DOVPRELA Tablet Ref.[111585] Active ingredients: Pretomanid

Treatment with pretomanid should be initiated and monitored by a physician experienced in the management of TB due to drug-resistant M. tuberculosis.

Pretomanid should be administered by directly observed therapy (DOT) or in accordance with local practice.

Posology

The recommended dosage is 200 mg (one tablet) pretomanid once daily, for 26 weeks.

Pretomanid should be administered only in combination with bedaquiline (400 mg once daily for 2 weeks followed by 200 mg 3 times per week [with at least 48 hours between doses] orally for a total of 26 weeks) and linezolid (600 mg daily orally for up to 26 weeks), with or without moxifloxacin (400 mg once daily for 26 weeks). See also below, on treatment duration.

In case of confirmed pulmonary TB resistant to rifampicin and a fluoroquinolone, with or without resistance to isoniazid, pretomanid should be combined with bedaquiline and linezolid, and moxifloxacin should be omitted.

The product information for bedaquiline, linezolid and moxifloxacin should be consulted for additional information on the use of these medicinal products.

In addition, see section 4.4 for information on the dose modification of linezolid that was applied during the ZeNix clinical study and see section 5.1 for details of the study.

Discontinuation of the pretomanid-bedaquiline-linezolid +/- moxifloxacin treatment regimen (see also sections 4.4, 4.8 and 5.1)

• If either bedaquiline or pretomanid is discontinued for any reason, the entire combination regimen should be discontinued.
• If linezolid is permanently discontinued during the initial four consecutive weeks of treatment, the entire combination regimen should be discontinued.
• If linezolid is discontinued after the initial four weeks of consecutive treatment, the regimen may be continued with only bedaquiline, pretomanid and with or without moxifloxacin.

Missed doses

Any missed doses of pretomanid, bedaquiline and moxifloxacin should be made up at the end of treatment. Doses of linezolid that are missed due to linezolid adverse reactions should not be made up at the end of treatment.

Refer to the product information of bedaquiline, linezolid and moxifloxacin for additional information on these medicinal products.

Treatment duration

The total duration of treatment with pretomanid in combination with bedaquiline, linezolid and with or without moxifloxacin is 26 weeks. Pretomanid in combination with bedaquiline and linezolid can be extended to a total of 39 weeks. This extension is justified in cases of failure to convert culture between months 4 and 6 while on treatment and it can be based on the clinical judgement of the treating physician. (see section 5.1).

Elderly population (≥65 years of age)

There is limited clinical data on the use of pretomanid in elderly patients. Hence, the safety and efficacy of pretomanid in elderly patients have not been established.

Hepatic impairment

The safety and efficacy of pretomanid in populations with hepatic impairment have not been established (see section 4.4).

Renal impairment

The safety and efficacy of pretomanid in populations with renal impairment have not been established. No data are available. Use in patients with renal impairment is not recommended.

Paediatric population

The safety and efficacy of pretomanid in children and adolescents have not yet been established. No data are available.

Method of administration

For oral use.

Pretomanid should be taken with food (see section 5.2).

Tablets should be swallowed with water. If the patient has trouble swallowing a whole tablet, crushing the tablets and mixing with water for administration may be an acceptable alternative. Intake should occur immediately after crushing and mixing with water.

There is no experience of acute overdose with pretomanid. General measures should be taken to support basic vital functions including monitoring of vital signs and ECG in case of deliberate or accidental overdose.

4 years.

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

High-density polyethylene (HDPE) bottles with polypropylene screw cap with a pulp liner and an absorbent cotton or an ullage filler.

Pack size: 26 tablets.

PVC/PVdC-Aluminium foil blisters packs.

Pack sizes: 14, 14 × 1 (unit dose), 182, 182 × 1 (unit dose) tablets.

Not all pack sizes may be marketed.

No special requirements for disposal.

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