Trileptal 60 mg/ml Oral Suspension

See additions in red.

Section 2

Excipient(s) with known effect: Each ml also contains 0.30 mg propylparahydroxybenzoate (E216), 1.20 mg methylparahydroxybenzoate (E218), 25 mg propylene glycol (E1520), 250 mg sorbitol (E420) 70 % liquid (non crystallising) and 0.9 mg ethanol.

Section 4.4: Other

Trileptal oral suspension contains ethanol, less than 100 mg per dose. It contains parabenes which may cause allergic reactions (possibly delayed). It contains sorbitol and, therefore, should not be administered to patients with rare hereditary problems of fructose intolerance. Sorbitol may cause gastrointestinal discomfort and mild laxative effect.

 

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiepileptics, ATC code: N03A F 02

Pharmacodynamic effects

The pharmacological activity of oxcarbazepine is primarily exerted through the metabolite (MHD) (see section 5.2). The mechanism of action of oxcarbazepine and MHD is thought to be mainly based on the blockade of voltage-sensitive sodium channels, thus resulting in stabilisation of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminishment of propagation of synaptic impulses. In addition, increased potassium conductance and modulation of high-voltage activated calcium channels may also contribute to the anticonvulsant effects. No significant interactions with brain neurotransmitter or modulator receptor sites were found.

Oxcarbazepine and its active metabolite (MHD), are potent and efficacious anticonvulsants in animals. They protected rodents against generalised tonic-clonic and, to a lesser degree, clonic seizures, and abolished or reduced the frequency of chronically recurring partial seizures in Rhesus monkeys with aluminum implants. No tolerance (i.e. attenuation of anticonvulsive activity) against tonic-clonic seizures was observed when mice and rats were treated daily for 5 days or 4 weeks, respectively, with oxcarbazepine or MHD.

A prospective, open-label, multicentre, non-comparative, 24 week observational post marketing study has been conducted in India. Out of a study population of 816 patients, 256 pediatric patients (1 month to 19 years) with generalised tonic-clonic seizures (either secondary or primary) were treated with oxcarbazepine monotherapy. The initial oxcarbazepine dose for all patients > 6 years was 8-10 mg/kg/day given in 2 divided doses. For the 27 subjects aged 1 month to 6 years, the dose range for the initial dose was 4.62 – 27.27 mg/kg/day and 4.29 – 30.00 mg/kg/day maintenance dose. The primary endpoint was reduction in seizure frequency from baseline at week 24. In the age group 1 month to 6 years (n=27) the number of seizures changed from 1 [range] [1-12] to 0 [0-2], in the age group 7 years to 12 years (n=77) the frequency changed from 1 [1-22] to 0 [0-1] and in the age group 13-19 years (n=152), the frequency changed from 1 [1-32] to 0 [0-3]. No specific safety concerns in the pediatric patients were identified. Data supporting benefit/risk from the study regarding children under the age of 6 are inconclusive (see section 4.2).

Based on the data from the randomized controlled trials, the use of oxcarbazepine is not recommended in children below the age of 6 since safety and efficacy have not been adequately demonstrated (see section 4.2).

 

In Section  4.2 Posology and method of administration

Information has been added on Therapeutic drug monitoring and Method of Administration

Information on Paediatric and older people has been updated in this section

 

In Section 4.4  Special warnings and precautions for use

Additional information has been added on  

·         Allele frequencies

·         Risk of seizure aggravation

·         Hypothyroidism

·         Renal function

·         Monitoring of plasma levels

 

In Section 4.5  Interaction with other medicinal products and other forms of interaction

Information on interaction with Lamotrigine has been updated.

 

In Section 4.6  Fertility, pregnancy and lactation

This section has been completely updated.

 

In Section 4.7  Effects on ability to drive and use machines

This section has been completely updated.

 

In Section 4.8 Undesirable effects

The following “Unknown” side effects have been added

Hypothyroidism, Inappropriate ADH secretion like syndrome with signs and symptoms of lethargy, nausea, dizziness, decrease in serum (blood) osmolality, vomiting, headache, confusional state or other neurological signs and symptoms, Speech disorders (including dysarthria); more frequent during up titration of Trileptal dose, There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with Trileptal. The mechanism by which Trileptal affects bone metabolism has not been identified, and Fall.

 

Reporting of suspected adverse reactions has been updated to reflect name change to HPRA.

 

In Section 4.9  Overdose

Additional signs and symptoms of overdose has been added.

 

In Section 5.2  Pharmacokinetic properties

Additional information on absorbtion

 

In Section 5.3  Preclinical safety data

Information has been added on Mutagenicity, Reproductive toxicity and Carcinogenicity.

 

 

Renamed SPC on Medicines.ie

In section 4.4 Special warnings and precautions for use; PhVWP required wording has been added.

In section 4.8 Undesirable effects; information has been updated.

Date of revision of text should be 14 June 2012

In Section 4.8, Undesirable effects, the following information has been added

There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with Trileptal. The mechanism by which Trileptal affects bone metabolism has not been identified.

Inlcusion of information on pregnancy in Section 4.6
Inclusion of "hypothyroidism" as an unknown side effect in Section 4.8
Inclusion of a statement on pregnancy in Section 5.2.

4.4 Inclusion of a warning on suicidal behaviour

 Section 4.8 has been updated