2.1 Adults
The usual recommended dosage for systemic and urinary tract infections for adults is 3.1 grams of TIMENTIN (3 grams ticarcillin and 100 mg clavulanic acid) given every 4 to 6 hours.
For gynecologic infections, TIMENTIN should be administered as follows (based on ticarcillin content): Moderate infections, 200 mg/kg/day in divided doses every 6 hours; severe infections, 300 mg/kg/day in divided doses every 4 hours.
For patients weighing less than 60 kg, the recommended dosage is 200 to 300 mg/kg/day given in divided doses every 4 to 6 hours.
The duration of therapy depends upon the severity of infection. The usual duration is 10 to 14 days; however, in difficult and complicated infections, more prolonged therapy may be required.
2.2 Pediatric Patients (≥3 Months of Age)
Patients <60 kg: Mild to moderate infections, 200 mg/kg/day based on ticarcillin content in divided doses every 6 hours; severe infections, 300 mg/kg/day in divided doses every 4 hours.
Patients ≥60 kg: Mild to moderate infections, 3.1 grams every 6 hours; severe infections, 3.1 grams every 4 hours.
2.3 Renal Impairment
For patients with renal insufficiency, an initial loading dose of 3.1 grams should be followed by doses based on creatinine clearance and type of dialysis as indicated in Table 1.
Table 1. Dosage Adjustments for Renal Impairment
Creatinine Clearance (mL/minute)a
Dosageb
Over 60
3 grams every 4 hours
30 to 60
2 grams every 4 hours
10 to 30
2 grams every 8 hours
Less than 10
2 grams every 12 hours
Less than 10 with hepatic dysfunction
2 grams every 24 hours
Patients on peritoneal dialysis
3 grams every 12 hours
Patients on hemodialysis
2 grams every 12 hours supplemented with 3 grams after each dialysis
a To calculate creatinine clearance1 from a serum creatinine value use the following formula:
Ccr = (140–Age) (weight in kg)/72 x Scr (mg/100 mL)
This is the calculated creatinine clearance for adult males; for females it is 15% less.
b Based on ticarcillin content.
2.4 Administration and Directions for Use
TIMENTIN should be administered by intravenous infusion over a 30-minute period.
Directions for Reconstitution and Further Dilution: 3.1‑gram Glass Vials: The 3.1‑gram vial should be reconstituted by adding approximately 13 mL of Sterile Water for Injection, USP, or Sodium Chloride Injection, USP, and shaking well. When dissolved, the concentration of ticarcillin will be approximately 200 mg/mL with a corresponding concentration of 6.7 mg/mL for clavulanic acid. The color of reconstituted solutions of TIMENTIN normally ranges from light to dark yellow, depending on concentration, duration, and temperature of storage.
The dissolved drug should be further diluted to desired volume using the recommended solution listed under Stability [see Dosage and Administration (2.5)] to a concentration between 10 mg/mL to 100 mg/mL.
Pharmacy Bulk Package: The container closure may be penetrated only one time utilizing a suitable sterile transfer device or dispensing set that allows measured distribution of the contents. A sterile substance that must be reconstituted prior to use may require a separate closure entry.
Restrict use of Pharmacy Bulk Packages to an aseptic area such as a laminar flow hood.
Reconstituted contents of the vial should be withdrawn immediately. However, if this is not possible, aliquoting operations must be completed within 4 hours of reconstitution. Discard the reconstituted stock solution 4 hours after initial entry.
Add 76 mL of Sterile Water for Injection, USP, or Sodium Chloride Injection, USP, to the 31‑gram Pharmacy Bulk Package and shake well. For ease of reconstitution, the diluent may be added in 2 portions. Each 1 mL of the resulting concentrated stock solution contains approximately 300 mg of ticarcillin and 10 mg of clavulanic acid.
The desired dosage should be withdrawn from the stock solution and further diluted to desired volume using the recommended solution listed under Stability [see Dosage and Administration (2.5)] to a concentration between 10 mg/mL to 100 mg/mL.
Directions for Intravenous Infusion: After reconstitution and further dilution and prior to administration, TIMENTIN should be inspected visually for particulate matter. If particulate matter is present, the solution should be discarded.
The solution of reconstituted drug may be administered over a 30-minute period by direct infusion or through a Y‑type intravenous infusion set. If this method of administration is used, it is advisable to temporarily discontinue the administration of any other solutions during the infusion of TIMENTIN.
