Micon

The chemical name of Micon trihydrate is -Azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, 3-[[5-[(dimethylamino)carbonyl]-3-pyrrolidinyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo, trihydrate, [4R-[3(3S*,5S*),4^α,5^β,6^β(R*)]]-.(4R,5S,6S)-3-[[(3S,5S)-5-(Dimethylcarbamoyl)-3-pyrrolidinyl]thio] -6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-carboxylic acid, trihydrate. The molecular formula of Micon trihydrate is C₁₇H₂₅N₃O₅S·3H₂O and its CAS number is 119478-56-7.

DBL Micon for Injection is presented as a sterile white to pale yellow crystalline powder containing Micon trihydrate equivalent to Micon, 500 mg or 1 g, blended with sodium carbonate anhydrous. DBL Micon for Injection contains 208 mg sodium carbonate anhydrous and 90.2 mg of sodium for each gram of Micon (anhydrous potency). It contains no antimicrobial preservative and is for use in one patient on one occasion only..

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Micon I.V. and other antibacterial drugs, Micon I.V. should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Micon I.V. is useful as presumptive therapy in the indicated condition (e.g., intra-abdominal infections) prior to the identification of the causative organisms because of its broad spectrum of bactericidal activity.

For information regarding use in pediatric patients [seeIndications and Usage (1.1), (1.2), (1.3), Dosage and Administration (2.3), Adverse Reactions (6.1), andClinical Pharmacology (12.3)].

Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of Age and Older Only)

Micon I.V. is indicated as a single agent therapy for the treatment of complicated skin and skin structure infections due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species.

Intra-abdominal Infections (Adult and Pediatric Patients)

Micon I.V. is indicated as a single agent therapy for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species.

Bacterial Meningitis (Pediatric Patients 3 Months of Age and Older Only)

Micon I.V. is indicated as a single agent therapy for the treatment of bacterial meningitis caused by Streptococcus pneumoniae‡, Haemophilus influenzae, and Neisseria meningitidis.

‡ The efficacy of Micon as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established.

Micon I.V. has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis.

Micon injection is used to treat infections caused by bacteria. It works by killing the bacteria or preventing their growth. Micon will not work for colds, flu, or other virus infections.

Micon is to be given only by or under the direct supervision of your doctor.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Micon is used in certain patients with the following medical condition:

• Febrile neutropenia (treatment).

Adults: The recommended dose of Micon injection of 500 mg is given every 8 hours for a skin and skin structure infections when treating infections caused by Pseudomonas aeruginosa, dose of 1 gram every 8 hours is recommended, and 1 gram given every 8 hours for intra-abdominal infections. Micon injection should be administered by intravenous infusion over approximately 15 to 30 minutes. Doses of 1 gram every 8 hours may also be administered as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.

Renal Impairment: Dosage should be reduced in patients with creatinine clearance less than 51 mL/min.

When only serum creatinine is available, the following formula (Cockroft and Gault equation) may be used to estimate creatinine clearance.

There is inadequate information regarding the use of Micon in patients on hemodialysis. There is no experience with peritoneal dialysis.

Hepatic Impairment: No dosage adjustment is necessary in patients with impaired hepatic function.

Elderly: No dosage adjustment is required for elderly patients with creatinine clearance values above 50 mL/min.

Children: For pediatric patients from 3 months of age and older, the Micon injection, dose is 10, 20 or 40 mg/kg every 8 hours (maximum dose is 2 g every 8 hours), depending on the type of infection (complicated skin and skin structure infections, intra-abdominal or meningitis). Pediatric patients weighing over 50 kg should be administered Micon injection at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 g every hour for intra-abdominal infections and 2 g every 8 hours for meningitis. Micon injection, should be given as intravenous infusion over approximately 15 to 30 minutes or as an intravenous bolus injection (5 to 20 mL) infusion over approximately 3-5 minutes. There is limited safety data available to support the administration of a 40 mg/kg (up to a maximum of 2 g) bolus dose.

See also:
What is the most important information I should know about Micon?

