Meropenem 500,0 mg/1000,0 mg Solution

MEROPENEM SHANUR is indicated for 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 influenza,
• Pseudomonas aeruginosa.

Urinary tract infections in adults and children, including complicating infections due to:

• Enterobacter cloacae,
• Escherichia coli,
• Morganella morganii,
• Proteus mirabilis,
• Pseudomonas aeruginosa,
• Serratia marcescens,
• Citrobacter freundii.

Pelvic Inflammatory Disease (including tubo-ovarian abscess) and endometritis due to:

• Enterococus faecalis,
• Staphylococcus aureus (methicillin-susceptible strains only) coagulase-negative Staphylococcus spp. (methicillin-susceptible strains only),
• Streptococcus agalactiae (Group B),
• Streptococcus viridans,
• Streptococcus spp.,
• Escherichia coli,
• Neisseria gonorrhoeae,
• Klebsiella pneumoniae,
• Enterobacter aerogenes,
• Enterobacter cloacae,
• Proteas mirabilis,
• Acinetobacter anitratus,
• Acinetobacter lwoffii,
• Gardnerella vaginalis,
• Bacteroides fragilis group,
• Peptostreptococcus anaerobius,
• Peptostreptococcus asaccharolyticus,
• Peptostreptococcus magnus.

Skin and skin structure infections in adults due to:

• Staphylococcus aureus (methicillin-susceptible strains only),
• coagulase-negative Staphylococcus spp. (methicillin-susceptible strains only),
• Streptococcus pyogenes (Group A),
• Streptococcus agalactiae,
• Streptococcus viridans,
• Enterococcus faecalis,
• Escherichia coli,
• Klebsiella pneumonia,
• Proteus mirabilis,
• Pseudomonas aeruginosa,
• Bacteroides fragilis,
• Peptostreptococcus spp.

Meningitis in adults and children due to:

• Streptococcus pneumoniae,
• Haemophilus influenzae,
• Neisseria meningitides.

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:

• Streptococcus epidermidis,
• Streptococcus mitis,
• Streptococcus sanguinis,
• Escherichia coli.

Intra-abdominal abscess and peritonitis due to:

• Streptococcus milleri,
• Enterococcus faecalis,
• Escherichia coli,
• Klebsiella pneumonia,
• Klebsiella oxytoca,
• Pseudomonas aeruginosa,
• Bacteroides fragilis group (including Bacteroides distasonis, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus),
• Clostridium perfringens,
• Streptococcus mitior.

Polymicrobial infections

Posology

Intravenous administration:

Adults:

Usual dose: 500 mg to 1 g by intravenous administration every 8 hours depending on the type and severity of infection, the known or suspected susceptibility of the pathogen(s), and the condition of the patient. See section 4.1 for types of infections and in vivo susceptible organisms.

Exceptions:

• (1) Febrile episodes in neutropenic patients- the dose should be 1 g every 8 hours.
• (2) Meningitis u2013 the dose should be 2 g every 8 hours.

Caution may be required in using beta-lactam antibiotics in critically ill patients with known or suspected Pseudomonas aeruginosa lower respiratory tract infections. Concomitant use of an aminoglycoside is recommended. Regular sensitivity testing is recommended when treating Pseudomonas aeruginosa.

MEROPENEM SHANUR should be given as an intravenous bolus injection over approximately 5 minutes or by intravenous infusion over approximately 15 - 30 minutes. (see Constitution, compatibility, and stability section for constitution details).

Dosage schedule for adults with impaired renal function:

Dosage should be reduced in patients with creatinine clearance less than 51 mL/minute, as scheduled below.

Creatinine clearance (mL/min) Dose (based on u201cunitu201d dose range of 500 mg to 2 g every 8 hours u2013 see above) Frequency

• 26 - 50 One unit dose Every 12 hours
• 10 - 25 One-half unit dose Every 12 hours
• < 10 One-half unit dose Every 24 hours

MEROPENEM SHANUR is cleared by haemodialysis, if continued treatment with MEROPENEM SHANUR is necessary, the unit dose is 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.

Use in adults with hepatic insufficiency: No dosage adjustment is necessary in patients with impaired hepatic metabolism.

Elderly: No dosage adjustment is required for the elderly with normal renal function or creatinine clearance values above 50 mL/minute.

Children: For infants and children over 3 months and up to 12 years of age the IV dose is 10 u2013 40 mg/kg every 8 hours depending on type and severity of infection, the known or suspected susceptibility of the pathogen(s), and the condition of the patient. In children over 50 kg weight, adult dosage should be used.

