Methotrexate

Name: Methotrexate

What brand names are available for methotrexate?

Otrexup, Rasuvo

What Is Trexall?

Trexall is the brand name of methotrexate sodium, a drug prescribed to treat psoriasis and rheumatoid arthritis.

It can also treat neoplastic diseases, or diseases that result from the abnormal growth of tissue, such as gestational choriocarcinoma, chorioadenoma destruens, and hydatidiform mole.

Trexall is also used to treat various types of cancer, including breast cancer and lung cancer, when used alone or in combination with other anticancer medications.

When used in combination with chemotherapeutic agents, it can help treat advanced stage non-Hodgkin lymphomas.

Trexall belongs to a class of drugs called antimetabolites, which work by slowing the growth of certain types of cells, especially rapidly growing cells, such as skin cells, bone marrow cells, and cancer cells.

It's not clear how Trexall treats rheumatoid arthritis, but it's believed the drug decreases the activity of the immune system.

Trexall may also be prescribed "off-label" to induce miscarriage in ectopic pregnancies (those that occur outside the uterus), and treat some autoimmune or inflammatory diseases, including Crohn's disease, multiple sclerosis, lupus, and dermatomyositis.

The Food and Drug Administration (FDA) approved Trexall in 2001. Trexall is currently manufactured by Teva Pharmaceutical Industries, which acquired the drug's original manufacturer, Barr Pharmaceuticals, in 2008.

Sandoz, a subdivision of the Novartis pharmaceutical company, produces an injectable, generic form of Trexall.

In 2013, Sandoz issued a nationwide recall of two lots of its methotrexate sodium drugs when particulate matter was found in some of the vials.

Trexall Warnings

Trexall carries a black-box warning that it should be used only by people with life-threatening neoplastic diseases, psoriasis, or rheumatoid arthritis that hasn't responded well to other treatments, because the drug can produce numerous potentially fatal reactions.

Using Trexall with certain non-steroidal anti-inflammatory drugs (NSAIDs) can cause severe and sometimes fatal bone marrow suppression, aplastic anemia (in which the body stops making new blood cells), and gastrointestinal toxicity.

When used along with radiotherapy, Trexall may increase the risk of cell death in soft tissues and bones.

People with kidney problems, ascites (fluid accumulation in the abdominal cavity), or pleural effusions (excess fluid in the lungs) may experience methotrexate toxicity, because they're unable to efficiently clear Trexall from their bodies.

Prolonged use of Trexall may cause liver damage, including cirrhosis (irreversible scarring of the liver), which may be fatal. High doses of Trexall can also damage the kidneys and cause acute kidney failure.

Trexall is known to produce toxic and sometimes fatal reactions in gastrointestinal, blood, neurologic, pulmonary, and dermatologic systems. For instance, it can cause seizures, Stevens-Johnson syndrome (a rare yet severe disorder of the skin and mucous membranes), and methotrexate-induced lung disease.

It may also cause potentially fatal infections to develop, particularly Pneumocystis jirovecii pneumonia.

In rare cases, people taking low doses of Trexall may develop tumors in the lymph system (malignant lymphomas), which may regress after the medication is stopped.

People taking Trexall who have rapidly growing tumors may develop tumor lysis syndrome, a condition in which tumor cells release their contents into the bloodstream, causing heart rhythm problems, seizures, even death.

Additionally, people with psoriasis or rheumatoid arthritis may not be candidates for Trexall if they:

  • Have alcoholism, alcoholic liver disease, or other chronic liver diseases
  • Have an immunodeficiency syndrome
  • Have a blood deficiency disorder, such as anemia (low red blood cell count), leukopenia (low white blood count), and thrombocytopenia (low blood platelet count)

Pregnancy and Trexall

Trexall can harm (and kill) fetuses or cause birth defects. Methotrexate is sometimes prescribed to induce an abortion.

Trexall also passes through breast milk and has the potential for to produce serious reactions in breast-fed infants, so it should not be taken by breastfeeding mothers.

Overdose

Leucovorin is indicated to diminish the toxicity and counteract the effect of inadvertently administered overdosages of methotrexate. Leucovorin administration should begin as promptly as possible. As the time interval between methotrexate administration and leucovorin initiation increases, the effectiveness of leucovorin in counteracting toxicity decreases. Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with leucovorin.

