IV: Note: Timentin® (ticarcillin/clavulanate) is a combination product; each 3.1 g contains 3 g ticarcillin disodium and 0.1 g clavulanic acid. Dosage recommendations are based on ticarcillin component:
General dosing, susceptible infection (Red Book, 2012): IV:
Body weight <1 kg:
PNA ≤14 days: 75 mg ticarcillin/kg/dose every 12 hours
PNA 15-28 days: 75 mg ticarcillin/kg/dose every 8 hours
Body weight ≥1 kg:
PNA ≤7 days: 75 mg ticarcillin/kg/dose every 12 hours
PNA 8-28 days: 75 mg ticarcillin/kg/dose every 8 hours
Note: Timentin has been discontinued from the US market for more than 1 year. Timentin (ticarcillin/clavulanate) is a combination product; each 3.1 g contains 3 g ticarcillin disodium and 0.1 g clavulanic acid. Dosage recommendations are based on ticarcillin component:
General dosing, susceptible infection: Infants, Children, and Adolescents: IV:
Mild to moderate infections: 200 mg ticarcillin/kg/day in divided doses every 6 hours; maximum daily dose: 12 g ticarcillin/day
Severe infections:
Manufacturer's labeling: 300 mg ticarcillin/kg/day in divided doses every 4 hours
AAP recommendations: 200-300 mg ticarcillin/kg/day in divided doses every 4-6 hours
Maximum daily dose: 18 g ticarcillin/day
Cystic fibrosis: Infants, Children, and Adolescents: IV: 400 mg ticarcillin/kg/day in divided doses every 6 hours; higher doses have been used: 400-750 mg ticarcillin/kg/day in divided doses every 6 hours (Zobell, 2013)
Note: Dosage recommendations are based on ticarcillin component:
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following have been used by some clinicians (Aronoff 2007): Dosing based on a usual dose of 200 to 300 ticarcillin mg/kg/day in divided doses every 6 hours.
GFR >30 mL/minute/1.73 m2: No adjustment required.
GFR 10-29 mL/minute/1.73 m2: 50 to 75 mg ticarcillin/kg every 8 hours
GFR <10 mL/minute/1.73 m2 (without concomitant hepatic failure): 50 to 75 mg ticarcillin/kg every 12 hours
GFR <10 mL/minute/1.73 m2 (with concomitant hepatic failure): 50 to 75 mg ticarcillin/kg every 24 hours
Intermittent hemodialysis (without concomitant hepatic failure): 50 to 75 mg ticarcillin/kg every 12 hours
Intermittent hemodialysis (with concomitant hepatic failure): 50 to 75 mg ticarcillin/kg every 24 hours
Peritoneal dialysis (without concomitant hepatic failure): 50 to 75 mg ticarcillin/kg every 12 hours
Peritoneal dialysis (with concomitant hepatic failure): 50 to 75 mg ticarcillin/kg every 24 hours
Continuous renal replacement therapy (CRRT): 50 to 75 mg ticarcillin/kg every 8 hours
There are no pediatric specific recommendations; based on experience in adult patients, dosing adjustment suggested with concomitant renal dysfunction.
(For additional information see "Ticarcillin and clavulanate (United States: Not available): Drug information")
Note: Timentin (ticarcillin/clavulanate) is a combination product; each 3.1 g dosage form contains 3 g ticarcillin disodium and 0.1 g clavulanic acid.
