Zonisamide dosing

Zonisamide 100 mg/day 100-300 mg q.d.-b.i.d. 30% 100% 75% 50% Manufacturer recommends that zonisamide not be used in patients with renai faiiure (estimated GFR <50 mi/min) dose recommendations for renai impairment based on ciearance ratios initiai dose shouid be 100 mg/day after 2 wk, the dose may be increased to 200 mg/day for at ieast 2 wk further dosage increases to 300 mg and 400 mg/day can then be made with a minimum of 2 wk between adjustments to achieve steady state at each dosage ievei zonisamide doses of 100-600 mg/day appear effective for normai renai function Dose for GFR< 10 mi/min Dose for GFR< 10 mi/min Dose for GFR10-50 mi/min... 

Placebo-controlled studies A study of zonisamide for weight loss randomized participants to receive zonisamide 200 mg/day, 400 mg/day, or placebo [204 ]. Altered taste, constipation, diarrhea, dry mouth, headache, fatigue, nausea/vomiting, somnolence, language and speech problems, impaired attention or concentration, memory problems, anxiety, and depression were more common with one or both of the zonisamide doses when compared to placebo. 

MISSELLANEOUS ANTICONVULSANTS. Valproic acid (Depakene) is unrelated chemically to the other anticonvulsants. This drug is absorbed rapidly when taken orally Tablets should not be chewed but swallowed whole to avoid irritation to the mouth and throat. The capsules may be opened and the drug sprinkled on a small amount of food, such as pudding or applesauce This mixture must be swallowed whole immediately and not chewed. Zonisamide is administered orally once a day or in divided doses. The dose may be increased by 100 mg day every 1 to 2 weeks until control of the seizures is obtained or the patient reaches the maximum dosage of 600 mg/d. 

Zonisamide Modulate sodium and calcium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 1 00-600 mg/day start at 100 mg/day and titrate upward as indicated by response Half-life 63 hours Apparent volume of distribution 1.45 L/kg Protein binding 40% Primary elimination route Hepatic Not established Dizziness, somnolence Metabolic acidosis, oligohidrosis, paresthesias, renal calculi... 

Adults Individualize dose starting with 100 mg/day. The dose may be increased after at least 2 weeks to 200 mg/day. Additional dose increases to 300 and 400 mg/day may be made at 2-week intervals to achieve steady state. Administer zonisamide once or twice/day, except during the 100 mg dosage initiation. The prescriber may wish to prolong the duration of treatment at lower doses to fully... 

Discontinuation of therapy Abrupt withdrawal of zonisamide in patients with epilepsy may precipitate increased seizure frequency or status epilepticus. Gradually reduce dose. 

Hazardous fas/cs Zonisamide may produce drowsiness, especially at higher doses. Advise patients not to drive a car or operate other complex machinery until the effect of zonisamide is known. 

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. 

The effects of concomitant carbamazepine, phenytoin, sodium valproate, and zonisamide on the steady-state serum concentrations of clonazepam have been investigated in 51 epileptic in-patients under 20 years of age (14). Serum concentrations of clonazepam correlated positively with the dose of clonazepam and negatively with the doses of carbamazepine and valproic acid, but not with phenytoin or zonisamide. These results confirm that as the oral doses of carbamazepine and sodium valproate increase, the serum concentration of clonazepam falls, but there is no interaction with either phenytoin or zonisamide. In the case of carbamazepine the mechanism of action is thought to be enzyme induction, increasing the metabolism of clonazepam. It is not known what the mechanism is with sodium valproate. In patients with epilepsy, the co-administration of either sodium valproate or carbamazepine will reduce the serum concentration of clonazepam and increase the risk of a seizure. When... 

Agents that inhibit CYP450 3A4 (such as nefazodone, fluvoxamine, and fluoxetine) may decrease the clearance of zonisamide, and increase plasma zonisamide levels, possibly requiring lower doses of zonisamide... 

Leppik I, Shellenberger K. Zonisamide pharmacokinetics direct relationship between oral dose and blood levels. Epilepsia 1999 40 286. 

Dosing and Administration. In adults, the initial recommended dose of zonisamide is 100 mg/day. Doses should be titrated by 100 mg daily every 2 weeks to patient response. The dosage range in adults is 100 to 600 mg/day. In children, zonisamide can be initiated at a dose of 2-4 mg/kg per day and titrated to 4-8 mg/kg per day up to a maximum of 12 mg/kg per day. Zonisamide is stable for 48 hours when mixed with water, apple juice, or pudding for patients who have trouble swallowing oral solid dosage forms. 

Disadvantages. The dose of zonisamide should be titrated slowly to patient response. Renal stones and oligohydrosis also have been associated with zonisamide. In addition, cognitive impairment may occur, especially if dosage is escalated rapidly. 

PHARMACOKINETICS Zonisamide is almost completely absorbed after oral administration, has a long tj, ( 63 hours), and is -40% bound to plasma protein. Approximately 85% of an oral dose is excreted in the urine, principally as unmetaboUzed zonisamide and a glucuronide of the CYP3A4 metabolite, sulfamoylacetyl phenol. Phenobarbital, phenytoin, and carbamazepine decrease the plasma concentration/dose ratio of zonisamide, whereas lamotrigine increases this ratio. Zonisamide has Uftle effect on the plasma concentrations of other antiseizure drugs. 

When a single 300-mg oral dose of zonisamide was given to healthy suh-jeets, it was found that cimetidine 300 mg four times daily for 13 days did not affeet the zonisamide clearance, half-life, apparent volume of distrihu-tion or the amount of drug recovered from the urine. The drugs were well tolerated. No special precautions would seem to be needed if both drugs are used. 

There was no difference in the pharmacokinetics of a single 300- or 400-mg dose of zonisamide when given in the fasted state or after breakfast in a study in healthy subjects. Zonisamide may be taken without regard to the timing of meals. ... 

In one study the ratio of plasma level to dose of zonisamide did not differ between 8 patients also taking elonazepam and 28 patients taking zonisamide alone, srrggesting elonazepam has no effeet on zonisamide levels. ... 

In one study the ratio of plasma level to dose of zonisamide was 29% lower in 11 patients also taking phenobarbital than in 28 patients taking zonisamide alone, suggesting that phenobarbital reduces zonisamide levels. Similarly, another study in healthy subjects found that pretreatment with phenobarbital increased the clearance of a single dose of zonisamide by about twofold. A further study found no changes in the serum levels of phenobarbital or primidone in 34 and 13 patients, respectively, who were also given zonisamide. ... 

Zonisamide 300 to 600 mg daily did not affect the phenytoin serum levels in 10 patients. Another study found that zonisamide did not affect the serum levels of phenytoin in 9 children. A further study similarly found no ehange in the plasma level of phenytoin in 33 patients also given zonisamide. In eontrast to these three studies, in a population pharmacokinetic analysis, the elearance of phenytoin at a given dose was 14% lower and the serum level 16% higher in 39 patients also taking zonisamide. Similarly, the preliminary results from 9 patients in another study showed that there was a 28% increase in the steady-state AUC of phenytoin when zonisamide 100 mg daily increased to 200 mg twice daily was given. However, a later study by the same authors, in 19 patients, found that zonisamide did not affect the pharmacokinetics of phenytoin to a clinically relevant extent. ... 

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