| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 0.5% (1 of 199) of reports.DangerH318 (72.9%): Causes serious eye damage [Danger Serious eye damage/eye irritation]P203, P260, P264+P265, P280, P305+P354+P338, P317, P318, P319, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 199 reports by companies from 22 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
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| Regulatorische Informationen | DEA schedule V controlled substance |
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| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl pregabalin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule V includes pregabalin, DEA Code #2782Drug class: Depressants. |
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| Hazard Classes and Categories | Eye Dam. 1 (72.9%) |
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| Lagerbedingungen | Store at 25 °C (77 °F)excursions permitted to 15 to 30 °C (59 to 86 °F). |
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| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
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| Wechselwirkungen | Patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines should be informed that they may experience additive CNS side effects, such as somnolence.The pharmacokinetic interactions of pregabalin and gabapentin were investigated in 12 healthy subjects following concomitant single-dose administration of 100-mg pregabalin and 300-mg gabapentin and in 18 healthy subjects following concomitant multiple-dose administration... Gabapentin pharmacokinetics following single- and multiple-dose administration were unaltered by pregabalin coadministration. The extent of pregabalin absorption was unaffected by gabapentin coadministration, although there was a small reduction in rate of absorption.Pregabalin coadministration had no effect on the steady-state pharmacokinetics of norethindrone and ethinyl estradiol (1 mg/35 mug, respectively) in healthy subjects.Multiple-dose administration of pregabalin in healthy subjects had no effect on the rate and extent of lorazepam single-dose pharmacokinetics and single-dose administration of lorazepam had no effect on the steady-state pharmacokinetics of pregabalin.For more Interactions (Complete) data for PREGABALIN (8 total), please visit the HSDB record page. |
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| Hepatotoxicity | Limited data is available on the hepatotoxicity of pregabalin. In prelicensure clinical trials in diabetic neuropathy and epilepsy, therapy with pregabalin was not associated with an increased frequency of serum aminotransferase elevations or liver toxicity. Since its approval and more wide scale use, however, pregabalin has been linked to rare instances of clinically apparent liver injury. Most cases were mild and frequently without jaundice. The latency to onset of injury was short, symptoms of liver injury arising within 3 to 14 days. Both cholestatic and hepatocellular patterns of injury have been reported. Signs of hypersensitivity (fever, rash, eosinophilia) and autoimmunity were not present. Some cases have been severe and associated with marked jaundice and prolongation of the prothrombin time, but all cases ultimately resolved after the medication was stopped without evidence of residual injury. |
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| Unerwünschte Wirkungen | Most reported adverse effects caused by pregabalin were mild to moderate intensity, dose-dependent, and occurred within the first 2 weeks of initiating treatment. |
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| Toxizitätsübersicht | Signs and Symptoms of Overdose |
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| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ In a double-blind, placebo-controlled clinical trial to assess the effect of pregabalin on sperm motility, 30 healthy male subjects were exposed to pregabalin at a dose of 600 mg/day. After 3 months of treatment (one complete sperm cycle), the difference between placebo- and pregabalin-treated subjects in mean percent sperm with normal motility was <4% and neither group had a mean change from baseline of more than 2%. Effects on other male reproductive parameters in humans have not been adequately studied./CASE REPORTS/ /Investigators/ present a patient who, after unintended rapid up-titration of pregabalin, experienced psychotic symptoms associated with rhythmic EEG-changes resolving completely after discontinuation of pregabalin and benzodiazepine administration./CASE REPORTS/ /Investigators/ report two patients with refractory epilepsy who developed unilateral painful gynecomastia and lower extremity pain (one of them localized and the other one diffuse), shortly after receiving Pregabalin (PGB). Neither of them had previous endocrinologic problems or complaints about pain on their medical history. PGB was stopped in one patient and reduced in the other one, with complete disparition of the symptoms in the following weeks in both patients./CASE REPORTS/ /Investigators/ present the cases of 5 men who reported mild to moderate erectile dysfunction or impotence for the first time when treated with the new antiepileptic drug pregabalin as add-on therapy.For more Human Toxicity Excerpts (Complete) data for PREGABALIN (7 total), please visit the HSDB record page. |
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| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)PregabalinvLess-DILI-concernNo matchDOI:10.1016/j.drudis.2016.02.015 |
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| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Skin lesions ranging from erythema to necrosis were seen in repeated-dose toxicology studies in both rats and monkeys. The etiology of these skin lesions is unknown. At the maximum recommended human dose, there is a 2-fold safety margin for the dermatological lesions. The more severe dermatopathies involving necrosis were associated with pregabalin exposures of approximately 3 to 8 times those achieved in humans given the MRD./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Ocular lesions (characterized by retinal atrophy [including loss of photoreceptor cells] and/or corneal inflammation/mineralization) were observed in two lifetime carcinogenicity studies in Wistar rats. These findings were observed at plasma pregabalin exposures (AUC) >/=2 times those achieved in humans given the maximum recommended dose... A no-effect dose for ocular lesions was not established. Similar lesions were not observed in lifetime carcinogenicity studies in two strains of mice or in monkeys treated for 1 year./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A dose-dependent increase in the incidence of malignant vascular tumors (hemangiosarcomas) was observed in two strains of mice (B6C3F1 and CD-1) given pregabalin (200, 1000, or 5000 mg/kg) in the diet for two years. Plasma pregabalin exposure (AUC) in mice receiving the lowest dose that increased hemangiosarcomas was approximately equal to the human exposure at the maximum recommended dose ... A no-effect dose for induction of hemangiosarcomas in mice was not established./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In fertility studies in which male rats were orally administered pregabalin (50 to 2500 mg/kg) prior to and during mating with untreated females, a number of adverse reproductive and developmental effects were observed. These included decreased sperm counts and sperm motility, increased sperm abnormalities, reduced fertility, increased preimplantation embryo loss, decreased litter size, decreased fetal body weights, and an increased incidence of fetal abnormalities. Effects on sperm and fertility parameters were reversible in studies of this duration (3-4 months). The no-effect dose for male reproductive toxicity in these studies was 100 mg/kg.For more Non-Human Toxicity Excerpts (Complete) data for PREGABALIN (11 total), please visit the HSDB record page. |
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| Populations at Special Risk | Advise diabetic patients to watch for skin damage while receiving pregabalin therapy, since increased risk of skin ulcerations associated with pregabalin therapy has been observed in animal studies.Because there are limited data regarding use of pregabalin in patients with New York Heart Association (NYHA) class III or IV congestive heart failure, the drug should be used with caution in these patients. |
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| Environmental Water Concentrations | While data specific to pregabalin were not located(SRC, 2007), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). |
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| Antidote and Emergency Treatment | There is no known antidote for pregabalin. Treatment is generally symptomatic and supportive. ... To enhance elimination- Hemodialysis indicated by the patients clinical statepatients with significant renal impairment may increase clearance of pregabalin approximately 50% in 4 hours. Monitoring of vital signs and observation of clinical status of the patient. Supportive care- Contacting a certified poison control center for up-to-date information on management of overdose with pregabalin.Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat stupor and coma if they occur. Protect the patient from self-injury caused by ataxia. Treat agitation and delirium if they occur. Monitor asymptomatic patients for a minimum of 4-6 hours. Admit symptomatic patients for at least 24 hours after lamotrigine, felbamate, topiramate, or zonisamide ingestions. ... Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. ... /Anticonvulsants, Newer/ |
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| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
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