TIMENTIN IN PLASTIC CONTAINER

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TIMENTIN IN PLASTIC CONTAINER (TIMENTIN IN PLASTIC CONTAINER).

How it works

Timentin is a combination of ticarcillin, a penicillin-class beta-lactam antibiotic, and clavulanate, a beta-lactamase inhibitor. Ticarcillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), while clavulanate irreversibly inhibits beta-lactamases, preventing degradation of ticarcillin.

What the body does with it

Metabolism	Hepatic metabolism is minimal; primarily renal excretion (glomerular filtration and tubular secretion) as unchanged drug. Clavulanate is extensively metabolized in the liver.
Excretion	Renal: ~70-80% of ticarcillin and ~60-70% of clavulanate excreted unchanged in urine within 6 hours. Biliary/fecal: Minor (<5%).
Half-life	Ticarcillin: ~1.2 hours; Clavulanate: ~1.0 hours. Prolonged in renal impairment (ticarcillin up to 15 hours in ESRD).
Protein binding	Ticarcillin: ~45% bound to albumin; Clavulanate: ~25% bound to albumin.
Volume of Distribution	Ticarcillin: ~0.2 L/kg; Clavulanate: ~0.3 L/kg. Distributing into extracellular fluid; low CNS penetration unless inflamed meninges.
Bioavailability	IV: 100% bioavailable. Not administered via other routes due to poor absorption.
Onset of Action	IV: Immediate (within 1 hour) for bactericidal effect. Peak serum concentrations achieved at end of infusion.
Duration of Action	Therapeutic levels persist ~4-6 hours; dosing every 4-6 hours required. Duration extended in renal failure.

Classification & Brands

Dosing & administration

3.1 g (ticarcillin 3 g + clavulanate 0.1 g) IV every 4 to 6 hours; maximum 18 g per day.

Dosage form	INJECTABLE
Renal impairment	CrCl >60 mL/min: 3.1 g IV q4-6h; CrCl 30-60 mL/min: 2 g IV q4h (ticarcillin 2 g); CrCl 10-30 mL/min: 2 g IV q8h; CrCl <10 mL/min: 2 g IV q12h; hemodialysis: 2 g IV q12h, supplemented with 3.1 g after each dialysis.
Liver impairment	No dose adjustment required for hepatic impairment.
Pediatric use	Children >3 months: 50 mg/kg (as ticarcillin) IV q4-6h (max 3.1 g per dose); neonates: 75 mg/kg IV q8h (for <1 week), q6h (for 1-4 weeks) based on ticarcillin component.
Geriatric use	Use with caution due to age-related renal decline; adjust dose based on renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TIMENTIN IN PLASTIC CONTAINER (TIMENTIN IN PLASTIC CONTAINER).

Breastfeeding	Ticarcillin and clavulanate are excreted into human breast milk in low concentrations. M/P ratio not established. Considered compatible with breastfeeding by the American Academy of Pediatrics; however, monitor infant for rash, diarrhea, and candidiasis.
Teratogenic Risk	FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; however, adequate human studies in pregnant women are lacking. Use only if clearly needed. First trimester: Theoretical risk based on animal data; avoid if possible. Second and third trimesters: Generally considered safe; no known fetal harm from penicillins.

Warnings & precautions

■ FDA Black Box Warning

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or sensitivity to multiple allergens.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of hypersensitivity to any penicillin, ticarcillin, or beta-lactam antibiotics. Contraindicated in patients with known hypersensitivity to clavulanate or any component of the formulation.

Clinical Precautions

Precautions

Serious hypersensitivity reactions (anaphylaxis) may occur; cross-allergenicity with cephalosporins. Clostridium difficile-associated diarrhea (CDAD). Bleeding abnormalities have been reported in high doses; monitor prothrombin time. Neurotoxicity (seizures) in renal impairment due to high CNS concentrations. Electrolyte imbalance due to high sodium content (4.75 mEq Na/g ticarcillin). Hypokalemia. Dosage adjustment required in renal impairment. Pseudomembranous colitis.

Clinical Tips & Counseling

Drug interactions

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TIMENTIN IN PLASTIC CONTAINER

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TIMENTIN IN PLASTIC CONTAINER (TIMENTIN IN PLASTIC CONTAINER).

How it works

What the body does with it

Metabolism	Hepatic metabolism is minimal; primarily renal excretion (glomerular filtration and tubular secretion) as unchanged drug. Clavulanate is extensively metabolized in the liver.
Excretion	Renal: ~70-80% of ticarcillin and ~60-70% of clavulanate excreted unchanged in urine within 6 hours. Biliary/fecal: Minor (<5%).
Half-life	Ticarcillin: ~1.2 hours; Clavulanate: ~1.0 hours. Prolonged in renal impairment (ticarcillin up to 15 hours in ESRD).
Protein binding	Ticarcillin: ~45% bound to albumin; Clavulanate: ~25% bound to albumin.
Volume of Distribution	Ticarcillin: ~0.2 L/kg; Clavulanate: ~0.3 L/kg. Distributing into extracellular fluid; low CNS penetration unless inflamed meninges.
Bioavailability	IV: 100% bioavailable. Not administered via other routes due to poor absorption.
Onset of Action	IV: Immediate (within 1 hour) for bactericidal effect. Peak serum concentrations achieved at end of infusion.
Duration of Action	Therapeutic levels persist ~4-6 hours; dosing every 4-6 hours required. Duration extended in renal failure.

Classification & Brands

Dosing & administration

3.1 g (ticarcillin 3 g + clavulanate 0.1 g) IV every 4 to 6 hours; maximum 18 g per day.

Dosage form	INJECTABLE
Renal impairment	CrCl >60 mL/min: 3.1 g IV q4-6h; CrCl 30-60 mL/min: 2 g IV q4h (ticarcillin 2 g); CrCl 10-30 mL/min: 2 g IV q8h; CrCl <10 mL/min: 2 g IV q12h; hemodialysis: 2 g IV q12h, supplemented with 3.1 g after each dialysis.
Liver impairment	No dose adjustment required for hepatic impairment.
Pediatric use	Children >3 months: 50 mg/kg (as ticarcillin) IV q4-6h (max 3.1 g per dose); neonates: 75 mg/kg IV q8h (for <1 week), q6h (for 1-4 weeks) based on ticarcillin component.
Geriatric use	Use with caution due to age-related renal decline; adjust dose based on renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TIMENTIN IN PLASTIC CONTAINER (TIMENTIN IN PLASTIC CONTAINER).

Breastfeeding	Ticarcillin and clavulanate are excreted into human breast milk in low concentrations. M/P ratio not established. Considered compatible with breastfeeding by the American Academy of Pediatrics; however, monitor infant for rash, diarrhea, and candidiasis.
Teratogenic Risk	FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; however, adequate human studies in pregnant women are lacking. Use only if clearly needed. First trimester: Theoretical risk based on animal data; avoid if possible. Second and third trimesters: Generally considered safe; no known fetal harm from penicillins.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

History of hypersensitivity to any penicillin, ticarcillin, or beta-lactam antibiotics. Contraindicated in patients with known hypersensitivity to clavulanate or any component of the formulation.