In cases of massive overdosage, hydration and urinary alkalinization may be necessary to prevent the precipitation of methotrexate and/or its metabolites in the renal tubules. Generally speaking, neither hemodialysis nor peritoneal dialysis have been shown to improve methotrexate elimination. However, effective clearance of methotrexate has been reported with acute, intermittent hemodialysis using a high-flux dialyzer (Wall, SM et al: Am J Kidney Dis28(6): 846-854, 1996).

In postmarketing experience, overdose with methotrexate has generally occurred with oral and intrathecal administration, although intravenous and intramuscular overdose have also been reported.

Reports of oral overdose often indicate accidental daily administration instead of weekly (single or divided doses). Symptoms commonly reported following oral overdose include those symptoms and signs reported at pharmacologic doses, particularly hematologic and gastrointestinal reaction. For example, leukopenia, thrombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, gastrointestinal bleeding. In some cases, no symptoms were reported. There have been reports of death following overdose. In these cases, events such as sepsis or septic shock, renal failure, and aplastic anemia were also reported.

Uses of Methotrexate

Oral/Injectable:

Methotrexate is a prescription medication used to treat the following conditions:

  • severe psoriasis
  • rheumatoid arthritis
  • polyarticular juvenile idiopathic arthritis (PJIA)
  • breast cancer
  • certain types of head and neck cancer
  • lung cancer
  • advanced non-Hodgkin lymphoma (NHL)
  • advanced mycosis fungoides (a type of cutaneous T-cell lymphoma)
  • osteosarcoma that has not spread to other parts of the body, following surgery to remove the primary tumor

Methotrexate is also used to treat the following types of gestational trophoblastic tumors:

  • Chorioadenoma destruens
  • Choriocarcinoma
  • Hydatidiform mole

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Methotrexate Brand Names

Methotrexate may be found in some form under the following brand names:

  • Folex PFS

  • Otrexup

  • Rasuvo

  • Rheumatrex

  • Trexall

  • Xatmep

Methotrexate Drug Class

Methotrexate is part of the drug class:

  • Folic acid analogues

Methotrexate Pharmacokinetics

Absorption

Bioavailability

Oral absorption appears to be highly variable and dose dependent;127 214 215 oral bioavailability may be <50%.215 Bioavailability decreases with increasing oral doses; absorption may be substantially reduced at doses >80 mg/m2.127 214 215 Following oral administration, peak serum concentrations are attained in 1–2 hours.127

Appears to be completely absorbed following IM administration at doses ≤100 mg;127 215 peak serum concentrations are attained within 30–60 minutes.127

Onset

In patients with rheumatoid arthritis, effects on articular swelling and tenderness may be observed after 3–6 weeks of treatment; improvement may continue for another 12 weeks or more.262 265

Duration

In patients with arthritis, limited data indicate that initial improvement is maintained for at least 2 years with continued therapy.262 265 Arthritis usually worsens within 3–6 weeks after methotrexate discontinuance.262 265

Food

Food delays absorption and decreases peak serum concentrations following oral administration.127 214

Special Populations

Absorbed through the ileum; placement of a Foley catheter or frequent emptying of the reservoir is advised in patients with long ileal loops or internal reservoirs during administration of methotrexate-containing regimens for the treatment of advanced or metastatic bladder cancer.205 206

Distribution

Extent

Widely distributed into body tissues, with highest concentrations in the kidneys, gallbladder, spleen, liver, and skin.a Distributes into third-space fluids.215 216

High-dose systemic therapy can result in peak CSF concentrations above the therapeutic threshold.216 219 Intrathecal administration may result in potentially cytotoxic serum concentrations that can persist for 24–48 hours.215

Crosses the placentaa and is distributed into milk.127 161 162

Plasma Protein Binding

About 50% (mainly albumin).127 215

Special Populations

Presence of pleural effusions or ascites can substantially alter drug disposition.215 216

Elimination

Metabolism

Undergoes hepatic and intracellular metabolism to polyglutamate metabolites;127 partially metabolized by intestinal flora after oral administration.127

Polyglutamate metabolites may be converted back to methotrexate by hydrolysis,127 and metabolites may remain in tissues for extended periods of time.127

