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. |
| Molecular Weight | 494.5 |
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 | Authorized for use; consider only if clearly needed. No evidence of harm in animal studies, but limited human data. |
| 2nd trimester | Authorized for use; consider only if clearly needed. No evidence of harm in animal studies, but limited human data. |
| 3rd trimester | Authorized for use; consider only if clearly needed. Caution due to potential alteration of gut flora in neonate if given near term. |
Clinical note
Comprehensive clinical and safety monograph for TIMENTIN (TIMENTIN).
| Placental transfer | Crosses placenta; detectable in fetal serum and amniotic fluid. |
| Breastfeeding | Ticarcillin and clavulanate are excreted into breast milk in low amounts; compatible with breastfeeding. Use with caution in infants with known hypersensitivity or diarrhea. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to ticarcillin, clavulanate, or any penicillinHistory of severe allergic reaction to beta-lactams
| 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 |
| Food/Dietary | No significant food interactions. May be taken with or without food. Avoid alcohol during therapy. |
Loading safety data…
| Lactation Rating |
| L2 (Safer) |
| 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. |
| 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. |
| Clinical Pearls | Timentin (ticarcillin/clavulanate) is an extended-spectrum penicillin/beta-lactamase inhibitor combination. Use with caution in patients with renal impairment; adjust dose for CrCl <60 mL/min. Not active against MRSA or Pseudomonas aeruginosa strains with upregulated efflux pumps. Monitor for bleeding risk due to ticarcillin's antiplatelet effect. Do not mix with aminoglycosides in same IV line; administer separately. |
| Patient Advice | Take this medication exactly as prescribed; finish the entire course even if you feel better. · Notify your doctor if you develop diarrhea, rash, or unusual bleeding/bruising. · Avoid alcohol while taking this medication to reduce risk of side effects. · Inform your doctor if you are pregnant, breastfeeding, or have kidney disease. · This medication may interfere with birth control pills; use an alternative method. |