TERIZIDON Capsules, hard Ref.[9609] Active ingredients:

Patients should be monitored during the inpatient and outpatient therapy phases due to the possibility of psychological side effects and nervous system side effects (see section 4.8). Outpatient treatment should not be initiated unless the patient was free of side effects during the previous inpatient treatment.

There is insufficient data available on the application, dosage and evaluation of the benefitrisk ratio of terizidone in children and teenagers. The application of TERIZIDON in this age group may therefore only be carried out in exceptional situations, if insufficient other active substances are available for therapy due to a severe pathogen resistance and the risk of a progressive course of the disease is accordingly high. Therapy using TERIZIDON on children and teenagers should take place under supervision and monitoring of the effectivity and side effects. In addition, the application of TERIZIDON in this age group should only then take place if the pathogen has been confirmed susceptible to terizidone or if pathogen susceptibility can be assumed within the scope of the case finding. A specialist experienced in the therapy of tuberculosis must be consulted.

TERIZIDON is contraindicated for patients with a case history of severe cerebral sclerosis, alcoholism, psychological disorders (depression, severe anxiety attacks, psychoses) or epilepsy because TERIZIDON can itself lead to disorders of the central nervous system (see section 4.8) and can additionally increase the risk of such side effects in the patients listed above.

Patients who take terizidone should also be given pyridoxine (vitamin B6) to prevent neurological side effects. The recommended dose is 50 mg vitamin B6/250 mg terizidone.

Simultaneous alcohol intake can increase the risk of disorders of the central nervous system (see section 4.8). Patients should not drink alcohol during therapy with TERIZIDON.

There are references that the simultaneous intake of terizidone and caffeine may increase the risk of side effects on the nervous system. Due to a current lack of knowledge on this subject, the simultaneous intake of caffeine in the form of food and drink should be undertaken with caution. The intake of certain beverages or stimulants with very high caffeine levels should be avoided as a precautionary measure (see section 4.5).

Terizidone, the active substance in TERIZIDON, can be dialyzed through haemodialysis and peritoneal dialysis. There are insufficient trials available which indicate that TERIZIDON is still clinically effective in case of continuous forms of dialysis (continuous peritoneal dialysis; CAPD) (see section 5.2).

Patients with the rare hereditary galactose intolerance, lactase deficiency or glucosegalactose malabsorption should not take TERIZIDON.

Interactive influences between TERIZIDON and other medicinal substances

Index 1: Contraindicated
Index 2: Simultaneous intake not recommended
Index 3: Simultaneous intake only under monitoring of efficacy and safety

Pregnancy

It is not known whether terizidone passes through the placenta. However, due to the fact that terizidone (prodrug) hydrolyzes to D-cycloserine, it can be expected that the intake of TERIZIDON means that relevant quantities of cycloserine do pass through the placenta and enter the embryonic blood circulation (see section 5.2).

Up to now, no or only very limited experience has been obtained with the application of cycloserine and terizidone in pregnant women. Animal experimentation studies produced no indications of direct or indirect adverse effects on health with regard to a reproduction toxicity (see section 5.3). During pregnancy, the administration of terizidone is not recommended due to side effects on the central nervous system.

Due to the lack of clinical experience, the application of TERIZIDON during pregnancy should only be carried out after careful benefit-risk assessment.

Breastfeeding

It is not known whether terizidone passes into a mother’s milk. However, due to the fact that terizidone (prodrug) hydrolyzes to D-cycloserine, it can be expected that the intake of TERIZIDON leads to relevant quantities of cycloserine passing into a mother’s milk (see section 5.2).

The risk of sensitisation, diarrhoea and yeast-like fungi on the mucous membranes cannot be excluded on breastfed babies.

A decision must be made on whether breastfeeding should be interrupted or treatment with TERIZIDON should be terminated. Here both the benefits of breastfeeding for the child and the benefits of the therapy for the mother should be taken into account.

Fertility

There is no data available on the effects of terizidone on fertility.

Due to central nervous side effects, TERIZIDON can alter reaction capabilities also when used according to the intended purpose. The ability for active participation in road traffic or the operation of machines may be restricted. This is in particular the case in interaction with alcohol.

The incidence rates of side effects are based on the following categories:

Very common: ≥1/10
Common: ≥1/100 to <1/10
Uncommon: ≥1/1,000 to <1/100
Rare: ≥1/10,000 to <1/1,000
Very rare: <1/10,000)
Not known: frequency cannot be estimated from the available data

Nervous system disorders

Commonly, central nervous disorders such as headaches, dizziness, excitability, tremor, insomnia and a feeling of drunkenness occur.

Rarely to uncommonly, epileptoid seizures and psychological reactions of a depressive and manic kind and anxiety attacks may occur.

Gastrointestinal disorders

Rarely to uncommonly, gastrointestinal disorders in the form of nausea, abdominal pain, meteorism, digestive disorders, diarrhoea or constipation occur.

The following side effects have occurred on administration of cycloserine (terizidone is a prodrug of the active substance cycloserine):

Congestive cardiac insufficiency, Stevens-Johnson syndrome, rashes, megaloblastic anaemia, liver toxicity, hypersensitivity reactions, central nervous system disorders (drowsiness, somnolence, comas, headaches, tremor, dysarthria, dizziness, confusion and disorientation with memory loss, nervousness, excitability, psychoses [possibly with suicidal behaviour], paranoia, catatonia, convulsions, hyperreflexia, vision impairments, paresis, epileptoid seizures and epileptiform absence) and encephalopathy. It can be expected that these side effects also occur on application of terizidone, as terizidone hydrolyzes into cycloserine.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

Bundesinstitut für Arzneimittel und Medizinprodukte (Federal Institute for Drugs and Medical Devices), Abt. Pharmakovigilanz (Department of Pharmacovigilance) Kurt-Georg-Kiesinger Allee 3, D-53175 Bonn, Website: www.bfarm.de

Not applicable.