Meropenem fresenius

/ Neopharm

Adults
The dosage and duration of therapy shall be established depending on type and severity of infection and the condition of the patient.
The recommended daily dosage is as follows:
500 mg IV every 8 hours in the treatment of pneumonia, UTI, gynaecological infections such as endometritis, pelvic inflammatory disease, skin and skin structure infections.
1000 mg IV every 8 hours in the treatment of nosocomial pneumonias, peritonitis, presumed infections in neutropenic patients, septicaemia.
In cystic fibrosis, doses up to 2 g every 8 hours have been used; most patients have been treated with 2 g every 8 hours.
In meningitis the recommended dosage is 2 g every 8 hours.
When treating infections known or suspected to be caused by Pseudomonas aeruginosa, a dose of at least 1g every 8 hours in adults (maximum approved dose is 6g daily given in 3 divided doses) and a dose of at least 20mg/kg every 8 hours in children (maximum approved dose is 120mg/kg/ daily given in 3 divided doses) are recommended.
Regular sensitivity testing is recommended when treating Pseudomonas aeruginosa infection.
There are limited safety data available to support the administration of a 2g bolus dose in adults as an intravenous bolus injection.
Dosage in Adults with Hepatic Insufficiency
No dosage adjustment is necessary in patients with hepatic insufficiency.
Elderly Patients
No dosage adjustment is required for the elderly with normal renal function or creatinine clearance values above 50 mL/min.
Children
For children over 3 months and up to 12 years of age the recommended dose is 10 to 20 mg/kg every 8 hours depending on type and severity of infection, susceptibility of the pathogen and the condition of the patient. In children over 50 kg weight, adult dosage should be used. In meningitis and cystic fibrosis the recommended dose is 40 mg/kg every 8 hours.
There is no experience in children with renal impairment.
See prescribing information for full details.

For treatment in adults and children of the following severe infections caused by single
or multiple susceptible bacteria sensitive to meropenem:
* Pneumonias and nosocomial pneumonias,
* Pulmonary infections in patients with cystic fibrosis
* Urinary tract infections
* Intra-abdominal infections
* Gynecological infections such as endometritis and pelvic inflammatory disease
* Skin and skin structure infections
* Meningitis
* Septicemia
Meropenem has proved efficacious alone or in combination with other antimicrobial agents in the treatment of polymicrobial infections.
There is no experience in pediatric patients with neutropenia or primary or secondary immunodeficiency.

* Hypersensitivity to the active substance or to any of the excipients.
* Hypersensitivity to any other carbapenem antibacterial agent.
* Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of betalactam antibacterial agent (e.g. penicillins or cephalosporins).

The selection of meropenem to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial agent based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial agents and the risk of selecting for carbapenem-resistant bacteria.
Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. resistance Resistance to penems of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in these bacteria to penems.
Hypersensitivity reactions
As with all beta-lactam antibiotics, serious and occasionally fatal hypersensitivity reactions have been reported.
Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta- lactam antibiotics may also be hypersensitive to meropenem. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics.
If a severe allergic reaction occurs, the medicinal product should be discontinued and appropriate measures taken. Severe cutaneous adverse reactions (SCAR), such as Stevens- Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalised exanthematous pustulosis (AGEP) have been reported in patients receiving meropenem. If signs and symptoms suggestive of these reactions appear, meropenem should be withdrawn immediately and an alternative treatment should be considered.
With other beta-lactam antibiotics there have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction).
Drug-induced liver injury (DILI)
Hepatic function should be closely monitored during treatment with meropenem due to the risk of DILI. If severe DILI occurs, treatment discontinuation should be considered as clinically appropriate. Meropenem should be reintroduced only if assessed as essential for treatment.
Use in patients with liver disease: patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem. There is no dose adjustment necessary.
Antibiotic-associated colitis
Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all anti-bacterial agents, including meropenem, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of meropenem. Discontinuation of therapy with meropenem and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
Seizures
Seizures have infrequently been reported during treatment with carbapenems, including meropenem.
Direct antiglobulin test (Coombs test) seroconversion
A positive direct or indirect Coombs test may develop during treatment with meropenem.
Concomitant use with valproic acid/sodium valproate/valpromide
The concomitant use of meropenem and valproic acid/sodium valproate/valpromide is not recommended.

Common: thrombocythaemia, headache, diarrhoea, abdominal pain, vomiting, nausea, transaminases increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, rash, pruritus, inflammation, pain.
See prescribing information for full details.

No specific medicinal product interaction studies other than probenecid were conducted.
Probenecid competes with meropenem for active tubular secretion and thus inhibits the renal excretion of meropenem with the effect of increasing the elimination half-life and plasma concentration of meropenem. Caution is required if probenecid is co-administered with meropenem.
valproic acid: Decreases in blood levels of valproic acid have been reported when it is co- administered with carbapenem agents resulting in a 60-100 % decrease in valproic acid levels in about two days. Due to the rapid onset and the extent of the decrease, co-administration of valproic acid/sodium valproate/valpromide with carbapenem agents is not considered to be manageable and therefore should be avoided.
Oral anti-coagulants: Simultaneous administration of antibiotics with warfarin may augment its anti- coagulant effects. There have been many reports of increases in the anti- coagulant effects of orally administered anti-coagulant agents, including warfarin in patients who are concomitantly receiving antibacterial agents. The risk may vary with the underlying infection, age and general status of the patient so that the contribution of the antibiotic to the increase in INR (international normalised ratio) is difficult to assess. It is recommended that the INR should be monitored frequently during and shortly after co- administration of antibiotics with an oral anti-coagulant agent.

Pregnancy: There are no or limited amount of data from the use of meropenem in pregnant women. As a precautionary measure, it is preferable to avoid the use of meropenem during pregnancy.
Lactation: Small amounts of meropenem have been reported to be excreted in human milk. Meropenem should not be used in breast-feeding women unless the potential benefit for the mother justifies the potential risk to the baby.   

Relative overdose may be possible in patients with renal impairment if the dose is not adjusted. Limited post-marketing experience indicates that if adverse reactions occur following overdose, they are consistent with the adverse reaction profile, are generally mild in severity and resolve on withdrawal or dose reduction. Symptomatic treatments should be considered.
In individuals with normal renal function, rapid renal elimination will occur. Haemodialysis will remove meropenem and its metabolite.