pregabalin and Abnormalities--Drug-Induced

In the recent past, many third-generation antiepileptic drugs (AEDs) including Pregabalin (PGB) were launched for the treatment of diverse forms of epilepsy with better efficacy and safety profile than first-and-second-generation AEDs, but their teratogenic safety has not been established so far.. The present study has been undertaken to evaluate the reproductive and teratogenic potential (external and skeletal) of a novel and third generation AED, PGB in pregnant albino rats.. In this study, pregnant subjects were exposed to clinically relevant doses (41, 82 and 123 mg) of PGB from gestation days 6-20, and sacrificed on GD-21, and their fetuses were collected and examined to identify the birth defects and skeletal anomalies.. This study revealed that prenatal exposure to PGB induced dose-dependent substantial fetal resorptions, litter size, fetal length and weight; and variety of minor external and internal malformations in fetuses predominant with limbs, tail, eyes, abdomen including hemorrhages, and poor skeletal ossification.. Thus, PGB was found to be teratogenic in rats at equivalent therapeutic doses, hence precaution should be taken before prescribing PGB to pregnant women with epilepsy.

Topics: Abnormalities, Drug-Induced; Animals; Anticonvulsants; Dose-Response Relationship, Drug; Female; Litter Size; Male; Pregabalin; Pregnancy; Rats; Teratogens

To assess whether first-trimester exposure to pregabalin is associated with an increased risk of major congenital malformations, as recently suggested in a pregnancy registry study.. We performed a cohort study nested in the US Medicaid Analytic eXtract (MAX). The study population included 1,323,432 pregnancies resulting in a live-born infant between 2000 and 2010. We examined the risk of major congenital malformations among infants born to women exposed to pregabalin during the first trimester compared with women unexposed to anticonvulsants. We used propensity score fine stratification to control for >50 potential confounders, and we estimated relative risks (RRs) and 95% confidence intervals (CIs) in generalized linear models. The analyses were replicated in the Truven Health MarketScan Commercial Database (MarketScan). Pooled estimates based on the adjusted RR produced in MAX, MarketScan, and the previous registry study were calculated.. Of 477 infants exposed to pregabalin during the first trimester in MAX, 28 (5.9%) had malformations compared to 3.3% in nonexposed infants. The crude RR of major congenital malformations for pregabalin was 1.80 (95% CI 1.26-2.58). After propensity score adjustment, the RR moved to 1.16 (95% CI 0.81-1.67). Restriction to pregabalin monotherapy and sensitivity analyses produced similar results. The adjusted RR for major congenital malformations for the 174 infants exposed in MarketScan was 1.03 (95% CI 0.56-1.90). The pooled RR was 1.33 (95% CI 0.83-2.15) for pregabalin any use and 1.02 (95% CI 0.69-1.51) for pregabalin monotherapy.. Findings did not confirm the suggested teratogenic effects of pregabalin, although they cannot rule out the possibility of a small effect.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Anticonvulsants; Child; Cohort Studies; Female; Humans; Medicaid; Middle Aged; Pregabalin; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Prevalence; Propensity Score; Registries; Risk; Sensitivity and Specificity; United States; Young Adult

Topics: Abnormalities, Drug-Induced; Calcium Channel Blockers; Female; Humans; Mental Disorders; Pain; Pregabalin; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth

To investigate pregnancy outcomes following maternal use of pregabalin.. This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs). Teratology Information Services systematically collected data between 2004 and 2013.. Data were collected from 164 exposed pregnancies and 656 controls. A significantly higher major birth defect rate in the pregabalin group was observed after exclusion of chromosomal aberration syndromes, and when cases with exposure during first trimester of pregnancy were analyzed separately (7/116 [6.0%] vs 12/580 [2.1%]; odds ratio 3.0, 95% confidence interval 1.2-7.9, p = 0.03). The rate of live births was lower in the pregabalin group (71.9% vs 85.2%, p < 0.001), primarily due to a higher rate of both elective (9.8% vs 5.0%, p = 0.02) and medically indicated (5.5% vs 1.8%, p = 0.008) pregnancy terminations. In the Cox proportional cause specific hazards model, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion.. This study demonstrated a signal for increased risk of major birth defects after first trimester exposure to pregabalin. However, several limitations such as the small sample size, differences across groups in maternal conditions, and concomitant medication exposure exclude definitive conclusions, so these results call for confirmation through independent studies.

Topics: Abnormalities, Drug-Induced; Adult; Central Nervous System Agents; Europe; Female; Humans; Incidence; Pharmacovigilance; Pregabalin; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Proportional Hazards Models; Prospective Studies; Risk

The study examines the potential genotoxicity of three antiepileptic drugs (phenytoin sodium, pregabalin, gabapentin) using the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster. Trans-heterozygous (two genetic markers mwh and flr) third-instar larvae of D. melanogaster were treated with different concentrations of the test compounds. A positive correlation was observed between total mutations and the number of wings with morphologically detectable mutations. The observed mutations were classified according to size and type of mutation per wing. Phenytoin clearly increased the frequency of total spots at all concentrations above 1.25 microg/ml. Gabapentin also increased the frequency of total spots at concentrations of 40 and 80 microg/ml. This study shows that phenytoin and gabapentin have genotoxic effects according to the SMART test; however, pregabalin displays lower genotoxicity in the SMAR assay when compared with the other two antiepileptics. The results also show that all AED concentrations lower the survival rate of the flies.

Topics: Abnormalities, Drug-Induced; Amines; Animals; Anticonvulsants; Cyclohexanecarboxylic Acids; Drosophila melanogaster; Female; Gabapentin; gamma-Aminobutyric Acid; Male; Mutagenicity Tests; Mutagens; Phenytoin; Pregabalin; Recombination, Genetic; Survival; Wings, Animal