COMPOSITION :
Doripenem Monohydrate Powder for Infusion 500 mg, each infusion bottle contains : Doripenem monohydrate equivalent to Doripenem 500 mg.
DESCRIPTIONS :
Doripenem Monohydrate containing Doripenem monohydrate (equivalent to Doripenem) as active ingredient is available in powder for infusion 500 mg.
INDICATIONS :
Doripenem Monohydrate is indicated for the treatment of infections in adult patients of the following infections :
- Nosocomial pneumonia (include pneumonia due to ventilator use).
- Complicated intra-abdominal infections.
Consideration should be given to proper management of antibacterial use.
DOSAGE AND ADMINISTRATIONS :
Dosage :
The recommended dosage and administration based on the infection shown in the following table :
| Infection | Dosage | Frequency | Infusion time |
| Nosocomial pneumonia (include due to ventilator use) | 500 mg | every 8 hours | 1 or 4 hours* |
| Complicated intra-abdominal
infection |
500 mg | every 8 hours | 1 hour |
* Mainly based on pharmacokinetic/pharmacodynamic considerations, 4 hours infusion time may be suitable for infection with less sensitive pathogens. This dosing regimen should also be considered especially in severe infections.
Duration of Doripenem therapy is usually between 5 – 14 days and should be monitored according to the severity, location of the infection and the patient’s clinical response. Doripenem usage over 14 days still not been proven in clinical studies. After a good clinical response arises in the use of intravenous Doripenem, therapy may be continued with appropriate oral therapy.
Dosage in pediatric patients :
Doripenem Monohydrate is not recommended for use in children below 18 years of age due a limited of safety and efficacy data.
Dosage in patients with decreased renal function :
In patients with mild renal impairment (i.e., creatinine clearance (CrCl) is 51 – 79 ml/minute), no dosage adjustment is required. In patients with moderate renal impairment (CrCl 30 – < 50 ml/minute), the dose of Doripenem Monohydrate to be administered is 250 mg every 8 hours. In patients with severe renal impairment (CrCl < 30 ml/minute), the dose of Doripenem Monohydrate to be administered is 250 mg every 12 hours. Special attention should be given to the patients with severe renal decreased function who use Doripenem Monohydrate due to limitations of clinical data and the possibility of increased exposure to Doripenem and its metabolites.
Dosage in patients on dialysis :
Doripenem Monohydrate could excreted through dialysis, however there is insufficient information to make dose adjustment recommendations for patients undergoing dialysis. Therefore, Doripenem Monohydrate is not recommended in patients undergoing dialysis.
Dosage in elderly patients (> 65 years of age) :
No dosage adjustment is required in elderly patients, unless a moderate to severe decreased renal function is detected.
Dosage in patients with decreased liver function :
No dose adjustment required.
Administration :
Doripenem Monohsedydrate should be reconstituted and further dilution before intravenous infusion for 1 or 4 hours.
Reconstitution instructions :
Doripenem Monohydrate may be reconstituted by adding one of the appropriate solvent to the mark (100 ml) and then shake well until completely dissolved. The solvent that can be used are NaCl 0.9% infusion solution; Dextrose 5% infusion solution in water.
Stability of reconstituted Doripenem monohydrate :
After reconstitution with Sodium chloride 9 mg/ml (0.9%) solution for injection or Dextrose 50 mg/ml (5%) solution for injection, Doripenem Monohydrate infusion stored at controlled room temperature or in refrigeration should be completed in times in the following table :
| Infusion solution | Solution stored at
room temperature |
Solution stored in a
refrigerator (2 – 8°C) |
| Sodium chloride 9 mg/ml (0.9%) solution for injection | 12 hours | 72 hours* |
| + Dextrose 50 mg/ml (5%) solution for injection | 4 hours | 24 hours* |
* Once removed from the refrigerator, infusion should be completed in room temperature stability time, given total cooling time, time to reach room temperature and the infusion time does not exceed the cooling stability time.
+ Dextrose 50 mg/ml (5%) solution for injection should not be used for infusion with durations more than 1 hour.
Chemical and physical in-use stability has been shown in the time and the solutions shown in the above table.
From a microbiological point of view, the product should be used immediately. If not immediately used, in-use storage time and pre-use conditions are user responsibility and usually not more than 24 hours at 2 – 8°C, unless reconstitution has occured in controlled and validated aseptic conditions.
Incompatibility :
This drug should not be mixed with other drugs except those mentioned above.
OVERDOSAGE :
Overdosage cases have not been reported. In the event of overdosage, Doripenem administration should be discontinued and supportive therapy given until Doripenem is eliminated by the kidneys. Doripenem can be removed by haemodialysis. However, no information is available on the use of haemodialysis to treat overdosage.
CONTRAINDICATIONS :
- Hypersensitive to Doripenem.
