Meroject 1 G/500 Mg Injection

MEROJECT is indicated for the treatment of the following infections, caused by single or multiple susceptible bacteria and as empiric therapy prior to the identification of the causative organisms:

• acute exacerbation of chronic bronchitis and pneumonia due to: Staphylococcus aureus (methicillin-susceptible strains only), Streptococcus pneumoniae, Streptococcus spp., Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Pseudomonas aeruginosa, Moraxella (Branhamella) catarrhalis, Klebsiella spp., Enterobacter cloacae, Enterobacter spp., Acinetobacter spp.
• pneumonia in children due to: Staphylococcus aureus (methicillin-susceptible strains only), Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa
• urinary tract infections in adults and children, including complicating infections due to: Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Serratia marcescens, Citrobacter freundii
• pelvic Inflammatory Disease (including tubo-ovarian abscess) and endometritis due to: Staphylococcus aureus (methicillin-susceptible strains only), Staphylococcus epidermidis, Streptococcus haemolyticus, Staphylococcus spp. (coagulase negative), Streptococcus agalactiae Group B, Pseudomonas aeruginosa, Streptococcus beta-haemolytic, Streptococcus faecalis, Staphylococcus gamma haemolyticus, Group D Streptococcus (enterococcus and non-enterocossus), Streptococcus viridans, Acinetobacter anitratus, Acinetobacter lwoffii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Neisseria gonorrhoeae, Proteus mirabilis, Enterococcus faecalis, Bacteroides fragilis group, Peptostreptococcus anaerobius, Peptostreptococcus asaccharolyticus, Peptostreptococcus magnus
• skin and skin structure infections in adults due to: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus (methicillin-susceptible strains only), Coagulase-negative Staphylococcus spp. (methicillin-susceptible strains only), Streptococcus agalactiae, Enterococcus faecalis, (Group A) Streptococcus, Streptococcus viridans, Bacteroides fragilis
• meningitis in adults and children due to: Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis
• septicaemia in adults and children due to: Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae
• empiric treatment, including initial monotherapy, for presumed bacterial infections in host-compromised neutropenic patients due to: Staphylococcus aureus, Micrococcus spp., Streptococcus sanguis, Streptococcus epidermidis, Streptococcus mitis, Escherichia coli, Pseudomonas aeruginosa
• intra-abdominal abscess and peritonitis due to: Streptococcus milleri, Streptococcus mitior, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, Bacteroides ovatus, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Klebsiella oxytoca, Clostridium perfringens.
• polymicrobial infections

In the treatment of infections caused by Pseudomonas aeruginosa, an aminoglycoside should be administered concomitantly.

Posology

Adults

Usual dose: Administration of 500 mg to 1 g by intravenous infusion every 8 hours.

Dose Exceptions

• a) Dose of 1 g every 8 hours for febrile episodes in neutropenic patients.
• b) Dose of 2 g every 8 hours for meningitis.

In critically ill patients with known or suspected Pseudomonas aeruginosa lower respiratory tract infections, concomitant use of an aminoglycoside is recommended, and regular sensitivity testing is recommended.

Special populations

Impaired renal function u2013 Adult dosage schedule: In adult patients with creatinine clearance below 51 mL/min the dosage of MEROJECT should be reduced as follows:

Meropenem is cleared by haemodialysis. If continued use with MEROJECT is necessary, the unit dose based on the infection type and severity is recommended at the completion of the haemodialysis procedure to re-institute effective treatment. There is no experience with peritoneal dialysis.

Impaired hepatic function

MEROJECT dosage need not be adjusted in patients with impaired hepatic function.

Elderly

MEROJECT dosage need not be adjusted for the elderly with normal renal function or creatinine clearance values above 50 ml/min.

Paediatric population

No data on meropenem is available for children. In children over 50 kg weight, the adult dosage schedule should be used. Children older than three months and up to 12 years are to be administered an intravenous dose of 10 to 40 mg/kg every 8 hours, depending on the type and severity of the infection, the condition of the patient and known susceptibility of the organism(s). Exceptions: Meningitis: An 8 hourly 40 mg/kg dose should be given. There is no experience in children with renal impairment.

Method of administration

MEROJECT is intended for intravenous injection administered by intravenous infusion over 15 to 30 minutes or by rapid intravenous injection of 3 to 5 minutes every 8 hours. In the treatment of beta-haemolytic streptococcal infections, a therapeutic dose should be administered for at least 10 days.

MEROJECT is contraindicated in:

• patients with hypersensitivity to meropenem or any of the other ingredients of MEROJECT (see section 6.1)
• patients hypersensitive (allergic) to carbapenems, penicillins or other beta-lactam antibacterials (e.g., cephalosporins, imipenem) may be hypersensitive to meropenem
• pregnancy and lactation (see section 4.6).

