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Ticarcillin and Clavulanate Potassium

Medically reviewed by Drugs.com. Last updated on Jul 31, 2023.

Pronunciation

(tye kar SIL in & klav yoo LAN ate poe TASS ee um)

Index Terms

Dosage Forms

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]

Detailed Clavulanate / ticarcillin dosage information

Brand Names: U.S.

Pharmacologic Category

Pharmacology

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

Metabolism

Clavulanic acid is metabolized hepatically

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)

Time to Peak

Immediately following completion of 30-minute infusion

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

Protein Binding

Ticarcillin: ~45%; Clavulanic acid: ~25%

Use: Labeled Indications

Bone and joint infections: Treatment of bone and joint infections caused by beta-lactamase-producing isolates of Staphylococcus aureus.

Endometritis: Treatment of endometritis caused by beta-lactamase-producing isolates of Prevotella melaninogenicus, Enterobacter species (including E. cloacae), Klebsiella pneumoniae, Escherichia coli, S. aureus, or Staphylococcus epidermidis.

Lower respiratory tract infections: Treatment of lower respiratory tract infections caused by beta-lactamase-producing isolates of S. aureus, Haemophilus influenzae, or Klebsiella species.

Peritonitis: Treatment of peritonitis caused by beta-lactamase-producing isolates of E. coli, K. pneumonia, or Bacteroides fragilis group.

Septicemia: Treatment of septicemia (including bacteremia) caused by beta-lactamase-producing isolates of Klebsiella species, E. coli, S. aureus, or Pseudomonas aeruginosa (or other Pseudomonas species).

Skin and skin structure infections: Treatment of skin and skin structure infections caused by beta-lactamase-producing isolates of S. aureus, Klebsiella species, or E. coli.

Urinary tract infections: Treatment of complicated and uncomplicated urinary tract infections caused by beta-lactamase-producing isolates of E. coli, Klebsiella species, P. aeruginosa (and other Pseudomonas species), Citrobacter species, Enterobacter cloacae, Serratia marcescens, or S. aureus.

Off Label Uses

Intra-abdominal infections

Based on the Infectious Diseases Society of America (IDSA), Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children guidelines, ticarcillin and clavulanate potassium is an effective and recommended treatment option for adults with community-acquired intra-abdominal infections of mild to moderate severity (eg, perforated or abscessed appendicitis).

Cystic fibrosis exacerbations

Data from a clinical review suggests the use of ticarcillin and clavulanate potassium in the management of cystic fibrosis exacerbations [Zobell 2013]. Additional trials may be necessary to determine the clinical efficacy of higher than FDA-approved doses for this condition.

Contraindications

Hypersensitivity (history of a serious reaction [eg, anaphylaxis, Stevens-Johnson syndrome]) to ticarcillin, clavulanate, or to other beta-lactams (eg, penicillins, cephalosporins)

Dosing: Adult

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)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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)

Reconstitution

Reconstitute 3.1 g vials with 13 mL sterile water for injection or NS; shake well; resulting concentration is ticarcillin 200 mg/mL and clavulanic acid 6.7 mg/mL. Reconstitute 31 g bulk vials with 76 mL sterile water for injection or NS; shake well; resulting concentration is ticarcillin 300 mg/mL and clavulanic acid 10 mg/mL. Further dilute to a final concentration of 10-100 mg/mL in D5W, LR, or NS.

Administration

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.

Dietary Considerations

Some products may contain potassium and/or sodium.

Storage

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.

Drug Interactions

Acemetacin: May increase the serum concentration of Penicillins. Monitor therapy

Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. Avoid combination

Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. 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. Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. 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. Consider therapy modification

Tetracyclines: May diminish the therapeutic effect of Penicillins. 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. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Clavulanate / ticarcillin drug interactions (more detail)

Test Interactions

Positive Coombs' test, false-positive urinary proteins

Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro, leading to a potential underestimation of aminoglycoside serum concentration.

Adverse Reactions

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 (formerly Clostridium) 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

Clavulanate / ticarcillin side effects (more detail)

Warnings/Precautions

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.

Monitoring Parameters

Observe for signs and symptoms of anaphylaxis during first dose; serum electrolytes, bleeding time, and periodic tests of renal, hepatic, and hematologic function

Pregnancy Risk Factor B Pregnancy Considerations

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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