Ztalmy

Package leaflet: Information for the patient

ZTALMY 50 mg/mL oral suspension

ganaxolone
This medicinal product is subject to additional monitoring. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you or the patient experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before you or your child takes this medicine,
because it contains important information.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours or your child's, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What ZTALMY is and what it is used for
2. What you or your child should know before taking ZTALMY
3. How to take ZTALMY
4. Possible side effects
5. How to store ZTALMY
6. Contents of the pack and other information

1. What ZTALMY is and what it is used for

ZTALMY contains the active substance ganaxolone, a neuroactive steroid that works by binding to specific receptors and prevents epileptic seizures from starting in the brain.
ZTALMY is used, in patients aged between 2 and 17 years, to treat a rare disease characterised by epileptic seizures called “cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder” (CDD). If ZTALMY helps control seizures, it may continue to be used when you or your child reach 18 years of age.
ZTALMY is used in combination with other antiepileptic medicines.
This medicine reduces the number of epileptic seizures you or your child may have each day.

2. What you or your child should know before taking ZTALMY

Do not take ZTALMY if you are allergic to ganaxolone or to any of the other ingredients of this
medicinal product (listed in section 6).
Warnings and precautions
Talk to your doctor or pharmacist before taking ZTALMY if:

• you or your child experience drowsiness ZTALMY may cause drowsiness or an excessive feeling of calmness and relaxation (i.e., sedation). Talk to your doctor or pharmacist before taking
  ZTALMY if you have any doubts about these effects or if you are taking central nervous system depressants, such as other medicines for seizure control, opioids,
  antidepressants, or alcohol, as these may increase the drowsiness and sedative effects of
  ZTALMY.

• you or your child have had thoughts of self-harm or suicide If you notice unusual changes in mood or behaviour, or if you have thoughts of self-harm or suicide, contact your doctor immediately. If you are caring for a child with CDKL5 deficiency disorder (CDD), you should monitor carefully for any unusual changes in mood or behaviour, or any comments that might suggest thoughts of self-harm or suicide. If you notice any of these behaviours, contact your doctor immediately.

• you or your child have a history of alcohol or substance abuse ZTALMY may be misused or taken for non-medical purposes. Talk to your doctor or pharmacist before taking ZTALMY if you have a history of alcohol or substance abuse.

• you or your child have severe liver problems Your doctor will closely monitor you or your child during treatment and may reduce the dose of ZTALMY.

Children and adolescents
ZTALMY must not be given to children under 2 years of age, as there is no information available on its use in children below this age group.
Other medicines and ZTALMY
Inform your doctor or pharmacist if you or your child are taking, have recently taken, or might take any other medicines. Taking ZTALMY together with certain other medicines may cause adverse effects, alter the action of other medicines, or alter the effect of ZTALMY.
Do not start or stop taking any other medicines without first consulting your doctor or pharmacist.
Inform your doctor if you or your child are taking any of the following medicines, as it may be necessary to adjust the dose of ZTALMY:

• medicines containing valproate, used to treat epilepsy, which may require a lower dose of ZTALMY;
• medicines that may reduce the effect of ZTALMY, which may require a higher dose of ZTALMY;
• other antiepileptic or anticonvulsant medicines, such as carbamazepine, phenytoin, phenobarbital, and primidone;
• antibiotics, such as rifampicin;
• St John’s wort (Hypericum perforatum), a herbal remedy used for mild depression.

The interaction between this medicine and oral contraceptives has not been studied. Talk to your doctor if you are taking oral contraceptives.
ZTALMY with alcohol
Alcohol must not be consumed, as it may increase drowsiness and the sedative effects of
ZTALMY.
Pregnancy
If you are pregnant or suspect you may be pregnant, consult your doctor or pharmacist before taking this medicine.
ZTALMY is not recommended during pregnancy and in women of childbearing potential who are not using contraception.
Breast-feeding
Do not use ZTALMY while breast-feeding unless your doctor decides that the benefits of taking ZTALMY outweigh the potential risks.
Driving and using machines
ZTALMY may make you feel drowsy/sleepy. If you experience these symptoms, you must not drive, ride a bicycle, or operate machinery until you feel alert.
ZTALMY contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per mL and is therefore essentially “sodium-free”.
ZTALMY contains sodium benzoate and benzoic acid
Each mL of this medicine contains 0.92 mg sodium benzoate and 0.00068 mg benzoic acid.
In neonates up to 4 weeks of age, sodium benzoate and benzoic acid may increase the risk of jaundice (yellowing of the skin and eyes).
ZTALMY contains benzyl alcohol
Each mL of this medicine contains 0.00023 mg of benzyl alcohol. Benzyl alcohol may cause allergic reactions. In young children, benzyl alcohol has been associated with a risk of serious adverse effects, including breathing problems (gasping syndrome). Do not administer to neonates up to 4 weeks of age unless otherwise recommended by the doctor. In young children (under 3 years of age), do not use for more than one week unless otherwise recommended by the doctor or pharmacist. The risk is higher in young children due to accumulation. In case of pregnancy or breast-feeding, or in case of liver or kidney disease, consult your doctor or pharmacist. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (known as metabolic acidosis).
ZTALMY contains methyl parahydroxybenzoate and propyl parahydroxybenzoate
This medicine contains 1.02 mg of methyl parahydroxybenzoate and 0.2 mg of propyl parahydroxybenzoate per mL, which may cause allergic reactions (including delayed reactions).