Elimination Route

Excreted principally by the kidneys and to a lesser extent via feces.a

Half-life

At low-doses (<30 mg/m2), terminal half-life is about 3–10 hours.127 262 265 At high doses, elimination half-life is about 8–15 hours.127 262 265

Special Populations

Excretion is impaired and accumulation occurs more rapidly in patients with impaired renal function, pleural effusion, or other substantial third-space accumulations (e.g., ascites).a 262 265

Uses For methotrexate

Methotrexate tablets are used alone or together with other medicines to treat several types of cancer such as breast, head and neck, lung, blood, bone, lymph node, uterus cancers, and severe rheumatoid arthritis. It is also used to control symptoms of severe psoriasis in adults who have not been helped by other treatments.

Methotrexate oral solution is used to treat acute lymphoblastic leukemia (ALL) in children, and help manage polyarticular juvenile idiopathic arthritis (pJIA) in children who had other treatments that did not work well.

Methotrexate belongs to the group of medicines known as antineoplastics (cancer medicines). It blocks an enzyme that is needed by cells to live. This interferes with the growth of cancer cells, which are eventually destroyed by the body. For patients with arthritis or psoriasis, methotrexate may work by improving the immune system.

methotrexate is available only with your doctor's prescription.

Precautions While Using methotrexate

It is very important that your doctor check your progress at regular visits to make sure methotrexate is working properly and to check for unwanted effects. Blood and urine tests may be needed to check for unwanted effects.

Using methotrexate while you are pregnant can harm your unborn baby. The medicine may also cause birth defects if it is used by the father when his sexual partner becomes pregnant. Men should use birth control during and for at least 3 months after the last dose. Women should use birth control during and for at least 6 months after the last dose. Tell your doctor right away if pregnancy occurs while you are using methotrexate.

Talk with your doctor before using methotrexate if you plan to have children. Some men and women who use methotrexate have become infertile (unable to have children).

Limit alcohol use with methotrexate. Alcohol may increase the risk for liver problems.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Methotrexate can lower the number of white blood cells in your blood, which increases the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

  • If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
  • Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
  • Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
  • Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
  • Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
  • Avoid contact sports or other situations where bruising or injury could occur.

methotrexate may cause stomach and bowel problems. Check with your doctor right away if you have abdominal or stomach pain, black, tarry stools, constipation, diarrhea, loss of appetite, nausea, pain in the back of the throat or chest when swallowing, or vomiting blood or material that looks like coffee grounds.

Check with your doctor right away if you have cough, fever, or shortness of breath. These could be symptoms of a serious lung or breathing problems.

While you are being treated with methotrexate, and after you stop treatment with it, do not have any immunizations (vaccines) without your doctor's approval. Methotrexate may lower your body's resistance and the vaccine may not work as well or you might get the infection the vaccine is meant to prevent. In addition, you should not be around other persons living in your household who receive live virus vaccines because there is a chance they could pass the virus on to you. Some examples of live vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Do not get close to them and do not stay in the same room with them for very long. If you have questions about this, talk to your doctor.

Serious skin reactions can occur with methotrexate. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, red skin lesions, severe acne or a skin rash, sores or ulcers on the skin, or fever or chills while you are using methotrexate.

methotrexate may cause a serious reaction called tumor lysis syndrome. Tell your doctor right away if you have a change in urine amount, joint pain, stiffness, or swelling, lower back, side, or stomach pain, rapid weight gain, swelling of the feet or lower legs, or unusual tiredness or weakness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Generic: 250 mg/10 mL (10 mL); 50 mg/2 mL (2 mL)

Solution, Injection [preservative free]:

Generic: 1 g/40 mL (40 mL); 100 mg/4 mL (4 mL); 200 mg/8 mL (8 mL); 250 mg/10 mL (10 mL); 50 mg/2 mL (2 mL)

Solution, Oral:

Xatmep: 2.5 mg/mL (120 mL) [contains methylparaben sodium, propylparaben sodium]

Solution Auto-injector, Subcutaneous [preservative free]:

Otrexup: 7.5 mg/0.4 mL (0.4 mL [DSC]); 10 mg/0.4 mL (0.4 mL); 12.5 mg/0.4 mL (0.4 mL); 15 mg/0.4 mL (0.4 mL); 17.5 mg/0.4 mL (0.4 mL); 20 mg/0.4 mL (0.4 mL); 22.5 mg/0.4 mL (0.4 mL); 25 mg/0.4mL (0.4 mL)