Gynecologic infections (eg endometritis): IV:
Moderate infections: 200 mg ticarcillin/kg/day in divided doses every 6 hours (maximum: 12 g daily)
Severe infections: 300 mg ticarcillin/kg/day in divided doses every 4 hours (maximum: 18 g daily)
Systemic infections: IV:
<60 kg: 200-300 mg ticarcillin/kg/day in divided doses every 4-6 hours (maximum: 18 g daily)
≥60 kg: 3.1 g every 4-6 hours
Urinary tract infections: IV:
<60 kg: 200-300 mg ticarcillin/kg/day in divided doses every 4-6 hours (maximum: 18 g daily)
≥60 kg: 3.1 g every 4-6 hours
Intra-abdominal infection, complicated, community-acquired, mild-to-moderate (off-label use): IV: 3.1 g every 6 hours for 4-7 days (provided source controlled) (Solomkin, 2010)
Loading dose: IV: 3.1 g one dose, followed by maintenance dose based on creatinine clearance:
CrCl 30-60 mL/minute: Administer 2 g of ticarcillin component every 4 hours
CrCl 10-30 mL/minute: Administer 2 g of ticarcillin component every 8 hours
CrCl <10 mL/minute: Administer 2 g of ticarcillin component every 12 hours
CrCl <10 mL/minute with concomitant hepatic dysfunction: 2 g of ticarcillin component every 24 hours
Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (20% to 50%): 2 g of ticarcillin component every 12 hours; supplemented with 3.1 g (ticarcillin/clavulanate) after each dialysis session. Alternatively, administer 2 g every 8 hours without a supplemental dose for deep-seated infections (Heintz, 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD): 3.1 g every 12 hours
Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
CVVH: Loading dose of 3.1g followed by 2 g every 6-8 hours
CVVHD: Loading dose of 3.1 g followed by 3.1 g every 6-8 hours
CVVHDF: Loading dose of 3.1 g followed by 3.1 g every 6 hours
Note: Do not administer in intervals exceeding every 8 hours. Clavulanate component is hepatically eliminated; extending the dosing interval beyond 8 hours may result in loss of beta-lactamase inhibition.
With concomitant renal dysfunction (Clcr <10 mL/minute): 2 g of ticarcillin component every 24 hours.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = discontinued product
Infusion [premixed, frozen]:
Timentin: Ticarcillin 3 g and clavulanic acid 0.1 g (100 mL [DSC]) [contains sodium 4.51 mEq and potassium 0.15 mEq per g]
Injection, powder for reconstitution:
Timentin: Ticarcillin 3 g and clavulanic acid 0.1 g (3.1 g [DSC], 31 g [DSC]) [contains sodium 4.51 mEq and potassium 0.15 mEq per g]
No
Not available in the US
Parenteral: Administer by IV intermittent infusion over 30 minutes
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
IV: Infuse over 30 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
Vials: Store intact vials at ≤24°C (≤75°F). Reconstituted solution is stable for 6 hours at room temperature and 72 hours when refrigerated. IV infusion in NS or LR is stable for 24 hours at room temperature (21°C to 24°C [70°F to 75°F]), 7 days when refrigerated (4°C [39°F]), or 30 days when frozen (-18°C [0°F]). IV infusion in D5W solution is stable for 24 hours at room temperature (21°C to 24°C [70°F to 75°F]), 3 days when refrigerated (4°C [39°F]), or 7 days when frozen (-18°C [0°F]. After freezing, thawed solution is stable for 8 hours at room temperature. Do not refreeze. Darkening of drug indicates loss of potency of clavulanate potassium.
Premixed solution: Store frozen at ≤-20°C (-4°F). Thawed solution is stable for 24 hours at room temperature (22°C [72°F]) or 7 days under refrigeration at (4°C [39°F]); do not refreeze.
