(tye kar SIL in & klav yoo LAN ate poe TASS ee um)
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.
Hypersensitivity (history of a serious reaction [eg, anaphylaxis, Stevens-Johnson syndrome]) to ticarcillin, clavulanate, or to other beta-lactams (eg, penicillins, cephalosporins)
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)
Refer to adult dosing
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.
Mild to moderate infections: Infants ≥3 months, Children, and Adolescents: IV:
<60 kg: 200 mg ticarcillin/kg/day in divided doses every 6 hours (maximum: 12 g daily)
≥60 kg: 3.1 g every 6 hours
Severe infections: Infants ≥3 months, Children, and Adolescents: IV:
<60 kg: 300 mg ticarcillin/kg/day in divided doses every 4 hours. (maximum: 18 g daily)
≥60 kg: 3.1 g every 4 hours
Cystic fibrosis (off-label use): 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 (maximum: 24-30 g ticarcillin daily) (Zobell, 2013)
Intra-abdominal infection, complicated (off-label use): Infants, Children, and Adolescents: IV: 200-300 mg ticarcillin/kg/day in divided every 4-6 hours (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.
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.
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.
Some products may contain potassium and/or sodium.
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.
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]
Stable in D5W, LR, NS, SWFI.
Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, azithromycin.
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Consider therapy modification
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. Avoid combination
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. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification
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
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Observe for signs and symptoms of anaphylaxis during first dose; serum electrolytes, bleeding time, and periodic tests of renal, hepatic, and hematologic function
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.
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: 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 (Limited to important or life-threatening): Altered sense of smell, chest discomfort, chills, decreased hematocrit, decreased hemoglobin, decreased serum potassium, dizziness, dysgeusia, erythema multiforme, flatulence, headache, hemorrhagic cystitis, hypersensitivity reaction, hypouricemia, increased blood urea nitrogen, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum creatinine, injection site reaction (burning, induration, pain, swelling), leukopenia, myalgia, myoclonus, neutropenia, prolonged prothrombin time, pruritus, pseudomembranous colitis (during or after antibacterial treatment), Stevens-Johnson syndrome, stomatitis, thrombocytopenia, toxic epidermal necrolysis, urticaria
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.
B
Adverse events were not observed in animal reproduction studies. Ticarcillin and clavulanate cross the placenta (Maberry, 1992). Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects (Crider, 2009; Santos, 2011). Ticarcillin/clavulanate is approved for the treatment of postpartum gynecologic infections, including endometritis, caused by susceptible organisms.
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.
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
Clavulanic acid is metabolized hepatically
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)
Immediately following completion of 30-minute infusion
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
Ticarcillin: ~45%; Clavulanic acid: ~25%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea or diarrhea. Have patient report immediately to prescriber signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), bruising, bleeding, injection site irritation or edema, seizures, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.