ZONEGRAN Hard capsule Ref.[9541] Active ingredients: Zonisamide

Posology – Adults

Dosage escalation and maintenance

Zonegran may be taken as monotherapy or added to existing therapy in adults. The dose should be titrated on the basis of clinical effect. Recommended escalation and maintenance doses are given in Table 1. Some patients, especially those not taking CYP3A4-inducing agents, may respond to lower doses.

Withdrawal

When Zonegran treatment is to be discontinued, it should be withdrawn gradually (see section 4.4). In clinical studies of adult patients, dose reductions of 100 mg at weekly intervals have been used with concurrent adjustment of other antiepileptic medicine doses (where necessary).

Table 1. Adults – recommended dosage escalation and maintenance regimen:

General dosing recommendations for Zonegran in special patient populations

Paediatric population (aged 6 years and above)

Dosage escalation and maintenance

Zonegran must be added to existing therapy for paediatric patients aged 6 years and above. The dose should be titrated on the basis of clinical effect. Recommended escalation and maintenance doses are given in Table 2. Some patients, especially those not taking CYP3A4-inducing agents, may respond to lower doses.

Physicians should draw the attention of paediatric patients and their parents/carers to the Patient Alert Box (in the package leaflet) on preventing heatstroke (see section 4.4: Paediatric population).

Table 2. Paediatric population (aged 6 years and above) – recommended dosage escalation and maintenance regimen:

Note:

^a To ensure a therapeutic dose is maintained the weight of a child should be monitored and the dose reviewed as weight changes occur up to a weight of 55kg. The dose regime is 6-8 mg/kg/day up to a maximum dose of 500 mg/day.

The safety and efficacy of Zonegran in children aged below 6 years or those below 20 kg have not yet been established.

There are limited data from clinical studies in patients with a body weight of less than 20 kg.

Therefore children aged 6 years and above and with a body weight less than 20 kg should be treated with caution.

It is not always possible to precisely achieve the calculated dose with the commercially available capsule strengths of Zonegran. In these cases it is therefore recommended that the Zonegran total dose should be rounded up or down to the nearest available dose that can be achieved with commercially available capsule strengths of Zonegran (25 mg, 50 mg and 100 mg).

Withdrawal

When Zonegran treatment is to be discontinued, it should be withdrawn gradually (see section 4.4). In clinical studies of paediatric patients, down-titration was completed by dose reductions at weekly intervals in increments of about 2 mg/kg (i.e. in accordance with the schedule in Table 3).

Table 3. Paediatric population (aged 6 years and above) – recommended down-titration schedule:

Note:

^* All doses are once daily.

Elderly

Caution should be exercised at initiation of treatment in elderly patients as there is limited information on the use of Zonegran in these patients. Prescribers should also take account of the safety profile of Zonegran (see section 4.8).

Patients with renal impairment

Caution must be exercised in treating patients with renal impairment, as there is limited information on use in such patients and a slower titration of Zonegran might be required. Since zonisamide and its metabolites are excreted renally, it should be discontinued in patients who develop acute renal failure or where a clinically significant sustained increase in serum creatinine is observed.

In subjects with renal impairment, renal clearance of single doses of zonisamide was positively correlated with creatinine clearance. The plasma AUC of zonisamide was increased by 35% in subjects with creatinine clearance <20 ml/min.

Patients with hepatic impairment

Use in patients with hepatic impairment has not been studied. Therefore use in patients with severe hepatic impairment is not recommended. Caution must be exercised in treating patients with mild to moderate hepatic impairment, and a slower titration of Zonegran may be required.

Method of administration

Zonegran hard capsules are for oral use.

Effect of food

Zonegran may be taken with or without food (see section 5.2).

There have been cases of accidental and intentional overdose in adult and paediatric patients. In some cases, the overdoses were asymptomatic, particularly where emesis or lavage was prompt. In other cases, the overdose was followed by symptoms such as somnolence, nausea, gastritis, nystagmus, myoclonus, coma, bradycardia, reduced renal function, hypotension and respiratory depression. A very high plasma concentration of 100.1 μg/ml zonisamide was recorded approximately 31 hours after a patient took an overdose of Zonegran and clonazepam; the patient became comatose and had respiratory depression, but recovered consciousness five days later and had no sequelae.

Treatment

No specific antidotes for Zonegran overdose are available. Following a suspected recent overdose, emptying the stomach by gastric lavage or by induction of emesis may be indicated with the usual precautions to protect the airway. General supportive care is indicated, including frequent monitoring of vital signs and close observation. Zonisamide has a long elimination half-life so its effects may be persistent. Although not formally studied for the treatment of overdose, haemodialysis reduced plasma concentrations of zonisamide in a patient with reduced renal function, and may be considered as treatment of overdose if clinically indicated.

3 years.

Do not store above 30°C.

PVC/PVDC/aluminium blisters, packs of 14, 28, 56 and 84 hard capsules.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.