Dosing and uses of Timentin (ticarcillin-clavulanate)
Adult dosage forms and strengths
ticarcillin/clavulanate
injection, powder for reconstitution
- (3g/100mg)/vial
- (30g/1g)/bulk vial
ready-to-use IV solution
- (3g/100mg)/100mL
Septicemia
Indicated for septicemia caused by beta-lactamase–producing isolates of Klebsiella spp, Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa
3.1 g IV q4-6hr
Lower Respiratory Infections
Indicated for lower respiratory infections caused by beta-lactamase–producing isolates of S. aureus, Haemophilus influenzae, or Klebsiella spp
3.1 g IV q4-6hr
Bone & Joint Infections
Indicated for bone and joint infections caused by beta-lactamase–producing isolates of S. aureus
3.1 g IV q4-6hr
Skin & Skin Structure Infections
Indicated for skin and skin structure infections caused by beta-lactamase–producing isolates of S. aureus, Klebsiella spp, or E. coli
3.1 g IV q4-6hr
Urinary Tract Infections
Indicated for UTIs (complicated or uncomplicated) caused by beta-lactamase–producing isolates of E. coli, Klebsiella spp, P. aeruginosa (or other Pseudomonas spp), Citrobacter spp, Enterobacter cloacae, Serratia marcescens, or S. aureus
3.1 g IV q4-6hr
Intra-abdominal Infections
Indicated for peritonitis caused by beta-lactamase–producing isolates of E. coli, K. pneumoniae, or Bacteroides fragilis group
3.1 g IV q4-6hr
Gynecologic Infections
Indicated for endometritis caused by beta-lactamase–producing isolates of Prevotella melaninogenicus, Enterobacter spp (including E. cloacae), E. coli, Klebsiella pneumoniae, S. aureus, or Staphylococcus epidermidis
Dose based on ticarcillin component
Moderate: 200 mg/kg/day IV divided q4-6hr
Severe: 300 mg/kg/day IV divided q4hr
Renal Impairment
Load: 3.1 g IV, THEN reduce maintenance dose based on creatinine clearance
CrCl 30-60 mL/min: 2 g q4hr
CrCl 10-30 mL/min: 2 g q8hr
CrCl <10 mL/min: 2 g q12hr
CrCl<10 mL/min & hepatic impairment: 2 g qDay
Peritoneal dialysis: 3 g q12hr
Hemodialysis: 2 g q12hr; supplement with 3 g after each dialysis session
Dosing Considerations
Treatment duration depends upon infection severity, but is typically 10-14 days; however, in difficult and complicated infections, more prolonged therapy may be required
Pediatric dosage forms and strengths
ticarcillin/clavulanate
injection, powder for reconstitution
- (3g/100mg)/vial
- (30g/1g)/bulk vial
ready-to-use IV solution
- (3g/100mg)/100mL
Infections
Dose based on ticarcillin component
<3 months: Safety and efficacy not established
<60 kg and >3 months: 200-300 mg/kg/day IV divided q4-6hr; not to exceed 24 g/day
≥60 kg: As adults; 3.1 g IV q4-6hr
Neonates
- (<7 days old, <2 kg) OR (>7 days old, <1.2 kg): 150 mg/kg/day IV divided q12hr
- (<7 days old, >2 kg) OR (>7 days old, 1.2-2 kg): 225 mg/kg/day IV divided q8hr
- >7 days old, >2 kg: 300 mg/kg/day IV divided q8hr
Cystic Fibrosis
300-600 mg/kg/day IV/IM divided q6hr; not to exceed 24 g/day
Indications
Septicemia caused by beta-lactamase–producing isolates of Klebsiella spp, Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa
Lower respiratory infections caused by beta-lactamase–producing isolates of S. aureus, or Klebsiella spp; note that use is not established for Haemophilus influenzae type B
Bone and joint infections caused by beta-lactamase–producing isolates of S. aureus
Skin and skin structure infections caused by beta-lactamase–producing isolates of S. aureus, Klebsiella spp, or E. coli
UTIs (complicated or uncomplicated) caused by beta-lactamase–producing isolates of E. coli, Klebsiella spp, P. aeruginosa (or other Pseudomonas spp), Citrobacter spp, Enterobacter cloacae, Serratia marcescens, or S. aureus
Peritonitis caused by beta-lactamase–producing isolates of E. coli, K. pneumoniae, or Bacteroides fragilis group
Timentin (ticarcillin-clavulanate) adverse (side) effects
1-10%
Rash
Nausea
Diarrhea
Phlebitis at injection site
Increased eosinophils
Increased ASt
Increased ALt
Postmarketing Reports
