Ticarcillin & Clavulanate
Common Brand Names: Timentin
Therapeutic Class: Penicillinase-resistant extended spectrum penicillin antibiotic
Common Injectable Dosage Forms:
Powder for Injection: 3 g ticarcillin (as disodium)/0.1 g clavulanate potassium
Solution for Injection: 3 g ticarcillin (as disodium)/0.1 g clavulanate potassium in 100 mL premixed, frozen vials
Dosage Ranges:
For the treatment of serious infections due to susceptible organisms including urinary tract infections (UTI), bone and joint infections, skin and skin structure infections, intra-abdominal infections, septicemia, postpartum endometritis or pelvic inflammatory disease, and lower respiratory tract infections: The usual dose is 3 g (ticarcillin) every 4-6 hours given as IV infusion. In the treatment of UTI, the normal dose is 3 g every 6-8 hours given as IV infusion. Dosage reduction may be necessary in the presence of renal impairment.
Administration and Stability: Dilute with 13 mL of Sterile Water for Injection or Sodium Chloride for Injection. Shake well after mixing. After dilution, the concentration of the solution will be 200 mg ticarcillin/mL. For intermittent IV infusion, dilute as described above and further dilute to a concentration of 10 mg/mL with a compatible solution (D5W, NS). Stable at concentrations between 10-100 mg/mL for 24 hours at room temperature and 7 days refrigerated in NS, and 24 hours at room temperature and 3 days refrigerated in D5W. pH 5.5-7.5
Pharmacology/Pharmacokinetics: Ticarcillin acts by inhibiting bacterial wall synthesis via acylation of the transpeptidase enzyme. It is susceptible to cleavage by beta-lactamase. Ticarcillin is active against many anaerobic, Gram-negative, and Gram-positive bacteria. It is particularly useful for Pseudomonas and Klebsiella, as well as certain indole-positive Proteus species. Clavulanate is an inhibitor of beta-lactamase penicillinase. Peak concentration occurs immediately after an IV infusion. The plasma half-life of ticarcillin is approximately 1 hour. Up to 45% is bound to plasma proteins. Distribution to the meninges occurs during inflammation. Excretion occurs predominantly through the urine by glomerular filtration and tubular secretion.
Drug and Lab Interactions: May inactivate aminoglycosides when mixed in the same solution. TETRACYCLINES may inhibit actions. May potentiate the actions of warfarin or heparin. Probenecid increases serum levels. May cause false-positive urine glucose tests if Clinitest, Benedict’s Solution or Fehling’s Solution is used. May cause a false-positive Coombs test.
Contraindications/Precautions: Contraindicated in patients hypersensitive to penicillins and/or cephalosporins. Use bacteriologic studies to determine optimum therapy. Severe neurovascular damage has occurred after administration of other penicillins so prompt attention must be given to any sign of a compromise of the blood supply distal, proximal, or at the injection site. As with all antibiotics, the possibility of superinfections should be considered. Pregnancy Category B.
Monitoring Parameters: Observe for signs and symptoms of anaphylaxis during first dose, CBC, LFTs, renal function.
Adverse Effects: Adverse effects are uncommon but may include diarrhea, nausea, taste and small disturbances, vomiting, headache, insomnia, rash, pruritus, and pain at the injection site. Large doses may cause reversible neurotoxicity or nephrotoxicity. May cause an increase in prothrombin time. If hypersensitivity reactions occur, manifested by urticaria, edema, laryngospasm, bronchospasm, or hypotension, discontinue use and institute supportive treatment. Severe diarrhea may be a sign of pseudomembranous colitis and warrants immediate attention. May elevate SGOT, SGPT, serum alkaline phosphatase, serum LDH, serum bilirubin, serum creatinine, and sodium.
Common Clinical Applications: Effective for bacterial septicemia, lower respiratory infections, bone and joint infections, skin and soft tissue infections, urinary tract and gynecological infections, and intra-abdominal infections.