COMPOSITIONS :
Imipenem Monohydrate – Cilastatin Sodium IV Powder for Infusion 1 g, each bottle contains : Imipenem monohydrate equivalent to Imipenem 500 mg and Cilastatin sodium equivalent to Cilastatin 500 mg.
DESCRIPTIONS :
Imipenem Monohydrate – Cilastatin Sodium with active ingredient Imipenem monohydrate (equivalent to Imipenem) and Cilastatin sodium (equivalent to Cilastatin) are available in 1 g of sterile powder for infusion in bottle pack.
INDICATIONS :
- Treatment :
Imipenem Monohydrate – Cilastatin Sodium is indicated for the treatment of infections caused by susceptible microorganisms in the conditions listed below :
- Intra-abdominal infections.
- Lower respiratory tract infections.
- Gynecological infections.
- Septicemia.
- Genitourinary tract infections.
- Bone and joint infections.
- Skin and soft tissue infections.
- Endocarditis.
Imipenem Monohydrate − Cilastatin Sodium is not indicated for the treatment of meningitis.
- Prophylaxis :
Imipenem Monohydrate − Cilastatin Sodium is indicated for the prevention of certain post-operative infections in patient undergoing contaminated surgical procedures or where the occurrence of post-operative infection could be especially serious.
DOSAGE AND ADMINISTRATIONS :
The dosage recommendations for Imipenem Monohydrate – Cilastatin Sodium represent the quantity of Imipenem to be administered. An equivalent amount of Cilastatin is also present. The total daily dosage and route administration of Imipenem Monohydrate – Cilastatin Sodium should be based on the type of severity of infection and given in equally divided doses based on consideration of degree of susceptibility of the pathogen (s), renal function and body weight. Doses cited are based on body weight of 70 kg.
ADULTS :
- Treatment :
Most infections respond to a daily dose of 1 − 2 g administered in 3 − 4 divided doses (see Table 1). For the treatment of moderate infection, a 1 g twice daily dosage regimen may also be used. In infections due to less susceptible organisms, the daily dosage of Imipenem Monohydrate – Cilastatin Sodium may be increased to a maximum of 4 g/day or 50 mg/kg/day, whichever is lower.
Each 250 mg or 500 mg dose of Imipenem Monohydrate – Cilastatin Sodium should be given by intravenous infusion over 20 to 30 minutes. Each 1000 mg dose should be infused over 40 to 60 minutes. In patients who develop nausea during the infusion, the rate of infusion may be slowed.
Table 1. Adult dosage of Imipenem Monohydrate – Cilastatin Sodium
| Severity of infection | Dose
(mg of Imipenem) |
Dosage interval | Total daily dosage |
| Mild | 250 mg | 6 hours | 1 g |
| Moderate | 500 mg
1000 mg |
8 hours
12 hours |
1.5 g
2 g |
| Severe – fully susceptible | 500 mg | 6 hours | 2 g |
| Severe and/or life threatening due to less
susceptible organisms (primarily some strains of P. aeruginosa) |
1000 mg
1000 mg |
8 hours
6 hours |
3 g
4 g |
Due to high antimicrobial activity of Imipenem Monohydrate – Cilastatin Sodium, it is recommended maximum total daily dosage not exceed 50 mg/kg/day or 4 g/day, whichever is lower. However, cystic fibrosis patients with normal renal function have been treated with Imipenem Monohydrate – Cilastatin Sodium at doses up to 90 mg/kg/day in divided dose, not exceeding 4 g/day.
- Prophylaxis :
For prophylaxis against post-surgical infections in adults, 1000 mg Imipenem Monohydrate – Cilastatin Sodium should be given intravenously on induction of anesthesia and 1000 mg 3 hours later.
For high risk (e.g., colorectal) surgery, two additional 500 mg doses can be given at 8 and 16 hours after induction.
