Section 4.4 - Patients treated with pregabalin should be monitored for signs and symptoms of pregabalin misuse, abuse or dependence, such as development of tolerance, dose escalation and drug-seeking behaviour.

Section 4.8 - UK removed

Section 5.1 - Pharmacotherapeutic group: Analgesics, other analgesics and antipyretics, ATC code: N02BF02

Section 4.4

Withdrawal symptoms

After discontinuation of short-term and long-term treatment with pregabalin withdrawal symptoms have been observed. The following symptoms have been reported: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, nervousness, depression, suicidal ideation, pain, convulsion, hyperhidrosis and dizziness. The occurrence of withdrawal symptoms following discontinuation of pregabalin may indicate drug dependence (see section 4.8). The patient should be informed about this at the start of the treatment. If pregabalin should be discontinued, it is recommended this should be done gradually over a minimum of 1 week independent of the indication (see section 4.2).

Section 4.8

After discontinuation of short-term and long-term treatment with pregabalin 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 start of the treatment.

Change to storage conditions

Update to storage conditions in section 6.4

Text added to section 4.4

Women of childbearing potential/Contraception

Pregabalin Zentiva use in the first‑trimester of pregnancy may cause major birth defects in the unborn child. Pregabalin should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus. Women of childbearing potential have to use effective contraception during treatment (see section 4.6).

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported rarely in association with pregabalin treatment. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, pregabalin should be withdrawn immediately and an alternative treatment considered (as appropriate).

Text added to section 4.6

Pregabalin has been shown to cross the placenta in rats (see section 5.2). Pregabalin may cross the human placenta.

Major congenital malformations

Data from a Nordic observational study of more than 2 700 pregnancies exposed to pregabalin in the first trimester showed a higher prevalence of major congenital malformations (MCM) among the paediatric population (live or stillborn) exposed to pregabalin compared to the unexposed population (5.9% vs. 4.1%).

The risk of MCM among the paediatric population exposed to pregabalin in the first trimester was slightly higher compared to unexposed population (adjusted prevalence ratio and 95% confidence interval: 1.14 (0.96-1.35)), and compared to population exposed to lamotrigine (1.29 (1.01–1.65)) or to duloxetine (1.39 (1.07–1.82)).

The analyses on specific malformations showed higher risks of malformations of the nervous system, the eye, orofacial clefts, urinary malformations and genital malformations, but numbers were small and estimates imprecise.

toxic epidermal necrolysis added under rare side effect

Change of ink composition in section 6.1