cefotetan (Rx)

1-10%

Diarrhea (1%)

Hepatic enzyme elevation (1%)

Hypersensitivity reaction (1%)

<1%

Prolongation of bleeding time

Neutropenia

Thrombocytopenia

Immune-mediated hemolytic anemia

Contraindications (additional)

Documented hypersensitivity

Coagulation disorders

Cautions (additional)

Reduce dosage by 1/2 if <10-30 mL/min creatinine clearance and by 1/4 if <10 mL/min; (high doses may cause CNS toxicity); bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy

Associated with rare but potentially fatal hemolytic anemia - monitor as needed

Current US formulation does not allow direct IV or IM administration

Inappropriate for pediatric mild-moderate infections (AAP)

Pregnancy

Available data from published observational studies and case reports over several decades with drug use in pregnant women have not established a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes

Animal data

• In animal reproduction studies, no adverse developmental effects were observed when pregnant rats and monkeys were treated, during period of organogenesis, at doses up to approximately 3 and 2 times maximum recommended human dose (MRHD), respectively
• Maternal gonorrhea may be associated with preterm birth, low neonatal birth weight, chorioamnionitis, intrauterine growth restriction, small for gestational age and premature rupture of membranes; perinatal transmission of gonorrhea to offspring can result in infant blindness, joint infections and bloodstream infections

Lactation

Published literature reports that drug is present in human milk at low levels following intravenous administration; there is no information regarding effects of cefotetan on milk production or the breastfed infant; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Second-generation cephalosporin used as single-drug therapy to provide broad gram-negative coverage and anaerobic coverage. Also provides some coverage of gram-positive bacteria. Half-life is 3.5 h. Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death

Pharmacokinetics

Half-Life: 2.8-4.6 hr

Peak Plasma Time: 1.5-3 hr (IM)

Protein Bound: 76-90%

Distribution: Body fluids & tissue, including bile, sputum, prostatic & peritoneal fluids, low in CSF

Metabolism: Liver

Excretion: urine primarily unchanged; feces (20%)

IV Incompatibilities

Additive: aminoglycosides, heparin, tetracyclines

Syringe: doxapram, promethazine

Y-site: cisatracurium(?), promethazine, vancomycin, vinorelbine

IV Compatibilities

Solution: D5W, NS

Y-site: allopurinol, amifostine, aztreonam, bivalirudin, dexmedetomidine, diltiazem, docetaxel, etoposide PO4, famotidine, fenoldopam, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, Hextend, reg insulin, linezolid, melphalan, meperidine, morphine SO4, paclitaxel, propofol, remifentanil, sargramostim, tacrolimus, teniposide, theophylline, thiotepa

IV Preparation (for powder)

Solution: add 10 mL diluent to 1 g vial; withdraw 10.5 mL (95 mg/mL)

IV Administration

Intermittent infusion over 20-60 min

Do not administer with other drugs

Canadian (but not US) formulations allow for IV inj or deep IM