- Patient with renal insufficiency :
As in patient with normal renal function dosing is based on the severity of the infection. The maximum dosage of Imipenem Monohydrate – Cilastatin Sodium for patients with various degrees of renal function impairment is shown in table 2. Doses cited are based on a body weight of 70 kg.
Proportionate reduction in dose administered should be made for patients with lower body weight.
Table 2. Maximum dosage Imipenem Monohydrate – Cilastatin Sodium in relation to renal function
| Renal function (creatinine clearance ml/minute/1.73m2) | Dose (mg) | Dosage interval
(hours) |
Maximum total daily dosage (g)* |
| Mild impairment
31 − 70 |
500 | 6 − 8 | 1.5 − 2 |
| Moderate impairment
21 − 30 |
500
|
8 − 12 | 1 − 1.5 |
| Severe **impairment
0 − 20 |
250 − 500 | 12 | 0.5 − 1.0 |
Note :
* = The higher dosage should be reserved for infections due to less susceptible organisms.
** = Patients with creatinine clearance of 6 to 20 ml/minute/1.73m2 should be treated with 250 mg (or 3.5 mg/kg whichever is lower) every 12 hours for must pathogens. When the 500 mg dose is used in these patients, there may be an increased risk of seizures. Patients with creatinine clearance of ≤ 5 ml/minute/1.73m2 should not receive Imipenem Monohydrate – Cilastatin Sodium. Unless hemodialysis is instituted within 48 hours.
Both Imipenem and Cilastatin are cleared from the circulation during hemodialysis. The patients should receive Imipenem Monohydrate – Cilastatin Sodium after hemodialysis and at 12 hours .intervals timed from the end of that hemodialysis session. Dialysis patients, especially those .with background CNS disease, should be carefully monitored; for patients on hemodialysis, .Imipenem Monohydrate – Cilastatin Sodium is recommended only when the benefit outweights the .potential risk of seizures.
Currently there are inadequate data to recommend use of Imipenem Monohydrate – Cilastatin Sodium for patients on peritoneal dialysis. Renal status of elderly patients may not be accurately .portrayed by measurement of BUN or creatinine alone. Determination of creatinine clearance is .suggested to provide guidance for dosing in such patients.
PEDIATRIC :
Safety and effectiveness in children below 12 years have not been established.
RECONSTITUTION INTRAVENOUS SOLUTION
- Imipenem Monohydrate − Cilastatin Sodium for intravenous infusion is supplied as a sterile powder in bottles containing 500 mg Imipenem and 500 mg Cilastatin equivalent..
- Imipenem Monohydrate − Cilastatin Sodium is buffered with sodium bicarbonate to provide solutions in the pH range of 6.5 to 7.5. There is no significant change in pH when solution are prepared and used as directed.
- Imipenem Monohydrate − Cilastatin Sodium 500 contains 37.5 mg of Sodium (1.6 mEq).
- Sterile powder Imipenem Monohydrate − Cilastatin Sodium should be reconstituted as shown in table 3. It should be shaken until a clear solution is obtained. Variations of color, from colorless to yellow, do not affect the potency of the product.
Table 3. Reconstitution of Imipenem Monohydrate – Cilastatin Sodium
| Dose IV
Imipenem Monohydrate – Cilastatin Sodium (mg of Imipenem) |
Volume of diluent
(ml) |
Approximate average Concentration of IV
(mg/ml of Imipenem) |
| 500 | 100 | 5 |
Reconstitution instruction :
Imipenem Monohydrate − Cilastatin Sodium IV can be reconstituted by adding one of the appropriate diluents (see stability of reconstituted of Imipenem Monohydrate − Cilastatin Sodium) to the mark (100 ml), and then shake well until completely dissolved.
- Stability of reconstituted of Imipenem Monohydrate − Cilastatin Sodium :
| Diluent | Stability period | |
| Cool temperature (25°C) | Refrigeration (5°C) | |
| Isotonic Sodium Chloride | 10 hours | 48 hours |
| Dextrose 5% in water | 4 hours | 24 hours |
CAUTION : Imipenem monohydrate – Cilastatin Sodium is chemically incompatible with lactate and should not be reconstituted in diluents containing lactate. Imipenem Monohydrate – Cilastatin Sodium can be administered, however, into an IV system through which a lactate solution is being infused.
