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GENERAL: There is some clinical and laboratory evidence of partial cross-allergenicity between TIENAM and the other beta-lactam antibiotics, penicillins and cephalosporins. Severe reactions (including anaphylaxis) have been reported with most beta-lactam antibiotics. Before therapy with TIENAM, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics. If an allergic reaction to TIENAM occurs, the drug should be discontinued and appropriate measures undertaken.
Case reports in the literature have shown that co-administration of carbapenems, including imipenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Increasing the dose of valproic acid or divalproex sodium may not be sufficient to overcome this interaction. The concomitant use of imipenem and valproic acid/divalproex sodium is generally not recommended. Anti-bacterials other than carbapenems should be considered to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of TIENAM is necessary, supplemental anti-convulsant therapy should be considered (See INTERACTIONS.)
Pseudomembranous colitis has been reported with virtually all antibiotics and can range from mild to life- threatening in severity. Antibiotics should, therefore, be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis. It is important to consider a diagnosis of pseudomembranous colitis in patients who develop diarrhea in association with antibiotic use. While studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic-associated colitis, other causes should also be considered.
CENTRAL NERVOUS SYSTEM: As with other beta-lactam antibiotics, CNS side effects such as myoclonic activity, confusional states, or seizures have been reported with the I.V. formulation, especially when recommended dosages based on renal function and body weight were exceeded. These experiences have been reported most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) and/or compromised renal function in whom accumulation of the administered entities could occur. Hence, close adherence to recommended dosage schedules is urged, especially in these patients (see DOSAGE & ADMINISTRATION). Anticonvulsant therapy should be continued in patients with a known seizure disorder.
If focal tremors, myoclonus or seizures occur, patients should be evaluated neurologically and placed on anticonvulsant therapy if not already instituted. If CNS symptoms continue, the dosage of TIENAM should be decreased or discontinued.
Patients with creatinine clearances of ≤ 5 mL/min/1.73m2 should not receive TIENAM unless hemodialysis is instituted within 48 hours. For patients on hemodialysis, TIENAM is recommended only when the benefit outweighs the potential risk of seizures.
EFFECTS ON ABILITY TO DRIVE OR OPERATE MACHINERY: There are some side effects associated with this product that may affect some patients' ability to drive or operate machinery (see SIDE EFFECTS).
USE IN PREGNANCY: There are no adequate and well-controlled studies in pregnant women. TIENAM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
USE IN LACTATION: Imipenem has been detected in human milk. If the use of TIENAM is deemed essential, the patient should stop nursing.
USE IN CHILDREN: Use of TIENAM in pediatric patients, neonates to 16 years of age, is supported by evidence from adequate and well-controlled studies of TIENAM in adults and by the following clinical studies and published literature in pediatric patients: Based on published studies of 178* pediatric patients ≥3 months of age (with non-CNS infections), the recommended dose of TIENAM is 15-25 mg/kg/dose administered every six hours. Doses of 25 mg/kg/dose in patients 3 months to <3 years of age, and 15 mg/kg/dose in patients 3-12 years of age were associated with mean trough plasma concentrations of imipenem of 1.1±0.4 µg/mL and 0.6±0.2 µg/mL following multiple 60-minute infusions, respectively; trough urinary concentrations of imipenem were in excess of 10 µg/mL for both doses. These doses have provided adequate plasma and urine concentrations for the treatment of non-CNS infections. Based on studies in adults, the maximum daily dose for treatment of infections with fully susceptible organisms is 2.0 g per day, and of infections with moderately susceptible organisms (primarily some strains of P. aeruginosa) is 4.0 g/day. (See Table 3, DOSAGE & ADMINISTRATION.) Higher doses (up to 90 mg/kg/day in older children) have been used in patients with cystic fibrosis. (See DOSAGE & ADMINISTRATION.)
* Two patients were less than 3 months of age.
Based on studies of 135** pediatric patients ≤3 months of age (weighing ≥1,500 gms), the following dosage schedule is recommended for non-CNS infections: <1 wk of age: 25 mg/kg every 12 hrs.
1-4 wks of age: 25 mg/kg every 8 hrs.
4 wks-3 mos. of age: 25 mg/kg every 6 hrs.
** One patient was greater than 3 months of age.
In a published dose-ranging study of smaller premature infants (670-1,890 gms) in the first week of life, a dose of 20 mg/kg q12h by 15-30 minutes infusion was associated with mean peak and trough plasma imipenem concentrations of 43 µg/mL and 1.7 µg/mL after multiple doses, respectively. However, moderate accumulation of cilastatin in neonates may occur following multiple doses of TIENAM The safety of this accumulation is unknown.
TIENAM is not recommended in pediatric patients with CNS infections because of the risk of seizures. TIENAM is not recommended in pediatric patients <30 kg with impaired renal function (serum creatinine >2 mg/dL), as no data are available. (See also Intravenous Infusion: Treatment: Pediatric Dosage Schedule under Dosage & Administration.)