Rasuvo: 7.5 mg/0.15 mL (0.15 mL); 10 mg/0.2 mL (0.2 mL); 12.5 mg/0.25 mL (0.25 mL); 15 mg/0.3 mL (0.3 mL); 17.5 mg/0.35 mL (0.35 mL); 20 mg/0.4 mL (0.4 mL); 22.5 mg/0.45 mL (0.45 mL); 25 mg/0.5 mL (0.5 mL); 27.5 mg/0.55 mL (0.55 mL [DSC]); 30 mg/0.6 mL (0.6 mL)

Solution Reconstituted, Injection [preservative free]:

Generic: 1 g (1 ea)

Tablet, Oral:

Rheumatrex: 2.5 mg [DSC] [scored]

Trexall: 5 mg, 7.5 mg, 10 mg, 15 mg [scored]

Generic: 2.5 mg

Pharmacologic Category

  • Antineoplastic Agent, Antimetabolite (Antifolate)
  • Antirheumatic, Disease Modifying
  • Immunosuppressant Agent

Special Populations Renal Function Impairment

An increase in serum levels occurs because of decreased elimination in patients with renal function impairment.

Dosing Geriatric

Refer to adult dosing; adjust for renal impairment.

Breast cancer: Patients >60 years: IV: CMF regimen: 30 mg/m2 days 1 and 8 every 4 weeks (in combination with cyclophosphamide and fluorouracil) for up to 12 cycles (Bonadonna 1995)

Meningeal leukemia: Intrathecal: Consider a dose reduction (CSF volume and turnover may decrease with age)

Non-Hodgkin lymphoma: CODOX-M/IVAC regimen (Mead 2008): Cycles 1 and 3 of CODOX-M (CODOX-M alternates with IVAC): IV: 100 mg over 1 hour (on day 10) followed by 900 mg over 23 hours (with leucovorin rescue)

Rheumatoid arthritis/psoriasis: Oral: Initial: 5 to 7.5 mg per week, not to exceed 20 mg per week

Pregnancy Risk Factor X (psoriasis, rheumatoid arthritis) Pregnancy Considerations

[US Boxed Warning]: Some products are contraindicated in pregnant women. Methotrexate has been reported to cause fetal death and/or congenital abnormalities. Methotrexate is not recommended for women of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Pregnant women with psoriasis or rheumatoid arthritis should not receive methotrexate. Studies in animals and pregnant women have shown evidence of fetal abnormalities; therefore, the manufacturer classifies methotrexate as pregnancy category X (for psoriasis or RA). A pattern of congenital malformations associated with maternal methotrexate use is referred to as the aminopterin/methotrexate syndrome. Features of the syndrome include CNS, skeletal, and cardiac abnormalities. Low birth weight and developmental delay have also been reported. The use of methotrexate may impair fertility and cause menstrual irregularities or oligospermia during treatment and following therapy. It is not known if fertility impairment is reversible. Methotrexate is approved for the treatment of trophoblastic neoplasms (gestational choriocarcinoma, chorioadenoma destruens, and hydatidiform mole) and has been used for the medical management of ectopic pregnancy and the medical management of abortion. Pregnancy should be excluded prior to therapy in women of childbearing potential. Use for the treatment of neoplastic diseases only when the potential benefit to the mother outweighs the possible risk to the fetus. Pregnancy should be avoided for ≥3 months following treatment in male patients and at least 6 months and ≥1 ovulatory cycle in female patients. A registry is available for pregnant women exposed to autoimmune medications including methotrexate. For additional information contact the Organization of Teratology Information Specialists, OTIS Autoimmune Diseases Study, at 877-311-8972.

Usual Adult Dose for Lymphoma

-Burkitt's tumor Stages I to II: 10 to 25 mg orally once a day for 4 to 8 days
-Burkitt's tumor Stage III: Methotrexate is commonly given concomitantly with other antitumor agents
-Duration of therapy: All stages usually require several courses of therapy interposed with 7 to 10 day rest periods
-Lymphosarcoma Stage III: 0.625 to 2.5 mg/kg orally daily as a part of combination chemotherapy

Uses:
-Burkitt's tumor
-Lymphoma

Usual Adult Dose for Meningeal Leukemia

12 mg (maximum 15 mg) intrathecally every 2 to 5 days until the cell count of the CSF returns to normal; at this point, one additional dose is advisable

Comments:
-Administration at intervals of less than 1 week may result in increased subacute toxicity.
-The preserved formulations of this drug contain benzyl alcohol and must not be used for intrathecal or high dose therapy.

