Pregabalin is an anticonvulsant and anxiolytic medication used in the treatment of epileptic seizures, neuropathic pain, restless leg syndrome, fibromyalgia, and generalized anxiety disorder. Gabapentin is an anticonvulsant medication used in the treatment of partial seizures and neuropathic pain. Both Pregabalin and gabapentin which are referred as “gabapentinoids” acts on voltage dependent calcium channels in the central nervous system. Pregabalin is marketed in both brand (Lyrica, Lyrica CR) and generic medicines. Gabapentin is marketed in different brand names (Neurontin, Gralise, Horizant) and generics.

Boxed Warnings

Pregabalin – Drug misuse

Pregabalin and Gabapentin – Drug abuse and dependence

Therapeutic and Goods Administration (TGA), Health authority of Australia released a box warning for medicines containing pregabalin and gabapentin for the risks of drug misuse, abuse, and dependence based on the continuous emerging safety data pertaining to these safety concerns.

Concomitant use of pregabalin and gabapentin with other sedating medicines, including opioids could pose serious risks, and sometimes life-threatening side effects.

Case reports (data as of 19 Jan 2021)

There are 184 case reports for pregabalin and 18 case reports for gabapentin received at Australia drug safety database (Database of Adverse Event Notifications) with safety information of suspected drug abuse, misuse, or dependence with pregabalin and gabapentin products. Total 111 cases were reported with fatal outcome and pregabalin is a suspected medicine in 110 case reports.

TGA advised that concomitant use of opioid medicines could result in severe sedation, respiratory depression, coma, and death. Patients who require concomitant treatment with CNS depressants, including opioids, should be carefully observed for signs of CNS depression, such as somnolence, sedation, and respiratory depression.

For achieving the desired therapeutic effect, limit the dosage and duration of treatment to the minimum possibility.

Following withdrawal symptoms were reported after discontinuation of both short-term and long-term treatment with gabapentinoids. If required, discontinuation should be done gradually over a period of minimum one week.

  • Insomnia, headache, nausea, anxiety, hyperhidrosis, and diarrhoea.

Drug Safety Communication:

United States Food and Drug Administration (USFDA) also released a drug safety communication with the warning of serious breathing problems associated with the use of pregabalin and gabapentin. USFDA advised to add the risk of respiratory depression to the prescribing information and asked marketing authorization holders of these medicines to conduct additional clinical studies for evaluation of abuse potential for pregabalin and gabapentin.

Important information for Patients and patient care providers:

Please inform about your current medications (including your OTC medicines), co-morbidities to your health care professional for a correct benefit-risk analysis by physician before prescribing.

To be watchful for below symptoms of respiratory problems which could be life-threatening.

  • Confusion or disorientation
  • Unusual dizziness or light-headedness
  • Extreme sleepiness or lethargy
  • Slowed, shallow, or difficult breathing
  • Unresponsiveness, which means a person does not answer or react normally or you cannot wake them up
  • Bluish-coloured or tinted skin, especially on the lips, fingers, and toes

Important information for healthcare professionals:

Perform a proper benefit-risk analysis before prescribing/dispensing gabapentinoids medicines based on the individual patient’s clinical condition (current medications, co-morbidities, age, history and signs of substance abuse and other risk factors etc.,)

Consider referring to reference safety information documents like prescribing information (USPI, SmPC) or package leaflets while doing benefit-risk analysis. If benefit-risk assessment has shown positive and medication is found to be a necessary/required treatment option for particular patient, then inform about the medicines expected safety concerns and to be watchful for any alarming symptoms (specified above) associated with potential central nervous system (CNS) and respiratory problems.

Educate patients or patient care givers with cautionary information about expected side effects of gabapentinoids medicines like dizziness, somnolence, and their potential for impaired ability to operate a car or complex machinery.

Encourage patients/patient care providers to read patient information leaflets (medication usage guidelines) before initiating/continuing/discontinuation of the treatment.

Inform patients/patient care providers to report any suspected adverse drug effects to a healthcare professional or to the nation’s spontaneous adverse drug reaction reporting system.

Voluntary ADR reporting

Every medicinal product has both benefits and risks. Medicines are authorized to market based on the favorable benefit-risk profile anticipated at the time of regulatory approval/entry into market. However, the safety profile of medicine would continuously updates owing to safety data from the postmarketing experience from public. If the rate of reporting of suspected adverse drug reactions (ADR) from public is line with the actual occurrence of ADRs, the time lapse for taking regulatory action can be reduced and thereby improving patient safety.

All health care professionals and consumers of pharmaceutical medicinal products are encouraged to be aware of this fact and observe/monitor for any possible adverse events, reactions, medication errors, or quality complaints of medicinal products and report the same to your respective national health authority.

This would accumulate safety evidence for medicinal products which in turn help health authorities to take regulatory actions at the earliest possibility for a better patient safety and overall public health.

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