Doribax

Posology The recommended dose and administration by infection is shown in the following table: Infection Dose Frequency Infusion time Nosocomial pneumonia including ventilator–associated pneumonia 500 mg or 1 g* every 8 hours 1 or 4 hours** Complicated intra-abdominal infection 500 mg every 8 hours 1 hour Complicated UTI, including pyelonephritis 500 mg every 8 hours 1 hour * 1 g every 8 hours as a 4-hour infusion may be considered in patients with augmented renal clearance (particularly those with creatinine clearance (CrCl) ≥ 150 ml/min) and/or in infections due to non-fermenting gram-negative pathogens (such as Pseudomonas spp.

). 1). 1). This dosing regimen should also be considered in particularly severe infections. Duration of treatment The usual treatment duration of doripenem therapy ranges from 5-14 days and should be guided by the severity, site of the infection, infecting pathogen and the patient’s clinical response.

The usual treatment duration for patients with nosocomial pneumonia, including ventilator-associated pneumonia is 10 to 14 days and is often in the upper range for patients infected with non-fermenting gram-negative pathogens (such as Pseudomonas spp.

1). Doripenem was given for up to 14 days in clinical studies and the safety of longer durations of therapy has not been established. 2). e. creatinine clearance (CrCl) is > 50 to  80 ml/min), no dose adjustment is necessary. 6). 6). In patients prescribed 1 g every 8 hours as a 4-hour infusion, the dose should be similarly adjusted (moderate renal impairment: 500 mg every 8 hours; severe renal impairment: 500 mg every 12 hours).

2). Dose in patients on dialysis Doribax dosing and administration recommendations for patients on continuous renal replacement therapies are shown in the following table. CRRT procedure Glomerular filtration rate Dose Frequency Infusion timea, b Target attainment (MIC) CVVH ≤ 30 ml/min 250 mg every 12 hours 4 hours ≤ 1 mg/l CVVHDF < 5 ml/min 250 mg every 12 hours 4 hours ≤ 1 mg/l CVVHDF 5-30 ml/min 500 mg every 12 hours 4 hours ≤ 1 mg/l CRRT: continuous renal replacement therapy; CVVH: continuous venovenous haemofiltration; CVVHDF: continuous venovenous haemodiafiltration; MIC: minimum inhibitory concentration a For patients with acute renal insufficiency on CRRT, an infusion time of 4 hours is required, taking into consideration the possible increases in non-renal clearance of carbapenems in patients with acute renal insufficiency.

Summary of the safety profile In 3,142 adult patients (1,817 of which received Doribax) evaluated for safety in phase II and phase III clinical trials, adverse reactions due to Doribax 500 mg every 8 hours occurred at a rate of 32%.

1% of patients overall. 2%). The most common adverse reactions were headache (10%), diarrhoea (9%) and nausea (8%). The safety profile in approximately 500 patients who received Doribax 1 g every 8 hours as a 4-hour infusion in phase I, II and III clinical trials, was consistent with the safety profile for patients receiving 500 mg every 8 hours.

Tabulated list of adverse reactions Adverse drug reactions identified during clinical trials and post-marketing experience with Doribax are listed below by frequency category.

Frequency categories are defined as follows:

Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

4) Vascular disorders Common: phlebitis Gastrointestinal disorders Common: nausea, diarrhoea Uncommon: C. 4) Hepatobiliary disorders Common: hepatic enzyme increasedMedicinal product no longer authorised 7 Skin and subcutaneous tissue disorders Common: pruritus, rash Not known: toxic epidermal necrolysis, Stevens-Johnson syndrome

General The selection of doripenem to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial agent based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial agents and the risk of selecting for carbapenem-resistant bacteria.

Caution on the choice of antibiotic agent and dose should be taken when treating patients with late-onset ventilator-associated pneumonia (> 5 days hospitalisation) and in other nosocomial pneumonia cases where pathogens with decreased susceptibility are suspected or confirmed, such as Pseudomonas spp.

and Acinetobacter spp. 1). 1). Hypersensitivity reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have occurred in patients receiving beta-lactam antibiotics. Before therapy with Doribax is started, careful inquiry should be made concerning a previous history of hypersensitivity reactions to other active substances in this class or to beta-lactam antibiotics.

Doribax should be used with caution in patients with such a history. Should a hypersensitivity reaction to doripenem occur, it should be discontinued immediately and appropriate measures taken. Serious acute hypersensitivity (anaphylactic) reactions require immediate emergency treatment.

8). g. stroke or history of seizures), compromised renal function and at doses greater than 500 mg. Pseudomembranous colitis Pseudomembranous colitis due to Clostridium difficile has been reported with Doribax and may range in severity from mild to life-threatening.

8). Overgrowth of non-susceptible bacteria Administration of doripenem, like other antibiotics, has been associated with emergence and selection of strains with reduced susceptibility. Patients should be carefully monitored during therapy.

If superinfection occurs, appropriate measures should be taken. Prolonged use of Doribax should be avoided. 5). Pneumonitis with inhalational use When Doribax was used investigationally via inhalation, pneumonitis occurred. Medicinal product no longer authorised 5 Continuous renal replacement therapy The exposure to the metabolite doripenem-M-1 in patients on continuous renal replacement therapy may be increased to levels where no in vivo safety data are presently available.

g. g. penicillins or cephalosporins).