NUPENTIN

Epilepsy

GABAPENTINE CRISTERS PHARMA is indicated in association in the treatment of partial epilepsies with or without secondary generalization in adults and children from 6 years (see section 5.1).

GABAPENTINE CRISTERS PHARMA is indicated as monotherapy in the treatment of partial epilepsies with or without secondary generalization in adults and adolescents from 12 years.

Treatment of Peripheral Neuropathic Pain

GABAPENTINE CRISTERS PHARMA is indicated in the treatment of peripheral neuropathic pain such as diabetic neuropathy and post-herpetic neuralgia in adults.

Cases of respiratory depression, sedation and death associated with the concomitant use of gabapentine and CNS depressants, including opioids, have been reported spontaneously and also exist in the literature. In some of these cases, authors considered the combination of gabapentine with opioids to be particularly concerning in frail patients, in the elderly, in patients with severe underlying respiratory disease, in polymedicated patients and in those with substance use disorders .

In a study conducted in healthy volunteers (N = 12), when a 60 mg extended-release morphine capsule was administered 2 hours before a 600 mg gabapentine capsule, the mean AUC of gabapentine was increased by 44 % compared to gabapentine administered without morphine.

Consequently, it is necessary to closely monitor patients requiring concomitant opioid treatment for signs of CNS depression, such as drowsiness, sedation and respiratory depression, and the dose of gabapentine or opioids should be reduced accordingly.

No interaction has been observed between gabapentine and phenobarbital, phenytoin, valproic acid or carbamazepine.

The pharmacokinetic parameters of gabapentine at steady state are similar in healthy subjects and in epileptic patients receiving these anti-epileptic agents.

Concomitant administration of gabapentine and oral contraceptives containing norethindrone and/or ethinylestradiol does not modify the steady-state pharmacokinetic parameters of each of these products.

Concomitant administration of gabapentine and antacids containing aluminium and magnesium may reduce the bioavailability of gabapentine by up to 24 %. It is recommended to take gabapentine at least two hours after taking an antacid.

The renal excretion of gabapentine is not modified by probenecid.

The slight decrease in the renal excretion of gabapentine observed during concomitant administration of cimetidine should not have a clinical impact.

Pregnancy

Risk related to epilepsy and anti-epileptic drugs (AEDs) in general

Prudent advice regarding the risk to the fetus related to both seizures and anti-epileptic treatment must be given to women of childbearing age, particularly those planning a pregnancy or who are pregnant. The necessity of anti-epileptic treatment must be reassessed when a woman is planning a pregnancy. In women treated for epilepsy, abrupt discontinuation of anti-epileptic treatment must be avoided as it can lead to a recurrence of seizures, which could have serious consequences for both the mother and the child. The implementation of monotherapy should be preferred whenever possible, as treatment with several AEDs could be associated with an increased risk of congenital malformations compared to monotherapy, depending on the anti-epileptic used.

Risk related to gabapentin

Gabapentin crosses the placental barrier.

Data from an observational study conducted in the Nordic countries involving more than 1 700 pregnancies exposed to gabapentin during the first trimester revealed no increased risk of major congenital malformations in the pediatric population exposed to gabapentin compared to the unexposed pediatric population and the pediatric population exposed to pregabalin, to lamotrigine associated with pregabalin, or to lamotrigine. Similarly, no increased risk of neurodevelopmental disorders was observed in the pediatric population exposed to gabapentin during pregnancy.

In newborns of women exposed to gabapentin, there was limited data of an increased risk of low birth weight and preterm birth but not of stillbirth, small size for gestational age, low Agpar score at 5 minutes or microcephaly.

Studies conducted in animals have shown reproductive toxicity (see section 5.3).

Gabapentin can be taken during the first trimester of pregnancy in case of clinical necessity.

Cases of neonatal withdrawal syndrome have been reported in neonates exposed in utero to gabapentin. Concomitant exposure to gabapentin and opiates during pregnancy may increase the risk of neonatal withdrawal syndrome. Neonates should be subject to close monitoring.

Breastfeeding

Gabapentin passes into breast milk. Given that the effect in the breastfed infant is unknown, gabapentin should be administered with caution in breastfeeding mothers. Gabapentin should be used in breastfeeding mothers only if the benefits clearly outweigh the risks.

Fertility

There is no effect on fertility in studies conducted in animals (see section 5.3).

Gabapentin may have a minor or moderate influence on the ability to drive vehicles and use machines. Gabapentin acts on the central nervous system and can cause drowsiness, dizziness or other related symptoms. Even if they were only of mild or moderate intensity, these side effects could potentially be dangerous in patients who drive or use machines. This is notably the case at the start of treatment and after each dose increase.

The adverse effects observed during clinical studies conducted in epilepsy (in combination and in monotherapy) and in neuropathic pain have been grouped into a single list appearing below, by class and by frequency: 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). When an adverse effect was observed at different frequencies in clinical studies, the highest frequency was attributed to it.

The adverse effects reported after marketing (in italics in the list below) are mentioned with an undetermined frequency (cannot be estimated on the basis of available data).

Within each frequency group, the adverse effects are presented in descending order of severity.

* After stopping or reducing the dose of a short or long-term treatment with gabapentine, withdrawal symptoms have been observed. Withdrawal symptoms may appear shortly after stopping or reducing the dose of the treatment, generally within 48 hours (see section 4.4). Cases of acute pancreatitis have been reported during gabapentine treatments. Causality with gabapentine is not elucidated (see section 4.4).

In patients undergoing hemodialysis due to end-stage renal failure, cases of myopathy with elevation of creatine kinase have been reported.

Respiratory infections, middle ear infections, convulsions and bronchitis have only been reported in clinical studies conducted in children. In clinical studies conducted in children, aggressive behaviour and hyperkinesia have also been frequently reported.

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 medicinal product. 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/ .