Etamep 1 g LYOPHILISED POWDER FOR SOLUTION FOR INJECTION

ETAMEP is indicated for the treatment of adult patients with the following moderate to severe infections caused by susceptible strains of the designated micro-organisms (see DOSAGE AND DIRECTIONS FOR USE):

• Complicated intra-abdominal infections due to Escherichia coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis.
• Complicated skin and skin structure infections including diabetic lower extremity and diabetic foot infections due to Staphylococcus aureus (methicillin susceptible strains only), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Porphyromonas asaccharolytica or Peptostreptococcus species.
• Community acquired pneumonia due to Streptococcus pneumoniae (penicillin susceptible strains only) including cases with concurrent bacteraemia, Moraxella catarrhalis. If community acquired pneumonia is caused by Haemophilus influenzae, ETAMEP should be used only following confirmation of culture and sensitivity results.
• Complicated urinary tract infections including pyelonephritis due to Escherichia coli, including cases with concurrent bacteraemia or Klebsiella pneumoniae.
• Acute pelvic infections including postpartum endomyometritis, septic abortion and post-surgical gynaecologic infections due to Streptococcus agalactiae, Escherichia coli, Bacteroides fragilis, Porphyromonas asaccharolytica, Peptostreptococcus species or Prevotelia bivia.

Paediatric use: Safety and effectiveness of ETAMEP in paediatric patients 3 months to 17 years of age are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in paediatric patients, and additional data from comparator-controlled studies in paediatric patients 3 months to 17 years of age with the following infections (see DOSAGE AND DIRECTIONS FOR USE).

• Complicated intra-abdominal infections
• Complicated skin and skin structure infections
• Community acquired pneumonia
• Complicated urinary tract infections
• Acute pelvic infections

Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify the causative organisms and to determine their susceptibility to ETAMEP. Therapy with ETAMEP may be initiated empirically before results of these tests are known; once results become available, antimicrobial therapy should be adjusted accordingly.

The usual dose of ETAMEP in patients 13 years of age and older is 1 gram (g) given once a day. The usual dose of ETAMEP in patients 3 months to 12 years of age is 15 mg/kg twice daily (not to exceed 1g/day). ETAMEP may be administered by intravenous (IV) infusion or intramuscular (IM) injection. When administered intravenously, ETAMEP should be infused over a period of 30 minutes. Intramuscular administration of ETAMEP may be used as an alternative to intravenous administration in the treatment of those infections for which intramuscular therapy is appropriate. The usual duration of therapy with ETAMEP is 3 to 14 days but varies by the type of infection and causative pathogen(s) (see INDICATIONS). When clinically indicated, a switch to an appropriate oral antimicrobial may be implemented if clinical improvement has been reported.

Dosage guidelines for adults and paediatric patients with normal renal function* and body weight:

• Complicated intra-abdominal Infection: 1 g (Adults), 15 mg/kg twice daily (Paediatric patients 3 months to 12 years) for 5 to 14 days
• Complicated skin and skin structure infections including diabetic lower extremity and diabetic foot infections: 1 g (Adults), 15 mg/kg twice daily (Paediatric patients 3 months to 12 years) for 7 to 14 days
• Community acquired pneumonia: 1 g (Adults), 15 mg/kg twice daily (Paediatric patients 3 months to 12 years) for 10 to 14 days
• Complicated urinary tract infections including pyelonephritis: 1 g (Adults), 15 mg/kg twice daily (Paediatric patients 3 months to 12 years) for 10 to 14 days
• Acute pelvic infections including postpartum endomyometritis, septic abortion and post-surgical gynaecologic infections: 1 g (Adults), 15 mg/kg twice daily (Paediatric patients 3 months to 12 years) for 3 to 10 days

* Defined as creatinine clearance greater than 90 mL/min/1.73 mu00b2

ETAMEP is contraindicated in patients with known bacterial meningitis and hypersensitivity to any component of ETAMEP or to other medicines in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactams. ETAMEP, when administered intramuscularly with lidocaine hydrochloride diluent, is contraindicated in patients with a known hypersensitivity to local anaesthetics of the amide type and in patients with severe shock or heart block. ETAMEP is not recommended in the treatment of meningitis due to lack of sufficient cerebrospinal fluid (CSF) penetration.

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING THERAPY WITH BETA-LACTAMS. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE HYPERSENSITIVITY REACTIONS WHEN TREATED WITH ANOTHER BETA-LACTAM. BEFORE INITIATING THERAPY WITH ETAMEP, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OTHER BETA-LACTAMS AND OTHER ALLERGENS. IF AN ALLERGIC REACTION TO ETAMEP OCCURS, DISCONTINUE THE ETAMEP IMMEDIATELY. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE/ADRENALINE, OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION. OTHER THERAPY MAY ALSO BE ADMINISTERED AS INDICATED.

