Topiramate is a broad-spectrum antiepileptic also used for migraine prophylaxis and weight loss.
Also known as: topamax, topiramat
DailyMed/FDA — Topamax; EMC-UK — Topiramate
DailyMed/FDA — Topamax; EMC-UK
Antiepileptic + antiepileptic: both inhibit carbonic anhydrase. Risk of renal stones and metabolic acidosis.
Topiramate inhibits carbonic anhydrase (isoenzymes II and IV), causing hyperchloraemic metabolic acidosis (5-10% of patients) and renal stones (1-2%). Valproate also weakly inhibits carbonic anhydrase. The combination significantly increases these risks. Monitor serum bicarbonate quarterly, GFR, and consider annual renal ultrasound. Maintain adequate hydration (>2 L/day). Supplement potassium citrate if bicarbonate <20 mEq/L.
Both inhibit carbonic anhydrase. Additive risk of renal stones and metabolic acidosis.
Topiramate and valproate both inhibit carbonic anhydrase. The combination increases the risk of hyperchloraemic metabolic acidosis and renal stones. Valproate may slightly increase topiramate levels.
Bicarbonate, GFR, renal ultrasound.
Symptomatic metabolic acidosis, nephrolithiasis.
Monitor serum bicarbonate and GFR. Maintain adequate hydration. Consider bicarbonate supplementation.
DailyMed/FDA; EMC-UK
CYP inducer + antiepileptic: carbamazepine reduces topiramate levels ~40%.
Carbamazepine is a potent inducer of CYP3A4 and UGT. Topiramate is partially metabolised by CYP3A4 (40%) and glucuronidated (50%). Co-administration reduces topiramate levels by ~40%, potentially compromising seizure control. Adjust topiramate dose based on clinical response. In some cases, it may be necessary to double the topiramate dose.
Carbamazepine induces CYP3A4/UGT, reducing topiramate levels ~40%. Risk of loss of seizure control.
Carbamazepine induces CYP3A4 and UGT, accelerating topiramate metabolism. Levels may decrease ~40%. It may be necessary to increase the topiramate dose.
Seizure control, serum bicarbonate.
Loss of seizure control.
Adjust topiramate dose based on clinical response. Monitor levels if possible.
DailyMed/FDA; EMC-UK
CYP inducer + antiepileptic: phenytoin may reduce topiramate levels 30-40%.
Phenytoin induces CYP3A4 and CYP2C9, accelerating topiramate metabolism. Levels may decrease 30-40%. The effect is dose-dependent — higher phenytoin doses cause greater reduction. Monitor seizure control and adjust topiramate dose.
Phenytoin induces CYP3A4/2C9, reducing topiramate 30-40%. Adjust dose based on response.
Phenytoin induces CYP3A4 and CYP2C9, accelerating topiramate metabolism. The effect is dose-dependent.
Seizure control.
Loss of seizure control.
Adjust topiramate dose. Monitor levels.
DailyMed/FDA; EMC-UK
Two carbonic anhydrase inhibitors: increased risk of renal stones and metabolic acidosis.
Both inhibit carbonic anhydrase (isoenzymes II and IV). The combination multiplies the risk of hyperchloraemic metabolic acidosis (may reach 10-15% of patients), hypokalaemia, and nephrolithiasis. Avoid this combination. If unavoidable, monitor bicarbonate, electrolytes, and GFR fortnightly for the first 3 months, then monthly.
Two carbonic anhydrase inhibitors: significant risk of metabolic acidosis and renal stones.
Both inhibit carbonic anhydrase. The combination significantly increases the risk of metabolic acidosis, hypokalaemia, and nephrolithiasis.
Bicarbonate, electrolytes, GFR, renal ultrasound.
Severe metabolic acidosis, nephrolithiasis.
Avoid combination if possible. If necessary, monitor bicarbonate, electrolytes, and GFR fortnightly.
DailyMed/FDA; EMC-UK
Biguanide + carbonic anhydrase inhibitor: additive risk of metabolic acidosis.
Topiramate inhibits carbonic anhydrase, causing hyperchloraemic metabolic acidosis (5-10%). Metformine may cause lactic acidosis (rare but serious). Although the mechanisms differ, topiramate-induced metabolic acidosis may mask early signs of metformine-induced lactic acidosis. Monitor serum bicarbonate and GFR regularly.
Biguanide + carbonic anhydrase inhibitor: additive risk of metabolic acidosis.
Topiramate inhibits carbonic anhydrase, causing hyperchloraemic metabolic acidosis. Metformine may cause lactic acidosis (rare). The combination increases the risk of acidosis.
Bicarbonate, GFR, signs of acidosis.
Metabolic/lactic acidosis.
Monitor serum bicarbonate and GFR. Avoid if eGFR <45.
DailyMed/FDA; EMC-UK
Alcohol potentiates topiramate CNS depression. Increased risk of sedation and cognitive impairment.
Avoid alcohol or severely limit.
CONTRAINDICATED in patients with history of kidney stones. Topiramate inhibits carbonic anhydrase, increasing stone risk.
Do not administer. Consider alternative (levetiracetam, lamotrigine).
DailyMed/FDA; EMC-UK
Partial hepatic metabolism (CYP3A4). Reduced clearance in hepatic impairment.
Reduce dose. Monitor liver function.
DailyMed/FDA; EMC-UK
30-50% excreted unchanged renally. Accumulation in renal impairment.
eGFR 30-50: reduce dose by 50%. eGFR <30: avoid.
DailyMed/FDA; EMC-UK
Risk of metabolic acidosis and reduced intrauterine growth. Limited data.
Insufficient data. Use minimum dose. Metabolic acidosis may affect fetus.
Excreted in breast milk in low concentrations.
Effects on fertility unknown.
DailyMed/FDA — Topamax; EMC-UK
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Broad-spectrum antiepileptic activity. Multiple mechanisms of action.
Blockade of voltage-gated Na⁺ channels (inactivation), potentiation of GABA-A-mediated currents, AMPA/glutamate receptor antagonism, carbonic anhydrase inhibition (isoenzymes II and IV).
Rapid oral absorption. Bioavailability: >80%. Peak: 1-4 h. Food does not affect Cmax but delays Tmax.
Hepatically metabolised (partial CYP3A4, ~40%). Glucuronidation (~50%). 30-50% excreted unchanged renally.
19-25 h.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
