What are the potential drug interactions with Meropenem?

Meropenem Drug Interactions

Meropenem has significant drug interactions with probenecid and valproic acid that require clinical attention, while it has minimal interaction with most other medications due to its limited metabolism through the cytochrome P450 system. 1

Key Drug Interactions

Probenecid

• Probenecid competes with meropenem for active tubular secretion, resulting in increased plasma concentrations of meropenem 1
• Co-administration of probenecid with meropenem is not recommended due to this interaction 1
• Probenecid inhibits renal excretion of meropenem, as meropenem is primarily eliminated through glomerular filtration and renal tubular secretion 2

Valproic Acid

• Co-administration of meropenem with valproic acid or divalproex sodium results in a significant reduction in valproic acid concentrations 1
• Valproic acid concentrations may drop below the therapeutic range (average drop of 66% within 24 hours), increasing the risk of breakthrough seizures 1, 3
• The mechanism appears to involve inhibition of the hydrolysis of valproic acid's glucuronide metabolite back to valproic acid 1
• If meropenem administration is necessary in patients on valproic acid, supplemental anti-convulsant therapy should be considered 1, 4
• This interaction has been documented to be clinically significant with electroclinical deterioration in 55% of patients receiving both medications 3

Other Antibiotics

• Meropenem shows low potential for clinically significant interactions with other antibiotics including linezolid, piperacillin, benzylpenicillin, tazobactam, and sulbactam 2
• When used in combination therapy for resistant organisms (such as carbapenem-resistant Enterobacterales), no significant adverse interactions have been reported with colistin, tigecycline, or aminoglycosides 5

Cytochrome P450 System

• Unlike many other antibiotics, meropenem has minimal interaction with the cytochrome P450 enzyme system, reducing the risk of drug interactions through this mechanism 6
• This makes meropenem a safer option when treating patients on multiple medications that are metabolized through CYP450 pathways 7

Special Considerations

Renal Impairment

• Meropenem is primarily eliminated renally, so dosage adjustment is necessary in patients with renal impairment (CrCl ≤50 mL/min) 1
• Drug interactions may be more pronounced in patients with renal dysfunction 2

Central Nervous System Effects

• Meropenem has a lower seizure potential compared to other carbapenems like imipenem 7, 6
• However, caution should be exercised when administering meropenem with other drugs that may lower the seizure threshold, particularly in elderly patients with central nervous system disorders 4

Clinical Recommendations

• Monitor valproic acid levels closely when co-administering with meropenem; consider alternative antibiotic therapy or supplemental anticonvulsant therapy 1, 4, 3
• Avoid concomitant use of probenecid with meropenem 1
• When using meropenem in combination therapy for resistant organisms, standard doses can generally be used without significant interaction concerns 5
• In patients with renal impairment, adjust meropenem dosing according to creatinine clearance to prevent drug accumulation 1

Meropenem's favorable drug interaction profile makes it a valuable option for treating serious infections, particularly in patients receiving multiple medications, as long as the specific interactions with probenecid and valproic acid are managed appropriately 7, 6.