Meropenem

Meropenem belongs to the pharmacological class of Carbapenem antibiotics.

Meropenem has been approved to relieve symptoms and also for the treatment and maintenance of Anthrax, bloodstream infections, acute pulmonary exacerbations in cystic fibrosis, moderate to severe diabetic foot infections, healthcare-associated or high-risk community-acquired intra-abdominal infections, intracranial and spinal epidural abscesses, melioidosis, bacterial meningitis, neutropenic enterocolitis, high-risk neutropenic fever in cancer patients, osteomyelitis and/or discitis, peritonitis, pneumonia, prosthetic joint infections, sepsis and septic shock, moderate to severe skin and soft tissue infections, and complicated urinary tract infections.

The drug is rapidly and completely absorbed when given intramuscularly, with a bioavailability of approximately 90%, while the bioavailability of intravenous meropenem is 100%. The plasma protein binding of meropenem is low (2%), and it has a volume of distribution of approximately 20 L.Meropenem undergoes hydrolysis by dehydropeptidase I in the kidneys, leading to increased renal clearance of the drug. The drug is excreted in the urine, with approximately 70% of the administered dose excreted as unchanged drug.

The common side effects involved in using Meropenem are Diarrhea, Nausea, Vomiting, Abdominal pain, Headache, Dizziness, Rash, and Itching.

Meropenem is available in the form of Powder for injection, Injectable solution, Intravenous infusion.

Meropenem is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Meropenem belongs to the pharmacological class of Carbapenem antibiotics.

Meropenem exerts its bactericidal activity by inhibiting the synthesis of the bacterial cell wall. The drug easily crosses the cell walls of both Gram-positive and Gram-negative bacteria to reach its target, the penicillin-binding-proteins (PBPs). Among the PBPs, meropenem demonstrates a high affinity for PBPs 2, 3, and 4 in Escherichia coli and Pseudomonas aeruginosa and PBPs 1, 2, and 4 in Staphylococcus aureus.

Meropenem has been approved to relieve symptoms and also for the treatment and maintenance of Bite wound infection, treatment, Anthrax, bloodstream infections, acute pulmonary exacerbations in cystic fibrosis, moderate to severe diabetic foot infections, healthcare-associated or high-risk community-acquired intra-abdominal infections, intracranial and spinal epidural abscesses, melioidosis, bacterial meningitis, neutropenic enterocolitis, high-risk neutropenic fever in cancer patients, osteomyelitis and/or discitis, peritonitis, pneumonia, prosthetic joint infections, sepsis and septic shock, moderate to severe skin and soft tissue infections, and complicated urinary tract infections.

The maximum concentration (Cmax) of meropenem in the bloodstream occurs within one hour of intravenous administration, and the maximum plasma concentration after intramuscular injection is achieved within 30 minutes. The onset of action of meropenem is rapid, with a bactericidal effect seen within a few hours of administration.

The duration of action of meropenem varies depending on the dose and the severity of the infection being treated. In general, the elimination half-life of meropenem is around 1 hour in patients with normal renal function. However, in patients with impaired renal function, the half-life may be prolonged, and the dosage regimen should be adjusted accordingly.

Meropenem is generally administered every 8 hours intravenously, and the duration of treatment may range from a few days to several weeks, depending on the indication being treated and the clinical response.

Meropenem is found to be available in the form of Powder for injection, Injectable solution, Intravenous infusion.

Meropenem can be used in the following treatment:

• Bloodstream infection
• Cystic fibrosis, acute pulmonary exacerbation
• Diabetic foot infection, moderate to severe
• Intra-abdominal infection
• Intracranial abscess and spinal epidural abscess
• Melioidosis
• Meningitis, bacterial
• Neutropenic enterocolitis
• Neutropenic fever, high-risk cancer patients
• Osteomyelitis and/or discitis
• Peritonitis, treatment
• Pneumonia
• Prosthetic joint infection
• Sepsis and septic shock
• Skin and soft tissue infection
• Urinary tract infection, complicated

Meropenem can help to relieve symptoms and also for the treatment and maintenance of Bite wound infection, treatment, Anthrax, bloodstream infections, acute pulmonary exacerbations in cystic fibrosis, moderate to severe diabetic foot infections, healthcare-associated or high-risk community-acquired intra-abdominal infections, intracranial and spinal epidural abscesses, melioidosis, bacterial meningitis, neutropenic enterocolitis, high-risk neutropenic fever in cancer patients, osteomyelitis and/or discitis, peritonitis, pneumonia, prosthetic joint infections, sepsis and septic shock, moderate to severe skin and soft tissue infections, and complicated urinary tract infections.

