Methotrexate with Dantrolene Interaction Details
Brand Names Associated with Methotrexate
- Amethopterin
- Methotrexate
- MTX
- Rheumatrex®
- Trexall®
Brand Names Associated with Dantrolene
- Dantrium®
- Dantrolene
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 17, 2023
Interaction Effect
Increased methotrexate exposure, an increased risk of methotrexate toxicity or methotrexate-related severe adverse reactions, reduced active metabolite formation and possibly reduced methotrexate efficacy
Interaction Summary
Coadministration of methotrexate with hepatotoxic agents like dantrolene may increase methotrexate plasma concentrations, which may increase the risk of methotrexate severe adverse reactions. In some cases, the coadministration of methotrexate with dantrolene 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. Increased organ specific adverse reactions may also occur when methotrexate is coadministered with hepatotoxic products . Use caution when using methotrexate in patients who are taking dantrolene as concomitant use may cause elevated methotrexate levels, resulting in methotrexate toxicity . One case report described methotrexate toxicity in a 16-year-old girl who had received both medications. Caution is recommended if the concomitant use of dantrolene and methotrexate is necessary .
Severity
Major
Onset
Rapid
Evidence
Probable
How To Manage Interaction
Coadministration of methotrexate with hepatotoxic agents like dantrolene may increase methotrexate plasma concentrations, which may increase the risk of methotrexate severe adverse reactions. In some cases, the coadministration of methotrexate with dantrolene 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. Increased organ specific adverse reactions may also occur when methotrexate is coadministered with hepatotoxic products ..
Mechanism Of Interaction
Impaired renal clearance of methotrexate; altered protein binding; additive hepatotoxicity
Literature Reports
A) In a case report, coadministration of dantrolene and methotrexate appeared to significantly increase methotrexate concentrations, resulting in methotrexate intoxication. A 16-year-old girl with non-metastatic femoral osteosarcoma was treated with high-dose methotrexate (12 g/m(2)), along with ondansetron and methylprednisolone, both of which were started concomitantly. She had also received intravenous nalbuphine and oral dantrolene for 4 days and 1 day, respectively. At 24 hours post initial methotrexate dose, methotrexate serum concentrations were significantly elevated (418 micromoles/liter), with evidence of methotrexate toxicity (cytolytic hepatitis, renal failure, grade I thrombopenia, and grade IV mucositis). The patient also experienced a seizure on day 9 due to elevated blood pressure. The patient received intense urine alkalinization, leucovorin rescue, carboxypeptidase-G2, and the dantrolene was stopped. The threshold value of 0.2 micromoles/liter was reached at 324 hours after the initial methotrexate dose was given. Methotrexate was resumed at a lower dose (total 10 g) 3 weeks later with good tolerance and standard decreases in plasma concentrations. Use of the Naranjo probability scale indicated a probable association between the methotrexate toxicity and dantrolene therapy in this patient. The mechanism of action was postulated to be altered renal excretion of methotrexate by dantrolene or its metabolite, 5-hydroxydantrolene, and altered protein binding of methotrexate to serum proteins .
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.
Dantrolene Overview
-
Dantrolene is used to treat spasticity (muscle stiffness and tightness) or muscle spasms associated with spinal cord injuries, stroke, multiple sclerosis, or cerebral palsy. It is also used to prevent, treat, or reduce the risk of malignant hyperthermia (disorder that causes a fast rise in body temperature and muscle contractions), Dantrolene is in a class of medications called skeletal muscle relaxants. Dantrolene acts on the spinal cord nerves to treat spasticity and to prevent and treat malignant hyperthermia.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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:
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.