Use: Treatment and prophylaxis of meningeal leukemia

Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Mouth lesions, low blood counts, poor appetite, nausea and abdominal discomfort are the most common side effects of methotrexate. Tiredness, dizziness, skin rash, hair loss, and an increased susceptibility to infection have also been reported.
  • May cause bone marrow, liver, lung and kidney disease; deaths have been reported from methotrexate use. Periodic liver biopsies are recommended for people taking methotrexate long-term.
  • May cause a potentially fatal and irreversible lung condition; incidence does not depend on the dosage of methotrexate or length of treatment.
  • May not be suitable for people with anemia, poor kidney function, immunodeficiency, bone marrow disorders, gastrointestinal conditions, liver disease, fluid in the lungs, or with alcoholism. Methotrexate is more likely to cause toxicity in these people. Should not be used with NSAIDs as it may cause bone marrow suppression, anemia, and damage the stomach and intestinal lining. Methotrexate may also not be suitable for people with folate deficiency, stomach ulcers, lung disease, who are receiving radiation treatment or with any type of infection.
  • Not recommended for women of childbearing age unless benefits clearly outweigh risks as can cause fetal death or birth defects. May affect a person's future ability to have children, whether they are a man or a woman. Women should not breastfeed while taking methotrexate.
  • May occasionally cause severe, potentially fatal skin reactions. These may occur following single or multiple doses of methotrexate.
  • Interacts with many drugs, particularly those that also bind to blood proteins such as aspirin, sulfonamides, tetracyclines, and phenytoin.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

Methotrexate Levels and Effects while Breastfeeding

Summary of Use during Lactation

Most sources consider breastfeeding to be contraindicated during maternal high-dose antineoplastic drug therapy with methotrexate. An abstinence period of at least 1 week after chemotherapy doses of methotrexate has been suggested.[1] Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[2] Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.[3]

Limited information indicates that a maternal dose of methotrexate up to 65 mg (or 50 mg/square meter) produces low levels in milk, leading some authors to state that low single or weekly doses, such as those used for ectopic pregnancy or rheumatoid arthritis, are of low risk to the breastfed infant,[4][5][6][7][8] although some expert opinion warns against this use.[9][10][11][12][13] Withholding breastfeeding for 24 hours after a weekly low lose of methotrexate may decrease the infant's dose by 40%.[14] If breastfeeding during long-term, low-dose methotrexate use is undertaken, monitoring of the infant's complete blood count and differential could be considered.

Drug Levels

Maternal Levels. One patient who was 1 month postpartum given 22.5 mg (15 mg/square meter) methotrexate daily by mouth for choriocarcinoma. Milk was collected at various times of the first 12 days of therapy. A peak milk level of 2.3 mcg/L occurred 10 hours after the first dose. However, the milk level was relatively constant during the period from 4 to 10 hours after the dose, after which it began to drop. Peak milk levels on the second and third days of administration were 2.7 mcg/L. The authors estimated that a cumulative amount of 0.32 mcg would be excreted in milk during the first 12 hours after this dose.[4]

A woman was given a single intramuscular dose of 65 mg (50 mg/square meter) of methotrexate for ectopic pregnancy. Six milk samples were obtained from 1 to 24 hours after the dose. Methotrexate was undetectable (<22.7 mcg/L) in all milk samples.[7]

A woman with rheumatoid arthritis received hydroxychloroquine, sulfasalazine and prednisone 10 mg daily during pregnancy and postpartum. On day 151 postpartum, methotrexate 25 mg was given subcutaneously. Breastmilk samples were obtained at 2, 12 and 24 hours after the dose. Milk levels were 0.05 micromolar (22.7 mcg/L) in all samples which was considered detectable, but not quantifiable. A fully breastfed infant would receive 3.4 mcg/kg in the first 24 hours after administration, or about 1% of the weight-adjusted maternal dosage.[8]