Meropenem is approved for use in the following clinical indications:

• Bloodstream infection
• Cystic fibrosis, acute pulmonary exacerbation
• Diabetic foot infection, moderate to severe
• Intra-abdominal infection
• Intracranial abscess and spinal epidural abscess
• Melioidosis
• Meningitis, bacterial
• Neutropenic enterocolitis
• Neutropenic fever, high-risk cancer patients
• Osteomyelitis and/or discitis
• Peritonitis, treatment
• Pneumonia
• Prosthetic joint infection
• Sepsis and septic shock
• Skin and soft tissue infection
• Urinary tract infection, complicated

• Powder for injection: Meropenem powder for injection is available in vials containing 500 mg, 1 gram, or 2 grams of the drug.
• Solution for injection: Meropenem solution for injection is available in vials containing 500 mg, 1 gram, or 2 grams of the drug.
• Powder for solution for injection: Meropenem powder for solution for injection is available in vials containing 500 mg, 1 gram, or 2 grams of the drug.

Powder for injection, Injectable solution, Intravenous infusion.

• Dosage Adjustments in Kidney Patients:

If the creatinine clearance (CrCl) is greater than 30 mL/min/1.73 m², no dosage adjustment is required for Meropenem. For patients with CrCl less than 30 mL/min/1.73 m² and end-stage renal disease (ESRD), the recommended dosage of Meropenem is 500 mg per day administered intravenously. In patients receiving dialysis, the recommended dosage is 500 mg per day administered intravenously; if Meropenem is given less than or equal to 6 hours before dialysis, a supplemental dose of 150 mg should be given after dialysis.

• Dosage Adjustments in Hepatic Impairment Patients:

There are found to be no dosage adjustments are needed for hepatic impairment.

• Dosage Adjustments in Pediatric Patients:

1. For susceptible infections (non-CNS):
2. Infants, children, and adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose. Extended infusions may be needed for infections due to isolates with elevated MICs.
3. Anthrax:
4. IV: 20 mg/kg/dose for every 8 hours; maximum dose: 1 gram/dose.
5. Cystic fibrosis, pulmonary exacerbation:
6. IV: 40 mg/kg/dose for every 8 hours; maximum dose is about 2 grams/dose.
7. Febrile neutropenia, empiric treatment:
8. IV: 20 mg/kg/dose for every 8 hours; maximum dose: 1 gram/dose.
9. Intra-abdominal infection, complicated:
10. IV: 20 mg/kg/dose for every 8 hours; maximum dose: 1 gram/dose.
11. Meningitis:
12. IV: 40 mg/kg/dose for every 8 hours; maximum dose: 2 grams/dose.
13. Skin and skin structure infection, complicated:
14. IV: 20 mg/kg/dose for every 8 hours; maximum dose: 1 gram/dose.

There are no specific dietary restrictions related to the use of Meropenem. However, following a healthy and balanced diet is essential as part of overall health and wellness.

Meropenem may be contraindicated under the following conditions:

• Patients who have a known hypersensitivity to any component of Meropenem or to other drugs in the same class, or who have experienced anaphylactic reactions to β-lactams, are contraindicated for the use of Meropenem

The physician should closely monitor the patients and keep pharmacovigilance as follows:

Patients receiving β-lactam therapy have reported serious and occasionally fatal hypersensitivity (anaphylactic) reactions, which are more likely to occur in those with a history of sensitivity to multiple allergens, including penicillins, cephalosporins, and other β-lactams. Before initiating therapy with Meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to these allergens. If an allergic reaction to the drug Meropenem occurs, the drug should be discontinued immediately, and serious anaphylactic reactions require emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management, including intubation.

