should not be used in patients having a history of hypersensitivity to chemically-related 5-HT1 receptor agonists. There have been reports of patients with known hypersensitivity to sulphonamides exhibiting an allergic reaction following administration of sumatriptan succinate. Reactions ranged from cutaneous hypersensitivity to anaphylaxis.
Special Population
Reproduction studies, performed in rats, have not revealed any evidence of impaired fertility, teratogenicity, or post-natal development due to sumatriptan succinate. Reproduction studies, performed in rabbits by the oral route, have shown increased incidence of variations in cervico-thoracic blood vessel configuration in the foetuses. These effects were only seen at the highest dose tested, which affected weight gain in the dams, and at which blood levels were in excess of 50 times those seen in humans after therapeutic doses. A direct association with sumatriptan succinate treatment is considered unlikely but cannot be excluded. Therefore, the use of sumatriptan is not recommended in pregnancy. In a rat fertility study, oral doses of sumatriptan succinate resulting in plasma levels approximately 150 times those seen in humans after a 6 mg subcutaneous dose and approximately 200 times those seen in humans after a 100 mg oral dose were associated with a reduction in the success of insemination. This effect did not occur during a subcutaneous study where maximum plasma levels achieved approximately 100 times those in humans; by the subcutaneous route and approximately 150 times those in humans by the oral route.
Sumatriptan succinate is excreted in human breast milk. Therefore, caution is advised when administering sumatriptan to nursing women. Infant exposure can be minimized by avoiding breast feeding for 24 hours after treatment.
The safety and efficacy of sumatriptan succinate in children has not been established and its use in this age group is not recommended.
Experience of the use of sumatriptan succinate in patients aged over 65 years is limited. Therefore the use of sumatriptan in patients over 65 years is not recommended.
:
No specific laboratory tests are recommended for monitoring patients prior to and/or after treatment with sumatriptan succinate.
Adverse Drug Reaction Overview
Serious cardiac events, including some that have been fatal, have occurred following the use of 5-HT1 agonists. 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 (see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS).
Clinical Trial Adverse Drug Reactions
Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
Typical 5-HT1 Agonist Adverse Reactions: As with other 5-HT1 agonists, sumatriptan succinate has been associated with sensations of heaviness, pressure, tightness or pain which may be intense. These may occur in any part of the body including the chest, throat, neck, jaw and upper limb.
Acute Safety.
In placebo-controlled migraine trials, 3095 patients received at least one dose of
oral sumatriptan succinate. Tables 6 lists adverse events occurring at an incidence of 1% or more in any of the sumatriptan succinate dose groups and that occurred at a higher incidence than in the placebo groups.
Table 2: Treatment-Emergent Adverse Events in Oral Placebo-Controlled Clinical Trials Reported by at least 1% of Patients with Migraine
| Placebo | Sumatriptan succinate 25 mg | Sumatripta n succinate 50 mg | Sumatripta n succinate 100 mg * * | |
| Number of Patients | 690 | 351 | 723 | 2021 |
| Number of Migraine Attacks Treated | 1187 | 945 | 1889 | 14750 |
| Symptoms of Potentially Cardiac Origin | ||||
| Chest Sensation * | 0.6% | 2.3% | 2.6% | 3.2% |
| Neck/Throat/Jaw Sensations * | 1.4% | 2.3% | 3.5% | 5.2% |
| Upper Limb Sensations * | 1.2% | 1.4% | 2.5% | 3.6% |
| Palpitations | 0.6% | 0.3% | 1.0% | 1.1% |
| Neurological | ||||
| Head/Face Sensations * | 1.3% | 2.3% | 2.5% | 4.7% |
| Dizziness | 2.5% | 3.1% | 3.3% | 6.2% |
| Headache | 3.3% | 4.0% | 2.2% | 3.3% |
| Vertigo | 0.6% | 1.1% | 1.1% | 1.0% |
| Drowsiness | 1.6% | 1.1% | 1.2% | 2.1% |
| Tremor | 0.4% | 0.9% | 0.4% | 1.1% |
| Gastrointestinal | ||||
| Nausea | 5.8% | 2.8% | 4.4% | 11.0% |
| Hyposalivation | 1.2% | 1.4% | 1.1% | 1.2% |
| Vomiting | 2.9% | 4.3% | 1.1% | 4.4% |
| Gastrointestinal Discomfort & Pain | 1.4% | 1.1% | 0.8% | 2.0% |
| Abdominal Discomfort & Pain | 0.3% | NR | 0.4% | 1.2% |
| Diarrhea | 0.9% | 0.3% | 0.6% | 1.1% |
| Musculoskeletal | ||||
| Musculoskeletal Pain | 0.7% | 2.3% | 0.4% | `1.4% |
