GAPREX

Neuropathic pain

Pregabalin is indicated in the treatment of peripheral and central neuropathic pain in adults.

Epilepsy

Pregabalin is indicated in adults in combination for the treatment of partial seizures with or without secondary generalization.

Generalized Anxiety Disorder

Pregabalin is indicated in the treatment of Generalized Anxiety Disorder (GAD) in adults.

Given that pregabalin is essentially eliminated in unchanged form in the urine, that it is only very weakly metabolized in humans (less than 2 % of the dose is found in the urine as metabolites), that it does not inhibit drug metabolism in vitro and that it does not bind to plasma proteins, it is unlikely to induce or undergo pharmacokinetic interactions.

In vivo studies and population pharmacokinetic analysis

No clinically significant pharmacokinetic interaction has been observed in in vivo studies between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analyses have shown that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on the clearance of pregabalin.

Oral contraceptives, norethisterone and/or ethinylestradiol

Concomitant administration of pregabalin with oral contraceptives such as norethisterone and/or ethinylestradiol does not influence the steady-state pharmacokinetic parameters of either of these substances.

Medicines affecting the central nervous system

Pregabalin may potentiate the effects of ethanol and lorazepam.

Reports of respiratory failure, coma and death have been reported post-marketing in patients receiving pregabalin and opioids and/or other central nervous system (CNS) depressants. The effect of pregabalin appears to add to that of oxycodone on the impairment of overall cognitive and motor function.

Interactions and elderly subjects

No specific pharmacodynamic interaction studies have been conducted in elderly volunteers. Interaction studies have only been performed in adults.

Pregabalin may have a minor or moderate influence on the ability to drive vehicles and use machines. PREGABALINE CRISTERS PHARMA may induce dizziness and somnolence and can therefore have an influence on the ability to drive or use machines. It is therefore advised that patients do not drive, do not use complex machines, nor undertake other potentially dangerous activities, before having assessed the possible impact of this medicine on their ability to perform these activities.

The clinical evaluation program for pregabalin was conducted in more than 8 900 patients exposed to pregabalin, with more than 5 600 of them having been exposed in double-blind, placebo-controlled trials. The most frequently reported adverse reactions were dizziness and somnolence. These adverse reactions were generally mild to moderate in intensity. In all controlled studies, discontinuation due to adverse reactions occurred in 12 % of patients receiving pregabalin and 5 % of patients receiving placebo. The most common adverse reactions resulting in discontinuation of pregabalin treatment were dizziness and somnolence.

Table 2 below lists, by type and by frequency, all adverse reactions that occurred at an incidence higher than placebo and in more than one patient (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), frequency not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The adverse effects listed may also be associated with the underlying disease and/or concomitant medications.

In the treatment of central neuropathic pain due to spinal cord injury, the incidence of adverse effects in general, of adverse effects affecting the CNS and of somnolence in particular, was increased (see section 4.4).

Additional effects reported post-marketing are listed in the list below in italics.

Table 2. Adverse Effects of Pregabalin

* increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST)

After discontinuation of short-term or long-term treatment with prégabaline, withdrawal symptoms have been observed. The following symptoms have been reported: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, convulsions, nervousness, depression, suicidal ideation, pain, hyperhidrosis, and dizziness. These symptoms may indicate drug dependence. The patient should be informed about this at the beginning of treatment. Concerning the discontinuation of long-term treatment with prégabaline, data suggest that the incidence and severity of withdrawal symptoms may be dose-dependent (see sections 4.2 and 4.4).

Paediatric population

The safety profile of prégabaline observed in five paediatric studies in patients with partial onset seizures with or without secondary generalisation (efficacy and safety study for 12 weeks in patients aged 4 to 16 years, n = 295; efficacy and safety study for 14 days in patients aged 1 month to less than 4 years, n = 175; pharmacokinetic and tolerability study, n = 65; and two open-label safety follow-up studies for 1 year, n = 54 and n = 431) was similar to that observed in studies conducted in adult epileptic patients. The most frequently observed adverse events during the 12-week study with prégabaline treatment were: somnolence, pyrexia, upper respiratory tract infection, increased appetite, weight gain and nasopharyngitis. The most frequently observed adverse events during the 14-day study with prégabaline treatment were: somnolence, upper respiratory tract infection and pyrexia (see sections 4.2, 5.1 and 5.2).

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 the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/.