Cefopen1 gm/vial

Cefopen is a third-generation, antipseudomonal cephalosporin antibiotic administered by injection. It is used to treat bacterial infections caused by susceptible organisms.

Established/approved uses

• Lower respiratory tract infections (e.g. pneumonia, bronchitis)
• Intra-abdominal infections, including peritonitis
• Biliary tract infections (cholecystitis, cholangitis) — Cefopen achieves high concentrations in bile
• Skin and soft-tissue infections
• Urinary tract infections
• Bacterial septicemia
• Pelvic inflammatory disease and other female genital tract infections (note: Cefopen has no activity against Chlamydia trachomatis, so a second agent is required if this organism is suspected or confirmed)

Combination therapy

For pelvic infections and certain mixed anaerobic/aerobic infections, Cefopen is frequently used together with another antimicrobial agent active against the organisms not covered by Cefopen alone. In many countries, Cefopen is also co-formulated with sulbactam (a beta-lactamase inhibitor) to extend coverage to beta-lactamase-producing organisms; that fixed-dose combination is a separate product and is not the subject of this entry, which describes Cefopen as a single agent.

Note: Cefopen should be reserved for infections proven or strongly suspected to be caused by susceptible bacteria, based on culture and sensitivity testing whenever possible, in line with antibiotic stewardship principles.

Cefoperazone for injection is supplied as a sterile powder for reconstitution, containing Cefoperazone (as cefoperazone sodium) as the active ingredient. It is available in vial strengths such as 1 g and 2 g of Cefoperazone per vial for intravenous or intramuscular use, formulated with sodium carbonate as a buffering agent (no preservative).

Cefopen is a semi-synthetic, third-generation cephalosporin antibiotic with broad-spectrum activity against many Gram-negative and Gram-positive bacteria, including notable activity against Pseudomonas aeruginosa, which distinguishes it from many other cephalosporins.

Cefopen is not absorbed orally and is therefore given only by intravenous (IV) or intramuscular (IM) injection. A distinctive pharmacologic feature is that Cefopen is eliminated mainly through biliary excretion rather than the kidneys, which makes it useful for hepatobiliary infections but means dosing must be adjusted in significant liver disease.

Cefopen belongs to the third-generation cephalosporin class of antibiotics, specifically the antipseudomonal cephalosporin subgroup (beta-lactam antibiotics).

Mechanism of action

Cefoperazone is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, blocking the final transpeptidation (cross-linking) step of peptidoglycan synthesis. This weakens the cell wall, leading to cell lysis and death of susceptible bacteria (bactericidal action).

Antimicrobial spectrum

Cefoperazone is active against many Gram-negative organisms, including Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, Proteus species, and Haemophilus influenzae, as well as some Gram-positive organisms such as streptococci. It has limited or no activity against methicillin-resistant staphylococci, enterococci, and Chlamydia trachomatis.

Pharmacokinetics

Cefoperazone is not absorbed from the gastrointestinal tract and must be given parenterally. It is highly (approximately 82–93%) but concentration-dependently bound to plasma proteins, with a serum half-life of roughly 2 hours. Unlike most cephalosporins, Cefoperazone is excreted predominantly (up to 70–75%) via biliary/fecal elimination, with only 20–30% recovered in urine; hepatic impairment or biliary obstruction can prolong its half-life two- to four-fold.

Cefopen is administered only by a healthcare professional, as a slow intravenous injection, intravenous infusion (over 15–60 minutes), or deep intramuscular injection — never orally. The powder must be reconstituted before use (see Reconstitution). Intravenous infusion is generally preferred for higher doses and in more seriously ill patients; intramuscular injection may be used for lower doses in less severe infections.

Alcohol (disulfiram-like reaction)

Cefopen contains an N-methylthiotetrazole (NMTT) side chain that can inhibit aldehyde dehydrogenase. Consuming alcohol during treatment with Cefopen, or within about 72 hours after the last dose, may cause a disulfiram-like reaction (flushing, throbbing headache, nausea, vomiting, sweating, tachycardia). Patients should be advised to avoid alcohol and alcohol-containing products during and for several days after finishing treatment.

Anticoagulants

Cefopen can lower vitamin K–dependent clotting factors and has been associated with hypoprothrombinemia. Concurrent use with warfarin or other anticoagulants may increase the risk of bleeding; more frequent monitoring of coagulation status (e.g. INR) is advised.

Aminoglycosides

Cefopen is sometimes used together with aminoglycoside antibiotics for synergistic coverage of severe infections, but the two drugs must never be physically mixed in the same syringe, IV bag, or infusion line, as this can inactivate both agents. When used concurrently, renal function should be monitored because of the additive risk of nephrotoxicity.

Other

As with other broad-spectrum antibiotics, concurrent use of Cefopen may reduce the effectiveness of some hormonal (estrogen-containing) contraceptives; an additional non-hormonal method of contraception is advisable during treatment.

Common side effects

• Diarrhea (reported in roughly 1 in 30 patients)
• Nausea and vomiting
• Skin rash
• Pain, swelling, or phlebitis at the injection site
• Mild, usually reversible reduction in white blood cell count (neutropenia)
• Mild, transient elevation of liver enzymes

Serious but less common side effects

• Severe hypersensitivity/anaphylactic reactions
• Severe skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis
• Clostridioides difficile-associated diarrhea/colitis, which can range from mild to life-threatening
• Bleeding or bruising due to reduced vitamin K–dependent clotting factors
• Encephalopathy (confusion, seizures), particularly with very high doses or in patients with impaired drug clearance

Patients should seek prompt medical attention for severe rash, difficulty breathing, swelling of the face/throat, severe or bloody diarrhea, unusual bleeding, or confusion.

