Medicinal Products

DORIBAX 250 mg

Generic drug of the therapeutic class: Infectiology - Parasitology
Active ingredients: Doripenem
laboratory: Janssen Cilag Internat NV

Powder for IV infusion solution
Box of 10 vials of 250 mg
All forms

Indication

Doribax is indicated in adults for the treatment of the following infections (see sections Warnings and Precautions and Pharmacodynamic Properties ):

• Nosocomial pneumonia (including mechanically ventilated pneumonia)

• Complicated intra-abdominal infections

• Complicated urinary tract infections

Official recommendations concerning the appropriate use of antibacterials should be taken into account.

Dosage DORIBAX 250 mg Powder for solution for infusion IV Box of 10 vials of 250 mg

Dosage

The recommended dosages as well as the modalities of administration according to the type of infection are presented in the table below:

Infection Dose Frequency Duration of infusion
Nosocomial pneumonia, including 500 mg every 8 hours 1 or 4 hours *
acquired pneumonia under ventilation
mechanical
Complicated intra-abdominal infections 500 mg every 8 hours 1 hour
Complicated urinary tract infections, 500 mg every 8 hours 1 hour
including pyelonephritis

* Based primarily on pharmacokinetic-pharmacodynamic considerations, a 4-hour infusion may be more appropriate for the treatment of infections with pathogens of diminished sensitivity (see section 5.1 ). This dosage regimen must also be taken into account in the treatment of particularly severe infections. For the expiry of infusion solutions, see the section " Shelf life" .

The duration of doripenem therapy is usually 5 to 14 days and depends on the severity of the infection, the site of infection and the clinical response of the patient. Doripenem has been administered for up to 14 days in clinical studies, and job security for longer treatment durations has not been established. After initiating intravenous doripenem therapy, it is possible to switch to an appropriate antibiotic administered orally as soon as clinical improvement is observed.

Pediatric population

Doribax is not recommended for children under the age of 18 due to a lack of data regarding job security and effectiveness.

Dosage in patients with renal insufficiency

No dose adjustment is required in patients with mild renal impairment (ie creatinine clearance (CrCl)> 50 at ≤ 80 ml / min). In patients with moderate renal impairment (CrCl ≥ 30 at ≤ 50 ml / min), Doribax should be administered at a dose of 250 mg every 8 hours (see section Instructions for Use, Handling and Disposal ). . In patients with severe renal impairment (CrCl <30 ml / min), Doribax should be administered at a dose of 250 mg every 12 hours (see section Instructions for use, handling and disposal ). Due to limited clinical data and an expected increase in exposure to doripenem and its metabolite (doripenem-M-1), Doribax should be used with caution in patients with severe renal impairment (see section 5.2 Pharmacokinetic properties ). .

Dosage in dialysis patients

The recommendations for dosing and administration of Doribax in patients undergoing continuous renal therapy are presented in the following table:

Technical

CRRT

GFR

Dose

Frequency

Duration of infusion a, b, c

Target value

(MIC)

CVVH

≤ 30 ml / min

250 mg

all the

4 hours

≤ 1 mg / l

12 hours

CVVHDF

<5 ml / min

250 mg

all the

4 hours

≤ 1 mg / l

12 hours

CVVHDF

5-30 ml / min

500 mg

all the

4 hours

≤ 1 mg / l

12 hours

CRRT: continuous renal purification; CVVH: continuous veno-venous hemofiltration; CVVHDF: continuous veno-venous haemodiafiltration; MIC: minimum inhibitory concentration

a In patients with acute renal failure under CRRT, a 4-hour infusion is required given possible increases in non-renal clearance of carbapenems in patients with acute renal failure.

b Patients with chronic renal failure under CRRT may be treated with a 1 or 4 hour infusion. Based primarily on pharmacokinetic / pharmacodynamic considerations, a 4-hour infusion may be more appropriate for optimizing the percentage of time between two doses during which the plasma concentration of doripenem exceeds the minimum inhibitory concentration (% T> MIC), (see section 5.3). Pharmacodynamic properties ).

c For the shelf life of the solution for infusion, see section Shelf life .