Seizures and other central nervous system (CNS) adverse experiences have been reported during treatment with ETAMEP. Pseudomembranous colitis (antibiotic-associated colitis) has been reported with nearly all antibacterial medicines, including ETAMEP, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial medicines. Treatment with antibacterial medicines alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of u201cantibiotic-associated colitisu201d. After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to ETAMEP discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial medicine clinically effective against Clostridium difficile colitis.

Lidocaine hydrochloride is the diluent for intramuscular administration of ETAMEP. During clinical investigations in adult patients treated with ETAMEP (1 g once a day), seizures, irrespective of medicine relationship, occurred in 0.5% of patients during study therapy plus 14-day follow-up period. These experiences have occurred most commonly in patients with CNS disorders (e.g. brain lesions or history of seizures) and/or compromised renal function. Close adherence to the recommended dosage regimen is urged, especially in patients with known factors that predispose to convulsive activity. Anticonvulsant therapy should be continued in patients with known seizure disorders. If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of ETAMEP re-examined to determine whether it should be decreased or the antibiotic discontinued. Dosage adjustment of ETAMEP is recommended in patients with reduced renal function (see DOSAGE AND DIRECTIONS FOR USE).

Probenecid inhibits the renal excretion of ETAMEP thereby increasing its plasma concentrations and prolonging its elimination half-life. In vitro studies indicate that ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine and that ertapenem is not a substrate for P-glycoprotein-mediated transport. In vitro studies in human liver microsomes indicate ertapenem does not inhibit metabolism mediated by any of the six major cytochrome P450 (CYP) isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. Drug interactions caused by inhibition of P-glycoprotein-mediated drug clearance or CYP-mediated drug clearance are unlikely (see Pharmacokinetic properties). No specific clinical drug interaction studies have been conducted.

Decreased serum levels of valproic acid with co-administration of ertapenem have been reported as post-marketing experiences. Careful monitoring of serum levels of valproic acid should be considered if ertapenem is to be co-administered with valproic acid.

Safety in pregnancy has not been established. ETAMEP is excreted in human milk (see Pharmacokinetic properties, Distribution). Safety in nursing mothers has not been established.

There is no data to suggest that ETAMEP affects the ability to drive and operate machinery. Due to the possibility of the side effects such as dizziness, seizures and altered mental status occurring, the patient should be advised not to drive or operate any heavy machinery until the effect of ETAMEP on the patient is known.

Immune system disorders: Less frequent: Allergic reaction. Frequency unknown: Anaphylaxis including anaphylactoid reactions.

Psychiatric disorders: Frequent: Altered mental status.

Nervous system disorders: Frequent: Headache. Less frequent: Seizures, anxiety, dizziness, insomnia. Frequency unknown: Hallucinations.

Cardiac disorders: Less frequent: Tachycardia.

Vascular disorders: Frequent: Infused vein complication. Less frequent: Phlebitis or thrombophlebitis, hypertension, hypotension.

Respiratory, thoracic and mediastinal disorders: Less frequent: Cough, dyspnoea or respiratory distress, pharyngitis.

Gastrointestinal disorders: Frequent: Diarrhoea, nausea. Less frequent: Pseudomembranous colitis, constipation, dyspepsia, oral candidiasis, vomiting, acid regurgitation.

Skin and subcutaneous tissue disorders: Less frequent: Erythema, pruritus, rash.

Musculoskeletal, connective tissue and bone disorders: Less frequent: Leg pain.

Reproductive system and breast disorders: Less frequent: Vaginitis.

Investigations: Frequent: Elevated ALT, AST, alkaline phosphatase, platelet count, decrease in neutrophil count. Less frequent: Increase in direct serum bilirubin, total serum bilirubin, eosinophils, indirect serum bilirubin, PTT, urine bacteria, serum urea, serum creatinine, serum glucose, monocytes, urine epithelial cells, urine red blood cells, decreases in segmented neutrophils, white blood cells, haematocrit and haemoglobin.

General disorders and administrative site conditions: Frequent: Chest pain, fever. Less frequent: Asthenia or fatigue, oedema.

In the event of an overdose, ETAMEP should be discontinued and general supportive treatment given until renal elimination takes place. ETAMEP can be removed by haemodialysis; however, no information is available on the use of haemodialysis to treat overdosage.