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Topiramate
drug data and news
Topiramate drug data, resources, and news articles (when available). Onconews.org provides news on cancer research. This section, which includes profiles on medicines that may or not be cancer-related is in beta form. If things run smoothly we will be releasing a new format late in the summer of 2006.
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| Generic name | Topiramate | ||
| Brand Names/Synonyms | CHEMBANK1823; Mcn-4853; Tipiramate [French]; Tipiramato [Spanish]; Topamax; Topamax Sprinkle; Topiramate; Topiramate [Usan:Ban:Inn]; Topiramato [Inn-Spanish]; Topiramatum [Inn-Latin]; Topiramatum [Latin] | ||
| Indication | Used for the treatment of partial or primary generalized tonic-clonic seizures also used as a treatment for adults with partial-onset seizures. Also indicated for prophylaxis of migraine headaches | ||
| Sponsored links | Description | Not Available | |
| Pharmacology | Topiramate is an anticonvulsant indicated in the treatment of epilepsy and migraine. The precise mechanisms by which Topiramate exerts its anticonvulsant and migraine prophylaxis effects are unknown; however, preclinical studies have revealed four properties that may contribute to Topiramate's efficacy for epilepsy and migraine prophylaxis. Electrophysiological and biochemical evidence suggests that Topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABAA receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV. | ||
| Mechanism Of Action | Topiramate most likely exerts its actions by four mechanisms: (1) blockage of voltage-dependent sodium channels, (2) augmentation of the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABAA receptor, (3) antagonism of the AMPA/kainate subtype of the glutamate receptor, (4) inhibition of the carbonic anhydrase enzyme. | ||
| Topiramate News (When available) |
Topiramate Effective Headache Prophylaxis in Chronic Migraineurs ... May 2, 2006 Topiramate Found Effective for Alcoholism Apr 20, 2006 Promising Early Results Reported for Experimental Diet Drug Qnexa May 12, 2006 Vivus shares rise on weight loss data May 11, 2006 Aripiprazole in the Treatment of Patients With Borderline ... May 10, 2006 Topamax Profile May 11, 2006 VIVUS Announces Positive Phase 2 Clinical Trial Results With Qnexa ... May 10, 2006 Topamax® Reduces Number Of Monthly Migraine Days In Chronic ... Apr 30, 2006 Neuropathic Pain: An Update on Effective Management Strategies May 5, 2006 Lamotrigine Improves Depressed Mood in Women With Epilepsy ... May 11, 2006 Police: Driver passed out, hit bicyclist Apr 26, 2006 Anticonvulsant Treatment for Psychiatric and Seizure Indications ... May 4, 2006 Exploring Phantom Limb Pain Apr 17, 2006 Reinventing Rehab Apr 19, 2006 Chronic nerve pain strikes in jaw and cheek Apr 17, 2006 | ||
| Dosage Forms | CAPSULE; TABLET | ||
| Drug_Category | Antiobesity Agents; Neuroprotective Agents; Anticonvulsants; ATC:N03AX11 | ||
| Absorption | Rapid with pleak plasma concentrations occurring after 2 hours. Bioavailability is 80% | ||
| Interactions | Interactions for Topiramate: In vitro studies indicate that topiramate does not inhibit enzyme activity for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4/5 isozymes. Antiepileptic Drugs Potential interactions between topiramate and standard AEDs were assessed in controlled clinical pharmacokinetic studies in patients with epilepsy. The effects of these interactions on mean plasma AUCs are summarized in Table 3. In Table 3, the second column (AED concentration) describes what happens to the concentration of the AED listed in the first column when topiramate is added. The third column (topiramate concentration) describes how the coadministration of a drug listed in the first column modifies the concentration of topiramate in experimental settings when Topiramate was given alone. Table 3: Summary of AED Interactions with Topiramate AED Co-administered AED Concentration Topiramate Concentration Phenytoin NC or 25% increasea 48% decrease Carbamazepine (CBZ) NC 40% decrease CBZ epoxide NC NE Valproic acid 11% decrease 14% decrease Phenobarbital NC NE Primidone NC NE Lamotrigine NC at TPM doses up to 400 mg/day 15% increase NC = Less than 10% change in plasma concentration. AED = Antiepileptic drug. NE = Not Evaluated. TPM = Topiramate In addition to the pharmacokinetic interaction described in the above table, concomitant administration of valproic acid and topiramate has been associated with hyperammonemia with and without encephalopathy. Other Drug Interactions Digoxin: In a single-dose study, serum digoxin AUC was decreased by 12% with concomitant Topiramate administration. The clinical relevance of this observation has not been established. CNS Depressants: Concomitant administration of Topiramate and alcohol or other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse events, topiramate should be used with extreme caution if used in combination with alcohol and other CNS depressants. Oral Contraceptives: In a pharmacokinetic interaction study in healthy volunteers with a concomitantly administered combination oral contraceptive product containing 1 mg norethindrone (NET) plus 35 mcg ethinyl estradiol (EE), Topiramate given in the absence of other medications at doses of 50 to 200 mg/day was not associated with statistically significant changes in mean exposure (AUC) to either component of the oral contraceptive. In another study, exposure to EE was statistically