ticarcillin disodium and clavulanate potassium
Timentin

Available forms
Available by prescription only
Injection: 3 g ticarcillin and 100 mg clavulanic acid

Indications and dosages
 Infections of the lower respiratory tract, urinary tract, bones and joints, and skin and skin structure; intra-abdominal infections; septicemia when caused by susceptible organisms. Adults: 3.1 g (contains 3 g ticarcillin and 0.1 g clavulanate potassium) diluted in 50 to 100 ml D₅W, saline solution, or lactated Ringer’s injection and administered by I.V. infusion over 30 minutes q 4 to 6 hours.
Children ages 3 months to 16 years who weigh less than 60 kg (132 lb): For mild to moderate infections, 200 mg/kg daily (contains 3 g ticarcillin and 0.1 g clavulanate potassium) I.V. infusion given in divided doses q 6 hours. For severe infections, 300 mg/kg daily (contains 3 g ticarcillin and 0.1 g clavulanate potassium) I.V. given in divided doses q 4 hours.
 Gynecologic infections. Adults who weigh 60 kg or more: 200 mg/kg daily in divided doses q 6 hours. For more severe infections, 300 mg/kg daily in divided doses q 4 hours.
≡ Dosage adjustment. For patients with renal impairment, loading dose is 3.1 g (3 g ticarcillin with 100 mg clavulanate).

Creatinine clearance (ml/min) Dosage in adults 30-60 2 g I.V. q 4 hr 10-30 2 g I.V. q 8 hr < 10 2 g I.V. q 12 hr < 10 with hepatic failure 2 g I.V. q 24 hr

Pharmacodynamics
Antibiotic action: Ticarcillin is bactericidal; it adheres to bacterial penicillin-binding proteins, inhibiting bacterial cell wall synthesis. Extended-spectrum penicillins are more resistant to inactivation by certain beta-lactamases, especially those produced by gram-negative organisms but are still susceptible to inactivation by certain others.
Clavulanic acid has only weak antibacterial activity and doesn’t affect the action of ticarcillin. However, clavulanic acid has a beta-lactam ring and is structurally similar to penicillin and cephalosporins; it binds irreversibly with certain beta-lactamases, preventing inactivation of ticarcillin and broadening its bactericidal spectrum.
Spectrum of activity of ticarcillin includes many gram-negative aerobic and anaerobic bacilli, many gram-positive and gram-negative aerobic cocci, and some gram-positive aerobic and anaerobic bacilli. The combination of ticarcillin and clavulanate potassium is also effective against many beta-lactamase-producing strains, including Staphylococcus aureus, Haemophilus influenzae, Neisseria gonorrhoeae, Escherichia coli, Bacteroides fragilis, and Klebsiella and Providencia species but it’s not effective against Pseudomonas aeruginosa.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Distributed widely. It penetrates minimally into CSF with uninflamed meninges; clavulanic acid penetrates into pleural fluid, lungs, and peritoneal fluid. Ticarcillin sodium achieves high levels in urine. Protein-binding is 45% to 65% for ticarcillin and 22% to 30% for clavulanic acid; both cross the placental barrier.
Metabolism: About 13% of a ticarcillin dose is metabolized by hydrolysis to inactive compounds; clavulanic acid is thought to undergo extensive metabolism, but its fate is as yet unknown.
Excretion: Ticarcillin is excreted primarily (83% to 90%) in urine by renal tubular secretion and glomerular filtration; it’s also excreted in bile and in breast milk. Metabolites of clavulanate are excreted in urine by glomerular filtration and in breast milk. Elimination half-life of ticarcillin in adults is about 1 hour and that of clavulanate is about 1 hour; in severe renal impairment, half-life of ticarcillin is extended to about 8 hours and that of clavulanate to about 3 hours. Both drugs are removed by hemodialysis but only slightly by peritoneal dialysis.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other penicillins. Use cautiously in patients with other drug allergies, especially to cephalosporins, impaired renal function, hemorrhagic conditions, hypokalemia, or sodium restrictions.

Interactions
Drug-drug. Aminoglycoside antibiotics: Chemically incompatible. Don’t mix in the same I.V. container.
Hormonal contraceptives: Decreases efficacy of contraceptive. Advise patient to use another contraceptive method.
Probenecid: Increases serum ticarcillin level. Monitor patient carefully.

Adverse reactions
CNS: seizures, neuromuscular excitability, headache, giddiness.
CV: vein irritation, phlebitis.
GI: nausea, diarrhea, stomatitis, vomiting, epigastric pain, flatulence, pseudomembranous colitis, taste disturbance.
Hematologic: leukopenia, neutropenia, eosinophilia, thrombocytopenia, hemolytic anemia, anemia, positive Coombs’ test.
Metabolic: hypokalemia, hypernatremia.
Skin: pain at injection site.
Other: hypersensitivity reactions (rash, pruritus, urticaria, chills, fever, edema, anaphylaxis), overgrowth of nonsusceptible organisms, smell disturbances.

Effects on lab test results
• May increase ALT, AST, alkaline phosphatase, LDH, and sodium levels. May decrease potassium level.
• May increase eosinophil count. May decrease hemoglobin and platelet, WBC, and granulocyte counts.

Overdose and treatment
Overdose may cause neuromuscular hypersensitivity and seizures.
 Ticarcillin disodium and clavulanate potassium can be removed by hemodialysis.

Special considerations
• The combination drug ticarcillin disodium and clavulanate potassium is almost always used with another antibiotic such as an aminoglycoside in life-threatening situations.
• Administer aminoglycosides 1 hour before or after administration of ticarcillin disodium and clavulanate potassium.
• Ticarcillin contains 5.2 mEq of sodium per gram of drug. Use cautiously in patients with sodium restriction.
• Because ticarcillin disodium and clavulanate potassium is dialyzable, patients undergoing hemodialysis may need dosage adjustments.
• Monitor renal and hepatic function.
• Monitor serum electrolytes. Observe for signs of hypernatremia and hypokalemia.
• Monitor neurologic status. High blood levels may cause seizures.
• The combination drug ticarcillin disodium and clavulanate potassium alters tests for urinary or serum proteins; it interferes with turbidimetric methods that use sulfosalicylic acid, trichloroacetic acid, acetic acid, or nitric acid. Ticarcillin disodium/clavulanate potassium doesn’t interfere with tests using bromophenol blue (Albustix, Albutest, MultiStix). It may falsely decrease serum aminoglycoside level.
Pregnant patients
• Use drug during pregnancy only when clearly needed.
Breast-feeding patients
• Ticarcillin and clavulanate potassium appear in breast milk. Use cautiously in breast-feeding women.
Geriatric patients
• Half-life may be prolonged in geriatric patients because of impaired renal function.

Patient education
• Advise patient of adverse effects and advise limiting salt intake during drug therapy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use