| Muscle Pain | 0.3% | 0.9% | 0.1% | 1.0% |
| Muscle Atrophy Weakness & Tiredness | NR | 0.6% | 0.4% | 1.4% |
| Placebo | Sumatriptan succinate 25 mg | Sumatripta n succinate 50 mg | Sumatripta n succinate 100 mg * * | |
| Ear, Nose & Throat | ||||
| Infections | 0.6% | 0.6% | 1.1% | 1.4% |
| Nasal Signs & Symptoms | 0.7% | 1.4% | 0.8% | 1.0% |
| Throat & Tonsil Symptoms | 0.6% | NR | 0.4% | 2.3% |
| Respiratory | ||||
| Viral Infection | 0.3% | 1.1% | 0.1% | 1.0% |
| Non-Site Specific | ||||
| Limb Sensations * | 0.4% | 1.1% | 0.4% | 1.5% |
| Sensations * (body region unspecified) | 4.5% | 5.7% | 8.0% | 9.0% |
| Malaise/Fatigue | 5.1% | 3.7% | 2.6% | 9.5% |
| Sweating | 0.4% | 0.6% | 0.6% | 1.6% |
* The term "sensations" encompasses adverse events described as pain and discomfort, pressure, heaviness, constriction, tightness, heat/burning sensation, paresthesia, numbness, tingling and strange sensations. * * Includes patients receiving up to 3 doses of 100 mg NR = Not Reported Sumatriptan succinate is generally well tolerated. Most of the events were transient in nature and resolved within 2 hours of oral administration. Minor disturbances of liver function tests have occasionally been observed with sumatriptan succinate treatment. There is no evidence that clinically significant abnormalities occurred more frequently with sumatriptan succinate than with placebo. Patients treated with sumatriptan succinate rarely exhibit visual disorders like flickering and diplopia. Additionally cases of nystagmus, scotoma and reduced vision have been observed. Very rarely a transient loss of vision has been reported. However, visual disorders may also occur during a migraine attack itself.
Premarketing Experience With Sumatriptan Succinate:
Of 6348 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of oral sumatriptan succinate two experienced clinical adverse events shortly after receiving oral sumatriptan succinate that may have reflected coronary vasospasm. Neither of these adverse events was associated with a serious clinical outcome.
Among the more than 1900 patients with migraine who participated in premarketing controlled clinical trials of subcutaneous sumatriptan, there were eight patients who sustained clinical events during or shortly after receiving sumatriptan that may have reflected coronary artery vasospasm. Six of these eight patients had ECG changes consistent with transient ischemia, but without accompanying clinical symptoms or signs. Of these eight patients, four had either findings suggestive of CAD or risk factors predictive of CAD prior to study enrollment. Among approximately 4,000 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of sumatriptan nasal spray, one patient experienced an asymptomatic subendocardial infarction possibly subsequent to a coronary vasospastic event.
Overview
Single dose pharmacokinetic drug interaction studies have not shown evidence of interactions with propranolol, flunarizine, pizotifen or alcohol. Multiple dose interaction studies have not been performed.
Drug-Drug Interactions
Ergot-Containing Drugs:
Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis for these effects being additive, ergot-containing or ergot-type medications (like dihydroergotamine or methysergide) are
contraindicated within 24 hours of sumatriptan administration (see CONTRAINDICATIONS). MAO Inhibitors: In studies conducted in a limited number of patients, MAO inhibitors reduce sumatriptan succinate clearance, significantly increasing systemic exposure. Therefore, the use of sumatriptan in patients receiving MAO inhibitors is contraindicated (see CONTRAINDICATIONS, and ACTIONS AND CLINICAL PHARMACOLOGY). Other Serotonergic Drugs: Rare postmarketing reports describe patients with weakness, hyperreflexia, and incoordination following the combined use of a selective serotonin reuptake inhibitor (SSRI) and 5-HT1 agonists. If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline), tricyclic antidepressant, or other drug with serotonergic activity is clinically warranted, appropriate observation of the patient for acute and long- term adverse events is advised. Other 5-HT1 agonists: The administration of sumatriptan succinate with other 5-HT1 agonists has not been evaluated in migraine patients. As an increased risk of coronary vasospasm is a theoretical possibility with co-administration of 5-HT1 agonists, use of these drugs within 24 hours of each other is contraindicated.
