Timentin

High urine concentrations of ticarcillin (>1500 mg/L 2 hours after an i.v. injection of 3.1 g Timentin) may produce false positive protein reactions (pseudoproteinuria) with the following methods: sulfosalicylic acid and boiling test, acetic acid test, biuret reaction, and nitric acid test. The bromphenol blue (Multi-stix) reagent strip test has been reported to be reliable.

The presence of clavulanic acid in Timentin may cause a non-specific binding of IgG and albumin by red cell membranes, leading to a false positive Coombs' test.

Timentin should not be mixed with an aminoglycoside in the same container. Penicillins can cause substantial inactivation of aminoglycosides.

Probenecid decreases the renal tubular secretion of ticarcillin, thereby increasing serum concentrations and prolonging serum half-life of the antibiotic. Concurrent administration of probenecid delays ticarcillin renal excretion but does not delay the excretion of clavulanic acid.

In common with other antibiotics, ticarcillin may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral contraceptives.

Trace quantities of Timentin are excreted in breast milk. Timentin may be administered during the period of lactation. With the exception of the risk of sensitization, there are no detrimental effects for the breast-fed infant.

The safety and efficacy for the treatment of infections in infants from birth to 1 month of age have not been established.

The safety of Timentin in the treatment of infections during human pregnancy is unknown. Timentin should only be used during pregnancy if the anticipated benefit to the mother justifies the potential risk to the fetus.

Each vial contains: sterile ticarcillin disodium equivalent to ticarcillin 30 g and sterile potassium clavulanate equivalent to clavulanic acid 1 g.

Store at or below 24°C.

Each vial contains: sterile ticarcillin disodium equivalent to ticarcillin 3 g and sterile potassium clavulanate equivalent to clavulanic acid 0.1 g.

C. difficile-associated Disease: C. difficile-associated disease (CDAD) has been reported with use of many antibacterial agents, including Timentin. CDAD may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration of any antibacterial agent. CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

Treatment with antibacterial agents may alter the normal flora of the colon and may permit overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. CDAD may cause significant morbidity and mortality. CDAD can be refractory to antimicrobial therapy.

If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should be initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not directed against C. difficile. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial agent clinically effective against C. difficile. Surgical evaluation should be instituted as clinically indicated, as surgical intervention may be required in certain severe cases (see Adverse Effects).

elevation of serum creatinine and/or BUN, hypernatremia. Reduction in serum potassium and uric acid. Hypokalaemia has been reported rarely. Hemorrhagic cystitis has been reported very rarely.

Increased muscle weakness in patients with myasthenia gravis has been reported.

disturbances of taste and smell, stomatitis, flatulence, nausea, vomiting and diarrhea, epigastric pain. Pseudomembranous colitis has been reported (see Warnings, Gastrointestinal, C. difficile-associated Disease).

a moderate rise in ALT and/or AST. Elevation of serum alkaline phosphatase, serum LDH, and serum bilirubin. Hepatitis and cholestatic jaundice have been reported very rarely.

skin rash, pruritus, urticaria, arthralgia, myalgia, drug fever, chills, chest discomfort, bronchospasm, wheezing, and anaphylactic reactions.

Bullous reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported very rarely.

thrombocytopenia, leukopenia, neutropenia, eosinophilia and reduction of hemoglobin or hematocrit. Prolongation of prothrombin time and bleeding time. Bleeding manifestations have occurred.

pain, burning, erythema, swelling and induration at the injection site and phlebitis and thrombophlebitis with i.v. administration.

headache, giddiness, or neuromuscular hyperirritability. Convulsions, particularly in patients with impaired renal function or in those receiving high doses.

Gastrointestinal effects such as nausea, vomiting and diarrhea may be evident and should be treated symptomatically.

Disturbances of the fluid and electrolyte balance may be evident and may be treated symptomatically.

Timentin overdosage has the potential to cause neuromuscular hyperirritability or convulsive seizures.

Ticarcillin and clavulanic acid may be removed from circulation by hemodialysis.

For surgical prophylaxis, administration should not exceed the recommended dosage regimen, since the continued administration of any antibiotic increases the risk of adverse reactions while, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.

A 3-dosage regimen is recommended as follows: Patients Undergoing Cesarean Section: Administer the first dose of 3.1 g Timentin as soon as the umbilical cord is clamped. The second and third dosage of 3.1 g should be administered at 4 hour intervals after the initial dose, for a total of 3 doses.

Patients Undergoing Abdominal Hysterectomy or Colorectal Surgery: Administer the first dose of 3.1 g Timentin one-half to 1 hour prior to the initial incision. The second and third dosage of 3.1 g should be administered at 4-hour intervals after the initial dose for a total of 3 doses.

Treatment: Dosage for any individual patient must take into consideration the site and severity of infection, the susceptibility of the organisms causing infection, and the status of the patient's host defense mechanisms.

The recommended dosage for adults (60 kg or greater) is 3.1 g every 4 to 6 hours.

For patients weighing less than 60 kg, the recommended dosage is 200-300 mg/kg/day, based on ticarcillin content, given in divided doses every 4 to 6 hours.

The duration of therapy depends upon the severity of infection. Generally, Timentin should be continued for at least 2 days after signs and symptoms of infection have disappeared. The usual duration is 10 to 14 days; however, in difficult and complicated infections, more prolonged therapy may be required. In certain infections, involving abscess formation, appropriate surgical drainage should be performed in conjunction with antimicrobial therapy.