Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Traditional IUPAC Name
pKa (strongest acidic)
pKa (Strongest Basic)
Dược Lực Học :
Topiramate is an anticonvulsant indicated in the treatment of epilepsy and migraine. Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. There is evidence that topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particular subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secundarily generalized tonic-clonic seizures in the kindling model, findings predective of a broad spectrum of antiseizure activities clinically.
Cơ Chế Tác Dụng :
Topiramate (brand name Topamax) is an anticonvulsant drug produced by Ortho-McNeil Neurologics, a division of Johnson & Johnson. It is used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). It is also Food and Drug Administration (FDA) approved for, and now most frequently prescribed for, the prevention of migraines. [Wikipedia]. A combination product containing phentermine and topiramate extended-release called QSYMIA® is indicated for the management of obesity. On August 2013, an extended released formulation, marketed as Trokendi XR has been approved for the management of partial onset, tonic-clonic, and Lennox-Gastaut Syndrome seizures.
The precise mechanism of action of topiramate is not known. However, studies have shown that topiramate blocks the action potentials elicited repetitively by a sustained depolarization of the neurons in a time-dependent manner, suggesting a state-dependent sodium channel blocking action. Topiramate also augments the activity of the neurotransmitter gamma-aminobutyrate (GABA) at some subtypes of the GABAA receptor (controls an integral chloride channel), indicating a possible mechanism through potentiation of the activity of GABA. Topiramate also demonstrates antagonism of the AMPA/kainate subtype of the glutamate excitatory amino acid receptor. It also inhibits carbonic anhydrase (particularly isozymes II and IV), but this action is weak and unlikely to be related to its anticonvulsant actions.
Dược Động Học :
▧ Absorption :
Rapid with pleak plasma concentrations occurring after 2 hours and a bioavailability of 80%. The pharmacokinetic profile of the extended release formulation is non linear at 25 mg due to binding of topiramate to carbonic anhydrase in red blood cells. The peak plasma concentration was 24 hours after a single 200 mg oral dose of the extended release formulation. It is also bioequivalent to immediate-release tablet that has been administered twice-daily. Fluctuation of topiramate plasma concentrations at steady-state for Trokendi XR™ administered once-daily was approximately 26% and 42% in healthy subjects and in epileptic patients, respectively, compared to approximately 40% and 51%, respectively, for immediate-release topiramate. When topiramate is given to elderly and young adults, the maximum plasma concentration was achieved in 1 to 2 hours.
▧ Protein binding :
15-41% (over the blood concentration range of 0.5 - 250 mg/mL). The fraction bound decreased as blood concentration increased. Carbamazepine and phenytoin do not alter the binding of immediate-release topiramate. Sodium valproate, at 500 mcg/mL (a concentration 5 to 10 times higher than considered therapeutic for valproate) decreased the protein binding of immediate-release topiramate from 23% to 13%. Immediate-release topiramate does not influence the binding of sodium valproate.
▧ Metabolism :
Not extensively metabolized, 70% of the dose is eliminated unchanged in the urine. The other 30% is metabolized hepatically to six metabolites (formed by hydroxylation, hydrolysis, and glucuronidation), none of which constitute more than 5% of an administered dose. There is evidence of renal tubular reabsorption of topiramate.
▧ Route of Elimination :
Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose).
▧ Half Life :
19 to 23 hours. The mean elimination half-life was 31 hours following repeat administration of the extended-release formulation.
▧ Clearance :
* Plasma clearance (CL/F) =20-30 mL/min [in humans following oral administration]
Clearance in adults was not affected by gender or race. Pediatric patients on adjunctive treatment exhibited a higher oral clearance compared to those on monotherapy. This may be because of concomitant administration with enzyme-inducing antiepileptic drugs.
Độc Tính :
Symptoms of overdose include abdominal pain, agitation, blurred vision, convulsions, depression, dizziness, double vision, drowsiness, impaired coordination, impaired mental activity, low blood pressure, reduced consciousness, severe diarrhea, sluggishness, and speech problems.
Chỉ Định :
Used for the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures and also for the prevention of migraine headaches. In children it is also used for treatment of Lennox-Gastaut syndrome. Qsymia® is indicated for the treatment and management of obesity.
Tương Tác Thuốc :
Additive renal carbonic anhydrase inhibition may occur increasing the risk of crystaluria and renal calculi. Increased risk of nephrolithiasis. Consider altnerate therapy.
As both brinzolamide and topiramate are carbonic anhydrase inhibitors, there is an increased risk of adverse effects.The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Avoid concurrent use of different carbonic anhydrase inhibitors when possible.
Carbamazepine may decrease the effectiveness of Topiramate by increase its clearance. Monitor for changes in the therapeutic and adverse effects of Topiramate if Carbamazepine is initiated, discontinued or dose changed. Adverse effects related to CNS depression have also been observed during concomitant therapy.
Thiazide diuretics such as chlorothiazide may enhance the hypokalemic effect of topiramate. Thiazide diuretics may increase the serum concentration of topiramate. Monitor for increased topiramate concentrations/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary.
Topiramate may decrease the effect of the oral contraceptive, Ethinyl estradiol. An alternate form of contraception should be used during concomitant therapy.
Increased phenytoin/decreased topiramate
Topiramate could modify lithium levels
Topiramate, a CYP3A4 inducer, may decrease the serum concentration of Maraviroc by increasing Maraviroc metabolism and clearance. A dose adjustment of Maraviroc may be required. Monitor for changes in Maraviroc therapeutic and adverse effects if Topiramate is initiated, discontinued or dose changed.
Topiramate may decrease the effect of the oral contraceptive, Mestranol. An alternate form of contraception should be used during concomitant therapy.
Increased phenytoin/decreased topiramate
Increased risk of nephrotoxicity
The CNS depressants, Triprolidine and Topiramate, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Concomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
Liều Lượng & Cách Dùng :
Capsule - Oral - 11.25 mg/69 mg (PHENTERMINE HYDROCHLORIDE/ TOPIRAMATE ER)
Capsule - Oral - 15 mg/92 mg (PHENTERMINE HYDROCHLORIDE/ TOPIRAMATE ER)
Capsule - Oral - 3.75 mg/23 mg (PHENTERMINE HYDROCHLORIDE/ TOPIRAMATE ER)
Capsule - Oral - 7.5 mg/46 mg (PHENTERMINE HYDROCHLORIDE/ TOPIRAMATE ER)
Capsule, coated pellets - Oral - 15 mg, 25 mg
Capsule, extended release - Oral - 25 mg, 50 mg, 100 mg, 200 mg
Tablet - Oral - 25 mg, 50 mg, 100 mg, 200 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Sản phẩm biệt dược : QUDEXY
Sản phẩm biệt dược : Topamax
Sản phẩm biệt dược : Trokendi XR
Tài Liệu Tham Khảo Thêm
National Drug Code Directory