Consumers and health professionals are advised that Boxed Warnings are being added to the Product Information (PI) and Consumer Medicine Information (CMI) for medicines containing pregabalin and gabapentin.
The enhanced warnings advise that pregabalin poses a risk of misuse, while both pregabalin and gabapentin pose risks of abuse and dependence. These risks can lead to serious side effects, some of which can be life-threatening. The risks are higher if medicines that can make you sleepy (sedating medicines), including opioids, are used at the same time.
The Boxed Warnings added to pregabalin and gabapentin products advise prescribers to assess a patient's risk of misuse (for pregabalin), and abuse or dependence (for pregabalin and gabapentin) before prescribing these medicines, and to monitor them regularly during treatment.
The decision to impose the Boxed Warnings has been taken after Therapeutic Goods Administration (TGA) investigation of continuing reports of misuse associated with pregabalin, and abuse and dependence associated with both pregabalin and gabapentin in Australia.
Pregabalin and gabapentin are used to treat neuropathic pain (pain caused by an abnormality of, or damage to, the nerves) and epilepsy. They may be used alone or in combination with other medicines. Pregabalin is marketed in Australia under the brand name Lyrica and various generic brands. Gabapentin is marketed under the brand name Neurontin, as well as various generic brands.
As with any medicine, health professionals and patients must assess the risk and benefits of using pregabalin and gabapentin based on the individual clinical situation. If, after consideration of the potential side effects associated with pregabalin and gabapentin, the decision is made to use these medicines, they should be used for as short a period as possible, at the lowest effective dose.
A PI is a document that has been written by the pharmaceutical company responsible for the medicine (known as the 'sponsor') and has been approved by the Therapeutic Goods Administration (TGA). It provides objective information about the quality, safety and effectiveness of the medicine, and is intended to assist doctors, pharmacists and other health professionals in prescribing and dispensing the medicine. Similarly, a CMI contains information on the safe and effective use of a medicine for consumers. PI and CMI for all prescription medicines included on the Australian Register of Therapeutic Goods are freely available on the TGA website.
Boxed Warnings are special warnings of potential serious side effects that the TGA sometimes requires sponsors to put prominently at the beginning of PI and CMI to help manage those risks.
TGA investigation
The TGA investigated continuing reports of misuse associated with pregabalin, and abuse and dependence associated with both pregabalin and gabapentin in Australia and referred the issue to the independent Advisory Committee for Medicines for expert advice.
The National Coronial Information System shows that deaths related to pregabalin rose from 16 in 2013 to 121 in 2016. A large majority of these deaths were unintentional. Additionally, a Medical Journal of Australia study of ambulance data in 2018 found a tenfold increase in the rate of pregabalin-related ambulance attendances since 2012, with patients frequently misusing pregabalin with other sedating medicines.
On 19 January 2021, the TGA's Database of Adverse Event Notifications included 184 and 18 reports of suspected abuse, misuse or dependence with pregabalin and gabapentin products respectively. There were 111 fatal cases and 110 of these identified pregabalin as a suspected medicine.
Information for consumers
If you or someone you provide care for takes pregabalin or gabapentin, please be aware that these medicines pose risks of abuse and dependence. These risks can lead to serious side effects, some of which can be life-threatening, and may be greater if these medicines are used with other sedating medicines and/or alcohol.
Tell your doctor if you have a history of drug misuse, abuse or dependence, as it will help them to assess whether these medicines are right for you.
It is important to follow your treating doctor's instructions, especially those relating to dose, and do not give your medicine to anyone else. Do not stop taking your medicine suddenly or without first consulting with your doctor.
If you have any questions or concerns about this issue, speak to the treating doctor. They are best placed to provide clinical advice based on individual circumstances.
Information for health professionals
Check for history of substance use disorder and signs of abuse or dependence before prescribing pregabalin or gabapentin.
Monitor patients regularly during treatment, particularly among patients with current or past use of opioids and/or benzodiazepines. In particular, monitor for increases in dosing or drug-seeking behaviours.
Caution is advised when prescribing pregabalin or gabapentin concomitantly with opioids due to risk of central nervous system (CNS) depression. Concomitant use of opioids may 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. Limit dosages and durations to the minimum required to achieve the desired therapeutic effect.
Withdrawal symptoms after discontinuation of both short-term and long-term treatment have been observed in some patients. The following events have been reported: insomnia, headache, nausea, anxiety, hyperhidrosis and diarrhoea. Discontinuation should be done gradually over a minimum of one week.
For further information about pregabalin and gabapentin, consult the relevant PI. The PI documents for these products are available online from the TGA's PI repository.
Reporting problems
Consumers and health professionals are encouraged to report problems with medicines or vaccines. Your report will contribute to the TGA's monitoring of these products.
The TGA cannot give advice about an individual's medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a medicine or vaccine.