Doripenem is indicated for the treatment of the following infections:

Complicated Intra-Abdominal Infections: Infections within the abdominal cavity caused by organisms such as 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: Includes infections caused by Escherichia coli (including cases with bacteremia), Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Acinetobacter baumannii.

Doripenem is a broad-spectrum carbapenem antibiotic effective against both aerobic and anaerobic Gram-positive and Gram-negative bacteria. It acts by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs), leading to cell death. In organisms such as E. coli and P. aeruginosa, Doripenem primarily binds to PBP-2 and also interacts with PBPs 3 and 4, contributing to disruption of cell structure.

Absorption: After a 1-hour intravenous infusion of a 500 mg dose, mean plasma concentrations reach approximately 23 mcg/mL. Pharmacokinetic parameters (Cmax and AUC) increase proportionally with doses ranging from 500 mg to 1 g. No drug accumulation is observed with repeated dosing every 8 hours over 7–10 days in patients with normal renal function.

Distribution: Approximately 8.1% of Doripenem binds to plasma proteins, independent of drug concentration. The steady-state volume of distribution is about 16.8 L, similar to extracellular fluid volume.

Metabolism: Doripenem is metabolized mainly to an inactive ring-opened metabolite (doripenem-M1) via dehydropeptidase-I. It is not significantly metabolized by hepatic CYP450 enzymes.

Excretion: The drug is primarily eliminated unchanged through the kidneys. The elimination half-life is about 1 hour, with plasma clearance around 15.9 L/hour and renal clearance about 10.8 L/hour. Approximately 70% (unchanged drug) and 15% (metabolite) are excreted in urine within 48 hours after a single dose.

The recommended dosage of Doripenem is 500 mg administered every 8 hours by intravenous infusion over one hour in patients ≥18 years of age-

• Complicated intra-abdominal infection: 500 mg every 8 hours for 5-14 days. Infusion time: 1 hour.
• Complicated UTI, including pyelonephritis: 500 mg every 8 hours for 10 days. Infusion time: 1 hour.

Dosage of Doripenem in patients with renal impairment-

• CrCl >50 mL/min: No dosage adjustment necessary
• CrCl ≥30 to ≤ 50 mL/min: 250 mg administered intravenously (over 1 hour) every 8 hours.
• CrCl >10 to <30 mL/min: 250 mg administered intravenously (over 1 hour) every 12 hours.

Geriatric Patients: No dosage adjustment is recommended for elderly patients with normal (for their age) renal function.

Administration

Preparation of Solutions: Doripenem does not contain a bacteriostatic preservative. Aseptic technique must be followed in preparation of the infusion solution.

Preparation of Doripenem 500 mg: Constitute the 500 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension. The resultant concentration is approximately 50 mg/mL.

CAUTION: The constituted suspension is not for direct injection. Withdraw the suspension using a syringe with a 21 gauge needle and add it to an infusion bag containing 100mLof normal saline or 5% dextrose, gently shake until clear. The final infusion solution concentration is approximately 4.5 mg/mL.

Preparation of Doripenem 250 mg: Constitute the 250 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension. The resultant concentration is approximately 25 mg/mL.

CAUTION: The constituted suspension is not for direct injection.

Withdraw the suspension using a syringe with a 21 gauge needle and add it to an infusion bag containing 50 or 100 mL of normal saline or 5% dextrose, gently shake until clear. The final infusion solution concentration is approximately 4.2 mg/mL(50 mL infusion bag) or approximately 2.3 mg/mL (100 mL infusion bag).

Doripenem should not be mixed with or physically added to solutions containing other drugs.

Co-administration with probenecid may increase plasma concentrations of Doripenem. It may also reduce plasma levels of valproic acid, thereby increasing the risk of seizures.

Doripenem is contraindicated in patients with known severe hypersensitivity to the drug, other agents in the same class, or in those with a history of anaphylactic reactions to beta-lactam antibiotics.

Common adverse effects include headache, diarrhea, nausea, phlebitis, rash, and vulvovaginal fungal infection.

Pregnancy Category B: Adequate and well-controlled studies in pregnant women are not available. Since animal studies may not always predict human response, Doripenem should be used during pregnancy only if clearly needed. It is unknown whether Doripenem is excreted in human breast milk; caution is advised when administered to nursing mothers.

Serious and sometimes fatal hypersensitivity (including anaphylaxis) and severe skin reactions have been reported with beta-lactam antibiotics. Before initiating Doripenem, a careful history of allergy to beta-lactam antibiotics should be obtained. If a hypersensitivity reaction occurs, the drug should be discontinued immediately and appropriate treatment initiated. Severe reactions require emergency management.

Other beta-lactam antibiotics

Store below 25°C, protect from light and moisture. Keep out of reach of children.