Pregnancy: There are no adequate and well-controlled studies of Cefopen in pregnant women. Animal reproduction studies have not shown evidence of fetal harm, but this does not guarantee safety in humans. Cefopen should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; a physician should be consulted before use.

Lactation: Cefopen is excreted in human breast milk in low concentrations. Caution is advised, and a physician should be consulted to weigh the benefits of treatment against the possibility of effects on the breastfed infant (such as diarrhea or effects on gut flora).

• Hypersensitivity/cross-reactivity: Use with caution in patients with a history of penicillin allergy, since partial cross-reactivity between penicillins and cephalosporins can occur (see Contraindications for severe reactions).
• Hepatic/biliary disease: Because Cefopen is eliminated mainly through bile, patients with significant liver disease or biliary obstruction can have markedly prolonged drug levels; dose adjustment and monitoring of liver function are recommended.
• Alcohol: Avoid alcohol during treatment with Cefopen and for several days after the last dose because of the risk of a disulfiram-like reaction (see Interactions).
• Bleeding risk: Prolonged use of Cefopen, particularly in malnourished patients or those with renal/hepatic impairment, may reduce vitamin K–dependent clotting factors and increase bleeding risk; vitamin K administration and coagulation monitoring may be needed in at-risk patients.
• Clostridioides difficile-associated diarrhea: As with virtually all antibacterial agents, Cefopen may allow overgrowth of C. difficile; evaluate patients who develop diarrhea during or after treatment.
• Superinfection: Prolonged use may result in overgrowth of non-susceptible organisms, including fungi.

Antibiotic stewardship: Take/receive Cefopen exactly as prescribed by your physician. Do not stop, extend, skip doses, or share this medicine with others without medical advice.

Specific data on Cefopen overdose are limited. Excessive doses could theoretically increase the risk of neurological effects (e.g. encephalopathy, seizures), bleeding due to vitamin K–dependent clotting factor suppression, or other exaggerated adverse effects listed above, especially in patients with impaired renal or hepatic clearance.

There is no specific antidote. If an overdose of Cefopen is suspected, seek immediate medical attention or contact emergency services/poison control. Treatment is supportive; Cefopen can be partially removed by hemodialysis in cases of severe toxicity in patients with renal failure.

Store unreconstituted Cefopen powder for injection at or below 25°C (77°F), protected from light and moisture, and keep out of reach of children. Once reconstituted, use according to the diluent-specific stability information provided by the manufacturer/pharmacist, and discard any unused reconstituted solution as directed.

• Pediatric patients: See Pediatric Uses — safety and efficacy have not been formally established in official labeling.
• Elderly patients: No specific dose adjustment is generally required based on age alone, but elderly patients often have reduced hepatic or renal reserve and should be monitored closely, particularly for bleeding and neurological effects.
• Hepatic impairment: Requires dose limitation/monitoring because Cefopen is mainly excreted in bile (see Dosage and Administration and Precautions).
• Renal impairment: Usual doses generally do not require adjustment, but monitoring is advised, especially if hepatic function is also impaired or if aminoglycosides are co-administered.
• Pregnancy and breastfeeding: See Pregnancy and Lactation.

Duration of Cefopen therapy depends on the site and severity of infection and the clinical response, and should be determined by the treating physician. As a general principle, antibiotic treatment, including Cefopen, is typically continued for at least 48–72 hours after the patient becomes afebrile and shows clinical improvement. Documented streptococcal infections should be treated with Cefopen for a minimum of 10 days to help prevent complications such as rheumatic fever. The full prescribed course of Cefopen should always be completed, even if symptoms improve earlier.

Cefopen for injection is supplied as a sterile powder that must be reconstituted before administration, and should only be prepared by a healthcare professional or pharmacist following the manufacturer's instructions.

• For intravenous use: Reconstitute with an appropriate diluent such as 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Sterile Water for Injection, then dilute further for intermittent infusion as directed.
• For intramuscular use: Reconstitute with Sterile Water for Injection; for injections containing 250 mg/mL or more, a 2% lidocaine solution (without epinephrine) may be used as the diluent to reduce injection-site pain, per local product labeling.

Shake well until completely dissolved. Once reconstituted, Cefopen solution should be used within the time frame specified by the manufacturer for the diluent used, and stored under refrigeration if not used immediately (do not freeze after reconstitution unless specifically directed).

Cephalosporins; Third-generation cephalosporins; Antipseudomonal (broad-spectrum) cephalosporins; Beta-lactam antibiotics

Cefoperazone is a beta-lactam antibiotic that binds to penicillin-binding proteins in the bacterial cell wall, inhibiting the final cross-linking (transpeptidation) step of peptidoglycan synthesis. This disrupts cell wall integrity and causes lysis and death of susceptible, actively dividing bacteria (bactericidal effect).

B

The safety and effectiveness of Cefopen in pediatric patients have not been formally established in official product labeling. Cefopen should be used in children only if a physician determines that the potential benefit justifies the potential risk, with dosing individualized and close clinical monitoring, since robust pediatric dosing data are limited. Parents/caregivers should not use Cefopen in a child without explicit medical direction.