Doriject IV Infusion

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.

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-

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

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 mLof 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.

Increased plasma concentration with probenecid. May decrease plasma levels of valproic acid thus, increasing the risk of seizures.

Doripenem is contraindicated in patients with known serious hypersensitivity to any component of the product or to other drugs in the same class or patients who have demonstrated anaphylactic reactions to beta-lactams.

• Headache
• Diarrhea
• Nausea
• Phlebitis
• Rash
• Vulvomycotic infection

Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive to human response, this drug should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when Doripenem is administered to a nursing woman.

Serious and occasionally fatal hypersensitivity (anaphylactic) and serious skin reactions have been reported in patients receiving beta-lactam antibiotics. Before therapy with Doriject is instituted, careful inquiry should be made concerning a previous history of hypersensitivity reactions to other active substances in this class or to beta-lactam antibiotics. Doriject should be used with caution in patients with such a history. Should a hypersensitivity reaction to Doriject occur, it should be discontinued immediately and appropriate measures should be taken. Serious acute hypersensitivity (anaphylactic) reactions require immediate emergency treatment.

Other beta-lactam Antibiotics

Keep away from light & protect from moisture. Do not store above 25°C temperature. Keep out of reach of children.