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For Micon, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to Micon or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Use Micon as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Micon is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Micon at home, a health care provider will teach you how to use it. Be sure you understand how to use Micon. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Micon if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• To clear up your infection completely, use Micon for the full course of treatment. Keep using it even if you feel better in a few days.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Micon, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Micon.

Use: Labeled Indications

Intra-abdominal infections: Treatment of complicated appendicitis and peritonitis in adult and pediatric patients caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, Bacteroides thetaiotaomicron, and Peptostreptococcus species.

Meningitis, bacterial: Treatment of bacterial meningitis in pediatric patients 3 months and older caused by Haemophilus influenzae, Neisseria meningitidis, and penicillin-susceptible isolates of Streptococcus pneumoniae.

Skin and skin structure infection, complicated: Treatment of complicated skin and skin structure infections in adults and pediatric patients 3 months and older caused by Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), P. aeruginosa, E. coli, Proteus mirabilis, B. fragilis, and Peptostreptococcus species.

Off Label Uses

Anthrax

Based on the Centers for Disease Control and Prevention (CDC) expert panel meetings on prevention and treatment of anthrax, Micon is an effective and recommended agent for the treatment of anthrax meningitis and an effective and recommended alternative agent for systemic anthrax.

Bite wound infection, treatment, animal or human bite

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs), Micon is an effective and recommended alternative agent for treatment of animal or human bite wounds.

Bloodstream infection (gram-negative bacteremia)

Based on the IDSA guidelines for the diagnosis and management of intravascular catheter-related infection, Micon is effective and recommended in the management of catheter-related bloodstream infection.

Clinical experience also suggests the utility of Micon for the treatment of bloodstream infection caused by gram-negative pathogens, including Pseudomonas aeruginosa.

See also:
What other drugs will affect Micon?

Probenecid competes with Micon for active tubular secretion and thus inhibits the renal excretion, with the effect of increasing the elimination half-life and plasma concentration of Micon. As the potency and duration of action of Micon dosed without probenecid are adequate, the co-administration of probenecid with Micon is not recommended.

The potential effect of Micon on the protein-binding of other drugs or metabolism has not been studied. The protein binding of Micon is low (approximately 2%) and, therefore, no interactions with other compounds based on displacement from plasma proteins would be expected.

Micon may reduce serum valproic acid levels. Subtherapeutic levels may be reached in some patients.

Micon has been administered concomitantly with other medications without adverse pharmacological interactions. However, no specific data regarding potential drug interactions is available (apart from probenecid as previous;y mentioned).

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 2 days. Due to the rapid onset and the extent of the decrease, co-administration of Micon in patients stabilised on valproic acid is not considered to be manageable and therefore should be avoided.

Oral Anticoagulants:

Incompatibilities: Micon must not be mixed with other medicinal products except those mentioned in Cautions for Usage.

See also:
What are the possible side effects of Micon?

Adult Patients: During reported clinical investigations, 2,904 immunocompetent adult patients were treated for infections outside the CNS with Micon (500 or 1,000 mg every 8 hrs). Deaths in 5 patients were assessed as possibly related to Micon; 36 patients (1.2%) had Micon discontinued because of adverse events. Many patients in these reported trials were severely ill and had multiple background diseases, physiological impairments, and were receiving multiple other drug therapies in the seriously ill patient population, it was not possible to determine the relationship between observed adverse events and therapy with Micon.

Local Adverse Reaction: Local adverse reactions that were reported irrespective of the relationship to therapy with Micon were as follows: Inflammation at the injection site (2.4%), injection site reaction (0.9%), phlebitis/thrombophlebitis (0.8%), pain at the injection site (0.4%), edema at the injection site (0.2%).

Systemic Adverse Reactions: Systematic adverse clinical reactions that were reported irrespective of the relationship to Micon occurring in >1% of the patients were diarrhea (4.8%), nausea/vomiting (3.6%), headache (2.3%), rash (1.9%), sepsis (1.6%), constipation (1.4%), apnea (1.3%), shock (1.2%) and pruritus (1.2%).

