Topiramate dosing

In a 42-year-old woman, the serum lithium concentration rose from 0.5 to 1.4 mmol/1 after she increased her topiramate dose from 500 to 800 mg/day (606). The authors speculated that topiramate had interfered with lithium excretion. On the other hand, in a crossover study in healthy volunteers, 6 days of treatment with topiramate did not significantly alter serum lithium concentrations however, the maximum topiramate dose was only 200 mg/ day and one subject did have about a 70% fall in lithium Cmax and AUC (607). 

Topiramate is routinely administered orally, absorbed rapidly, and metabolized minimally, but its disposition is affected by CyP 2C19. Serum concentrations of other anticonvulsant drugs are not significantly affected by the concurrent administration of topiramate, with the exception in individual patients on phenytoin who exhibit increased phenytoin plasma concentrations after addition of topiramate. Co-administration of phenytoin or carbamazepine decreases topiramate serum concentrations. Changes in cotherapy with phenytoin or carbamazepine (e.g., addition or withdrawal) for patients stabilized on topiramate therapy may require topiramate dose adjustment. As with other... 

In a study in 12 epileptic patients topiramate titrated up to a maximum of 400 mg twice daily had no effect on the steady-state plasma levels of carbamazepine 300 to 800 mg every 8 hours or on its main metabolite, carbamazepine-10,11-epoxide. An earlier study in epileptic patients also reported that topiramate does not affect the pharmacokinetics of carbamazepine. In contrast, another report describes 2 patients taking a maximum tolerated dose of carbamazepine who started treatment with topiramate and subsequently developed symptoms suggestive of carbamazepine toxicity. In both these cases, the symptoms resolved when the carbamazepine dose was reduced, and this enabled continued titration of the topiramate dose in one. A review of the clinical use of these two drugs found another 23 cases that fitted this pattern. Carbamazepine levels were not reported. ... 

The interaction between topiramate and phenytoin appears to be established, and topiramate dose adjustments may be required if phenytoin is added or discontinued. No reduction in the phenytoin dosage seems necessary in the majority of patients, but be aware that a few patients may have increased phenytoin levels, particularly at high topiramate doses. Monitor phenytoin levels. 

Yang Y, Li Q, Shuaib A. Enhanced neuroprotection and reduced hemorrhagic incidence in focal cerebral ischemia of rat by low dose combination therapy of urokinase and topiramate. Neuropharmacology 2000 39 881-888. 

Topiramate Topamax Suspension 300 mg/5 mL Tablet 25, 100, 200 mg Doses should be slowly adjusted up and down according to response and adverse effects (e.g., 150-300 mg twice daily and increase by 300-600 mg/day at weekly intervals) 50-200 mg/day in divided doses drug-drug interactions than carbamazepine, but causes more gastrointestinal side effects and hyponatremia Evidence is limited regarding efficacy Not recommended for the... 

Peripheral neuropathy is the most common complication reported in type 2 DM. This complication generally presents as pain, tingling, or numbness in the extremities. The feet are affected more often than the hands and fingers. A number of treatment options have been tried with mixed success. Current options include pregabalin, gabapentin, low-dose tricyclic antidepressants, duloxetine, venlafaxine, topiramate, non-steroidal anti-inflammatory drugs, and topical capsaicin. 

Risperidone Aripiprazole 2D6 > 3A4 2D6, 3A4 Carbamazepine and phenytoin topiramate hypericum (St. John s Wort). Paroxetine, fluoxetine, sertraline (high dose) grapefruit juice 2D6 or 3A4 substrates acting as competitive inhibitors. 

Quetiapine 3A4 2D6, 2C9 Carbamazepine and phenytoin topiramate prednisolone. Fluvoxamine fluoxetine sertraline (high dose) CYP3A4 substrates grapefruit juice. 

