Meropenem, sold under the brand name Merrem among others, is an intravenous carbapenem antibiotic used to treat a variety of bacterial infections.[2] Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax.[2]
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Clinical data | |
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Trade names | Merrem, others |
AHFS/Drugs.com | Monograph |
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Routes of administration | Intravenous |
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Pharmacokinetic data | |
Bioavailability | 100% |
Protein binding | Approximately 2% |
Elimination half-life | 1 hour |
Excretion | Kidney |
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ECHA InfoCard | 100.169.299 |
Chemical and physical data | |
Formula | C17H25N3O5S |
Molar mass | 383.46 g·mol−1 |
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Common side effects include nausea, diarrhea, constipation, headache, rash, and pain at the site of injection.[2] Serious side effects include Clostridioides difficile infection, seizures, and allergic reactions including anaphylaxis.[2] Those who are allergic to other
Meropenem was patented in 1983.[3] It was approved for medical use in the United States in 1996.[2] It is on the World Health Organization's List of Essential Medicines.[4][5] The World Health Organization classifies meropenem as critically important for human medicine.[6]
Medical uses
editThe spectrum of action includes many Gram-positive and Gram-negative bacteria (including Pseudomonas) and anaerobic bacteria. The overall spectrum is similar to that of imipenem, although meropenem is more active against Enterobacteriaceae and less active against Gram-positive bacteria. It works against extended-spectrum
In 2017, the U.S. Food and Drug Administration (FDA) granted approval for the combination of meropenem and vaborbactam to treat adults with complicated urinary tract infections.[12]
Administration
editMeropenem is administered intravenously as an aqueous solution. Meropenem is stored in vials as white crystalline powder (containing meropenem as the trihydrate blended with anhydrous sodium carbonate).[13] For intravenous administration, the powder is dissolved in 5% monobasic potassium phosphate solution, since meropenem is soluble in 5% monobasic potassium phosphate solution and only sparingly soluble in water (5.63 mg/mL).[14][15][16] For intravenous bolus administration, injection vials are reconstituted with sterile water for injection.[14]
Reconstituted (dissolved) meropenem degrades over time.[17][18] The degradation may be associated with color change of the solution, typical for a hydrolysis of the amide bond of the
Meropenem is administered every 8 hours.[14]
Dosing must be adjusted for altered kidney function and for haemofiltration.[23]
Studies recomment application of meropenem therapeutic drug monitoring for optimal application.[24]
As with other
Meropenem exhibit poor permeability across the gut and low oral bioavailability because of its hydrophilic properties, which inhibit its passive diffusion across the intestinal epithelium.[27] The challenges related to research of oral delivery of meropenem are related to high susceptibility of meropenem to degradation through hydrolysis of the amide bond in the
There is insufficient data regarding the administration of meropenem during breastfeeding. However, it has been observed that, in general, the concentration of this beta-lactam antibiotic in breast milk is relatively low, therefore, beta-lactam antibiotics are not anticipated to induce detrimental effects in infants who are breastfed. Nonetheless, there have been sporadic reports of disturbances in the gastrointestinal flora of the infant, manifesting as diarrhea or oral candidiasis (thrush), associated with the use of beta-lactam antibiotics, however, these potential side effects have not been thoroughly investigated specifically in the context of meropenem use, therefore, the safety profile of meropenem in breastfeeding mothers and their infants is unknown.[28]
Although merapenem is not approved for intramuscular or subcutaneous routes of administration in humans, there were studies that evaluated the drug bioavailability in cats and reported bioavailability of 99.69% for intramuscular route and 96.52 % for subcutaneous route of administration; these studies also compared elimination half-lives for intravenous, intramuscular or subcutaneous routes of administration in cats and reported duration of 1.35, 2.10 and 2.26 hours, respectively.[29] There was also a small study on local tolerance of meropenem intramuscrular administration in humans, and it was reported as generally good.[29][30][31]
Side effects
editThe most common adverse effects are diarrhea (4.8%), nausea and vomiting (3.6%), injection-site inflammation (2.4%), headache (2.3%), rash (1.9%) and thrombophlebitis (0.9%).[32] Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin.[33][34] Meropenem has a reduced potential for seizures in comparison with imipenem. Several cases of severe hypokalemia have been reported.[35][36]
Interactions
editMeropenem rapidly reduces serum concentrations of valproic acid. As a result, people who use valproic acid for epilepsy are at increased risk of seizures during treatment with meropenem. In situations where the use of meropenem cannot be avoided, prescription of an additional anticonvulsant should be considered.[37]
Pharmacology
editMechanism of action
editMeropenem is bactericidal except against Listeria monocytogenes, where it is bacteriostatic. It inhibits bacterial cell wall synthesis like other
In 2016, a synthetic peptide-conjugated PMO (PPMO) was found to inhibit the expression of New Delhi metallo-beta-lactamase, an enzyme that many drug-resistant bacteria use to destroy carbapenems.[38][39]
While
Research directions
editNebulized meropenem (inhaled route) is researched, but is not approved, for prevention of bronchiectasis exacerbation.[41]
Society and culture
editTrade names
editCountry | Name | Maker |
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India | UNOMERO | Scutonix Lifesciences, Bombay |
India | Inzapenum | Dream India |
Aurobindo Pharma | ||
Penmer | Biocon | |
Meronir | Nirlife | |
Merowin | Strides Acrolab | |
Aktimer | Aktimas Biopharmaceuticals | |
Neopenem | Neomed | |
Mexopen | Samarth life sciences | |
Meropenia | SYZA Health Sciences LLP | |
Ivpenem | Medicorp Pharmaceuticals | |
Merofit | ||
Lykapiper | Lyka Labs | |
Winmero | Parabolic Drugs | |
Bangladesh | ||
Meroject | Eskayef Pharmaceuticals Ltd. | |
Merocon | Beacon Pharmaceuticals | |
Indonesia | Merofen | Kalbe |
Brazil | Zylpen | Aspen Pharma |
Japan, Korea | Meropen | |
Australia | Merem | |
Taiwan | Mepem | |
Germany | Meronem | |
Nigeria | Zironem | Lyn-Edge Pharmaceuticals |
Ukraine[42] | Meropenem | Lekhim-Kharkiv |
Panlaktam (Panlaktam) | "Darnytsia" | |
Mepenam | Kyivmedpreparat | |
Merobicide | Borshchahiv HFZ | |
US | Meronem | AstraZeneca |
Indonesia | Merosan | Sanbe Farma |
Indonesia | Merobat | Interbat |
Zwipen | ||
Carbonem | ||
Ronem | Opsonin Pharma, BD | |
Neopenem | ||
Merocon | Continental | |
Carnem | Laderly Biotech | |
Penro | Bosch | |
Meroza | German Remedies | |
Merotrol | Lupin) | |
Meromer | Orchid Chemicals | |
Mepenox | BioChimico | |
Meromax | Eurofarma | |
Ropen | Macter | |
mirage | adwic | |
Meropex | Apex Pharma Ltd. | |
Merostarkyl | Hefny Pharma Group[43] |
References
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