The US Food and Drug Administration (FDA) is warning that serious breathing difficulties may occur in patients using gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) who have respiratory risk factors. These include the use of opioid pain medicines and other drugs that depress the central nervous system (CNS), and conditions such as chronic obstructive pulmonary disease (COPD) that reduce lung function. The elderly are also at higher risk.
FDA evaluation shows that the use of these medicines, often referred to as gabapentinoids, has been growing for prescribed medical use, as well as misuse and abuse. Gabapentinoids are often being combined with CNS depressants, which increases the risk of respiratory depression. CNS depressants include opioids, anti-anxiety medicines, antidepressants, and antihistamines. There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone.
FDA is requiring new warnings about the risk of respiratory depression to be added to the prescribing information of the gabapentinoids. FDA has also required the drug manufacturers to conduct clinical trials to further evaluate their abuse potential, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression. Special attention will be paid to the respiratory depressant effects during this abuse potential evaluation.
Patients and caregivers should seek medical attention immediately if they or someone they are caring for experience symptoms of respiratory problems, because these can be life-threatening. Symptoms to watch for include: confusion or disorientation, unusual dizziness or lightheadedness, extreme sleepiness or lethargy, slowed, shallow, or difficult breathing, unresponsiveness, bluish-colored or tinted skin, especially on the lips, fingers, and toes. Always inform their health care professional about all the drugs they are taking, including prescription and over-the-counter (OTC) medicines and other substances such as alcohol.
Health care professionals should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when co-prescribing gabapentinoids with an opioid or other CNS depressant such as a benzodiazepine. Patients with underlying respiratory disease and elderly patients are also at increased risk and should be managed similarly.
FDA recognizes that incorporating one or more medications with non-drug therapies is the prevailing approach for optimizing analgesia. However, pairing an opioid with any CNS depressant will increase the risk of respiratory depression. Shifting treatment from one CNS depressant to another may pose similar risks. Be aware of the potential additive effects of all these CNS depressants and plan accordingly, by starting with low doses, titrating carefully, and informing patients of the potential for CNS and respiratory depression and their symptoms. The gabapentinoid prescribing information already includes guidance for health care professionals to caution patients about dizziness, somnolence, and the potential for impaired ability to operate a car or complex machinery.
FDA reviewed several sources of data, including case reports submitted to FDA or published in the medical literature, observational studies, clinical trials, and animal studies. Reports submitted to FDA and data from the medical literature show that serious breathing difficulties can occur when gabapentinoids are taken by patients with pre-existing respiratory risk factors. Among 49 case reports submitted to FDA over the 5-year period from 2012 to 2017, 12 people died from respiratory depression with gabapentinoids, all of whom had at least one risk factor. This number includes only reports submitted to FDA, so there may be additional cases about which we are unaware. FDA also reviewed the results of two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals. One trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function. The other trial showed gabapentin alone increased pauses in breathing during sleep. The three observational studies at one academic medical center showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after different kinds of surgeries. FDA also reviewed several animal studies that showed pregabalin alone and pregabalin plus opioids can depress respiratory function.
Please refer to the following website in FDA for details:
http://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin
In Hong Kong, there are 25 registered pharmaceutical products containing gabapentin, and 49 products containing pregabalin. All products are prescription-only medicines. So far, the Department of Health (DH) has received adverse drug reaction related to gabapentin (3 cases) and pregabalin (10 cases), but these cases are not related to respiratory depression.
Related news on risk of severe respiratory depression of gabapentin and concomitant use of gabapentin and opioids was previously issued by the United Kingdom Medicines and Healthcare products Regulatory Agency, and was posted on the Drug Office website on 27 Oct 2017. Letters to inform local healthcare professionals were issued by DH on the same day. In Dec 2017, the Registration Committee of the Pharmacy and Poisons Board discussed the matter, and decided that relevant safety information should be included in gabapentin-containing products.
Also, related news on increased risk of opioid overdose and serious side effects (including respiratory depression) when taking gabapentin or pregabalin with an opioid was previously issued by Health Canada, and was posted on the Drug Office website on 18 Sep 2019. Letters to inform local healthcare professionals were issued by DH on the same day.
In light of the above FDA’s announcement on the addition of relevant warnings of respiratory depression to the prescribing information of pregabalin and gabapentin, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/Friday, Dec 20, 2019
Issued at HKT 17:00
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