ZTALMY Oral suspension Ref.[51076] Active ingredients: Ganaxolone

Treatment should be initiated and supervised by physicians with experience in the treatment of epilepsy.

Posology

Children and adolescents

ZTALMY should be titrated gradually to achieve individual clinical response and tolerability. Any patient not tolerating the dosing steps shown in the tables below, can be maintained at the lower dose for additional days before advancing to the next dose. If the next dose is still not tolerated, patients can drop back to the previous lower dose.

It is recommended that total daily dose is administered in 3 equal doses throughout the day. If this is not tolerated by a patient, the dose can be adjusted to manage symptoms (e.g., somnolence), provided that the total daily dose is administered.

Patients weighing ≤28 kg

The recommended maximum daily dose is 63 mg/kg/day given in three separate doses (every 8 hours). A minimum dose of 33 mg/kg/day is generally required.

The recommended titration schedule for patients weighing 28 kg or less is shown below:

Patients weighing >28 kg

The recommended maximum daily dose is 1 800 mg per day given in three separate doses (every 8 hours). A minimum dose of 900 mg/day is generally required.

The recommended titration schedule for patients weighing more than 28 kg is shown below:

Adults

The efficacy and safety of treatment initiation with ZTALMY in patients aged over 17 years have not yet been established. In adolescents in whom a clear treatment benefit has been demonstrated, treatment may be continued into adulthood. However, treatment initiation in adults is not recommended as efficacy and safety have not yet been established in this population (see sections 5.1 and 5.2).

Discontinuation

If ZTALMY must be discontinued, the dose should be decreased gradually. For patients weighing 28 kg or less, the decrease in total daily dose should be 15 mg/kg every four days. For patients weighing more than 28 kg, the decrease in total daily dose should be 450 mg every four days. ZTALMY may be stopped immediately and without down-titration in the case of an emergency, however, a down-titration is recommended to minimize the risk of increased seizure frequency and status epilepticus.

Missed doses

Missed doses may be taken up to 4 hours before the next scheduled dose. When the next dose is due in less than 4 hours, it is recommended to skip the dose and to continue with the next scheduled dose.

Special populations

Elderly

There is no information on the use of ZTALMY in patients with CDD who are 65 years of age and over. Doses in elderly patients should be chosen carefully based on clinical status and concomitant medicinal products. Close clinical monitoring is recommended when initiating treatment in the elderly.

Renal impairment

ZTALMY can be administered to patients with mild, moderate, or severe renal impairment without dose adjustment. There is no experience in patients with end-stage renal disease. It is not known if ZTALMY is dialysable (see section 5.2).

Hepatic impairment

Dose adjustment is not required in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment (see section 4.4).

For patients with severe hepatic impairment (Child-Pugh C) the initial target dose should be one-half the recommended target dose. The dose titration should be performed as detailed in the table(s) below.

The dose in patients with severe hepatic impairment weighing 28 kg or less is shown below:

The dose in patients with severe hepatic impairment weighing more than 28 kg is shown below:

Higher or lower doses may be considered in patients with severe hepatic impairment based on individual clinical response and tolerability.

Paediatric population

There is no relevant use of ZTALMY in infants below 6 months of age. The safety and efficacy of ZTALMY in children aged less than 2 years have not yet been established. No data are available.

Method of administration

Oral use only. No data are available on the feasibility of administration through an enteral feeding tube.

ZTALMY must be taken with or shortly after meals and each dose should be administered with similar types of food, if possible (see section 5.2). Do not mix with food or drinks prior to administration.

ZTALMY should only be administered using the reusable oral dosing syringes provided in each pack for a more accurate dose administration.

Each 12 mL reusable oral syringe is graduated in 0.25 mL increments (each 0.25 mL increment corresponds to 12.5 mg ganaxolone) and each 3 mL reusable oral dosing syringe is graduated in 0.1 mL increments (each 0.1 mL increment corresponds to 5 mg ganaxolone). The calculated dose should be rounded to the nearest graduated increment. If the calculated dose is 3 mL (150 mg) or less, the smaller 3 mL oral syringe should be used. If the calculated dose is more than 3 mL (150 mg) the larger 12 mL oral syringe should be used.

There is limited clinical trial experience regarding overdose. Adverse events of the central nervous system (e.g., somnolence, sedation) have been reported to be dose dependent.

In the event of overdose, the patient should be observed and appropriate symptomatic treatment given, including monitoring of vital signs.

2 years.

Use within 30 days of first opening the bottle.

This medicinal product does not require any special temperature storage conditions.

High-density polyethylene (HDPE) bottle with a polypropylene (PP) child resistant (CR) cap lined with an induction foil liner packed into a carton along with calibrated reusable oral dosing syringes (HDPE plunger and polypropylene barrel), and a bottle adaptor(s) (low-density polyethylene).

Each carton contains either:

• one 110 mL-bottle with two 3 mL oral dosing syringes, two 12 mL oral dosing syringes, and one bottle adaptor, or
• five 110 mL-bottles with five 12 mL oral dosing syringes, and five bottle adaptors.

Each 12 mL syringe is graduated in 0.25 mL increments and each 3 mL syringe is graduated in 0.1 mL increments.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material (including any used/unused bottle adaptors and reusable oral dosing syringes) should be disposed of in accordance with local requirements.