The appropriateness of using a carbapenem antibacterial medicine (as MEROJECT) should be based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial medicines and the risk of selecting for carbapenem-resistant bacteria.

Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. resistance: Prescribers are advised to consider the local prevalence of resistance in these bacteria to penem antibiotics.

Hypersensitivity reactions

Serious and occasionally fatal hypersensitivity reactions have been reported (see sections 4.3 and 4.8). Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may also be hypersensitive to MEROJECT. Before initiating therapy with MEROJECT, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics.

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 (see section 4.8). If signs and symptoms suggestive of these reactions appear, MEROJECT should be withdrawn immediately, and an alternative treatment should be considered.

There have been reports of serious and occasionally fatal hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arterio-spasm that can result in myocardial infarction) (see section 4.8). If a severe allergic reaction occurs, MEROJECT should be discontinued, and appropriate measures taken.

Antibiotic-associated colitis

Antibiotic-associated colitis and pseudomembranous colitis have been reported with MEROJECT 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 MEROJECT and the administration of specific treatment for Clostridium difficile should be considered. Medicines that inhibit peristalsis should not be given.

Seizures

Care is necessary in patients with CNS disorders such as epilepsy as seizures have been infrequently reported during the treatment with carbapenems, including meropenem, as contained in MEROJECT (see section 4.8).

Hepatic function monitoring

Liver function monitoring is essential in patients with pre-existing liver disorders during treatment with MEROJECT due to the risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytolysis) and vanishing bile duct syndrome. There is no dose adjustment necessary.

Direct antiglobulin test (Coombs test) seroconversion

A positive direct or indirect antiglobulin (Coombs) test may develop.

Concomitant use with valproic acid/sodium valproate/valpromide

The concomitant use of MEROJECT (powder for injection) and valproic acid/sodium valproate/valpromide is not recommended (see section 4.5).

MEROJECT contains sodium

MEROJECT 500 mg contains 45 mg sodium/vial, equivalent to approximately 2,25 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. MEROJECT 1 g contains 90 mg sodium/vial, equivalent to approximately 4,5 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. MEROJECT is considered high in sodium. This should be particularly considered for those on a low salt diet.

Paediatric population

MEROJECT is not recommended in infants under 3 months old because efficacy and tolerability have not been established.

Probenecid inhibits the renal excretion of MEROJECT thereby increasing its plasma concentrations and prolonging the elimination half-life. As the potency and duration of action of MEROJECT dosed without probenecid are adequate, the co-administration of probenecid with MEROJECT is not recommended.

The potential effect of meropenem on the protein binding of other medicines or metabolism has not been studied. However, the protein binding is so low that no interactions with other compounds would be expected. Meropenem has been administered concomitantly with many other medicines without apparent adverse interactions.

Valproic acid plasma levels may be reduced by meropenem when it is co-administered with carbapenem medicines 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 medicines is not considered to be manageable and therefore should be avoided (see section 4.4).

Simultaneous administration of MEROJECT 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 medicines (including warfarin) in patients who are concomitantly receiving antibacterial medicines. 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 MEROJECT with an oral anti-coagulant medicine such as warfarin.

Paediatric population

Interaction studies have only been performed in adults. However, no specific data regarding other potential medicine interactions are available.

Pregnancy

The safety of MEROJECT has not been established during pregnancy and the use of MEROJECT is not recommended (see section 4.3).

Breastfeeding

The use of MEROJECT is not recommended during breastfeeding.

Fertility

There is no data on fertility and the use of MEROJECT.

Although no data is available, MEROJECT is not expected to affect the ability to drive or operate machinery. However, when driving or operating machines, it should be considered that headache, paraesthesia, and convulsions have been reported for meropenem.

Summary of the safety profile

Adverse reactions most frequently reported in a conducted review of patients with meropenem treatment exposures, were diarrhoea (2,3 %), rash (1,4 %), nausea/vomiting (1,4 %) and injection site inflammation (1,1 %). The most commonly reported meropenem-related laboratory adverse events were thrombocytosis (1,6 %) and increased hepatic enzymes (1,5 - 4,3 %).

Tabulated list of adverse effects

a. Paediatric population

MEROJECT can be used in children over 3 months of age. There is no reported evidence of an increased risk of any adverse drug reaction in children. All reported reactions were consistent with events observed in adult population.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. An email can be sent directly to the company, [email protected], to ensure safety of the product.

Signs and symptoms: Renal impairment may lead to accidental overdosage of MEROJECT if the dose is not adjusted as described in Section 4.2. Limited post-marketing experience indicates that if adverse reactions occur following overdose, they are consistent with the adverse reaction profile described in section 4.8 and are generally mild in severity and resolve on withdrawal or dose reduction.

Management of overdose: The treatment is symptomatic and supportive, and haemodialysis is to be implemented in patients with renal impairment to remove meropenem and its metabolite.