Additionally, seizures and other CNS adverse experiences have been reported during treatment with Meropenem, particularly in patients with CNS disorders or bacterial meningitis and/or compromised renal function. Dosage adjustment is recommended in patients with advanced age and/or reduced renal function, and 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 Meropenem re-examined to determine whether it should be decreased or the antibiotic discontinued.

Pseudomembranous colitis, a potentially life-threatening condition, has been reported with nearly all antibacterial agents, including meropenem. Therefore, it is important to consider this diagnosis in patients who suffer with diarrhea subsequent to the administration of antibacterial agents. Treatment with the antibacterial agents alters the normal flora of the colon and might permit overgrowth of clostridia, which produce a toxin that is a primary cause of "antibiotic-associated colitis." After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated, and in moderate-to-severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

It is important to prescribe Meropenem only when there is a proven or strongly suspected bacterial infection or a prophylactic indication, as prescribing it in the absence of such indications is unlikely to benefit the patient and increases the risk of developing drug-resistant bacteria. Close adherence to the recommended dosage regimens is also urged, especially in patients with known factors that predispose to convulsive activity. In patients with renal dysfunction, thrombocytopenia has been observed, but no clinical bleeding has been reported. If superinfection occurs during therapy, then appropriate measures should be taken. There is inadequate information regarding the use of the drug Meropenem in patients on hemodialysis.

It is generally recommended to avoid consuming alcohol while taking Meropenem. Alcohol consumption can affect the metabolism and elimination of the medication, potentially leading to increased risk of side effects or reduced effectiveness of the treatment.

In addition, meropenem is often prescribed to treat serious bacterial infections, and consuming alcohol may weaken the immune system and interfere with the body's ability to fight off the infection.

It is not known if Meropenem is excreted in human breast milk, so it is advised that caution should be exercised when administering Meropenem to nursing mothers.

Pregnancy Category B:

Studies investigating the effects of meropenem on reproduction have been conducted on rats and cynomolgus monkeys, with doses up to 1000 mg/kg/day and 360 mg/kg/day respectively (based on AUC comparisons), which is approximately 1.8 times and 3.7 times the human exposure at the typical dosage of 1 g every 8 hours. These studies did not indicate any impairment of fertility or harm to the fetus due to the drug meropenem. However, in rats, there were slight changes in fetal body weight at doses of about 250 mg/kg/day (based on AUC comparisons, which is 0.4 times the human exposure at a dose of 1 g every 8 hours) and higher. It is important to note that there are currently no sufficient and well-controlled studies in pregnant women, and animal reproduction studies may not always predict human response. Therefore, meropenem should only be used during pregnancy if absolutely necessary.

There are no known food warnings related to the use of Meropenem.

The adverse reactions related to Meropenem can be categorized as follows:

Common

• Diarrhea
• Nausea
• Vomiting
• Skin rash
• Pain or inflammation at the injection site
• Headache

Less Common

• Dizziness
• Itching
• Abdominal pain
• Fungal infections, such as thrush or vaginal yeast infections
• Low white blood cell count (leukopenia)
• High liver enzymes (transaminases)
• High levels of bilirubin in the blood (hyperbilirubinemia)
• High levels of creatinine in the blood (hypercreatinemia)
• Elevated potassium levels (hyperkalemia)
• Elevated sodium levels (hyponatremia)
• Hallucinations

Rare

• Seizures
• Anaphylaxis (a severe allergic reaction)
• Blood disorders, such as thrombocytopenia or hemolytic anemia
• Stevens-Johnson syndrome (a serious skin condition)
• Toxic epidermal necrolysis (a rare and potentially life-threatening skin condition)

The clinically relevant drug interactions of Meropenem are briefly summarized here:

Probenecid obstructs the active tubular secretion of meropenem, leading to a decrease in its renal excretion. This results in significant increases in both the elimination half-life (by 38%) and the systemic exposure (by 56%). Consequently, it is not advisable to administer probenecid together with meropenem.

There is indication that meropenem may lower the serum levels of valproic acid to levels below the therapeutic range (50 to 100 μg/mL total valproate).