Hypersensitivity reactions: Skin rash, pruritus, urticaria, arthralgia, myalgia, drug fever, chills, chest discomfort, anaphylactic reactions, and bullous reactions (including erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome)
CNS: Headache, giddiness, neuromuscular hyperirritability, or convulsive seizures
Gastrointestinal: Disturbances of taste and smell, stomatitis, flatulence, nausea, vomiting and diarrhea, epigastric pain, and pseudomembranous colitis have been reported; onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment
Hemic and lymphatic systems: Thrombocytopenia, leukopenia, neutropenia, eosinophilia, reduction of hemoglobin or hematocrit, and prolongation of prothrombin time and bleeding time
Hepatic function tests: Elevation of AST, ALT, serum alkaline phosphatase, serum LDH, and serum bilirubin; transient hepatitis and cholestatic jaundice reported
Renal: Hemorrhagic cystitis, elevation of serum creatinine and/or BUN, hypernatremia, reduction in serum potassium, and uric acid
Local reactions: Pain, burning, swelling, and induration at the injection site, and thrombophlebitis with IV administration
Warnings
Contraindications
Allergy to penicillins or other beta-lactam antibacterials (eg, cephalosporins, imipenem)
Cautions
Serious and occasionally fatal hypersensitivity reactions reported
Clostridium difficile associated diarrhea reported with use of nearly all antibacterial agents, including ticarcillin
Seizures reported when dose exceeded, especially in presence of renal impairment
Risk of bleeding complication
Potential for microbial overgrowth or bacterial resistance
Laboratory tests: High urine concentrations of ticarcillin may produce false-positive protein reactions; clavulanate may cause a nonspecific binding of IgG and albumin by RBC leading to a false-positive Coombs test
Hypokalemia reported
Monitor renal, hepatic, and hematologic function
Pregnancy and lactation
Pregnancy category: B
Lactation: excreted into breast milk at low concentrations; use caution
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.
Pharmacology of Timentin (ticarcillin-clavulanate)
Mechanism of action
Inhibits cell wall biosynthesis by binding to 1 of more penicillin binding proteins, which subsequently inhibits bacterial cell wall synthesis and has a bactericidal effect
Absorption
Absorption: 86% (IM)
Peak Plasma Time: 30-75 min (IM)
Peak Plasma Concentration: 324 mcg/mL (immediately after 30 min IV infusion of 3.1 g)
AUC: 485 mcg•hr/mL (ticarcillin); 8.2 mcg•hr/mL (clavulanic acid)
Distribution
Protein Bound: 45 (ticarcillin); 25% (Clavulanate)
Distributed into bile, low concentrations in CSF
Metabolism
Liver
Elimination
Half-life: 1.1 hr adults; 4.4 hr neonates; 1 hr infants/children
Excretion: 60-70% urine (ticarcillin), 35-45% (clavulainic acid), excreted unchanged in first 6 hr after administration
Administration
IV Incompatibilities
Additive: sodium bicarbonate, aminoglycosides, ciprofloxacin(?)
Y-site: alatrofloxacin, amphotericin B cholesteryl sulfate, azithromycin, cisatracurium(?), topotecan(?), vancomycin(?)
IV Compatibilities
Solution: compatible w/ most common solvents
Y-site: (partial list) allopurinol, clarithromycin, diltiazem, fluconazole, heparin, meperidine, morphine, ondansetron, propofoL
IV Preparation
Reconstitute 3.1 g vial with 13 mL SWI or NS; final concentration 200 mg/6.7 mg/mL
For intermittent IV infusion, further dilute to 10-100 mg/mL (ticarcillin component with compatible IV solution
Bulk vial 30 g/1 g
- Not for direct infusion
- Reconstitute with 76 mL SWI or NS; final concentration 300 mg/10 mg/mL
- Further dilute before administration to 10-100 mg/mL (ticarcillin component)
IV Administration
Intermittent IV infusion over 30 min
Administer 1 hr apart from aminoglycosides
Storage
Reconstituted solution is stable for 6 hr at room temperature and 72 hr when refrigerated
IV infusion in NS is stable for 24 hr at room temperature and 7 days when refrigerated, or 30 days when frozen
Darkening indicates loss of potency
