Tigecycline

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

vials containing 50 mg lyophilised powder for reconstitution
Approved indication: complicated skin and soft tissue infections and complicated intra-abdominal infections
Australian Medicines Handbook section 5.1.11

Tigecycline is structurally related to the tetracycline class of antibiotics and is a derivative of minocycline. It has broad spectrum in vitro activity against Gram-positive, Gram-negative and anaerobic organisms and also tetracycline-resistant bacteria. Coverage includes multiresistant bacteria such as methicillin-resistant Staphylococcus aureus(MRSA) and vancomycin-resistant enterococci. Tigecycline has poor activity against Pseudomonas species.

Tigecycline is not absorbed from the gut so it must be administered by slow intravenous infusion. It is extensively distributed in the body and has a serum half-life of 40 hours. The tissue half-life is not known. Tigecycline is not extensively metabolised and so most of the drug is excreted unchanged in the urine and faeces.

The safety and efficacy of tigecycline were evaluated for the treatment of skin and skin-structure infections from pooled data of two trials totalling 1116 hospitalised adults. Soft tissue infections, abscesses and infected ulcers were the most common type of infections in these patients. In both trials, tigecycline (100 mg intravenously followed by 50 mg every 12 hours) was compared to a combination of vancomycin and aztreonam for 5-14 days of therapy. Microbiological data were available for 540 patients and clinical data were available for 833 patients. Cure rates for tigecycline and vancomycin/aztreonam were similar in both sets of data, with approximately 86% of tigecycline recipients responding to treatment compared to approximately 88% of vancomycin/aztreonam recipients. Both treatments were equally effective in patients with underlying comorbidities such as diabetes mellitus and peripheral vascular disease.¹

The safety and efficacy of tigecycline were also evaluated for the treatment of complicated intra-abdominal infections, such as complicated appendicitis, from pooled data of two studies totalling 1642 hospitalised adults. Patients received tigecycline or a combination of imipenem and cilastatin for 5-14 days. Of the 685 patients with clinically evaluable data, a total of 594 responded to tigecycline, compared to 607 of 697 patients with clinically evaluable data in the comparator group. Similar levels of drug efficacy were reflected in the 1025 patients who were microbiologically evaluable.²

Although tigecycline has in vitro activity to multidrug resistant bacteria, there were limited data in these trials to support its use in patients with these infections. However, tigecycline was effective at eradicating MRSA in 25 out of 32 patients with complicated skin infections.¹

There were two reports of bacterial resistance to tigecycline in the intra-abdominal infection pooled analysis. Both patients infected with these resistant isolates failed to respond to tigecycline treatment.²

In all four trials, there were slightly more drug-related adverse events reported by tigecycline recipients (986 of 1383 patients) than by patients receiving the comparator treatments (927 of 1375 patients). The most common events in the tigecycline-treated patients were nausea and vomiting. Nausea was experienced by 394 of the patients given tigecycline and 202 patients in the comparator group. Vomiting occurred in 268 patients taking tigecycline and 138 patients taking the comparator treatments. Overall there were 30 deaths in the tigecycline groups and 18 deaths in the control groups. One death of a tigecycline recipient, after septic shock, was possibly related to the study drug.

Tigecycline is not recommended for pregnant women or children. Tetracycline class effects, such as photosensitivity, may also occur in patients taking tigecycline.

Tigecycline provides an alternative antibiotic therapy for the treatment of serious infections in hospitalised adults. However, its effectiveness in treating multidrug resistant infections remains to be fully evaluated. Advice from an infectious disease specialist or bacteriologist should be sought before using tigecycline.

Manufacturer provided the clinical evaluation

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.