The following are the side effects involving Meropenem:

• Nausea and vomiting
• Diarrhea
• Headache
• Skin rash
• Pain, redness, or swelling at the injection site
• Fever
• Abdominal pain
• Dizziness or lightheadedness
• Changes in taste or smell
• Insomnia or trouble sleeping

Pregnancy:

Pregnancy Category B:

Studies investigating the effects of meropenem on reproduction have been conducted on rats and cynomolgus monkeys, with doses up to 1000 mg/kg/day and 360 mg/kg/day respectively (based on AUC comparisons), which is approximately 1.8 times and 3.7 times the human exposure at the typical dosage of 1 g every 8 hours. These studies did not indicate any impairment of fertility or harm to the fetus due to the durg meropenem. However, in rats, there were slight changes in the fetal body weight at doses of 250 mg/kg/day (based on AUC comparisons, 0.4 times the human exposure at a dose of 1 g every 8 hours) and higher. It is important to note that there are currently no sufficient and well-controlled studies in pregnant women, and animal reproduction studies may not always predict human response. Therefore, meropenem should only be used during pregnancy if absolutely necessary.

Nursing Mothers

It is not known if Meropenem is excreted in human breast milk, so it is advised caution should be exercised when administering Meropenem to nursing mothers.

Pediatric Use

Meropenem has been deemed safe and effective for use in pediatric patients who are three months of age or older. In the case of bacterial meningitis, the use of Meropenem is backed by sufficient evidence from well-controlled studies in the pediatric population. Similarly, for intra-abdominal infections, although the supporting data comes from controlled clinical trials in adults, there is additional evidence from pediatric pharmacokinetics studies and controlled clinical trials in pediatric patients. For complicated skin and skin structure infections, an adequate and well-controlled study in adults, as well as data from pediatric pharmacokinetics studies, support the use of Meropenem in pediatric patients.

Geriatric Use

Approximately 30% of the total number of subjects in clinical studies of Meropenem were 65 years of age and older, while 11% were 75 years and older. Similarly, in a study of 511 patients with complicated skin and skin structure infections, 18% were 65 years of age and older, while 7% were 75 years and older. No significant differences were observed in safety or effectiveness between elderly and younger subjects. However, caution should be exercised in elderly patients with renal insufficiency, as a pharmacokinetic study has shown a correlation between age-related reduction in creatinine clearance and a reduction in plasma clearance of meropenem. Since Meropenem is predominantly excreted by the kidneys, the risk of toxic reactions may be greater in patients with impaired renal function. As a result, dosage selection in elderly patients should be carefully considered, and renal function monitoring may be beneficial.

Physicians should be knowledgeable as well as vigilant about the treatment as well as the identification of overdosage of Meropenem.

An overdose of meropenem can cause serious health problems, and prompt treatment is essential in such cases.

Symptoms of meropenem overdose can include seizures, confusion, loss of consciousness, and difficulty breathing. If you suspect an overdose, you should seek emergency medical attention immediately.

The treatment for meropenem overdose will depend on the severity of the symptoms. In mild cases, your doctor may simply monitor your vital signs and wait for the medication to clear from your system. In more severe cases, you may need to be hospitalized and receive supportive care, such as intravenous fluids, oxygen therapy, and anticonvulsant medications.

Pharmacodynamics

Meropenem is a type of carbapenem antibiotic that has a broad range of activity against both Gram-positive and Gram-negative bacteria. Its mechanism of action involves easy penetration into bacterial cells and disruption of the production of essential components of the cell wall, which ultimately causes the death of the bacterial cell.

Pharmacokinetics

Absorption:

● No data available on the absorption of meropenem

Volume of Distribution:

● No data is available on the volume of distribution of meropenem

Protein Binding:

● Meropenem is approximately 2% bound to plasma proteins

Metabolism:

● Meropenem is primarily excreted unchanged

● One metabolite of meropenem is microbiologically inactive

Route of Elimination:

● Approximately 70% of the intravenously administered dose of meropenem is excreted unchanged in the urine over 12 hours

● After 12 hours, there is little detectable urinary excretion of meropenem.

• https://medlineplus.gov/druginfo/meds/a696038.html#:~:text=Meropenem injection is used to,class of medications called antibiotics.
• https://go.drugbank.com/drugs/DB00760
• https://www.webmd.com/drugs/2/drug-13960/meropenem-intravenous/details
• https://www.drugs.com/mtm/meropenem.html
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050706s037lbl.pdf
• https://www.pfizer.com/products/product-detail/merrem_i_v