SIRTURO Tablet Ref.[7595] Active ingredients: Bedaquiline

Treatment with SIRTURO should be initiated and monitored by a physician experienced in the management of multi-drug resistant Mycobacterium tuberculosis.

Consideration should be given to WHO guidelines when selecting the appropriate combination regimen.

Only use SIRTURO in combination with other medicinal products to which the patient’s MDR-TB isolate has been shown to be susceptible in vitro, or is likely to be susceptible. Refer to the Summary of Product Characteristics of the medicinal products used in combination with SIRTURO for their specific dosing recommendations.

It is recommended that SIRTURO is administered by directly observed therapy (DOT).

Posology

Adult Patients

The recommended dosage for SIRTURO in adult (18 years and older) patients is shown in Table 1.

Table 1. Recommended Dosage of SIRTURO in Adult Patients:

^a = At least 48 hours between doses

The total duration of treatment with SIRTURO is 24 weeks. SIRTURO should be taken with food.

Paediatric Patients

The recommended dosage for SIRTURO in paediatric patients (5 years to less than 18 years of age) is based on body weight and shown in Table 2.

Table 2. Recommended Dosage of SIRTURO in Paediatric Patients (5 years to less than 18 years of age):

^a = At least 48 hours between doses

The total duration of treatment with SIRTURO is 24 weeks. SIRTURO should be taken with food.

Treatment duration

The total duration of treatment with SIRTURO is 24 weeks. Data on longer treatment duration is very limited. When treatment with SIRTURO is considered necessary beyond 24 weeks to obtain a curative treatment, a longer duration of therapy may be considered under close safety surveillance (see section 4.8).

Missed doses

Patients should be advised to take SIRTURO exactly as prescribed and to complete the full course of therapy.

If a dose is missed during the first two weeks of treatment, patients should not make up the missed dose, but should continue the usual dosing schedule.

If a dose is missed from week three onwards, patients should take the missed dose as soon as possible and then resume the three times a week regimen. The total dose of SIRTURO during a 7 day period should not exceed the recommended weekly dose (with at least 24 hours between each intake).

Elderly population (≥65 years of age)

There is limited clinical data (n=2) on the use of SIRTURO in elderly patients.

Hepatic impairment

No dose adjustment is necessary for SIRTURO in patients with mild or moderate hepatic impairment (see section 5.2). SIRTURO should be used with caution in patients with moderate hepatic impairment (see section 5.2). SIRTURO has not been studied in patients with severe hepatic impairment and is not recommended in this population.

Renal impairment

No dose adjustment is required in patients with mild or moderate renal impairment. In patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease requiring haemodialysis or peritoneal dialysis, SIRTURO should be used with caution (see section 5.2).

Paediatric population

The safety and efficacy of SIRTURO in children aged <5 years or weighing less than 15 kg have not yet been established. No data are available.

SIRTURO may be included in the treatment regimen for children greater than or equal to 5 years of age and weighing at least 15 kg with confirmed or with probable MDR-TB disease which is diagnosed based on clinical signs and symptoms of pulmonary MDR-TB, appropriate epidemiological context, and in line with international/local guidelines (see section 4.1).

Method of administration

SIRTURO should be taken orally with food, as administration with food increases oral bioavailability by about 2-fold (see section 5.2). There is one method of administration of SIRTURO 100 mg tablet and four different options for administration of SIRTURO 20 mg tablet. Each administration method requires SIRTURO to be taken with food.

SIRTURO 20 mg tablets

Administration of 20 mg Tablets to Patients who Can Swallow Intact Tablets

SIRTURO 20 mg tablet should be swallowed whole, or in two equal halves divided along the functional score line, with water and taken with food

Administration of 20 mg Tablets to Patients who Cannot Swallow Intact Tablets

Dispersed in Water and Administered with Beverage or Soft Food:

For patients who have difficulty swallowing intact tablets, SIRTURO 20 mg tablet can be dispersed in water and administered. To aid with administration, the dispersed mixture in water can be further mixed with a beverage (e.g., water, milk product, apple juice, orange juice, cranberry juice or carbonated beverage) or soft food (e.g., yoghurt, apple sauce, mashed banana or porridge) as follows:

• Disperse tablets in water (maximum of 5 tablets in 5 mL of water) in a drinking cup.
• Mix the contents of the cup well until the tablets are completely dispersed and then orally administer the contents of the cup immediately with food. To aid with administration, the dispersed mixture in water can be further mixed with at least 5 mL of beverage or 1 teaspoonful of soft food and then orally administer the contents of the cup immediately.
• If the total dose requires more than 5 tablets, repeat the above preparation steps with the appropriate number of additional tablets until the desired dose is reached.
• Ensure no tablet residue is left in the cup, rinse with beverage or add more soft food and orally administer the contents of the cup immediately.

Crushed and Mixed with Soft Food:

SIRTURO 20 mg tablet can be crushed and mixed with soft food (e.g., yoghurt, apple sauce, mashed banana or porridge) immediately prior to use and administered orally. Ensure no tablet residue is left in container, add more soft food and administer the contents immediately.

Refer to section 6.6 for information on administration through a feeding tube.

SIRTURO 100 mg tablets

SIRTURO 100 mg tablets should be swallowed whole with water.

Cases of intentional or accidental acute overdose with bedaquiline were not reported during clinical trials. In a study in 44 healthy adult subjects receiving a single 800 mg dose of SIRTURO, adverse reactions were consistent with those observed in clinical studies at the recommended dose (see section 4.8).

There is no experience with the treatment of acute overdose with SIRTURO. General measures to support basic vital functions including monitoring of vital signs and electrocardiogram (QT interval) monitoring should be taken in case of deliberate or accidental overdose. Further management should be as clinically indicated or as recommended by the national poisons centre, where available. Since bedaquiline is highly protein-bound, dialysis is not likely to significantly remove bedaquiline from plasma. Clinical monitoring should be considered.

Shelf life

SIRTURO 20 mg tablets: 3 years.

SIRTURO 100 mg tablets: 3 years.

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

SIRTURO 20 mg tablets: Store in the original container and keep the container tightly closed in order to protect from light and moisture. Do not remove desiccant.

SIRTURO 100 mg tablets: Store in the original container or package in order to protect from light.

SIRTURO 20 mg tablets: White, opaque, high-density polyethylene (HDPE) bottle with child-resistant polypropylene (PP) closure with aluminium induction seal liner. Each bottle contains 60 tablets and silica gel desiccant.

SIRTURO 100 mg tablets: White HDPE bottle with child-resistant PP closure with aluminium induction seal liner containing 188 tablets.

Carton containing 4 push-through blister strips (containing 6 tablets per strip). Tablets are packaged in aluminium/aluminium foil blisters.

Not all pack sizes may be marketed.

This medicinal product may pose a risk to the environment (see section 5.3). Any unused product or waste material should be disposed of in accordance with local requirements (see section 5.3).

SIRTURO 20 mg tablet can also be administered through a feeding tube (8 French or greater) as follows:

• Disperse 5 tablets or less in 50 mL of non-carbonated water and mix well. Mixture should be white to almost white with visible particles expected.
• Administer through feeding tube immediately.
• Repeat with additional tablets until desired dose is reached.
• Rinse and flush with 25 mL of additional water to ensure no tablet residue is left in materials used for preparation or the feeding tube.