Ticarcillin and clavulanate potassium

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach.
• Loose stools (diarrhea).
• Irritation where the shot is given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If you need to store ticarcillin and clavulanate potassium at home, talk with your doctor, nurse, or pharmacist about how to store it.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

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]

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.

Distribution

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

Metabolism

Clavulanic acid is metabolized hepatically

Excretion

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)

Time to Peak

Immediately following completion of 30-minute infusion

Half-Life Elimination

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

Protein Binding

Ticarcillin: ~45%; Clavulanic acid: ~25%

Intra-abdominal infections

Based on the Infectious Diseases Society of America (IDSA), Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children guidelines, ticarcillin and clavulanate potassium is an effective and recommended treatment option for children with community-acquired intra-abdominal infections and adults with community-acquired intra-abdominal infections of mild to moderate severity (eg, perforated or abscessed appendicitis).

Cystic fibrosis exacerbations

Data from a clinical review suggests the use of ticarcillin and clavulanate potassium in the management of cystic fibrosis exacerbations [Zobell 2013]. Additional trials may be necessary to determine the clinical efficacy of higher than FDA-approved doses for this condition.

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)

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.

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.