Topiramate drug interactions
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Drug-drug interactions
Severity level | Drug and description of interaction |
| 4 | alcohol,other CNS depressants: The risk of CNS and cognitive depression, as well as other neurocognitive and psychiatric adverse events, is increased when topiramate is co-administered with alcohol and other CNS depressants. The manufacturer recommends extreme caution when topiramate is co-administered with alcohol and other CNS depressants.[1]
acetazolamide: other carbonic anhydrase inhibitors: Acetazolamide and other carbonic anhydrase inhibitors may increase the carbonic anhydrase inhibitory effects of topiramate. Concomitant use of carbonic anhydrase inhibitors with topiramate may increase the risk for renal stone formation; therefore, the manufacturer recommends that carbonic anhydrase inhibitors be avoided.[1] phenytoin, carbamazepine, valproic acid: other anticonvulsant drugs: Enzyme-inducing anticonvulsant drugs, such as carbamazepine and phenytoin, result in an increased clearance of topiramate and a reduced plasma concentration of topiramate. Studies by the manufacturer demonstrated that therapeutic doses of phenytoin resulted in a 48% decrease in plasma concentration of topiramate, and carbamazepine resulted in a 40% decrease in plasma concentration of topiramate. oral contraceptives: In a study by the manufacturer, topiramate doses of 50-200 mg/day, in the absence of other medications, did not statistically significantly change the AUC of a concomitantly administered oral contraceptive containing 1 mg norethindrone and 35 mcg ethinyl estradiol. Another study by the manufacturer demonstrated that ethinyl estradiol AUC was significantly decreased in patients taking topiramate at doses of 200-800 mg/day and concomitant valproic acid. The manufacturer noted that both studies demonstrated that topiramate doses of 50-800 mg/day did not significantly decrease the AUC of norethindrone. Therefore, it has been postulated that topiramate may induce the metabolism of only the estrogenic component of oral contraceptives. The manufacturer noted that there was no significant change in AUC for ethinyl estradiol at topiramate doses of 50-200 mg/day, but there was a significant dose dependent decrease in AUC for ethinyl estradiol at topiramate doses of 200-800 mg/day. The manufacturer recommends that patients should be informed of decreased contraceptive efficacy and increased breakthrough bleeding when using topiramate. In addition, it may be advised that if a patient must use an oral contraceptive with topiramate, then an oral contraceptive with 50 mcg ethinyl estradiol should be recommended.[1][2][3][4] |
| 3 | phenytoin, valproic acid, lamotrigine: other anticonvulsant drugs: Topiramate, possibly through topiramate-mediated enzymatic inhibition of CYP2C19, may affect phenytoin concentrations in some patients. CYP2C19 is a minor metabolic pathway of phenytoin; therefore, topiramate CYP2C19 inhibition may decrease phenytoin clearance and increase phenytoin plasma concentrations in some patients. Studies by the manufacturer demonstrated that phenytoin plasma concentration may be increased by 25% when concomitant topiramate therapy is added. Valproic acid (Dekapote) is traditionally known as a CYP450 inhibitor. However, studies by the manufacturer demonstrated that valproic acid plasma concentration was reduced by 11% when concomitant topiramate therapy was added. In addition, studies by the manufacturer demonstrated that the plasma concentration of topiramate was reduced by 14% when concomitant valproic acid therapy was added. Studies by the manufacturer demonstrated that lamotrigine plasma concentrations were not changed with concomitant topiramate therapy, at doses of topiramate up to 400 mg/day. However, studies by the manufacturer demonstrated that the plasma concentration of topiramate was reduced by 13% when concomitant lamotrigine therapy was added.[1][5] |
| 2 | digoxin: Patients taking topiramate who were concurrently taking digoxin showed a decrease in digoxin AUC of 12%.[1]
hydrochlorothiazide (HCTZ): A study by the manufacturer revealed that HCTZ 25 mg daily co-administered with topiramate 100 mg twice daily resulted in an increased topiramate Cmax by 27% and an increased topiramate AUC by 29%. The study by the manufacturer found that the pharmacokinetics of HCTZ were not changed by topiramate. The manufacturer recommends that the topiramate dose may need to be adjusted down with concomitant HCTZ use. The manufacturer also found that serum potassium was decreased to a greater extent when topiramate and HCTZ were administered concomintantly, versus the use of HCTZ alone.[1] metformin: A study by the manufacturer revealed that metformin and topiramate resulted in an increased metformin mean Cmax by 18% and an increased metformin mean AUC by 25%. This study also found that metformin mean Cl/F decreased by 20% when metformin was given with concomitant topiramate therapy. In addition, this study found that topiramate oral plasma clearance was reduced when topiramate was co-administered with metformin. Since metformin Cl was decreased, with a concomitant increase in metformin AUC and Cmax, the risk for hypoglycemia may be increased; consequently, the manufacturer recommends judicious routine monitoring of blood sugar in diabetic patients on metformin who have the addition or withdrawal of topiramate to their therapeutic regimen.[1] pioglitazone: A study by the manufacturer revealed that pioglitazone and topiramate resulted in a decreased pioglitazone AUC by 15%, as well as a decreased AUC by 60% of the active keto-metabolite of pioglitazone. Since the AUC of pioglitazone was decreased, the risk for hyperglycemia may be increased; consequently, the manufacturer recommends judicious routine monitoring of blood sugar in diabetic patients on pioglitazone who have the addition or withdrawal of topiramate to their therapeutic regimen.[1] lithium: A study by the manufacturer revealed that multiple dosing of topiramate 100 mg twice daily decreased the AUC and Cmax of lithium by 20%, when lithium was administered at a dose of 300 mg every 8 hours.[1] amitriptyline: A study by the manufacturer revealed that amitriptyline and 200 mg/day topiramate resulted in an increased amitriptyline AUC and Cmax of about 12%. Therefore, some patients on concomitant amitriptyline and topiramate therapy may have an increased amitriptyline concentration. The manufacturer recommends that the dose for amitriptyline should be adjusted based on the patient's clinical response and not on amitriptyline plasma levels.[1] risperidone: A study by the manufacturer revealed that 2 mg/day risperidone and 200 mg/day topiramate resulted in a 25% decrease in risperidone AUC. The manufacturer recommends that patients receiving risperidone with concomitant topiramate therapy should be judiciously monitored for risperidone clinical response.[1] |
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References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Topamax® (topiramate) package insert. Titusville, NJ; Ortho-McNeil Neurologics, Inc.; 2007 March.
- ↑ Harden CL, Leppik I. Optimizing therapy of seizures in women who use oral contraceptives. Neurology. 2006;67(12 Supplement 4): S56-58.
- ↑ Doose DR, Wang SS, Padmanabhan M, Schwabe S, Jacobs D, Bialer M. Effects of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia. 2003;44(4):540-549.
- ↑ Crawford P. Interactions between antiepileptic drugs and hormonal contraception. CNS Drugs. 2002;16(4):263-272.
- ↑ Sachdeo RC, Sachdeo SK, Levy RH, Streeter AJ, Bishop FE, Kunze KL, Mather GG, Roskos LK, Shen DD, Thummel KE, Trager WF, Curtin CR, Doose DR, Gisclon LG, Bialer M. Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Epilepsia. 2002;43(7):691-696.
