TIMENTIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TIMENTIN (TIMENTIN).
Timentin is a combination of ticarcillin, a penicillin-class antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), and clavulanic acid, a beta-lactamase inhibitor that irreversibly inhibits a wide range of beta-lactamase enzymes, thereby preventing degradation of ticarcillin and extending its spectrum to include beta-lactamase-producing organisms.
| Metabolism | Ticarcillin is primarily excreted unchanged in the urine via glomerular filtration and tubular secretion; only a small amount is metabolized to penicilloic acid. Clavulanic acid is extensively metabolized (approximately 70%) and excreted in urine and feces. |
| Excretion | Renal: 60-80% ticarcillin and 50-70% clavulanate excreted unchanged in urine via glomerular filtration and tubular secretion. Fecal: minimal. |
| Half-life | Ticarcillin: ~1.1 hours; clavulanate: ~1.0 hours. Prolonged in renal impairment (CrCl <10 mL/min: ticarcillin half-life ~13 hours). |
| Protein binding | Ticarcillin: ~45% bound to albumin; clavulanate: ~25% bound to albumin. |
| Volume of Distribution | Ticarcillin: 0.2-0.3 L/kg; clavulanate: 0.3 L/kg. Distributed widely in tissues including lungs, pleural fluid, bile, and peritoneal fluid. |
| Bioavailability | IV only; oral bioavailability not applicable. Ticarcillin is not absorbed orally; clavulanate is absorbed orally but combination is only approved as IV formulation. |
| Onset of Action | IV: immediate distribution; clinical effect within 1-2 hours. |
| Duration of Action | 6-8 hours for susceptible organisms; dosing every 4-6 hours due to short half-life. |
3.1 g (ticarcillin 3 g + clavulanic acid 0.1 g) IV every 4-6 hours; for moderate infections, 3.1 g IV every 6 hours; for severe infections, 3.1 g IV every 4 hours.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >60 mL/min: 3.1 g IV every 4-6 hours. CrCl 30-60 mL/min: 3.1 g IV every 6 hours. CrCl 10-30 mL/min: 2 g IV every 8 hours. CrCl <10 mL/min (not on dialysis): 2 g IV every 12 hours. Hemodialysis: 2 g IV every 12 hours; administer dose after dialysis. Peritoneal dialysis: 2 g IV every 12 hours. |
| Liver impairment | No specific dose adjustments for hepatic impairment are recommended; use with caution in severe hepatic dysfunction. |
| Pediatric use | Infants and children <60 kg: 200-300 mg/kg/day (based on ticarcillin component) divided every 4-6 hours; maximum 18 g/day. Neonates: <1.2 kg: 75 mg/kg IV every 12 hours; 1.2-2 kg: 75 mg/kg IV every 12 hours (0-7 days) or every 8 hours (>7 days); >2 kg: 75 mg/kg IV every 8 hours (0-7 days) or every 6 hours (>7 days). |
| Geriatric use | Dose based on renal function; patients >65 years often have decreased CrCl; use renal adjustment guidelines. No specific age-based adjustments beyond renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TIMENTIN (TIMENTIN).
| Breastfeeding | Excreted into breast milk in low concentrations (M/P ratio not established). Considered compatible with breastfeeding; potential for diarrhea and allergic sensitization in infant. Use with caution in mothers of preterm or ill neonates. |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies. Limited human data; risk cannot be excluded. Use if clearly needed. First trimester: not associated with major malformations in available studies. Second/third trimester: no known fetal harm; may cause alterations in intestinal flora. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to ticarcillin, clavulanic acid, any penicillin, or any component of the formulation","History of cholestatic jaundice or hepatic dysfunction associated with ticarcillin/clavulanic acid"]
| Precautions | ["Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have occurred in patients on penicillin therapy","Clostridium difficile-associated diarrhea (CDAD) can occur","Convulsions may occur with high doses or in patients with renal impairment","Hepatic toxicity, including hepatitis and cholestatic jaundice","Electrolyte imbalance, especially in patients with renal insufficiency due to high sodium content","Alterations in coagulation tests (prolongation of prothrombin time) in patients receiving high doses","Renal impairment requires dose adjustment"] |
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| Fetal Monitoring |
| Monitor for allergic reactions, superinfection, and bleeding diatheses. Assess renal function periodically. Monitor for signs of neonatal infection if used near term. |
| Fertility Effects | No known effects on fertility in animal studies. No human data available. |