Effect of concomitant use of montelukast and efavirenz on neuropsychiatric adverse events

To report the case of an HIV patient who developed neuropsychiatric disturbances when montelukast was added to her therapy containing efavirenz.

A 41-year-old woman with HIV infection had been on treatment with efavirenz, emtricitabine, and tenofovir disoproxil fumarate since 2007 with good tolerance. In November 2011, montelukast was started for asthma and shortly thereafter neuropsychiatric symptoms appeared, consisting of disturbed sleep, vivid dreams, irritability, confusion, and concentration difficulties. In January 2012, 2 months after the introduction of montelukast, she continued to report unbearable symptoms without any improvement; so, montelukast was withdrawn and the psychiatric symptoms completely disappeared.

The combination of efavirenz and montelukast has not previously been associated with any pharmacokinetic interactions or worsening of neuropsychiatric symptoms. This case report indicates the possibility of adverse effects developing when the 2 drugs are used together. These symptoms might either be related to a drug-drug interaction or increased by the similar side effect profiles of the 2 drugs. The higher score on the Karch-Lasagna scale suggests that an adverse effect is the more likely explanation. We cannot, however, rule out a drug interaction, given that efavirenz inhibits the CYP 2C9, 2C19, and 3A4 isoenzymes and CYP 3A4, 2C9, and 2C8 are involved in the metabolism of montelukast.

Considering that efavirenz is frequently used in antiretroviral therapy and that neuropsychiatric symptoms can limit its use, clinicians should consider the possibility of worsening of these symptoms, such as mood disorders and abnormal dreams, when montelukast is introduced.