LYRICA

Neuropathic pain

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

Epilepsy

PREGABALINE BIOGARAN is indicated in adults in association with other treatments in the treatment of partial seizures with or without secondary generalization.

Generalized Anxiety Disorder

PREGABALINE BIOGARAN is indicated in the treatment of Generalized Anxiety Disorder (TAG) in adults.

Given that pregabalin is primarily eliminated unchanged in the urine, that it undergoes negligible metabolism in humans (less than 2 % of the dose is recovered in the urine as metabolites), that it does not inhibit drug metabolism in vitro and that it is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions.

In vivo studies and population pharmacokinetic analysis

No clinically significant pharmacokinetic interactions were observed in in vivo studies between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analyses showed that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on pregabalin clearance.

Oral contraceptives, norethisterone and/or ethinylestradiol

Co-administration of pregabalin with oral contraceptives such as norethisterone and/or ethinylestradiol does not influence the steady-state pharmacokinetics of either substance.

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 taking pregabalin and opioids and/or other central nervous system (CNS) depressant medicines. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone.

Interactions and the elderly

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

PREGABALINE BIOGARAN may have a minor or moderate influence on the ability to drive vehicles and use machines. PREGABALINE BIOGARAN may induce dizziness and drowsiness 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 8900 patients exposed to pregabalin, with more than 5600 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 those receiving placebo. The most common adverse reactions resulting in discontinuation of pregabalin treatment were dizziness and somnolence.

Table 2 below lists, by type and frequency, all adverse reactions that occurred at an incidence greater than placebo and in more than one patient (very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10 000 to <1/1000), 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 included 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 PREGABALINE, withdrawal symptoms have been observed. The following symptoms have been reported: insomnia, headache, nausea, anxiety, diarrhea, 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 discontinuation of long-term treatment with PREGABALINE, data suggest that the incidence and severity of withdrawal symptoms may be dose-dependent (see sections 4.2 and 4.4).

Pediatric population

The safety profile of pregabalin observed in five pediatric studies in patients with partial epileptic seizures with or without secondary generalization (a 12-week efficacy and safety study in patients aged 4 to 16 years, n = 295; a 14-day efficacy and safety study in patients aged 1 month to less than 4 years, n = 175; a 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 patients with epilepsy. The most frequently observed adverse events during the 12-week study of 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 of pregabalin treatment were: somnolence, upper respiratory tract infection, and fever (see sections 4.2, 5.1, and 5.2).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It enables continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reaction through the national reporting system: the French National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - website: https://signalement.social-sante.gouv.fr/.