HomePenicillin G BenzathinePenicillin G Benzathine + Methotrexate

Does Penicillin G Benzathine Interact with Methotrexate?

Penicillin G Benzathine and Methotrexate have a major drug interaction according to U.S. FDA drug labeling data. Penicillin G benzathine may reduce the renal excretion of methotrexate, causing a potential increase in its toxicity. The mechanism involves reduced renal excretion of methotrexate. Patients taking both medications should consult their healthcare provider before starting, stopping, or changing the dosage of either drug. This information is based on official FDA drug labeling sourced from OpenFDA and the NIH National Library of Medicine.

Severity
Major
Methotrexate Class
Folate Analog Metabolic Inhibitor
Management
Close medical supervision required
Data Source
U.S. FDA via OpenFDA

How This Interaction Works

The interaction between Penicillin G Benzathine and Methotrexate occurs because reduced renal excretion of methotrexate. Clinically, this means penicillin g benzathine may reduce the renal excretion of methotrexate, causing a potential increase in its toxicity. This is classified as a major interaction, meaning it could cause serious harm if not properly managed. Your healthcare provider may need to adjust dosages, substitute one medication, or increase monitoring frequency.

What To Tell Your Doctor or Pharmacist

If you are taking Penicillin G Benzathine and your doctor is considering prescribing Methotrexate (or vice versa), make sure to:

  • Inform your doctor and pharmacist of all current medications, including over-the-counter drugs and supplements
  • Ask whether the benefits of combining these medications outweigh the risks for your specific situation
  • Ask what symptoms to watch for that would indicate the interaction is causing problems
  • Ask how frequently you should be monitored while these are co-prescribed
  • Ask whether any dosage adjustments are needed
  • Never stop or change either medication without first consulting your healthcare provider
💊 Penicillin G Benzathine(Bicillin L-A)+💊 Methotrexate(Otrexup)

Severity & Interaction Details

⚠️
major
Use with caution — major interaction
Serious risk of clinically significant harm. Generally avoid; if used, monitor closely.
Severity scale
MinorContra
On record
Yes
Drug A class
Drug B class
Folate Analog Metabolic Inhibitor
Source
NLP:penicillin g benzathin

What this means in plain English

Penicillin G benzathine may reduce the renal excretion of methotrexate, causing a potential increase in its toxicity.

About Penicillin G Benzathine and Methotrexate

Methotrexate is a Folate Analog Metabolic Inhibitor. You may recognize them by the brand names Bicillin L-A and Otrexup. Both medications are given by intramuscular injection. Both Penicillin G Benzathine and Methotrexate carry an FDA boxed warning — the agency's most serious safety designation.

What the FDA label says

"Reduced renal excretion of methotrexate"

📖 Source: NLP:penicillin g benzathin

Share this result:

WhatsAppText / SMSEmail
Also share on:XFacebook
Add more drugs
Check Penicillin G Benzathine and Methotrexate against your full medication list

Most patients take more than two medications. CDI checks every pair across up to 20 drugs simultaneously — including OTCs and common supplements.

Add more drugs →
Data integrity: Every interaction shown is extracted directly from official U.S. FDA drug labeling via openFDA and the U.S. National Library of Medicine (NIH) — no interactions are invented, inferred, or manually edited. Maintained by CheckDrugInteractions.com. See our methodology or report a correction at support@checkdruginteractions.com.

Data sourced from U.S. FDA drug labeling via openFDA and the NIH National Library of Medicine, supplemented with a small number of well-established interactions from curated clinical references. For informational purposes only. Always consult your pharmacist or physician.