Ticarcillin Disodium–Clavulanate Potassium

Brand names Timentin

Medication error None reported potential

Contraindications Contraindications: In patients with a known serious hypersensitivity to ticarcillin, cla- and warnings vulanate, or any of the beta-lactams(2) Warnings: Serious hypersensitivity and occasionally fatal anaphylactic reactions have been reported.(2) These are more likely in patients who are sensitive to multiple allergens and in those with a history of type I reaction to or .(2) (See Appendix C for specific information.) Ticarcillin–clavulanate use may cause superinfection and/or Clostridium difficile-associated diarrhea (CDAD), which has been reported and may range in severity from mild diarrhea to fatal colitis.(2) If CDAD is suspected or confirmed, appropriate fluid and electrolyte management, protein supplementation, treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.(2) Patients with renal impairment are at higher risk for bleeding; they are also at risk for convulsions when higher than recommended doses are used.(2)

Infusion-related None reported cautions

Dosage Dosage is based on ticarcillin component. Clavulanate is a beta-lactamase inhibitor that extends the spectrum of ticarcillin.(2) If meningitis is suspected or documented an alternate agent with demonstrated clinical efficacy in this setting should be used.(2) Neonates: Safety and efficacy has not been established in those <3 months of age.(2)

PNA 1200–2000 g ≥2000 g

<7 days 150–160 mg/kg/day 150–240 mg/kg/day divided q 12 hr(3,4) divided q 8–12 hr(3,5)

≥7 days 160–225 mg/kg/day 225–240 mg/kg/day divided q 8 hr(3,5)* divided q 8 hr(3,5)

*Until 4 weeks of age One study of 11 premature neonates weighing <2200 g suggested a dose of 200 mg/kg/day divided q 6 hr.(6) Infants and children 200–300 mg/kg/day divided q 4–6 hr(2,3,7-9)

Dosage adjustment Adjust dose in renal dysfunction.(2,13) If CrCl is >30 mL/min, give a normal dose; if CrCl in organ dysfunction is 10–29 mL/min, give 50–75 mg/kg q 8 hr; if <10 mL/min, give 50–75 mg/kg q 12 hr; and if <10 mL/min and hepatic insufficiency, give 50–75 mg/kg q 24 hr.(13) Alternatively, the manufacturer recommends for adults if CrCl 30–60 mL/min, give a two-third normal dose q 4 hr; if CrCl 10–30 mL/min, give a two-third dose q 8 hr; if CrCl <10 mL/min, give a two-third dose q 12 hr; and if CrCl <10 mL/min with hepatic insufficiency, give a two-third dose q 24 hr.(2)  818 Ticarcillin Disodium–Clavulanate Potassium

Maximum dosage 300 mg/kg/day,(2,3) up to 400 mg/kg/day has been reported as safe in pediatric patients with cystic fibrosis.(14) Not to exceed 18 g/day of ticarcillin.(2,3)

Additives Contains 4.51 mEq of sodium and 0.15 mEq of potassium per g of ticarcillin.(2,15) The frozen injection of 3.1 g/100 mL contains 0.187 mEq/mL of sodium and 0.005 mEq/mL of potassium.(2,15)

Suitable diluents D5W, LR, SW, or NS(15)

Maximum <100 mg/mL (ticarcillin).(15,2) 43 mg/mL in NS, 48 mg/mL in D5W, and 86 mg/mL in SW concentration for peripheral infusion.(15)

Preparation and Delivery system issues: The mixing of ticarcillin with an aminoglycoside in vitro can delivery result in substantial inactivation of the aminoglycoside. (See Appendix C for more specific information.) Stability: Store intact vials at <24°C.(15) Diluted solutions in NS or LR are stable for 24 hours at room temperature, 7 days when refrigerated, or 30 days when frozen. Solu- tion in D5W is stable for 24 hours at room temperature, 3 days when refrigerated, or 7 days when frozen. After freezing, thawed solution is stable for 8 hours at room tem- perature. Store frozen at ≤−18°C. Thawed solution should be used within 8 hours.(2) Do not refreeze.(2,15) Darkened solution indicates loss of potency of clavulanate.(15) Compatibility: See Appendix D for PN compatibility information.(16)

IV push Not used

Intermittent infusion Over 30 minutes(2,15)

Continuous infusion Has been reported in pediatric patients with CF(22) and adults.(17)

Other routes of None administration

Comments Rare adverse effects: Neurotoxicity may occur with large doses of , especially in patients with renal insufficiency.(2,18-20) Thrombocytopenia and bleeding disorders associated with abnormalities in clotting time, platelet aggregation, and prothrombin time have been reported with ticarcillin.(2,21) These are more likely to occur in patients with renal impairment.(2) If bleeding manifestations appear, treatment should be discontinued and appropriate therapy instituted.(2) Elevation of serum transaminases, serum alkaline phosphatase, serum lactate dehydro- genase, and serum bilirubin have been noted.(2) Hepatitis and cholestatic jaundice have also been reported.(2) Laboratory interference: High urine concentrations may produce false-positive protein reactions (pseudoproteinuria); however, the bromphenol blue reagent strip test appears reliable.(2) The presence of may cause a nonspecific binding of IgG and albumin by red cell membranes leading to a false-positive Coombs test.(2)

REFERENCES 2. Timentin [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; June 2014. 3. American Academy of Pediatrics; Kimberlin DW. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015. 4. Fayed SB, Sutton AM, Turner TL, et al. The prophylactic use of ticarcillin/clavulanate in the neonate. J Antimicrob Chemother. 1987;19(1):113–118. 5. Miall-Allen VM, Whitelaw AG, Darrell JH. Ticarcillin plus clavulanic acid (Timentin) compared with standard antibiotic regimes in the treatment of early and late neonatal infections. Br J Clin Pract. 1988;42(7):273–279.  819