Doripenem

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Generic Name of Doripenem - Learn More

Doripenem

Doripenem Precaution - What You Need to Know

Doripenem is an intravenous carbapenem antibiotic primarily used to treat serious bacterial infections. Caution should be exercised in patients with a history of hypersensitivity to beta-lactam antibiotics (e.g., penicillins, cephalosporins), as cross-reactivity may occur. It should be used cautiously in patients with renal impairment, as it is primarily eliminated through the kidneys, and dose adjustments are necessary to avoid toxicity. In patients with a history of seizures, Doripenem should be used with caution, as carbapenems, including Doripenem, have been associated with a slightly increased risk of seizures, especially in those with predisposing factors such as renal impairment or underlying central nervous system disorders.

Pregnant and breastfeeding women should use Doripenem only if the potential benefit justifies the potential risk, as there is limited data on its safety in these populations. Monitoring renal function during treatment is essential, particularly in patients with pre-existing kidney disease or those receiving prolonged therapy. Blood tests should be performed regularly to monitor for any adverse renal effects. There is also a potential for antibiotic-associated diarrhea, including Clostridium difficile-associated diarrhea, especially with extended use. Therefore, patients should be monitored for signs of gastrointestinal issues, including abdominal pain, cramping, and diarrhea.

Doripenem Indication - Uses and Benefits

Doripenem is indicated for the treatment of serious bacterial infections caused by susceptible organisms, including complicated intra-abdominal infections, complicated urinary tract infections, and hospital-acquired pneumonia (including ventilator-associated pneumonia). It is commonly used in critically ill patients due to its broad spectrum of activity against both Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. Doripenem is also effective in treating infections caused by multi-drug-resistant organisms, making it a valuable option for patients with limited treatment choices.

Off-label uses of Doripenem may include treating infections caused by multidrug-resistant organisms (MDROs), though these should be guided by microbiological testing and susceptibility profiles. Due to its broad antibacterial coverage, it may be used empirically in severe infections pending identification of the causative pathogen, especially when resistant organisms are suspected.

Doripenem Contraindications - Important Warnings

Doripenem is contraindicated in patients with a known hypersensitivity to Doripenem, other carbapenems, or any component of the formulation. It should not be used in patients who have had a previous serious allergic reaction to a beta-lactam antibiotic, such as anaphylaxis or severe skin reactions, due to the potential for cross-sensitivity with other beta-lactam antibiotics like penicillins or cephalosporins.

Additionally, Doripenem is contraindicated in patients with severe renal impairment who do not receive appropriate dose adjustments. Use in patients with a history of seizures or central nervous system disorders should be avoided unless the benefits outweigh the risks, as carbapenems have been associated with increased seizure risk, particularly in those with renal dysfunction.

Pregnancy category C and caution should be exercised in pregnant women, especially in the first trimester, due to limited data on its safety during pregnancy. While not contraindicated in breastfeeding, it should be used with caution, as Doripenem is excreted into breast milk, and the effects on the infant are unknown.

Doripenem Side Effects - What to Expect

Common side effects of Doripenem include nausea, vomiting, diarrhea, and headache. These gastrointestinal effects are generally mild but should be monitored, especially if they lead to dehydration or electrolyte imbalance. Other frequent side effects include rash, fever, and pain at the injection site.

More serious side effects, though less common, include allergic reactions (e.g., anaphylaxis, angioedema), seizures, and significant renal impairment. In patients with pre-existing kidney disease, renal dysfunction can worsen, so kidney function should be closely monitored throughout therapy. As with other antibiotics, prolonged use of Doripenem can lead to superinfection, including Clostridium difficile-associated diarrhea.

Severe adverse effects, such as hepatotoxicity and thrombocytopenia, are rare but may occur. If patients develop signs of liver dysfunction (e.g., jaundice, elevated liver enzymes) or bleeding tendencies, therapy should be reevaluated.

To minimize side effects, hydration is important, and patients should be monitored for signs of gastrointestinal issues, allergic reactions, or renal problems. Dose adjustments may be necessary for patients with renal impairment to avoid excessive drug accumulation.

