Pregabalin (Lyrica), gabapentin (Neurontin) and risk of abuse and dependence: new scheduling requirements from 1 April

As of 1 April 2019, pregabalin and gabapentin are controlled under the Misuse of Drugs Act 1971 as Class C substances and scheduled under the Misuse of Drugs Regulations 2001 as Schedule 3. Evaluate patients carefully for a history of drug abuse before prescribing pregabalin and gabapentin and observe patients for development of signs of abuse and dependence.

Advice for healthcare professionals:

  • to reflect growing concern about abuse, both pregabalin and gabapentin are now classified as Class C controlled substances (under the Misuse of Drugs Act 1971) and scheduled under the Misuse of Drugs Regulations 2001 (as amended) as Schedule 3, but are exempt from the safe custody requirements (see new legal requirements and resources for prescribers and dispensers below)
  • evaluate patients carefully for a history of drug abuse and dependence before prescribing pregabalin and gabapentin
  • observe patients on pregabalin and gabapentin for possible signs of abuse and dependence, for example, drug-seeking behaviour, dose escalation, and development of tolerance
  • ensure patients are aware of the risk of potentially fatal interactions with other medicines that cause CNS depression, particularly opioid medicines, and with alcohol
  • report suspected adverse drug reactions to pregabalin and gabapentin on a Yellow Card, including cases of abuse and dependence

Risk of abuse and dependence

The product information for gabapentin and pregabalin contain warnings about cases of abuse and dependence. Patients should be carefully evaluated for a history of drug abuse and observed for possible signs of misuse, abuse, or dependence. These include, for example, drug-seeking behaviour, dose escalation, and development of tolerance.

As for all medicines, patients should be given information on the expected benefits and potential risks of pregabalin and gabapentin, including through provision of the Patient Information Leaflet at dispensing. Prescribers should be aware of all medicines (including any over-the-counter products or illicit drugs) patients are taking to minimise or avoid drug interactions.

Cases reported of abuse and dependence in the UK

The MHRA monitors the benefits and risks of medicines in the UK and asks healthcare professionals and patients to report cases of abuse and dependence associated with medicines.

Since authorisation and up to 10 April 2019, we have received 113 reports of abuse and 98 reports of dependence with pregabalin. Since authorisation and up to 10 April 2019, we have received 11 reports of abuse and 9 reports of dependence associated with gabapentin.

Gabapentin and pregabalin can cause depression of the central nervous system, resulting in drowsiness, sedation, and potentially fatal respiratory depression, particularly if used concomitantly with opioid medicines and alcohol.

As of 1 April 2019, pregabalin and gabapentin are classified as Class C controlled substances (under the Misuse of Drugs Act 1971) and scheduled under the Misuse of Drugs Regulations 2001 (as amended) as Schedule 3 for Great Britain. For legislation changes, see S.I. 2018/1356 and S.I. 2018/1383 of The Misuse of Drugs and Misuse of Drugs (Safe Custody) (Amendment) (England and Wales and Scotland) Regulations 2018. These legal changes are mirrored in legislation for Northern Ireland in the Misuse of Drugs and Misuse of Drugs (Safe Custody) (Amendment) Regulations (Northern Ireland) 2019.

Following these changes, it is illegal for people to possess pregabalin and gabapentin without a prescription and illegal for a patient to supply or sell them to others (see NHS England patient leaflet).

Prescribers – responsibilities and resources

Prescribers need to adhere to guidance for prescribing of medicines of this Class and Schedule (see NHS England guidance document, and alert for prescribers in Wales from the Chief Pharmaceutical Officer).

Resources available for prescribers about the change (other resources may be available):

Pharmacists – responsibilities and resources

Prescriptions need to be dispensed by a pharmacist within 28 days of the prescription being written. Pregabalin and gabapentin are in the list of “exempted drugs” in the safe custody regulations for pharmacies. Pharmacies will need to denature before disposal.

Resources available for pharmacists about the change (other resources may be available):

Government review of misuse

In 2016, following concerns about misuse, illegal diversion, and dependence, the Advisory Council on the Misuse of Drugs (ACMD) recommended that both pregabalin and gabapentin, their salts and their esters are:

  • controlled under the Misuse of Drugs Act 1971 as Class C substances

  • scheduled under the Misuse of Drugs Regulations 2001 (as amended) as Schedule 3

The Home Office accepted the ACMD’s advice but as a result of the public consultation, pregabalin and gabapentin are also being inserted into Schedule 1 to the Misuse of Drugs (Safe Custody) Regulations 1973, which means that they are exempted from the safe custody requirements under the 1973 Regulations.

As for all medicines, the MHRA will continue to closely monitor the benefits and risks of pregabalin and gabapentin and take action as required.

Background

Gabapentin (Neurontin) is indicated as monotherapy or adjunctive therapy for partial seizures with and without secondary generalisation. It is also indicated for peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia (see NHS website guidance for patients)

Pregabalin (Lyrica) is indicated as adjunctive therapy for partial seizures with or without secondary generalisation. It is also indicated for peripheral and central neuropathic pain and for generalised anxiety disorder (see NHS website guidance for patients).

Call for reporting

Report suspected adverse drug reactions, including those associated with abuse or dependence, to the Yellow Card Scheme. Your report helps the MHRA to monitor the safety of medicines and take action to prevent future harm.

Article citation: Drug Safety Update volume 12, issue 9: April 2019: 4.

Published 16 April 2019