Drug-Food Interactions
Interactions with food have not been established.
Drug-Herb Interactions
Interactions with herbal products have not been established.
Drug-Laboratory Test Interactions
Sumatriptan succinate is not known to interfere with commonly employed clinical laboratory tests.
Recommended Dose and Dosage Adjustment
In addition to relieving the pain of migraine, sumatriptan succinate has also been shown to be effective in relieving associated symptoms of migraine (nausea, vomiting, phonophobia, photophobia). Sumatriptan succinate is equally effective when administered at any stage of a migraine attack. Long term (12-24 months) clinical studies with maximum recommended doses of sumatriptan succinate indicate that there is no evidence of the development of tachyphylaxis, or medication-induced (rebound) headache. Significant relief begins about 30 minutes following oral administration. The minimal effective single adult dose of phl-SUMATRIPTAN tablets is 25 mg. The maximum recommended single dose is 100 mg. The optimal dose is a single 50 mg tablet. However, depending on individual patient's needs and response to treatment, some patients may require 100 mg. Clinical trials have shown that approximately 50 - 75% of patients have headache relief within two hours after oral dosing with 100 mg, and that a further 15 - 25% have headache relief by 4 hours. Comparator studies have shown similar efficacy rates with the 50 mg and 100 mg tablets. There is evidence that doses of 50 and 1 00 mg may provide greater effect than 25 mg. If the migraine headache returns, or if a patient has a partial response to the initial dose, the dose may be repeated after 2 hours. Not more than 200 mg should be taken in any 24 hour period. If a patient does not respond to the first dose of phl-SUMATRIPTAN tablets, a second dose should not be taken for the same attack, as it is unlikely to be of clinical benefit. phl- SUMATRIPTAN may be taken to treat subsequent migraine attacks. The tablet should be swallowed whole with water, not crushed, chewed or split.
In patients with mild or moderate hepatic impairment, plasma sumatriptan succinate concentrations up to two times those seen in healthy subjects have been observed. Therefore, a 25 mg dose (single tablet) may be considered in these patients (see WARNINGS AND PRECAUTIONS). Sumatriptan succinate should not be administered to patients with severe hepatic impairment (see CONTRAINDICATIONS).
There have been some reports of overdosage with sumatripan succinate. Doses up to 400 mg orally were not associated with side effects other than those mentioned. If overdosage with sumatriptan succinate occurs, the patient should be monitored and standard supportive treatment applied as required. Toxicokinetics are not available. The effect of hemodialysis or peritoneal dialysis on the serum concentration of sumatriptan succinate is unknown.
Pharmacodynamics
Sumatriptan succinate has been shown to be effective in relieving migraine headache. It is an agonist for a vascular 5-hydroxytryptamine1D (5-HT1D) receptor subtype (a member of the 5-HT1 family), and has only weak affinity for 5-HT1A receptors and no significant activity (as measured using standard radioligand binding assays) or pharmacological activity at 5-HT2, 5-HT3, 5-HT4, 5-HT5A, or 5-HT7 receptor subtypes, or at alpha1- , alpha2-, or beta-adrenergic; dopamine, or dopamine2; muscarinic; or benzodiazepine receptors. The therapeutic activity of sumatriptan succinate in migraine is generally attributed to its agonist activity at 5-HT1B/5-HT1D receptors. Two current theories have been proposed to explain the efficacy of 5-HT1 receptor agonists in migraine. One theory suggests that activation of 5-HT1 receptors located on intracranial blood vessels, including those on the arteriovenous anastomoses, leads to vasoconstriction, which is believed to be correlated with the relief of migraine headache. The other hypothesis suggests that activation of 5-HT1 receptors on perivascular fibres of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release. These theories are not mutually exclusive. Experimental data from animal studies shows that sumatriptan succinate also activates 5- HT1 receptors on peripheral terminals of the trigeminal nerve which innervates cranial blood vessels. This causes the inhibition of neuropeptide release. It is thought that such an action may contribute to the anti-migraine action of sumatriptan succinate in humans.