- Hypersensitive to any other Carbapenem antibacterial agent.
- Severe hypersensitivity (e.g., anaphylactic reaction, severe skin reaction) to all other type of beta-lactam antibacterial agent (e.g., Penicillins or Cephalosporins).
WARNINGS AND PRECAUTIONS :
- Hypersensitivity reaction : Serious hypersensitivity reactions and occasionally fatal (anaphylactic) have occurred in patient receiving betalactam antibiotics. Before initiation of therapy with Doripenem, an examination history of hypersensitivity to other active substances in this class or to betalactam antibiotics should be performed. Doripenem should be used with caution in patients with that a history. When hypersensitivity reactions occur, Doripenem administration should be discontinued immediately and appropriate measures should be taken. Serious acute hypersensitivity (reactions) anaphylactic required immediate emergency treatment.
- Seizures : Although rare, seizures have been reported to occur during treatment with Carbapenem.
- Pseudomembranous colitis : Same as the use of other antibacterial agent, pseudomembranous colitis caused by Clostridium difficile have been reported in the use of Doripenem with variations in severity ranging from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea during or after Doripenem administration (see ADVERSE REACTIONS).
- Superinfection : Doripenem administration like other antibiotics, has been associated with emergence and selection of strains with decreased sensitivity. Patients should be monitored carefully during therapy. If superinfection occurs, appropriate measures should be taken. Long-term use of Doripenem should be avoided.
- Pneumonitis : Pneumonitis may occur if Doripenem is used by inhalation. Therefore, Doripenem should not be administered by inhalation.
- Pregnancy : Clinical data on the use of Doripenem in pregnancy is very limited. The potential risk for humans is unknown. Doripenem should not be used during pregnancy unless it is necessary.
- Lactation : It is not known whether Doripenem is excreted in human breast milk. Studies in mice showed Doripenem and its metabolites were excreted through breast milk. A decision to continue/discontinue breastfeeding or therapy with Doripenem should be established by considering the benefits of breastfeeding for childern and the benefits of Doripenem therapy for mother.
- Effects on ability to drive and use machines : There is no specific study on the effects of Doripenem on ability to drive and use machines. Based on adverse effects were found, Doripenem does not affect that ability. The use of Doripenem 1 g every 8 hours for 7 days showed a higher mortality rate than the administration of Imipenem-cilastatin for 10 days.
DRUG INTERACTIONS :
- Doripenem is only slightly not even completely metabolized through the cytochrome P450 (CYP450). Based on in vitro studies Doripenem does not inhibit or induce CYP450 activity. Therefore, there is no drug interaction associated with CYP450.
- Carbapenem antibacterial agent may decrease Valproic acid serum levels. Valproic acid serum levels should be monitored if Doripenem is administered concomitantly with Valproic acid.
- Probenecid competes with Doripenem in secretion in the renal tubules and decreases the Doripenem clearance through the kidneys. In an interaction study, the average of Doripenem AUC increased by 75% after use along with Probenecid. Therefore, co-administration Probenecid with Doripenem is not recommended. Interactions with other drugs that are eliminated by renal tubular secretion should also be considered.
ADVERSE REACTIONS :
Adverse reaction that cause discontinuation of Doripenem is nausea, diarrhea, itching, vulvomycotic infections, elevated liver enzymes and skin rashes. Common adverse reaction are headache, diarrhea and nausea.
| Identified adverse reactions | |
| Infection and infestation | Oral candidiasis, vulvomycotic infection |
| Immune system disorders | Hypersensitivity reactions (see WARNINGS AND PRECAUTIONS) |
| Nervous system disorders | Headache |
| Vascular disorders | Phlebitis |
| Gastrointestinal disorders | Nausea, diarrhea, Colitis caused by C. difficile colitis (see WARNINGS AND PRECAUTIONS) |
| Hepatobiliary disorders | Elevated liver enzymes |
| Skin and subcutaneous tissue disorders | Itchy, rash |
| Identified adverse reaction during post marketing | |
| Blood and system lymphatic disorders | Not known : Neutropenia |
| Immune system disorders | Not known : Anaphylaxis (see WARNINGS AND PRECAUTIONS) |
PRESENTATION :
Doripenem Monohydrate Powder for Infusion 500 mg Box, 1 bottle@ 500 mg
Reg. No. GKL1702355480A1
STORAGE :
STORE BELOW 30ºC
After reconstituted, Doripenem Monohydrate with Sodium chloride 9 mg/ml (0.9%) solution for injection can be stored up to 12 hours at room temperature and 72 hours at refrigeration (2 – 8°C). Meanwhile, Doripenem Monohydrate with Dextrose 50 mg/ml (5%) in water solution for injection can be stored up to 4 hours at temperature room and 24 hours at refrigeration (2 – 8ºC).
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