Topiramate is recently approved by the FDA for migraine prophylaxis. Dose is initiated at 25 mg/day and increased slowly to minimize side effects, which may include paresthesias, fatigue, anorexia, diarrhea, weight loss, difficulty with memory, and nausea. Kidney stones, acute myopia, acute angle-closure glaucoma, and oligohidrosis have been infrequently reported. 

Concomitant therapy On occasion, the addition of topiramate to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. The addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with topiramate may require adjustment of the dose of topiramate. 

Hemodialysis Topiramate is cleared by hemodialysis 4 to 6 times greater than in a healthy individual a prolonged period of dialysis may cause topiramate levels to fall below that required to maintain an antiseizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of the dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed. 

Absorption/Distribution - Absorption of topiramate is rapid, with peak plasma concentrations occurring at approximately 2 hours following a 400 mg oral dose. The relative bioavailability of topiramate from the tablet formulation is approximately 80% compared with a solution. The bioavailability of topiramate is not affected by food. 

MefaboZ/sm/Excref/on- Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose). The mean plasma elimination half-life is 21 hours after single or multiple doses. Overall, plasma clearance is approximately 20 to 30 mL/min following oral administration. 

Metabolic acidosis Hyperchloremic, nonanion gap, metabolic acidosis is associated with topiramate treatment. This metabolic acidosis is caused by renal bicarbonate loss because of the inhibitory effect of topiramate on carbonic anhydrase. Generally, topiramate-induced metabolic acidosis occurs early in treatment, although cases can occur at any time during treatment. Bicarbonate decrements usually are mild to moderate rarely, patients can experience severe decrements to values below 10 mEq/L. Conditions or therapies that predispose to acidosis may be additive to the bicarbonate lowering effects of topiramate. If metabolic acidosis develops and persists, consider reducing the dose or discontinuing topiramate. 

With the exception of topiramate (which also requires a high-dose oestroprogestogen), second generation AEDs are not considered to interfere with oestroprogestogen metabolism. The enzyme induction capacity of oxcarbazepine is much weaker than that of carbamazepine. 

Small open-label pilot studies or challenge studies have been reported for the treatment of tics with various agents such as topiramate (Abuzzahab and Brown, 2001), levodopa (Black and Mink, 2000), low-dose naloxone (van Wattum et ah, 2000), donepezil (Hoopes, 1999), cyproterone (Izmir and Dursun, 1999), and ondansetron (Toren et ah, 1999). The safety and effectiveness of the chronic use of these agents, especially in children, requires more systematic studies. 

At least three drugs are effective against absence seizures. Two are nonsedating and therefore preferred ethosuximide and valproate. Clonazepam is also highly effective but has disadvantages of dose-related adverse effects and development of tolerance. Lamotrigine and topiramate may also be useful. 

Specific myoclonic syndromes are usually treated with valproate an intravenous formulation can be used acutely if needed. It is nonsedating and can be dramatically effective. Other patients respond to clonazepam, nitrazepam, or other benzodiazepines, although high doses may be necessary, with accompanying drowsiness. Zonisamide and levetiracetam may be useful. Another specific myoclonic syndrome, juvenile myoclonic epilepsy, can be aggravated by phenytoin or carbamazepine valproate is the drug of choice followed by lamotrigine and topiramate. 

Topiramate, another antiepileptic drug, may also be helpful in a dose of 400 mg daily, built up gradually. Small quantities of alcohol may suppress essential tremor but only for a short time. Alprazolam (in doses up to 3 mg daily) or gabapentin (100-2400 mg/d) is helpful in some patients. Others are helped by intramuscular injections of botulinum toxin. Thalamic stimulation by an implanted electrode and stimulator is often worthwhile in advanced cases refractory to pharmacotherapy. Diazepam, chlordiazepoxide, mephenesin, and antiparkinsonism agents have been advocated in the past but are generally worthless. Anecdotal reports of benefit from mirtazapine were not confirmed in a double-blind study, which found no effect on the tremor in most patients. 

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