For bacteria with MIC> 1 mg / l, no dose recommendation has been established in patients undergoing continuous renal therapy due to a risk of accumulation of doripenem and its metabolite, doripenem-M-1 ( see sections Warnings and Precautions and Pharmacokinetic Properties ). Due to limited clinical data and an expected increase in exposure to the doripenem M-1 metabolite, careful safety monitoring is recommended for patients undergoing continuous renal purification (see Warnings and Precautions section). of employment ).

There is insufficient data to make recommendations for dose adjustment in patients under other types of dialysis (see section 5.2 ).

Dosage in elderly patients (≥ 65 years)

No dose adjustment is required in elderly patients except in patients with moderate to severe renal impairment (see section 4.2).

5.2).

Dosage in patients with hepatic impairment

No dosage adjustment is necessary.

Administration mode

Doribax must be reconstituted and then diluted (see section Instructions for Use, Handling and Disposal ) before administration as an intravenous infusion over a period of 1 to 4 hours.
ANSM alert of 19/07/12:

• The results of a recent clinical study have shown that the currently approved 1 mg or 4 hour infusion of 500 mg every 8 hours is insufficient in some patients with nosocomial pneumonia (PN).

• A dose of 1 g of doripenem every 8 hours in a 4-hour infusion may be considered for treatment of PN, including mechanically ventilated pneumonia (VAP), in patients with creatinine clearance ≥150 ml / min and / or in case of infections due to Gram-negative non-fermentative pathogenic bacteria.

• The usual duration of treatment for PN patients, including VAP, is 10 to 14 days.

• The usual duration of treatment for patients with nosocomial pneumonia (including mechanically ventilated pneumonia) is 10 to 14 days; Patients infected with Gram-negative non-fermentative pathogenic bacteria (such as Pseudomonas spp., and Acinetobacter spp.) most often require the longest duration of treatment.

Against indications

• Hypersensitivity to the active substance

• Hypersensitivity to any other antibacterial agent of the carbapenem class

• Severe hypersensitivity (eg anaphylactic reaction, severe skin reaction) to any other antibiotic in the beta-lactam family (eg penicillins or cephalosporins).

Doribax side effects

In the 3, 142 adult patients (1, 817 of whom were treated with Doribax) for whom safety of use was evaluated in the Phase II and III clinical trials, the incidence of adverse effects observed with Doribax 500 mg administered every 8 hours was 32%. Doribax was stopped due to adverse effects in 0.1% of all patients. Adverse events that led to discontinuation of Doribax treatment were: nausea (0.1%), diarrhea (0.1%), pruritus (0.1%), vulvar mycosis (0.1%) elevated hepatic enzyme activity (0.2%) and rash (0.2%). The most common adverse events were headache (10%), diarrhea (9%) and nausea (8%).

Adverse reactions reported during clinical trials and since the marketing of Doribax are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); frequent (≥ 1/100 to <1/10); uncommon (≥ 1/1000 to <1/100); indeterminate frequency (can not be estimated based on available data).

Within each frequency category, adverse effects are presented in order of decreasing severity.

Adverse reactions reported during clinical trials and since marketing of Doribax

Infections and infestations

Common: oral candidiasis, vulvar mycosis

Blood and lymphatic system disorders

Uncommon: thrombocytopenia, neutropenia

Immune system disorders

Uncommon: hypersensitivity reactions (see Warnings and precautions for use ) Frequency not known: anaphylaxis (see Warnings and Precautions section )

Nervous system disorders

Very common: headache

Vascular disorders

Frequent: phlebitis

Gastrointestinal disorders

Common: nausea, diarrhea

Uncommon: C. difficile colitis (see Warnings and Precautions section )

Hepatobiliary disorders

Frequent: Elevated activity of liver enzymes

Skin and subcutaneous tissue disorders

Common: pruritus, rash Not known: Lyell's syndrome, Stevens Johnson syndrome

Popular Posts

Category Medicinal Products, Next Article