Bedaquiline (Sirturo), a diarylquinoline antimycobacterial, has been approved through the accelerated approval program of the Food and Drug Administration to treat multidrug-resistant tuberculosis. The drug, which must be administered as part of combination therapy for multidrug-resistant tuberculosis, inhibits the enzyme (mycobacterial ATP synthase) that's needed to generate energy in Mycobacterium tuberculosis. Approval for use is based on two phase 2 clinical trials (one of which was still under way at time of publication). In these studies the sputum cultures of patients treated with bedaquiline were negative for growth of M. tuberculosis sooner than sputum cultures of patients treated without bedaquiline.

Bedaquiline is reserved for use when other antitubercular therapy cannot be used in treating multidrug-resistant pulmonary tuberculosis. This limitation is the result of two serious complications noted in boxed warnings on the drug's label. The first is that, when compared with placebo in clinical trials, bedaquiline was associated with an elevated risk of death; the second is that it can prolong the QT interval, causing serious cardiac ventricular arrhythmias. Bedaquiline shouldn't be used to treat latent tuberculosis or tuberculosis outside of the lungs, nor should it be used if the mycobacteria are sensitive to other drug therapy.

The most common adverse effects are nausea, arthralgia, and headache; hemoptysis and chest pain are also fairly common. Adverse hepatic effects are possible.

Because bedaquiline is to be administered orally through direct observational therapy (to prevent drug resistance) three times per week for 24 weeks, nurses should make the necessary arrangements for the patient to receive the drug.

Nurses should take a complete drug history when patients are prescribed bedaquiline because drug interactions are possible. Bedaquiline is highly metabolized by an isoenzyme in the cytochrome P-450 (CYP) enzyme system, CYP3A4. Changes in CYP3A4 levels will alter circulating drug levels of bedaquiline. Coadministration of bedaquiline with drugs that are strong CYP3A4 inducers should be avoided because it will increase bedaquiline metabolism and decrease circulating levels of the drug. Coadministration of strong inhibitors of CYP3A4 for more than 14 days should also be avoided because it will decrease metabolism and increase circulating levels of bedaquiline, placing the patient at increased risk for adverse effects. Other drugs with the capability of lengthening the QT interval should also be avoided. Coadministration of other drugs that induce hepatotoxicity should be avoided during bedaquiline therapy, too, especially if the patient has diminished liver function, to decrease the risk of adverse hepatic effects.

Nurses should confirm that baseline electrolyte levels have been assessed and that imbalances, which could contribute to cardiac arrhythmias, are corrected prior to the start of bedaquiline therapy. A baseline electrocardiogram (ECG) should be obtained and then repeated at regular intervals during treatment. Syncope can indicate QT prolongation; obtain an ECG if syncope occurs.

Nurses should confirm that liver-specific laboratory tests (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin) are ordered periodically throughout treatment and that the patient's laboratory values don't indicate hepatic injury. Significantly elevated laboratory values indicate that the drug should be discontinued. Evidence of new or worsening liver dysfunction (such as liver tenderness, hepatomegaly, fatigue, dark urine, or anorexia) requires a complete evaluation by the prescriber. Instruct the patient not to drink alcohol while taking bedaquiline because it can worsen liver function.

For complete prescribing information, go to http://1.usa.gov/XGESNr.