Imipenem monohydrate – Cilastatin Sodium should not be mixed with or physical added to other antibiotics.
CONTRAINDICATION :
Patients who have shown hypersensitivity to any component of this product.
WARNINGS AND PRECAUTIONS :
- Patients known to be hypersensitive to Penicillins, Cephalosporins or other beta-lactams because of the possibility of cross-allergenicity.
- Caution in patient with a history of gastrointestinal disease, particularly colitis. It is important to consider a diagnosis of pseudomembranous colitis in patient with develop diarrhea is association with antibiotic use. While studies indicate that a toxin produced by Clostridium difficile is primary cause of antibiotics associated colitis, other cause should also be considered.
- Prolonged use of Imipenem − Cilastatin may result in overgrowth of nonsusceptible organisms.
- Use in pregnancy : Imipenem − Cilastatin should be used during pregnancy only if clearly needed.
- Use in nursing woman : Imipenem − Cilastatin is deemed essential, the patients should stop nursing.
- Patients with CNS disorders : CNS side effects such as myoclonic activity, confusional states or seizures have been reported. 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 Imipenem − Cilastatin should be decreased or discontinued.
- Patients with creatinine clearance of ≤ 5 ml/minute/1.73m2 should not receive Imipenem − Cilastatin unless hemodialysis is instituted within 48 hours. Imipenem − Cilastatin is recommended only when the benefit outweights the potential risk of seizures.
DRUG INTERACTIONS :
- Generalized seizures have been reported in patients who received Ganciclovir and Imipenem − Cilastatin.
- Concomitant administrations of Imipenem − Cilastatin and Probenecid results in only minimal increase in plasma levels and plasma half-life of Imipenem. It is not recommended that Probenecid be given with Imipenem monohydrate − Cilastatin sodium.
- Imipenem monohydrate − Cilastatin sodium should not be mixed with or physically added to other antibiotics. However, Imipenem − Cilastatin may be administered concomitantly with other antibiotics, such as Aminoglycosides.
ADVERSE REACTIONS :
- Local reactions : Erythema, local pain and induration, thrombophlebitis.
- Allergic reactions : Rash, pruritus, urticaria, toxic epidermal necrolysis (rarely), fever, anaphylactic reactions.
- Gastrointestinal : Nausea, vomiting, diarrhea, pseudomembranous colitis.
- Blood : Eosinophilia, leucopenia, neutropenia, including agranulocytosis, thrombocytopenia, thrombocytosis, and decreased hemoglobin and hepatitis (rarely) have been reported. A positive direct Coomb’s test may develop some individuals.
- Liver function : Mild increase in serum transaminases, bilirubin and/or serum alkaline phosphatase have been reported.
- Renal function : Oliguria/anuria, polyuria, acute renal failure (rarely), elevations in serum creatinine and blood urea nitrogen, reddish urine discoloration.
- Central nervous system : Agitation and dyskinesia
Myoclonic activity, psychic disturbances, confusional states or seizure have been reported.
- Special senses : Taste perversion.
PRESENTATION :
Imipenem Monohydrate – Cilastatin Sodium IV Powder for Infusion 1 g Box, 1 bottle @ 1 g
Reg. No. GKL1202346680A1
STORAGE :
STORE BELOW 25ºC AND DRY PLACE
After reconstitution, Imipenem Monohydrate – Cilastatin Sodium IV with Isotonic Sodium Chloride diluent can be stored up to 10 hours at cool temperature (25ºC) and 48 hours at refrigeration (5ºC). Meanwhile, Imipenem Monohydrate – Cilastatin Sodium IV with Dextrose 5% in water can be stored up to 4 hours at cool temperature (25ºC) and 24 hours at refrigeration (5ºC).
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo − Indonesia
