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.
Invanz (Merck Sharp & Dohme)
vials containing 1 g as powder
Approved indication: specified infections
Australian Medicines Handbook Section 5.1.3
Ertapenem is one of the carbapenem antibiotics. These drugs have a broad spectrum of activity so are held in reserve for severe infections.
By inhibiting cell wall synthesis, ertapenem has a bactericidal action. In vitro it is active against anaerobes, Gram positive and Gram negative aerobic bacteria. Ertapenem is resistant to some beta-lactamases, but its in vitro activity against enterococci is limited and it is not effective against methicillin-resistant strains of staphylococci. Ertapenem is not active against Pseudomonas aeruginosa.
Although ertapenem can be used for infections caused by susceptible micro-organisms that are resistant to all other antibiotics, it has specific approval to be used empirically in acute pelvic infections and complicated intra-abdominal infections. It can be infused intravenously or injected intramuscularly. Infusions should take 30 minutes and should not be mixed with dextrose or other medications. Lignocaine 1% is used to reconstitute ertapenem for intramuscular injections.
Although the half-life of ertapenem is four hours, only one daily dose is needed. Most of the drug and its metabolites are excreted in the urine.
Ertapenem was compared with piperacillin/tazobactam in 665 patients with complicated intra-abdominal infections. There was a favourable clinical and microbiological response in more than 80% of the evaluable patients. Success rates exceeding 90% were seen, for both drugs, in the treatment of 412 women with acute pelvic infections. These infections included septic abortion and postpartum endomyometritis as well as post-surgical sepsis.
Serious infections can be life-threatening and cause symptoms which could be confused with adverse drug reactions. Approximately 20% of the patients given ertapenem had a drug-related adverse experience. Common adverse events include diarrhoea, headache, nausea and problems at the injection site. Seizures can occur and people with neurological disorders are particularly at risk. Abnormal laboratory results include altered liver function and neutropenia. There is a risk of anaphylaxis in patients who are hypersensitive to penicillin.
While there is now a choice of three carbapenems there currently seems little reason to switch to ertapenem apart from its once daily dose. Few clinical trials have been published and in vitro studies suggest its activity against some bacteria is less than that of imipenem and meropenem. This may limit its usefulness as an empirical treatment.
During the preparation of this new drug comment, some discrepancies emerged between the Australian product information and the prescribing information in the USA. There may be technical explanations for these differences, but the Editorial Executive Committee would like to draw readers' attention to some examples.
1. The adverse reactions section of the Australian product information does not include the American observation that there were more deaths (4.7% versus 2.6%) among the patients given ertapenem for complicated intra-abdominal infections.
2. The activity of ertapenem in vitroand in clinical infections varies between the documents. In the USA ertapenem has only been shown to be active against penicillin-susceptible strains of Streptococcus pneumoniaeand beta-lactamase negative strains of Haemophilus influenzae. These caveats do not appear in the Australian product information.