Pitomate

Pitomate

topiramate

Manufacturer:

Siam Bheasach

Distributor:

Siam Pharmaceutical

Marketer:

Siam Pharmaceutical
Full Prescribing Info
Contents
Topiramate.
Description
Pitomate (25 mg tablet): Each tablet contains: Topiramate 25 mg.
Pitomate (50 mg tablet): Each tablet contains: Topiramate 50 mg.
Pitomate (100 mg tablet): Each tablet contains: Topiramate 100 mg.
Action
Pharmacology: Pharmacodynamics: Topiramate, a sulfamate-substituted derivative of the monosaccharide D-fructose, is an anticonvulsant agent that also is used for prophylaxis of migraine headache. Topiramate blocks voltage-dependent sodium channels; augments the activity of γ-aminobutyric acid (GABA) at some subtypes of the GABA-A receptor; antagonizes the AMPA/kainate subtype of the glutamate receptor; and inhibits carbonic anhydrase (particularly the CA-II and CA-IV isoenzymes).
Pharmacokinetics: Absorption: Topiramate is rapidly absorbed with peak plasma concentrations occurring about 1 to 4 hours in adults, 1 to 2.8 hours in children 4 to 17 years and 3.7 hours in children 9 months to less than 4 years, following an oral dose. The bioavailability of Topiramate is about 80%. Food does not appear to affect bioavailability of the drug. .
Distribution: Topiramate's volume of distribution is 0.6 to 0.8 L/kg. Approximately 15-41% of Topiramate is bound to plasma proteins, with the fraction of protein binding decreasing as blood concentration increases.
Metabolism: Minor amounts metabolized in liver via hydroxylation, hydrolysis, and glucuronidation. None of any metabolites constitutes more than 5% of an administered dose. There is evidence of renal tubular reabsorption; percentage of dose metabolized in liver and clearance are increased in patients receiving enzyme inducers (eg. carbamazepine, phenytoin).
Elimination: Approximately 70% of an administered dose is eliminated principally in urine as unchanged drug. The mean elimination half-life of Topiramate is summarized in Table 1. (See Table 1.)

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Elimination in patients with moderate to severe renal impairment (CrCl 30-69 mL/minute/1.73 m2 to less than 30 mL/minute/1.73 m2): The clearance of Topiramate was reduced by 42 or 54% respectively. However, since Topiramate also undergoes substantial tubular reabsorption, the creatinine clearance may not always predict clearance of Topiramate.
Elimination in patients undergoing hemodialysis: The clearance of Topiramate is 4-6 times more rapid than in healthy individuals.
Elimination in patients with hepatic impairment: The clearance of Topiramate may have been decreased with unknown mechanism.
Elimination in geriatric patients: Half-life elimination is longer. Plasma and renal clearance were reduced 21% and 19%, respectively. Reduced clearance resulted in slightly higher Cmax and area under the curve (AUC) 23% and 25% respectively. Topiramate clearance is decreased only to the extent that renal function is reduced.
Elimination in pediatric patients : Pediatric patients have a 50% higher clearance and shorter half-life than adults.
Indications/Uses
Epilepsy: Topiramate is used as initial monotherapy or adjunctive therapy in patients older than 2 years for the management of partial-onset, primary generalized tonic-clonic seizure.
Topiramate is used as adjunctive therapy in patients older than 2 years for the management of seizures associated with Lennox-Gastaut syndrome.
Migraine Prophylaxis: Topiramate is also used in the prophylaxis of migraine headache in adults and adolescent ≥12 years.
Note: the efficacy of the drug in the acute treatment of migraine headache has not been established.
Dosage/Direction for Use
Administer without regard to meals. It is not recommended to crush, break or chew the tablets. Do not abruptly discontinue therapy; taper dosage gradually to prevent rebound effects.
Dosage in adult patients: Epilepsy, monotherapy in Partial-onset seizure and primary generalized tonic-clonic seizure: Usual dosage: 400 mg/day in 2 divided doses.
Initiate 25 mg daily (in the evening) or 25 mg twice daily in the first week, may increase weekly by 50 mg daily up to 100 mg twice daily in the forth week of therapy. The further dosage titration may increase weekly by 100 mg daily up to the recommended 200 mg twice daily.
Epilepsy, adjunctive therapy in Partial-onset seizure, primary generalized tonic-clonic seizure or Lennox-Gastaut syndrome: The usual maintenance dose of Topiramate is 100-200 mg twice daily. The dosage is generally not exceeded 400 mg daily.
Initiate 25 mg once or twice daily for 1 week, may increase weekly by 25 mg daily up to 50 mg daily until response.
Migraine prophylaxis: Initiate 25 mg once daily (in evening); may increase weekly by 25 mg daily up to the recommended dose of 100 mg daily given in 2 divided doses. Increased intervals between dose adjustments may be considered. Doses more than 100 mg per day have shown no additional benefit.
Dosage in pediatric patients: Epilepsy, monotherapy in Partial-onset seizure and primary generalized tonic-clonic seizure: Children 2 to <10 years: Initiate 25 mg once daily (in evening); may increase to 25 mg twice daily in week 2; thereafter, may increase by 25 to 50 mg daily at weekly intervals over 5 to 7 weeks up to the minimum recommended maintenance dose (as stated in the table as follows) and further increase by 25 to 50 mg daily at weekly intervals up to following maximum recommended maintenance dose if the additional seizure control is needed or the therapy is tolerated. (See Table 2.)

