LYRICA

Neuropathic pain

PREGABALINE TEVA SANTE is indicated in the treatment of peripheral and central neuropathic pain in adults.

Epilepsy

PREGABALINE TEVA SANTE is indicated in adults in association in the treatment of partial epileptic seizures with or without secondary generalization.

Generalized anxiety disorder

PREGABALINE TEVA SANTE is indicated in the treatment of Generalized Anxiety Disorder (TAG) 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

Consequently, 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 pharmacokinetic parameters at steady state of either of these substances.

Medicines affecting the central nervous system

Pregabalin may potentiate the effects of ethanol and lorazepam. Post-marketing reports of respiratory failure, coma and death have been reported 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.

PREGABALINE TEVA SANTE may have a minor or moderate influence on the ability to drive vehicles and use machines. PREGABALINE TEVA SANTE may induce dizziness and somnolence and may therefore have an influence on the ability to drive vehicles 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 eventual impact of this medicine on their ability to perform these activities.

The clinical evaluation program of pregabalin was conducted in more than 8 900 patients exposed to pregabalin, more than 5 600 of whom were so in the context of double-blind placebo-controlled trials. The most frequently reported adverse effects were dizziness and somnolence. These adverse effects were generally of mild to moderate intensity. In all controlled studies, treatment interruptions related to adverse effects were 12 % for patients receiving pregabalin and 5 % for those receiving placebo. The most frequent adverse effects leading to discontinuation of pregabalin treatment were dizziness and somnolence.

Table 2 below lists, by type and frequency, all adverse effects occurring at an incidence higher than that of placebo and in more than one patient (very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1 000, < 1/100), rare (≥ 1/10 000, < 1/1 000), very rare (< 1/10 000), undetermined frequency (cannot be estimated on the basis of available data). Within each frequency group, adverse effects are presented in descending order of severity.

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

An increase in the incidence of adverse effects in general, adverse effects affecting the central nervous system and, more particularly somnolence, has been noted in the treatment of central neuropathic pain due to a spinal cord lesion (see section 4.4).

Additional adverse effects reported after marketing are listed below in italics.

Table 2. Adverse effects of pregabalin

* increase in alanine aminotransferase (ALAT), increase in aspartate aminotransferase (ASAT)

After discontinuation of short-term or long-term treatment with pregabalin, withdrawal symptoms have been observed. The following symptoms have been reported: insomnia, headache, nausea, anxiety, diarrhea, flu-like syndrome, convulsions, nervousness, depression, suicidal ideation, pain, hyperhidrosis and dizziness. These symptoms may indicate drug dependence. The patient should be informed of this at the start of treatment.

Regarding the interruption of prolonged treatment with pregabalin, 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 pregabalin observed in five pediatric studies in patients presenting with partial epileptic seizures with or without secondary generalization (12-week efficacy and safety study in patients aged 4 to 16 years, n = 295; and 14-day efficacy and safety study in patients aged 1 month to less than 4 years, n = 175; pharmacokinetic and tolerability study, n = 65; and two 1-year open-label safety follow-up studies, 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 pregabalin treatment were: somnolence, fever, upper respiratory tract infection, increased appetite, weight gain and nasopharyngitis. The most frequently observed adverse events during the 14-day study with pregabalin treatment were: somnolence, upper respiratory tract infection and fever (see sections 4.2, 5.1 and 5.2).

Reporting of suspected adverse effects

Reporting suspected adverse effects after medicinal product authorization is important. It allows for continuous monitoring of the benefit/risk ratio of the medicine. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/.