Daptomycin and eosinophilic pneumonia

HSA would like to bring to the attention of healthcare professionals the potential risk of patients developing eosinophilic pneumonia during treatment with daptomycin (Cubicin®, AstraZeneca).

Cubicin®, an antibacterial drug belonging to the class of cyclic lipopeptides, has been licensed in Singapore since July 2008 for the treatment of complicated skin and skin structure infections (cSSSI) and Staphylococcus aureus bacteraemia, including those with right-sided infective endocarditis.¹

Regulatory actions by the US Food and Drug Administration (FDA)

In July 2010, the US FDA reviewed published case reports of Cubicin®-associated eosinophilic pneumonia and conducted a review of post-marketing adverse event reports from the FDA's Adverse Event Reporting System (AERS).² FDA's review identified six cases of eosinophilic pneumonia reported to AERS between 2004 and 2010 that were most likely associated with Cubicin®. One additional case of eosinophilic pneumonia most likely associated with Cubicin® was identified in the medical literature. These occurred in patients ranging from 60 to 87 years old who were prescribed Cubicin® for off-label indications, including osteomyelitis (n=4), prosthetic hip infection (n=1), enterococcal endocarditis (n=1), and aortic valve endocarditis (n=1).

In all seven cases, eosinophilic pneumonia developed two to four weeks after initiating Cubicin® treatment, and improvement or resolution of symptoms was reported after Cubicin® was discontinued. Five of the seven cases received treatment with systemic corticosteroids. Two cases reported recurrence of eosinophilic pneumonia after Cubicin® was restarted.

FDA also identified a further 36 cases of eosinophilic pneumonia which were possibly associated with Cubicin® use.² Although these cases did not meet the full criteria used by FDA to define a likely association of eosinophilic pneumonia with Cubicin® use, they do provide additional support for a potential causal relationship.

Based on these reviews, FDA assessed that there appears to be a temporal association between Cubicin® administration and the development of eosinophilic pneumonia. FDA had also requested that Cubist, the manufacturer of Cubicin®, update the package insert to include a warning on this association. Cubist has fulfilled FDA's request and updated the US package insert accordingly.

Local situation and HSA's advisory

To date, HSA has received five local adverse drug reaction (ADR) reports associated with Cubicin®.Of these, one case reported eosinophilia, monocytosis and fever in a 79 year-old patient with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. However, no respiratory symptoms were reported, suggesting that this ADR was likely generalised eosinophilia rather than eosinophilic pneumonia. In addition, the patient was on multiple medications, including vancomycin, which has been associated with eosinophilia.

HSA is working with the company to strengthen the local package insert for Cubicin® to include warnings that reflect the above safety issue. Physicians are advised to monitor their patients carefully for signs and symptoms of eosinophilic pneumonia after initiating Cubicin® treatment, including new onset or worsening fever, dyspnoea, hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates on chest imaging studies. This condition improves when Cubicin® is discontinued and steroid therapy initiated.

Healthcare professionals are also strongly encouraged to report any adverse reactions suspected to be associated with Cubicin® to the Vigilance Branch of HSA.

References

1. Singapore Package Insert for daptomycin (Cubicin®, AstraZeneca).

2. FDA Drug Safety Communication: Eosinophilic pneumonia associated with the use of Cubicin (daptomycin).
   http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm220273.htm ↗ (opens in new tab)