Doripenem Pregnancy Category ID - Safety Information

2

Doripenem Mode of Action - How It Works

Doripenem is a broad-spectrum beta-lactam antibiotic that works by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) on the bacterial cell wall, disrupting the final stages of peptidoglycan synthesis, which is crucial for bacterial cell wall integrity. Without a functional cell wall, the bacteria are unable to maintain their shape and structural integrity, leading to lysis and death of the bacterial cell.

Doripenem's spectrum of activity includes Gram-positive organisms, such as Streptococcus pneumoniae, and a wide range of Gram-negative bacteria, including Pseudomonas aeruginosa and Escherichia coli. It also demonstrates activity against some anaerobic organisms, making it an effective choice for treating infections in complex or polymicrobial environments like intra-abdominal infections.

Pharmacokinetically, Doripenem has a half-life of approximately 1 hour, with a time-dependent killing effect. It is administered via intravenous infusion and is rapidly distributed throughout the body, including in the lungs, kidneys, and liver. It is primarily eliminated unchanged by the kidneys, requiring dose adjustments in patients with renal dysfunction.

Doripenem Drug Interactions - What to Avoid

Doripenem may interact with several drugs, and these interactions should be monitored. The use of Doripenem with probenecid can increase its plasma concentration by inhibiting renal tubular secretion, leading to an increased risk of toxicity. Thus, it is advisable to avoid co-administration with probenecid or monitor renal function closely if combined.

Doripenem may reduce the effectiveness of oral contraceptives, and women using hormonal contraception should be advised to use additional non-hormonal methods during treatment. It may also interact with other antibiotics, especially those with overlapping or complementary effects, such as aminoglycosides, which can lead to an increased risk of nephrotoxicity. Caution is advised when Doripenem is used in combination with other nephrotoxic agents, and renal function should be closely monitored.

There is no significant food interaction, but intravenous administration should be avoided alongside parenteral administration of other medications that could compete for renal excretion. Additionally, as Doripenem is metabolized in the liver, combining it with hepatic enzyme inhibitors or inducers may affect its metabolism and clinical outcomes.

Doripenem Adult Dose - Recommended Dosage

For adult patients, the standard dose of Doripenem is 500 mg administered intravenously every 8 hours, with the infusion typically lasting 1 hour. In more severe infections or patients with infections caused by less susceptible organisms, the dose may be increased to 1 g every 8 hours. The total duration of therapy generally ranges from 7 to 14 days, depending on the severity and type of infection being treated.

For patients with renal impairment, the dose should be adjusted based on the patient's creatinine clearance. For mild renal impairment (CrCl 50–80 mL/min), no dose adjustment is necessary. In moderate renal impairment (CrCl 30–50 mL/min), the dose is typically reduced to 500 mg every 12 hours. For severe renal impairment (CrCl <30 mL/min), the dose should be reduced to 500 mg every 24 hours. Hemodialysis may further require adjustments, and doses should be administered after dialysis.

Doripenem Child Dose - Dosage for Children

The use of Doripenem in pediatric patients is not approved for all indications, but when prescribed, the typical dose is 10 mg/kg every 8 hours. For severe infections, the dose may be increased to 15 mg/kg every 8 hours, depending on the clinical condition and severity of infection. The maximum dose in children is generally capped at 500 mg per dose.

Special caution is necessary when using Doripenem in pediatric patients, particularly those with renal impairment. Dosing adjustments should be based on the child's weight, renal function, and clinical response to therapy. Careful monitoring of vital signs and renal function is essential during treatment to prevent adverse outcomes.

Doripenem Renal Dose - Dosage for Kidney Conditions

In patients with renal impairment, Doripenem requires dosage adjustments to avoid drug accumulation, which can increase the risk of toxicity. For patients with mild renal impairment (CrCl 50–80 mL/min), the standard dosing regimen of 500 mg every 8 hours is appropriate. For moderate renal impairment (CrCl 30–50 mL/min), the dose should be reduced to 500 mg every 12 hours. In severe renal impairment (CrCl <30 mL/min), the dose should be further reduced to 500 mg every 24 hours.

Patients on hemodialysis should receive their dose after the dialysis session, as Doripenem is removed by hemodialysis. In patients with end-stage renal disease or those undergoing other forms of renal replacement therapy, careful monitoring is essential, and dose adjustments should be made based on serum creatinine levels and dialysis schedules.