Treatment of infections caused by susceptible organisms involving the lower respiratory tract, urinary tract, skin and skin structures, bone and joint, gynecologic, intra-abdominal infections, and septicemia (FDA approved in ages ≥3 months and adults). Clavulanate expands activity of ticarcillin to include beta-lactamase producing strains of S. aureus, H. influenzae, Moraxella catarrhalis, B. fragilis, Klebsiella, Prevotella, P. aeruginosa, Stenotrophomonas maltophilia, E. coli, and Proteus species
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Local thrombophlebitis (with IV injection)
Central nervous system: Confusion, drowsiness, headache, seizure
Dermatologic: Skin rash
Endocrine & metabolic: Electrolyte disturbance, hypernatremia, hypokalemia
Gastrointestinal: Clostridioides difficile-diarrhea, diarrhea, nausea
Genitourinary: Proteinuria (false positive)
Hematologic & oncologic: Bleeding complication, eosinophilia, hemolytic anemia, positive direct Coombs' test (false positive)
Hepatic: Hepatotoxicity, increased serum ALT, increased serum AST, jaundice
Immunologic: Jarisch Herxheimer reaction
Infection: Superinfection (fungal or bacterial)
Renal: Interstitial nephritis (acute)
Miscellaneous: Anaphylaxis
Postmarketing and/or case reports: Abdominal pain, altered sense of smell, arthralgia, chest discomfort, chills, decreased hematocrit, decreased hemoglobin, decreased serum potassium, dizziness, dysgeusia, erythema multiforme, fever, flatulence, headache, hemorrhagic cystitis, hypersensitivity reaction, hypouricemia, increased blood urea nitrogen, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum bilirubin, increased serum creatinine, injection site reaction (burning, induration, pain, swelling), leukopenia, myalgia, myclonus, neutropenia, prolonged prothrombin time, pruritus, pseudomembranous colitis (during or after antibacterial treatment), Stevens-Johnson syndrome, stomatitis, thrombocytopenia, toxic epidermal necrolysis, urticaria, vomiting
Hypersensitivity (history of a serious reaction [eg, anaphylaxis, Stevens-Johnson syndrome]) to ticarcillin, clavulanate, or to other beta-lactams (eg, penicillins, cephalosporins)
Concern related to adverse effects:
• Hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients.
• Bleeding disorders: Particularly in patients with renal impairment, bleeding disorders have been observed; discontinue if thrombocytopenia or bleeding occurs.
• Hypokalemia: Hypokalemia has been reported; monitor serum potassium in patients with fluid and electrolyte imbalance and in patients receiving prolonged therapy.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Heart failure (HF): Use with caution in patients with HF, due to high sodium load.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.
None known.
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tetracyclines: May diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Some products may contain potassium and/or sodium.
Ticarcillin and clavulanate cross the placenta (Maberry 1992).
As a class, penicillin antibiotics are widely used in pregnant women. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Lamont 2014; Muanda 2017a; Muanda 2017b).
Ticarcillin/clavulanate is approved for the treatment of postpartum gynecologic infections, including endometritis, caused by susceptible organisms.
Serum electrolytes, periodic renal, hepatic and hematologic function tests; observe IV injection site for signs of extravasation; observe for signs and symptoms of anaphylaxis during first dose
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs), which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Distribution: Ticarcillin is distributed into tissue, interstitial fluid, pleural fluid, and bile; low concentrations of ticarcillin distribute into the CSF but increase when meninges are inflamed; Vdss:
Ticarcillin: 0.22 L/kg
Clavulanic acid: 0.4 L/kg
Protein binding: Ticarcillin: ~45%; Clavulanic acid: ~25%
Metabolism: Clavulanic acid is metabolized hepatically
Half-life elimination:
Neonates: Ticarcillin: 4.4 hours; Clavulanic acid: 1.9 hours
Children (1 month to 9.3 years): Ticarcillin: 66 minutes; Clavulanic acid: 54 minutes
Adults: Ticarcillin: 66 to 72 minutes; 13 hours (in patients with renal failure); Clavulanic acid: 66 to 90 minutes; clavulanic acid does not affect the clearance of ticarcillin
Time to peak, plasma: Immediately following completion of 30-minute infusion
Excretion:
Children: Ticarcillin: Urine (71% 50% as unchanged drug over 4 hour); Clavulanic acid: Urine (50% as unchanged drug over 4 hours)
Adults: Ticarcillin: Urine (60% to 70% as unchanged drug); Clavulanic acid: Urine (35% to 45% as unchanged drug)
Solution (reconstituted) (Timentin Intravenous)
31 g (1): $159.56
Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly.