Exceptions: Meningitis u2013 the dose should be 40 mg/kg every 8 hours.

MEROPENEM SHANUR should be given as an IV bolus over approximately 5 minutes or by intravenous infusion over approximately 15 u2013 30 minutes (see Constitution, compatibility and stability section for details). There is no experience in children with renal impairment.

Method of Administration

For intravenous use only.

• Hypersensitivity to meropenem or to any of the excipients listed in section 6.1.
• Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics, may also be hypersensitive to MEROPENEM SHANUR.

Prescribers should adhere to the principles of antibiotic stewardship. The selection of meropenem to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial medicine (such as meropenem) based on factors such as severity of the infection, prevalence of resistance to other suitable antibacterial medicines and the risk of selecting for carbapenem-resistant bacteria.

Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. Resistance

Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. resistance to penems such as meropenem has been reported. Prescribers are advised to take into account the local prevalence of resistance in these bacteria to penems.

Paediatric use

Efficacy and tolerability in infants under 3 months old have not been established, therefore, MEROPENEM SHANUR is not recommended for use below this age.

Hypersensitivity reactions

Serious and occasionally fatal hypersensitivity reactions have been reported with meropenem. Before initiating therapy with MEROPENEM SHANUR, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics. If a severe allergic reaction occurs with MEROPENEM SHANUR treatment, it 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 (see section 4.8). If signs and symptoms suggestive of these reactions appear, meropenem should be withdrawn immediately and an alternative treatment should be considered.

Antibiotic-associated colitis

Overgrowth of non-susceptible organisms may occur, and repeated evaluation of each patient is necessary. Pseudomembranous colitis has been reported with MEROPENEM SHANUR, therefore, it is important to consider its diagnosis in patients who develop diarrhoea in association with MEROPENEM SHANUR use. Medicines that inhibit peristalsis should not be given.

Seizures

Seizures have been reported during treatment with meropenem, such as MEROPENEM SHANUR.

Use in patients with liver disease

Patients with pre-existing liver disorders must have liver function monitored during treatment with MEROPENEM SHANUR, due to the risk of hepatotoxicity such as cholestasis and cytolysis.

Direct antiglobulin test seroconversion

A positive direct or indirect antiglobulin test may develop.

Concomitant use with valproic acid/sodium valproate/valpromide

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

Excipients of MEROPENEM SHANUR

MEROPENEM SHANUR contains sodium, and this should be taken into consideration by patients on a controlled sodium diet.

MEROPENEM SHANUR may reduce serum valproic acid levels. Subtherapeutic levels may be reached in some patients. 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. As the potency and duration of action of MEROPENEM SHANUR dosed without probenecid are adequate the co-administration of probenecid with MEROPENEM SHANUR is not recommended.

The potential effect of MEROPENEM SHANUR 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 SHANUR has been administered concomitantly with many other medicines without apparent adverse interaction. However, no specific data regarding other interactions are available.

Oral anti-coagulants

Simultaneous administration of MEROPENEM SHANUR with warfarin may augment its anti-coagulant effects. There have been many reports of increases in the anti-coagulant effects of orally administered anticoagulant 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 normalized ratio) is difficult to assess. It is recommended that the INR should be monitored frequently during and shortly after coadministration of antibiotics with an oral anticoagulant medicine.

Pregnancy

The safety of MEROPENEM SHANUR in human pregnancy has not been established. MEROPENEM SHANUR should not be given to pregnant women.

Breastfeeding

Meropenem is detectable at very low concentrations in animal breast milk. MEROPENEM SHANUR should not be used in breastfeeding women.

Fertility

No data on fertility available.

No studies on the effect on the ability to drive and use machines have been performed. However, when driving or operating machines, it should be taken into account that headache, paraesthesia and convulsions have been reported for meropenem.

a) Tabulated list of adverse reactions

The table below shows all adverse drug reactions (ADRs) observed during clinical trials and postmarket spontaneous reports with meropenem.

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 asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 Suspected adverse reactions can also be reported directly to the HCR via [email protected]

Over-dosing could occur particularly in patients with renal impairment. Limited post-marketing experience indicates that if adverse events occur following over dosage, they are consistent with the adverse event profile described in section 4.9, are generally mild in severity and resolve on withdrawal or dose reduction. Symptomatic treatment should be considered. In normal individuals rapid renal elimination will occur. Haemodialysis will remove MEROPENEM SHANUR and its metabolite.