Cardiovascular Effects
In vitro studies in human isolated epicardial coronary arteries suggest that the predominant contractile effect of 5-HT is mediated via 5-HT2 receptors. However, 5-HT1 receptors also contribute to some degree to the contractile effect seen. Transient increases in systolic and diastolic blood pressure (up to 20 mmHg) of rapid onset (within minutes), have occurred after intravenous administration of up to 64 ug/kg (3.2 mg for 50 kg subject) to healthy volunteers. These changes were not dose related and returned to normal within 10-15 minutes. Following oral administration of 200 mg or intranasal administration of 40 mg, however, mean peak increases in blood pressure were smaller and of slower onset than after intravenous or subcutaneous administration.
Pharmacokinetics
Pharmacokinetic parameters following oral administration is shown in Table 1. Sumatriptan succinate is rapidly absorbed after oral administration. The low oral bioavailability is primarily due to metabolism (hepatic and pre-systemic) and partly due to incomplete absorption. The oral absorption of sumatriptan succinate is not significantly affected either during migraine attacks or by food. Inter-patient and intra-patient variability was noted in most pharmacokinetic parameters assessed.
| Parameter | Oral |
| Bioavailability | 14% |
| C m ax (ng/mL) | 100 mg: 50 - 60 ng/mL 25 mg: 18 ng/mL |
| T max | 100 mg: 0.5 - 5 hr * |
| T 1/2 | 2 hr (1.9-2.2 hr) |
| Protein Binding | 14-21% |
| Volume of Distribution | 170L |
| Total Plasma Clearance | 1160 mL/min |
| Renal Plasma Clearance | 260 mL/min |
*70% to 80% of Cmax values were attained within 30-45 minutes of dosing.
In vitro
studies with human microsomes suggest that sumatriptan succinate is metabolized by monoamine oxidase (MAO), predominantly the A isoenzyme. In studies conducted in a limited
number of patients, MAO inhibitors reduce sumatriptan succinate clearance, significantly increasing systemic exposure. Non-renal clearance of sumatriptan succinate accounts for about 80% of the total clearance. The major metabolite, the indole acetic acid analogue of sumatriptan succinate is mainly excreted in the urine where it is present as a free acid (35%) and the glucuronide conjugate (11%). It has no known 5-HT1 or 5-HT2 activity. Minor metabolites have not been identified. No differences have been observed between the pharmacokinetic parameters in healthy elderly volunteers compared with younger volunteers (less than 65 years old).
phl-SUMATRIPTAN Tablets should be stored between 4oC and 30oC.
Availability of Dosage Forms
phl-SUMATRIPTAN Tablets 25 mg are white to off-white, sugar coated round tablets, with "P" on one side and "S25" on the other side. phl-SUMATRIPTAN Tablets 50 mg are white to off-white, sugar coated triangular tablets, with "P" on one side and "S50" on the other side. phl-SUMATRIPTAN Tablets 100 mg are pink, sugar coated triangular tablets, with "P" on one side and "S100" on the other side. Each tablet contains 25 mg or 50 mg or 100 mg sumatriptan (base) as the succinate salt. phl-SUMATRIPTAN Tablets 25 mg, 50 mg and 100 mg are available in bottles of 100 tablets and blister packs of 30 tablets (5 x 6 tablets) in a box.
Composition
phl-SUMATRIPTAN Tablets contain 25mg, 50 mg or 100 mg Sumatriptan (base) as the succinate salt. phl-SUMATRIPTAN Tablets also contain (alphabetically): Carnauba wax, Colloidal Silicon Dioxide, Lactose Monohydrate, Magnesium Stearate, Microcrystalline Cellulose, Sodium Starch Glycolate, Sucrose, Talc, Titanium Dioxide and Triethyl Citrate. The 100 mg tablets also contain Red Iron Oxide.