3. How to take ZTALMY

ZTALMY is administered under the supervision of a physician experienced in the treatment of epilepsy. Always take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
This is an oral suspension (a liquid to be swallowed). Your doctor or pharmacist will inform you of the amount (in mL) of oral suspension to take each day and how many times per day to take it.
The doctor will calculate the dose based on body weight. You may start with a low dose, which the doctor will gradually increase over time.
If you have severe hepatic impairment, your doctor will start treatment with a lower dose and follow a different titration schedule.

Patient with body weight less than or equal to 28 kg
For you or your child, the dose will be gradually increased over 4 weeks until reaching the recommended maximum daily dose of 63 mg/kg/day, administered in three divided doses every 8 hours.

Patient with body weight greater than 28 kg
For you or your child, the dose will be gradually increased over 4 weeks until reaching the recommended maximum daily dose of 1,800 mg/day, administered in three divided doses every 8 hours.

It is recommended to take three equal doses throughout the day. However, since ZTALMY may cause drowsiness, your doctor may decide to administer a lower dose during the day and a higher dose in the evening to minimize daytime drowsiness.

Contact your doctor if you have any doubts about the dose or if you think it may need to be adjusted.

How to take ZTALMY

• Take the medicine during or immediately after meals
• If possible, try to take it with similar types of food (e.g., with a similar fat content) each time, to ensure consistent effects
• Do not mix ZTALMY with food or drinks
• To ensure accurate dosing, use the reusable oral dosing syringes provided in each package

Instructions for use
Each pack containing 1 vial includes:

1 bottle of oral suspension closed with child-resistant cap
2 reusable 12 mL oral dosing syringes and 2 reusable 3 mL oral dosing syringes

1 bottle adapter

ZTALMY is also available in a pack containing 5 bottles of oral suspension, 5 reusable 12 mL oral administration syringes, and 5 bottle adapters. The pack containing 5 bottles of ZTALMY does not include a reusable 3 mL oral administration syringe.

• Consult your doctor, pharmacist, or nurse if you have any doubts about how to prepare or take the prescribed dose of ZTALMY.
• The pack containing 1 bottle includes reusable oral administration syringes of 12 mL and 3 mL. If the dose is less than or equal to 3 mL, use the smaller 3 mL syringe to draw up the medicine. If the dose is greater than 3 mL, use the larger 12 mL syringe to draw up the dose.
• For oral administration, always use the correct reusable syringe provided with ZTALMY to ensure the accurate amount of ZTALMY is measured. Do not use kitchen spoons. For administration, do not mix ZTALMY with food or drinks.
• Each 3 mL oral administration syringe can be used for 16 consecutive days. After 16 days, discard the used syringe and use the spare syringe supplied in the box.
• Use ZTALMY within 30 days of first opening the bottle. The bottle label includes a space to record the date by which the bottle should be discarded after opening, to help you remember.
• After 30 days, discard any unused ZTALMY and start a new bottle.

Preparation of the bottle

1. Hold the bottle and shake it well for 1 minute. Always shake the bottle well for 1 minute, then let it stand for 1 minute to allow any foam formed during shaking to settle before measuring and administering each dose of ZTALMY. This helps ensure the correct amount of medicine is measured. NB: this step must be performed for each dose of the medicine.
2. Remove the child-resistant cap from the bottle by pushing down and turning it to the left (counterclockwise).
3. Pierce and remove the induction seal from the bottle. NB: this step is required only the first time the bottle is used.
4. Hold the bottle firmly with one hand and firmly push the adapter into the bottle neck with the other hand, ensuring it is fully inserted. If the adapter is not fully inserted, it may become detached and cause choking. NB: once inserted, do not remove the press-in adapter from the bottle.