When TIMENTIN is given in combination with another antimicrobial, such as an aminoglycoside, each drug should be given separately in accordance with the recommended dosage and routes of administration for each drug [see Drug Interactions (7.1)].
GALAXY® Container (PL 2040 Plastic): Prior to administration, TIMENTIN should be inspected visually for particulate matter. If particulate matter is present, the solution should be discarded.
Caution: Do not use plastic containers in series connections. Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.
Preparation for Administration: See How Supplied/Storage and Handling (16) for thawing and handling instructions:
•
Suspend the container from eyelet support.
•
Remove protector from outlet port at bottom of container.
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Attach administration set. Refer to complete directions accompanying set.
2.5 Stability
NOTE: TIMENTIN is incompatible with Sodium Bicarbonate.
3.1‑gram Glass Vials: The concentrated stock solution at 200 mg/mL is stable for up to 6 hours at room temperature 21° to 24°C (70° to 75°F) or up to 72 hours under refrigeration 4°C (40°F).
If the concentrated stock solution (200 mg/mL) is held for up to 6 hours at room temperature 21° to 24°C (70° to 75°F) or up to 72 hours under refrigeration 4°C (40°F) and further diluted to a concentration between 10 mg/mL and 100 mg/mL with any of the diluents listed below, then the following stability periods apply.
STABILITY PERIOD
(3.1‑gram Vials)
Intravenous Solution
(ticarcillin concentrations of
10 mg/mL to 100 mg/mL)
Room Temperature
21° to 24°C (70° to 75°F)
Refrigerated
4°C (40°F)
Dextrose Injection 5%, USP
24 hours
3 days
Sodium Chloride Injection, USP
24 hours
7 days
Lactated Ringer’s Injection, USP
24 hours
7 days
If the concentrated stock solution (200 mg/mL) is stored for up to 6 hours at room temperature and then further diluted to a concentration between 10 mg/mL and 100 mg/mL, solutions of Sodium Chloride Injection, USP, and Lactated Ringer’s Injection, USP, may be stored frozen –18°C (0°F) for up to 30 days. Solutions prepared with Dextrose Injection 5%, USP, may be stored frozen –18°C (0°F) for up to 7 days. All thawed solutions should be used within 8 hours or discarded. Once thawed, solutions should not be refrozen.
Unused solutions must be discarded after the time periods listed above.
Pharmacy Bulk Package: Aliquots of the reconstituted stock solution at 300 mg/mL are stable for up to 6 hours between 21° and 24°C (70° and 75°F) or up to 72 hours under refrigeration 4°C (40°F). The reconstituted stock solution should be held under refrigeration 4°C (40°F).
If the aliquots of the reconstituted stock solution (300 mg/mL) are held up to 6 hours between 21° and 24°C (70° and 75°F) or up to 72 hours under refrigeration 4°C (40°F) and further diluted to a concentration between 10 mg/mL and 100 mg/mL with any of the diluents listed below, then the following stability periods apply.
STABILITY PERIOD
(31‑gram Pharmacy Bulk Package)
Intravenous Solution
(ticarcillin concentrations of
10 mg/mL to 100 mg/mL)
Room Temperature
21° to 24°C (70° to 75°F)
Refrigerated
4°C (40°F)
Dextrose Injection 5%, USP
24 hours
3 days
Sodium Chloride Injection 0.9%, USP
24 hours
4 days
Lactated Ringer’s Injection, USP
24 hours
4 days
Sterile Water for Injection, USP
24 hours
4 days
If an aliquot of concentrated stock solution (300 mg/mL) is stored for up to 6 hours between 21° and 24°C (70° and 75°F) and then further diluted to a concentration between 10 mg/mL and 100 mg/mL, solutions of Sodium Chloride Injection, USP, Lactated Ringer’s Injection, USP, and Sterile Water for Injection, USP, may be stored frozen –18°C (0°F) for up to 30 days. Solutions prepared with Dextrose Injection 5%, USP, may be stored frozen –18°C (0°F) for up to 7 days. All thawed solutions should be used within 8 hours or discarded. Once thawed, solutions should not be refrozen.
Unused solutions must be discarded after the time periods listed above.
GALAXY Container (PL 2040 Plastic): Do not add supplementary medication to the container. The thawed solution is stable for 24 hours at room temperature 22°C (72°F) or for 7 days under refrigeration at 4°C (39°F).
