Methotrexate with Doxycycline Interaction Details

Brand Names Associated with Methotrexate

Brand Names Associated with Doxycycline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 17, 2023

Interaction Effect

Increased methotrexate exposure, an increased risk of methotrexate toxicity, reduced active metabolite formation and possibly reduced methotrexate efficacy

Interaction Summary

Coadministration of methotrexate with a highly protein bound drug like doxycycline may increase methotrexate plasma concentrations, which may increase the risk of methotrexate severe adverse reactions. In some cases, the coadministration of methotrexate with doxycycline may also subsequently reduce active metabolite formation, which may decrease the clinical effectiveness of methotrexate. If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions. A patient with malignant osteogenic sarcoma developed methotrexate-induced gastrointestinal and hematologic toxicities following a course of therapy with high-dose methotrexate and doxycycline, which was being administered for an eye infection. Previous cycles of methotrexate, which did not include doxycycline, had not resulted in toxicities. Possible mechanisms for this interaction include the displacement of methotrexate from its binding to plasma proteins, inhibition of methotrexate metabolism, competition for renal tubular secretion, or the inhibition of renal synthesis of prostaglandins .

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Coadministration of methotrexate with a highly protein bound drug like doxycycline may increase methotrexate plasma concentrations, which may increase the risk of methotrexate severe adverse reactions. In some cases, the coadministration of methotrexate with doxycycline may also subsequently reduce active metabolite formation, which may decrease the clinical effectiveness of methotrexate. If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions.

Mechanism Of Interaction

Displacement of methotrexate from its binding to plasma proteins

Literature Reports

A) A 17-year-old female with osteosarcoma of the left femur had received ten cycles of high-dose methotrexate (12 g/m2). She developed a palpebral abscess in her left eye which was treated with topical tobramycin, chloramphenicol, and hydrocortisone ointment. System therapy with doxycycline 100 mg twice daily was also prescribed. Her eleventh cycle of methotrexate was administered while therapy for her eye abscess continued. Within the first 24 hours following chemotherapy, she developed facial erythema, malaise, and vomiting. None of these problems had occurred during the first ten cycles of methotrexate. Doxycycline therapy was discontinued, but methotrexate hematologic toxicity grade 3 (hemoglobin 7.7 g/dL, white blood cell count 2.7 x 10(3)/mm3, platelets 137 x 10(3)/mm3) was apparent on day 6 following chemotherapy. Pharmacokinetic data revealed that the plasma concentration of methotrexate from 10 minutes to 168 hours following infusion was higher during the eleventh cycle as compared to the first ten cycles. Similarly, the half-life of methotrexate was 2.27 hours and 2.46 hours at 12 hours and 24 hours, respectively, for the first ten cycles, and was 4.67 hours and 5.43 hours, respectively, during the eleventh cycle. The patient's hospital stay was prolonged by eleven days because of the methotrexate toxicity, and 48 hours after discharge she was readmitted for an additional 12 days, which had obvious repercussions on quality of life and associated costs .

Methotrexate Overview

• Methotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body) that cannot be controlled by other treatments. Methotrexate is also used along with rest, physical therapy, and sometimes other medications to treat severe active rheumatoid arthritis (RA; a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) that cannot be controlled by certain other medications. Methotrexate is also used to treat certain types of cancer including cancers that begin in the tissues that form around a fertilized egg in the uterus, breast cancer, lung cancer, certain cancers of the head and neck, certain types of lymphoma, and leukemia (cancer that begins in the white blood cells). Methotrexate is in a class of medications called antimetabolites. Methotrexate treats cancer by slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells to stop scales from forming. Methotrexate may treat rheumatoid arthritis by decreasing the activity of the immune system.

Doxycycline Overview

• Doxycycline is used to treat a variety of infections caused by certain types of bacteria. Doxycycline is also used to treat or prevent anthrax (a serious infection that may be spread on purpose as part of a bioterror attack) in people who may have been exposed to anthrax in the air and to treat plague and tuleramia (serious infections that may be spread on purpose as part of a bioterror attack). It is also used to prevent malaria. Doxycycline is also used along with other medications to treat acne and rosacea (a skin disease that causes redness, flushing, and pimples on the face). Doxycycline (Oracea) is used only to treat pimples and bumps caused by rosacea. Doxycycline is in a class of medications called tetracycline antibiotics. It works to treat infections by preventing the growth and spread of bacteria. It works to treat acne by killing the bacteria that infects pores and decreasing a certain natural oily substance that causes acne. It works to treat rosacea by decreasing the inflammation that causes this condition.

• Antibiotics such as doxycycline will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.