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Children ≥10 years and Adolescents: Refer to adult dosing.
Epilepsy, adjunctive therapy in Partial-onset seizure, primary generalized tonic-clonic seizure, or Lennox-Gastaut syndrome: Children 2 to Adolescents <17 years: Initiate 25 mg once daily (based on a range of 1 to 3 mg/kg/day, in evening) for 1 week; may increase every 1 to 2 weeks in increments of 1 to 3 mg/kg/day up to the recommended dose of 5 to 9 mg/kg in two divided doses.
Adolescents >17 years: Refer to adult dosing.
Migraine prophylaxis: Adolescents >12 years: Refer to adult dosing.
Dosage in geriatric patients: Most older adults have creatinine clearances <70 mL/minute/1.73 m2; obtain a serum creatinine and calculate creatinine clearance prior to initiation of therapy. An initial dose of 25 mg/day may be recommended, followed by incremental increases of 25 mg at weekly intervals until an effective dose is reached; refer to adult dosing for titration schedule.
Dosage in hepatic impairment: Use with caution. The clearance of Topiramate may be reduced.
Dosage in renal impairment: CrCl <70 mL/minute/1.73 m2: Administer 50% dose and titrate more slowly. In the patients with hemodialysis, supplemental dose may be needed during hemodialysis.
Overdosage
Overdoses of Topiramate have been reported. Signs and symptoms included convulsions, drowsiness, speech disturbances, blurred vision, diplopia, impaired mentation, lethargy, abnormal coordination, stupor, hypotension, abdominal pain, agitation, dizziness and depression. The clinical consequences were not severe in most cases, but deaths have been reported after overdoses with multiple medicinal products including Topiramate.
Topiramate overdose can result in severe metabolic acidosis.
Treatment: In acute Topiramate overdose, if the ingestion is recent, the stomach should be emptied immediately by lavage or by induction of emesis. Activated charcoal has been shown to adsorb Topiramate in vitro. Treatment should be appropriately supportive and the patient should be well hydrated. Hemodialysis has been shown to be an effective means of removing Topiramate from the body.
Contraindications
Hypersensitivity to Topiramate or any component of the formulation or container.
Warnings
This product may cause drowsiness. Patients should avoid driving, working with machine and using concomitantly with alcohol or alcohol-containing product while using this product.
This product may cause of hematologic abnormality.
Do not use this product in pregnant women because it may cause of neonatal abnormality.
Use this product with caution in patients with hepatic or renal impairment.
This product may cause of acute myopia and secondary angle closure glaucoma.
If there are any visual abnormalities occurred while using this product; such as blurred vision, ophthalmic pain, stop using the product immediately and go to see physicians.
Adequate fluid intake is recommended to prevent the formation of kidney stone.
Special Precautions
Do not discontinue abruptly. For seizure disorders, the daily dosage should be decreased in weekly intervals by 50-100 mg in adults and over a 2-8 week period in pediatric patients. For migraine prophylaxis, the daily dosage should be decreased in weekly intervals by 25-50 mg.
Use with caution in patients with renal impairment, hepatic impairment; clearance may be reduced. Dosage adjustment may be required.
Topiramate exhibits weak carbonic anhydrase inhibitory properties and may increase the risk of renal calculus. Adequate hydration is recommended to reduce the risk of developing renal calculi, especially in predisposed patients.
Patients should be monitored for signs/symptoms of depression, suicide tendencies and other unusual behavior changes.
Topiramate has been associated with acute myopia and secondary angle closure glaucoma in adults and children, typically within 1 month of initiation; discontinue in patients with acute onset of decreased visual acuity and/or ocular pain.
Topiramate may be associated with hyperchloremic nonanion gap metabolic acidosis due to inhibition of carbonic anhydrase and increased renal bicarbonate loss. Metabolic acidosis may occur at dosage as low as 50 mg/day. Monitor serum bicarbonate as well as potential complications of chronic acidosis. Consider dose reduction or discontinuation (by tapering dose) in patients with persistent or severe metabolic acidosis. If treatment is continued, consider alkali supplementation.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy category: D.
Topiramate was found to cross the placenta and can cause fetal harm when administered to pregnant women. Use of the drug during the first trimester of pregnancy is associated with an increased risk of the development of oral clefts. Topiramate has demonstrated selective development toxicity, including teratogenicity and embryotoxicity in animals. Metabolic acidosis may be induced by Topiramate and may result in adversed effects and fetal death. Pregnant women and their newborns should be monitored for metabolic acidosis. Maternal serum concentration may decrease during the second and third trimesters of pregnancy therefore therapeutic drug monitoring should be considered in pregnant women who require therapy. Topiramate should be used during pregnancy only when the potential benefits outweigh the possible risks.
Lactation: Topiramate is excreted into breast milk. Infant plasma concentrations of Topiramate have been reported as 10% to 20% of the maternal plasma concentration. Use with caution in a nursing woman.
Adverse Reactions
See Table 3.