significantly decreased at doses of 200, 400, and 800 mg/day (18%, 21%, and 30%, respectively) when given as adjunctive therapy in patients taking valproic acid. In both studies, Topiramate (50 mg/day to 800 mg/day) did not significantly affect exposure to NET. Although there was a dose dependent decrease in EE exposure for doses between 200-800 mg/day, there was no significant dose dependent change in EE exposure for doses of 50-200 mg/day. The clinical significance of the changes observed is not known. The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with Topiramate. Patients taking estrogen containing contraceptives should be asked to report any change in their bleeding patterns. Contraceptive efficacy can be decreased even in the absence of breakthrough bleeding. Metformin: A drug-drug interaction study conducted in healthy volunteers evaluated the steady-state pharmacokinetics of metformin and topiramate in plasma when metformin was given alone and when metformin and topiramate were given simultaneously. The results of this study indicated that metformin mean Cmax and mean AUC0-12h increased by 18% and 25%, respectively, while mean CL/F decreased 20% when metformin was co-administered with topiramate. Topiramate did not affect metformin tmax. The clinical significance of the effect of topiramate on metformin pharmacokinetics is unclear. Oral plasma clearance of topiramate appears to be reduced when administered with metformin. The extent of change in the clearance is unknown. The clinical significance of the effect of metformin on topiramate pharmacokinetics is unclear. When Topiramate is added or withdrawn in patients on metformin therapy, careful attention should be given to the routine monitoring for adequate control of their diabetic disease state. Lithium: Multiple dosing of topiramate 100 mg every 12 hrs decreased the AUC and Cmax of Lithium (300 mg every 8 hrs) by 20% (N=12, 6 M; 6 F). Haloperidol: The pharmacokinetics of a single dose of haloperidol (5 mg) were not affected following multiple dosing of topiramate (100 mg every 12 hr) in 13 healthy adults (6 M, 7 F). Amitriptyline: There was a 12% increase in AUC and Cmax for amitriptyline (25 mg per day) in 18 normal subjects (9 male; 9 female) receiving 200 mg/day of topiramate. Some subjects may experience a large increase in amitriptyline concentration in the presence of topiramate and any adjustments in amitriptyline dose should be made according to the patient's clinical response and not on the basis of plasma levels. Sumatriptan: Multiple dosing of topiramate (100 mg every 12 hr) in 24 healthy volunteers (14 M, 10 F) did not affect the pharmacokinetics of single dose sumatriptan either orally (100 mg) or subcutaneously (6 mg). Risperidone: There was a 25% decrease in exposure to risperidone (2 mg single dose) in 12 healthy volunteers (6 M, 6 F) receiving 200 mg/day of topiramate. Therefore, patients receiving risperidone in combination with topiramate should be closely monitored for clinical response. Propranolol: Multiple dosing of topiramate (200 mg/day) in 34 healthy volunteers (17 M, 17 F) did not affect the pharmacokinetics of propranolol following daily 160 mg doses. Propranolol doses of 160 mg/day in 39 volunteers (27M, 12F) had no affect on the exposure to topiramate at a dose of 200 mg/day of topiramate. Dihydroergotamine: Multiple dosing of topiramate (200 mg/day) in 24 healthy volunteers (12 M, 12 F) did not affect the pharmacokinetics of a 1 mg subcutaneous dose of dihydroergotamine. Similarly, a 1 mg subcutaneous dose of dihydroergotamine did not affect the pharmacokinetics of a 200 mg/day dose of topiramate in the same study. Others: Concomitant use of Topiramate, a carbonic anhydrase inhibitor, with other carbonic anhydrase inhibitors, e. g., acetazolamide or dichlorphenamide, may create a physiological environment that increases the risk of renal stone formation, and should therefore be avoided. Drug/Laboratory Tests Interactions: There are no known interactions of topiramate with commonly used laboratory tests. | ||
| Toxicity | Side effects include ataxia, impaired concentration, confusion, dizziness, fatigue, paraesthesia, somnolence and abnormal thinking | ||
| Organisms Affected | Humans and other mammals | ||
| Chemical IUPAC Name | 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate | ||
| Chemical Formula | C12H21NO8S | ||
| Molecular Weight | 339.363 g/mol | ||
| Smiles String | CC1(OC2COC3(C(C2O1)OC(O3)(C)C)COS(=O)(=O)N)C | ||
| Melting Point | Not Available | ||
| Water Solubility | 9.8 mg/mL | ||
| State | Solid | ||
| LogP/Hphobicity | Not Available | ||
| Isoelectric Point | Not Available | ||
| Biotransformation | Not extensively metabolized, largely eliminated unchanged in the urine. 6 metabolites have been identified, but none constitute more than 5% of an administered dose. | ||
| Half Life | 21 hours | ||
| Protein Binding [%] | 15%-41% | ||
| RxList Link | RXlist | ||
| Sponsored links | |||
| Drug Reference |
http://www.drugs.com/cons/Topiramate.html http://www.rxlist.com/cgi/generic2/topiram.htm http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/top1541.shtml | ||
| Drug Type | Approved Drug | ||
| Accession No | APRD00237 | ||
| CAS Registry Number | 97240-79-4 | ||
| KEGG Compound ID | C07502 | ||
| PubChem ID | SID:194321 | ||
| PharmGKB ID | PA451728 | ||
| SwissProt ID | Not Available | ||
| GenBank ID | Not Available | ||
| Drug ID Number [DIN] | 2239908 |
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