Doripenem

Approved Indications:

• Complicated intra-abdominal infections (cIAI): Treatment in combination with metronidazole or as monotherapy where appropriate.
• Complicated urinary tract infections (cUTI), including pyelonephritis.
• Nosocomial pneumonia, including ventilator-associated pneumonia (VAP).
• Other serious infections caused by susceptible aerobic and anaerobic Gram-positive and Gram-negative bacteria, as determined by susceptibility testing.

Off-label / Clinically accepted uses:

• Severe infections caused by multidrug-resistant pathogens sensitive to carbapenems.
• Febrile neutropenia empiric therapy (less common, off-label).

Route: Intravenous infusion only.

Adults:

• Complicated intra-abdominal infections: 500 mg IV every 8 hours infused over 1 hour.
• Complicated urinary tract infections: 500 mg IV every 8 hours infused over 1 hour.
• Nosocomial pneumonia (including VAP): 500 mg IV every 8 hours infused over 4 hours (extended infusion recommended).

Duration:

• Typically 7–14 days, depending on infection severity and clinical response.

Pediatrics:

• Safety and efficacy not well established; dosing not routinely recommended.

Elderly:

• Same as adults; no routine dose adjustment but monitor renal function.

Renal impairment:

• Creatinine clearance (CrCl) 30–50 mL/min: 250 mg every 8 hours.
• CrCl 10–29 mL/min: 250 mg every 12 hours.
• CrCl <10 mL/min: 250 mg every 24 hours or as per dialysis schedule.
• Dosage adjustments required to avoid accumulation.

Doripenem is a broad-spectrum carbapenem antibiotic that inhibits bacterial cell wall synthesis. It binds to and inactivates penicillin-binding proteins (PBPs), particularly PBP1 and PBP2, essential for peptidoglycan cross-linking in the bacterial cell wall. This inhibition weakens the cell wall, leading to bacterial cell lysis and death. Doripenem exhibits strong activity against a wide range of aerobic and anaerobic Gram-positive and Gram-negative bacteria, including many resistant strains.

• Absorption: Not applicable (IV administration).
• Distribution: Widely distributed into body tissues and fluids; volume of distribution approximately 17 L.
• Metabolism: Minimally metabolized; majority excreted unchanged.
• Half-life: Approximately 1 hour in patients with normal renal function.
• Elimination: Primarily renal via active tubular secretion (~70% unchanged in urine).

• Pregnancy: FDA Category B
• Animal studies show no evidence of fetal harm; human data limited.
• Use only if clearly needed and benefits justify potential risks.
• Lactation:
• Unknown if excreted in human milk.
• Caution advised; avoid breastfeeding or monitor infant if treatment necessary.

• Primary class: Carbapenem antibiotic
• Subclass: Beta-lactam antibiotic with broad-spectrum activity

• Known hypersensitivity to doripenem, other carbapenems, beta-lactams, or excipients.
• History of severe allergic reactions (anaphylaxis) to beta-lactam antibiotics.

• Seizure risk: Increased risk in patients with CNS disorders or renal impairment; monitor and adjust dose accordingly.
• Hypersensitivity reactions: Potential for severe allergic reactions including anaphylaxis.
• Clostridioides difficile-associated diarrhea: Possible during or after treatment; monitor for persistent diarrhea.
• Renal impairment: Dose adjustment essential; monitor renal function.
• Use with caution in patients with history of seizures or CNS disorders.
• Potential for superinfection: Monitor for secondary infections.

Common:

• Headache
• Nausea, vomiting, diarrhea
• Rash
• Injection site reactions

Less common:

• Elevated liver enzymes
• Hypersensitivity reactions (rash, pruritus)
• Dizziness

Rare / Serious:

• Seizures (especially in predisposed patients or overdose)
• Anaphylaxis
• Clostridioides difficile colitis
• Hematologic abnormalities (e.g., eosinophilia, thrombocytopenia)

• Valproic acid: May reduce serum levels of valproate, risking loss of seizure control.
• Probenecid: May increase plasma concentration of doripenem by reducing renal excretion.
• No significant CYP450 interactions.

• Guidelines emphasize doripenem’s role in treating serious multidrug-resistant infections.
• Extended infusion times (e.g., 4 hours) for pneumonia recommended to optimize pharmacodynamics.
• FDA warnings highlight seizure risk especially with predisposing conditions.
• Doripenem recommended as alternative carbapenem in hospital-acquired infections with resistant pathogens.

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Store reconstituted solutions refrigerated (2°C to 8°C) and use within recommended time (usually 24 hours)
• Do not freeze