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Drug Interactions
Avoid concomitant use of Topiramate with ethyl alcohol, azelastine (nasal), carbonic anhydrase inhibitors, orphenadrine, paraldehyde, thalidomide, ulipristal.
Topiramate exhibits weak CYP2C9 inhibitors so that it has the pharmacokinetic interactions with drug metabolized by CYP2C19 including some anticonvulsants, CNS depressants and oral contraceptives.
Topiramate may increase the levels/effects of alpha-/beta-agonists, amitriptyline, amphetamines, blonanserin, buprenorphrine, CNS depressants, flecainide, fosphenytoin, hydrocodone, lithium, memantine, metformin, methotrimeprazine, metyrosine, mirtazapine, oxycodone, phenytoin, pramipexole, primidone, quinidine, ropinirole, rotigotine, selective serotonin reuptake inhibitors, suvorexant, valproate products, zolpidem.
Topiramate may decrease the levels/effects of contraceptives (estrogens, progestins), methenamine, primidone, glyburide, digoxin, diltiazem.
The levels/effects of Topiramate may be increased by anticholinergic agents, brimonidine (topical), cannabis, doxylamine, dronabinol, droperidol, hydroxyzine, kava kava, loop diuretics, magnesium sulfate, methotrimeprazine, minocycline, nabilone, perampanel, rufinamide, salicylates, sodium oxybate, tapentadol, tetrahydrocannabinol, thiazide and thiazide-like diuretics.
The levels/effects of Topiramate may be decreased by carbamazepine, fosphenytoin, mefloquine, mianserin, orlistat, phenytoin, valproic acid.
Ketogenic diet may increase the possibility of acidosis and/or kidney stones. Monitoring for symptoms of acidosis or kidney stones is needed.
Storage
Store below 30°C.
ATC Classification
N03AX11 - topiramate ; Belongs to the class of other antiepileptics.
Presentation/Packing
FC tab 25 mg (white round, biconvex engraved with "
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" logo on one side and "25" on the other side) x 6 x 10's. 50 mg (pale-yellowish round, biconvex engraved with "
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" logo on one side and "50" on the other side) x 6 x 10's. 100 mg (yellow round, biconvex engraved with "
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" logo on one side and "
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" on the other side) x 6 x 10's.
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