EMCITATE Dispersible tablet Ref.[114870] Active ingredients: Tiratricol

Treatment should be initiated and monitored by physicians who are experienced in the management of patients with rare genetic disorders such as MCT8 deficiency.

Posology

Dosing of Emcitate should be titrated on an individual patient basis based on the patient’s thyroid hormone levels.

The dose should be increased stepwise approximately every two weeks during a titration period until a maintenance dose has been reached. It is generally recommended to titrate the dose until the serum T3 level is below the midpoint of the normal range for age. The dose may be further adjusted based on the patient’s response to treatment on clinical features of MCT8 deficiency.

The need for further dose adjustments should be reassessed on a regular basis in accordance with clinical practice (see section 4.4).

TSH and (F)T4 levels may provide further information to guide individual dosing.

Adults, adolescents, children, and infants with a body weight of 10 kg or above

Dose titration and adjustment

The recommended starting dose for patients with a body weight of 10 kg or above is 350 micrograms daily.

A recommended dose titration regimen is shown in Table 1. The daily dose should be gradually increased by 350 micrograms every two weeks until a maintenance dose has been reached. It is generally recommended to titrate the dose until the serum T3 level is below the midpoint of the normal range for age. Smaller dose escalation steps (half tablets) may be used when a patient is approaching target serum T3 levels, as appropriate. The dose may be further adjusted based on the patient’s response to treatment on clinical features of MCT8 deficiency. The total daily dose should be administered in 1 to 3 doses, spread throughout the day (e.g. morning, midday, evening).

Table 1. Recommended dose titration regimen in patients with a body weight of 10 kg or above:

Dose titration should continue in increments of 350 micrograms until a maintenance dose has been reached. It is not recommended to exceed a daily dose of 80 micrograms/kg in patients with a body weight between 10 and 40 kg; 60 micrograms/kg in patients with a body weight between 40 and 60 kg; and 50 micrograms/kg in patients with a body weight above 60 kg.

Children and infants with a body weight below 10 kg

Dose titration and adjustment

The recommended starting dose for patients with a body weight below 10 kg is 175 micrograms (a half tablet) daily.

A recommended dose titration regimen is shown in Table 2. The daily dose should be gradually increased by 175 micrograms every two weeks until a maintenance dose has been reached. It is generally recommended to titrate the dose until the serum T3 level is below the midpoint of the normal range for age. The dose may be further adjusted based on the patient’s response to treatment on clinical features of MCT8 deficiency. The total daily dose should be administered in 1 to 3 doses, spread throughout the day (e.g. morning, midday, evening).

Table 2. Recommended dose titration regimen in patients with a body weight below 10 kg:

Dose titration should continue in increments of 175 micrograms until a maintenance dose has been reached. It is not recommended to exceed a daily dose of 100 micrograms/kg in patients with a body weight below 10 kg.

Maintenance dose

The dose of Emcitate is titrated on an individual basis until a maintenance dose has been reached. It is generally recommended to titrate the dose until the serum T3 level is below the midpoint of the normal range for age. The dose may be further adjusted based on the patient’s response to treatment on clinical features of MCT8 deficiency. The need for further dose adjustments should be reassessed on a regular basis in accordance with clinical practice (see section 4.4).

Missed or delayed dose

If a dose is missed and there are more than 4 hours to the next scheduled dose, it should be taken as soon as possible. If a dose is missed and the next dose is scheduled within 4 hours, the dose should be omitted and the next dose taken according to the regular schedule. Laboratory tests (T3 measurements) It is recommended to measure individual T3 levels using a liquid chromatography tandem mass spectrometry (LC/MS/MS) method. Tiratricol cross-reacts with T3 when assessed by immunoassay, which may cause unreliable test results. Expert advice should be sought for test result interpretation when initiating, titrating and adjusting the dose of tiratricol using immunoassay method (see section 4.4).

Hypermetabolic signs and symptoms

If hypermetabolic signs and symptoms (such as hyperhidrosis, irritability, anxiety, insomnia, nightmares, hyperthermia, tachycardia, transient elevations in systolic blood pressure (SBP), or diarrhoea) either occur for the first time or worsen, and do not resolve within 2 weeks, the dose should be reduced according to the steps in the dose titration regimen until signs and symptoms resolve (see Table 1 or Table 2). Following the resolution of hypermetabolic signs and symptoms, dose titration may be resumed, as clinically appropriate (see section 4.4).

Special populations

Hepatic impairment

No specific studies have been performed in patients with hepatic impairment. In these patients, careful dose titration and regular monitoring of serum concentrations of T3 are recommended (see section 4.4).

Renal impairment

No specific studies have been performed in patients with renal impairment. In these patients, careful dose titration and regular monitoring of serum concentrations of T3 are recommended (see section 4.4).

Method of administration

For oral use or administration through gastroenteral feeding tube.

Oral use

Emcitate dispersible tablets are intended to be dispersed in water before being swallowed.

The dispersion should be prepared in a dedicated small glass, by dispersing the tablet(s) (maximum 4 tablets at each dosing occasion) in 30 mL of drinking water, by stirring with a teaspoon for 1 minute. No other liquids should be used. The dispersion should be cloudy white. The dispersion should then be withdrawn from the glass with a 40 mL oral syringe and given orally to the patient with the syringe without delay. It must be ensured that the plunger is slowly and gently pushed down to gently squirt the dispersion into the inside of the cheek of the patient.

An additional 10 mL of drinking water should be added to the glass and stirred with a teaspoon for around 5 seconds to ensure that any remaining product is dispersed. This dispersion should be withdrawn from the glass with the same syringe, and given to the patient without delay.

Through gastroenteral feeding tube

Emcitate can be administered through a gastroenteral feeding tube.

The preparation of the dispersion should be performed as described above for oral use.

It must be ensured that the gastroenteral feeding tube is free from obstruction before administration and the instructions for the selected gastroenteral feeding tube regarding flushing, administration, and rinsing procedures must be followed.

The contents of the syringe should be administered immediately into the gastroenteral feeding tube (30 mL + 10 mL for all age groups).

For additional information regarding administration through gastroenteral feeding tube, and stability of the dispersion, see section 6.6.

Signs and symptoms of a hypermetabolic state may appear in cases of overdose. Decreasing the dose of Emcitate or temporarily discontinuing treatment alleviates these symptoms.

18 months.

After dispersion:

The 30 mL dispersion can be stored below 25 °C for up to 4 hours in the glass, and then be resuspended by stirring for 1 minute with a teaspoon prior to administration.

Store in a refrigerator (2°C–8°C).

Store in the original package in order to protect from light.

For storage conditions after dispersion of the medicinal product, see section 6.3.

PVC/Aluminium blister.

Pack size of 60 dispersible tablets.

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

The product can be administered through a gastroenteral feeding tube.

The product has been tested using a percutaneous endoscopic gastrostomy (PEG) silicone tube (lumen 12 French, maximum length 34 cm), and nasogastric (NG) polyurethane tubes (lumen 6 French and 8 French, maximum length 56 cm). This product has not been tested with other types of tubes or tube materials. A 3 mL flush volume (water) is recommended.