Preparation of the dose

5. Insert the tip of the appropriate reusable oral syringe into the vial adapter and, once the syringe is in place, turn the vial upside down. It is important to use the correct reusable oral syringe to measure the dose: • if the dose is equal to or less than 3 mL (150 mg), use the smaller 3 mL syringe • if the dose is greater than 3 mL (150 mg), use the larger 12 mL syringe.
6. Slowly pull back the plunger of the syringe so that the required volume (number of mL) of oral suspension is drawn into the syringe. Align the end of the plunger with the required volume marking, as shown in the figure on the side. If there is an air bubble in the syringe, push the liquid back into the vial while keeping the vial inverted and repeat step 6 until the air bubble disappears.
7. Place the vial upright and carefully remove the oral syringe from the adapter.

Administration or intake of ZTALMY

8. Place the tip of the oral syringe inside the cheek and gently push the plunger to allow the medicine to be dispensed. Do not push the plunger forcefully, nor direct the medicine toward the back of the mouth or throat.

9. Screw the child-resistant cap tightly back onto the bottle, turning the cap to the right (clockwise). It is not necessary to remove the bottle adapter; the cap will fit over it.
10. Wash the oral syringe immediately after use. Remove the plunger from the syringe barrel and rinse both parts with room-temperature tap water. Caution: Do not use bleach or other harsh solutions for cleaning. Do not wash the oral syringe in a dishwasher.
11. Remove water from both parts of the syringe and allow them to air-dry separately until next use. Make sure both parts are completely dry before reinserting the plunger into the syringe barrel for the next use. If both parts are not completely dry before the next dose, use the spare syringe provided in the package. If using the 12 mL syringe supplied with each bottle, do not discard the reusable oral syringes until the bottle is empty. If using the 3 mL syringe, discard it after 16 days.
12. Repeat steps 1-3 and 6-12 for each subsequent dose.

If you take more ZTALMY than you should
If you accidentally take more ZTALMY than you should, inform your doctor or pharmacist immediately or contact the emergency department of the nearest hospital, and bring the medicine with you. You may experience drowsiness after taking an excessive amount of the medicine.

If you forget to take ZTALMY
If you forget to take a dose, you may take the missed dose up to 4 hours before the next scheduled dose. If less than 4 hours remain before the next dose, you should skip the missed dose and continue with your next scheduled dose.

If you stop taking ZTALMY
Do not reduce the dose or stop taking ZTALMY without first consulting your doctor. Stopping this treatment suddenly may increase seizures. Your doctor will advise you on how to gradually discontinue ZTALMY.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur with this medicine. Tell your doctor if you experience any of the
following:

Very common (may occur in more than 1 out of 10 people):

• feeling sleepy;
• fever.

Common (may occur in more than 1 out of 100 people):

• feeling overly calm or relaxed;
• excessive tiredness during the day or sleeping longer than usual at night;
• lack of energy;
• drooling;
• production of more saliva than normal.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system listed in Annex V. By reporting
side effects, you can help provide more information on the safety of this medicine.

5. How to store ZTALMY

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and on the label of the
bottle after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Dispose of the medicine 30 days after first opening.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ZTALMY contains

• The active substance is ganaxolone. Each mL of oral suspension contains 50 mg of ganaxolone.
• The other components are: hypromellose (E464), polyvinyl alcohol (E1203), sodium lauryl sulfate (E487), methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), sodium benzoate (E211), anhydrous citric acid (E330), disodium citrate dihydrate (E311), artificial cherry flavour [containing propylene glycol (E1520) and benzyl alcohol (E1519)], sucralose (E955), simethicone emulsion [simethicone, polysorbate 65, methylcellulose, polyethylene glycol monostearate, glyceryl monostearate, xanthan gum, benzoic acid (E210), sorbic acid and purified water], purified water (see also section 2 "ZTALMY contains sodium", "ZTALMY contains sodium benzoate and benzoic acid", "ZTALMY contains benzyl alcohol" and "ZTALMY contains methyl parahydroxybenzoate and propyl parahydroxybenzoate").

Description of the appearance of ZTALMY and contents of the pack
ZTALMY is a white to off-white oral suspension. It is supplied in a plastic bottle with a child-resistant plastic cap. Each bottle contains 110 mL of oral suspension.
ZTALMY is available in the following pack sizes:

• one bottle of oral suspension, two 12 mL oral dosing syringes, two 3 mL oral dosing syringes, and one bottle adapter; or
• five bottles of oral suspension, five 12 mL oral dosing syringes, and five bottle adapters.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Immedica Pharma AB
113 63 Stockholm
Sweden

Manufacturer
Orion Corporation Orion Pharma
Joensuunkatu 7
FI-24100 Salo
Finland

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.