Two lactating women receiving subcutaneous methotrexate 25 mg once weekly donated 4 to 7 milk samples over a 1-week period between doses. Peak breastmilk methotrexate milk concentrations occurred between 1 and 12 hours after the dose and were 4 nmol/L (1.8 mcg/L). Peak breastmilk milk concentrations of the active metabolite, 7-hydroxymethotrexate, occurred at 24 hours after the dose and were 1.8 nmol/L (846 ng/L). Milk methotrexate concentrations were less than 2.5 nmol/L (1.1 mcg/L) during the rest of the dosing interval after the peak. One patient had undetectable (<91 ng/L) milk levels between 5 and 7 days after the dose. The authors estimated that if the peak methotrexate level were sustained throughout the feeding, the relative infant dose would be 0.5% of the weight-adjusted maternal dose and if breastfeeding were withheld for the first 24 hours after the dose, this value would decrease to 0.3% of the weight-adjusted maternal dose.[14]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

On day 151 postpartum, weekly methotrexate 25 mg subcutaneously begun a nursing mother. The estimated intake of the infant at that time was 3.4 mcg/kg in the first 24 hours after administration. The mother continued to breastfeed (extent not stated) for an additional 9 months while receiving subcutaneous methotrexate 25 mg weekly. No adverse effects were noted in the infant.[9]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Rheumatoid Arthritis) Auranofin, Etanercept, Gold Sodium Thiomalate, Hydroxychloroquine, Infliximab, Penicillamine, Sulfasalazine

References

1. Pistilli B, Bellettini G, Giovannetti E et al. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: How should we counsel cancer patients about breastfeeding? Cancer Treat Rev. 2013;39:207-11. PMID: 23199900

2. Urbaniak C, McMillan A, Angelini M et al. Effect of chemotherapy on the microbiota and metabolome of human milk, a case report. Microbiome. 2014;2:24. PMID: 25061513

3. Stopenski S, Aslam A, Zhang X et al. After chemotherapy treatment for maternal cancer during pregnancy, is breastfeeding possible? Breastfeed Med. 2017;12:91-7. PMID: 28170295

4. Johns DG, Rutherford LD et al. Secretion of methotrexate in human milk. Am J Obstet Gynecol. 1972;112:978-80. PMID: 5042796

5. Moretti ME, Lee A, Ito S. Which drugs are contraindicated during breastfeeding? Can Fam Physician. 2000;46:1753-7. PMID: 11013791

6. Ostensen M. Management of early aggressive rheumatoid arthritis during pregnancy and lactation. Expert Opin Pharmacother. 2009;10:1469-79. PMID: 19505214

7. Tanaka T, Walsh W, Verjee Z et al. Methotrexate use in a lactating woman with an ectopic pregnancy. Birth Defects Res A Clin Mol Teratol. 2009;85:494. Abstract. Assay sensitivity per Shinya Ito, MD. DOI: doi:10.1002/bdra.20605

8. Thorne JC, Nadarajah T, Moretti M, Ito S. Methotrexate use in a breastfeeding patient with rheumatoid arthritis. J Rheumatol. 2014;41:2332. PMID: 25362724

9. Nguyen GC, Seow CH, Maxwell C et al. The Toronto Consensus Statements for the Management of IBD in Pregnancy. Gastroenterology. 2016;150:734-57. PMID: 26688268

10. Mahadevan U, Matro R. Care of the pregnant patient with inflammatory bowel disease. Obstet Gynecol. 2015;126:401-12. PMID: 26241432

11. Kavanaugh A , Cush JJ, Ahmed MS et al. Proceedings from the American College of Rheumatology Reproductive Health Summit: The management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res (Hoboken). 2015;67:313-25. PMID: 25385050

12. van der Woude CJ, Ardizzone S, Bengtson MB et al. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis. 2015;9:107-24. PMID: 25602023

13. Flint J, Panchal S, Hurrell A et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016;55:1693-7. PMID: 26750124

14. Delaney S, Colantonio D, Ito S. Methotrexate in breast milk. Birth Defects Res. 2017;109 (Special Issue: Si):711. Abstract. DOI: doi:10.1002/bdr2.1061

Administrative Information

LactMed Record Number

466

Last Revision Date

20170706

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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