To reduce the development of drug-resistant bacteria and maintain the effectiveness of Doripenem and other antibacterial drugs, Doripenem should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting and modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Complicated Intra-Abdominal Infections: Doripenem injection is indicated as a single agent for the treatment of complicated intra-abdominal infections caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides caccae, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Streptococcus intermedius, Streptococcus constellatus and Peptostreptococcus micros. Complicated Urinary Tract Infections, Including Pyelonephritis: Doripenem injection is indicated as a single agent for the treatment of complicated urinary tract infections, including pyelonephritis caused by Escherichia coli including cases with concurrent bacteremia, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Acinetobacter baumannii.
Doripenem is a broad-spectrum carbapenem class of antibacterial with activity against aerobic and anaerobic Gram-positive and Gram-negative bacteria.Doripenem exerts its bactericidal activity by inhibiting bacterial cell wall biosynthesis. Doripenem inactivates multiple essential penicillin-binding proteins (PBPs) resulting in inhibition of cell wall synthesis with subsequent cell death. In E. coli and P. aeruginosa,Doripenem binds to PBP 2, which involved in the maintenance of cell shape, as well as to PBPs 3 and 4.
Absorption: Mean plasma concentrations of Doripenem following a single 1-hour intravenous infusion of a 500 mg dose to 24 healthy subjects is 23.0 (6.6) pg/mL. The pharmacokinetics of Doripenem (Cmax and AUC) are linear over a dose range of 500 mg to 1 g when intravenously infused over 1 hour. There is no accumulation of Doripenem following multiple intravenous infusions of either 500 mg or 1 g administered every 8 hours for 7 to 10 days in subjects with normal renal function.
Distribution: The average binding of Doripenem to plasma proteins is approximately 8.1% and is independent of plasma drug concentrations. The median (range) volume of distribution at steady state in healthy subjects is 16.8 L (8.09-55.5 L), similar to extracellular fluid volume (18.2 L).
Metabolism: Metabolism of doripenem to a microbiologically inactive ring-opened metabolite (doripenem-M1) occurs primarily via dehydropeptidase-l. In pooled human liver microsomes, no in vitro metabolism of Doripenem could be detected, indicating that Doripenem is not a substrate for hepatic CYP450 enzymes.
Excretion: Doripenem is primarily eliminated unchanged by the kidneys. The mean plasma terminal elimination half-life of Doripenem in healthy non-elderly adults is approximately 1 hour and mean (SD) plasma clearance is 15.9 (5.3) L/hour. Mean renal clearance is 10.8 (3.5) L/hour. In healthy adults given a single 500 mg dose a mean of 70% and 15% of the dose was recovered in urine as unchanged drug and the ring-opened metabolite, respectively, within 48 hours.
Intravenous- Complicated intra-abdominal infections: 500 mg 8 hrly infused over 1 hr for 5-14 days. May switch to an appropriate oral therapy, after at least 3 days of parenteral therapy. Complicated UTI, Pyelonephritis: 500 mg 8 hrly infused over 1 hr for 10 days. May switch to an appropriate oral therapy, after at least 3 days of parenteral therapy. Patient with concurrent bacteraemia: Duration can be extended up to 14 days. Renal impairment- CrCI (30-50 ml/min): 250 mg every 8 hr by IV infusion over 1 hr CrCI (11 -29 ml/min): 250 mg every 12 hr by IV infusion over 1 hr
Increased plasma concentration with probenecid. May decrease plasma levels of valproic acid thus, increasing the risk of seizures.
Hypersensitivity to doripenem, other carbapenem antibacterial agents; history of anaphylactic reaction to ?-lactams (e.g. penicillins, cephalosporins). Patient with known or suspected CNS disorders (e.g. brain lesions, history of seizures). Not intended for treatment of any type of pneumonia. Renal impairment. Pregnancy and lactation. Monitoring Parameters Monitor renal function and for signs of anaphylaxis during 1st dose. Consider haematologic assessment during prolonged therapy.
Headache, nausea, diarrhoea, rash, pruritus, phlebitis, elevated hepatic enzymes, oral candidiasis, anaemia, vulvomycotic infection, thrombocytopenia, neutropenia.
Pregnancy Category B. Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).
Keep away from light & protect from moisture. Do not store above 25°C temperature. Keep out of reach of children.
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