Additional adverse systemic clinical reactions that were reported irrespective of relationship to therapy with Micon and occurring in ≤1% but >0.1% of the patients are listed as follows within each body system in order of decreasing frequency: Bleeding Events were Seen as Follows: Gastrointestinal hemorrhage (0.5%), melena (0.3%), epistaxis (0.2%), hemoperitoneum (0.2%), summing to 1.2%.

Body as a Whole: Pain, abdominal pain, chest pain, fever, back pain, abdominal enlargement chills, pelvic pain.

Cardiovascular: Heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension, syncope.

Digestive System:

Oral moniliasis, anorexia, cholestatic jaundice/jaundice, ileus, hepatic failure, dyspepsia, intestinal obstruction.

Hemi/Lymphatic: Anemia, hypochromic anemia, hypervolemia.

Metabolic/Nutritional: Peripheral edema, hypoxia.

Nervous System: Insomnia, agitation/delirium, confusion, dizziness, seizure, nervousness, paresthesia, hallucinations, somnolence, anxiety depression, asthenia.

Respiratory: Respiratory disorder, dyspnea, pleural effusion, asthma, increased cough, lung edema.

Skin Appendages: Urticaria, sweating, skin ulcer.

Urogenital System: Dysuria, kidney failure, vaginal moniliasis, urinary incontinence.

Adverse Laboratory Changes: Adverse Laboratory Changes that were Reported Irrespective of Relationship to Micon and Occurring in >0.2% of the Patients Were as Follows: Hepatic: Increased serum glutamic-pyruvic transaminase (SGPT), alanine transaminase (ALT), serum glutamic-oxaloacetic transaminase (SGOT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), and bilirubin. Hematologic increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased whole blood count (WBC), shortened prothrombin time and shortened partial thromboplastin time, leukocytosis, hypokalemia.

Urinalysis: Presence of red blood cells.

Renal: Increased creatinine and increased blood urea nitrogen (BUN).

Note: For patients with varying degrees of renal impairment, the incidence of head failure, kidney failure, seizure and shock reported irrespective of relationship to Micon increased in patients with moderately severe renal impairment CrC >10-26 mL/min.

Complicated Skin and Skin Structure Infection: In a reported study of complicated skin and skin structure infection, the type of clinical adverse reactions were similar to those listed as mentioned previously. The patients with the most common adverse events with an incidence of >5% were: Headache (7.8%), nausea (7.8%), constipation (7%), diarrhea (7%), anemia (5.5%) and pain (5.1 %). Adverse events with an incidence of >1%, and not listed as mentioned previously, include: Pharyngitis, accidental injury gastrointestinal disorder; hypoglycemia; peripheral vascular disorder and pneumonia.

Pediatric Patients: Micon was studied in 515 pediatric patients (>3 months to <13 years) with serious bacterial infections (excluding meningitis) at dosages of 10-20 mg/kg every 8 hrs. The types of clinical adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably or definitely related to Micon and their rates of occurrence as follows: Diarrhea (3.5%), rash (1.6%), nausea and vomiting (0.8%).

Meropem was studied in 321 pediatric patients (>3 months to <17 years) with meningitis at a dosage of 40 mg/kg every 8 hrs. The types of clinical adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably or definitely related to Micon and their rates of occurrence as follows: Diarrhea (4.7%), rash (most diaper area moniliasis) (3.1%), oral moniliasis (1.9%), glossitis (1%).

In the meningitis studies the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received Micon and those who received comparator agents (either cefotaxime or ceftriaxone). In the Micon treated group, 12/15 patients with seizures had late onset seizures (defined as occurring or later) versus 7,120 in the comparator arm.

Adverse Laboratory Changes: Laboratory abnormalities seen in the pediatric-aged patients in both the pediatric and the meningitis studies are similar to those reported in adult patients. There is no experience in pediatric patients with renal impairment.

Post-Marketing Experience: World wide post-marketing adverse events not previously listed in the product label and reported as possibly, probably or definitely drug related are listed within each body system in order of decreasing severity.

Hematology: Agranulocytosis, neutropenia and leukopenia; a positive Coombs' test and hemolytic anemia toxic epidermal necrolysis, Stevens-Johnson syndrome (SJS), angioedema and erythema multiform.