The Food and Drug Administration (FDA) is requiring the inclusion of a new warning on the labeling of all gabapentinoids, including gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica and Lyrica CR). Gabapentin and pregabalin are used to treat a variety of neurologic conditions including seizures, nerve pain, and restless legs syndrome.

The new warning concerns the risk of potentially fatal respiratory depression with this class of drugs. The risk of respiratory depression is higher when the patient already has respiratory risk factors, such as use of opioids or other central nervous system (CNS) depressants; respiratory conditions that decrease lung function, such as chronic obstructive pulmonary disease; and being an older adult. The gabapentinoids are frequently prescribed as combination therapy with other CNS depressants (opioids, anxiolytics, antidepressants, and antihistamines). They appear to pose less risk when used as monotherapy.

The revised labeling was prompted by the FDA's evaluation of case reports submitted to the FDA Adverse Event Reporting System (FAERS) database or published in medical journals. A FAERS database search from January 1, 2012, to October 26, 2017, identified 49 cases of respiratory depression (15 with gabapentin, 34 with pregabalin). Nearly all patients had a respiratory risk factor. Twelve of the patients died from respiratory depression. The FDA's review of small clinical trials using healthy volunteers found rising end-tidal carbon dioxide levels and an increased number of apneic episodes during sleep in those treated with gabapentinoids. Other studies found an increased risk of postoperative respiratory depression.

NPs who prescribe gabapentin and pregabalin should consider the additive effects of gabapentinoids and other CNS depressants on respiratory depression and follow the FDA's guidance when coadministration is necessary: begin the gabapentinoid at the lowest dose; adjust the gabapentinoid dose if the patient has renal impairment or receives hemodialysis; monitor for symptoms of respiratory depression and sedation; and manage any symptoms of respiratory depression with close observation, supportive measures, and stopping or reducing the dose of the gabapentinoid or other CNS depressants.

Nurses should teach patients prescribed gabapentin or pregabalin about the risk and signs of respiratory depression (confusion or disorientation; dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish tinted skin, especially on the lips, fingers, and toes). These signs or symptoms require immediate medical attention. Nurses should also warn that CNS depression from gabapentinoids can impair a patient's ability to drive safely or operate machinery. Nurses should carefully assess for use of other CNS depressants, including alcohol and nonprescription drugs. If patients develop respiratory depression during gabapentinoid use, nurses and health care providers should contact the FDA MedWatch program at http://www.accessdata.fda.gov/scripts/medwatch.

To read the FDA Drug Safety Communication regarding gabapentinoids, see http://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-br.