Pharmacologic class (EPC) · 7 drug pages

Folate analog metabolic inhibitor: adverse event reports filed with FDA

312,274 reports list a drug in this class as a suspect or interacting product, 2004–2026.

Read first · FDA's statement on these data

Adverse event reports submitted to FDA do not undergo extensive validation or verification. Therefore, a causal relationship cannot be established between product and reactions listed in a report. While a suspected relationship may exist, it is not medically validated and should not be the sole source of information for clinical decision making or other assumptions about the safety or efficacy of a product. Additionally, it is important to remember that adverse event reports represent a small percentage of total usage numbers of a product. Common products may have a higher number of adverse events due to the higher total number of people using the product. openFDA, FDA

FDA adds: "There is no certainty that the reported event (adverse event or medication error) was actually due to the product. FDA does not require that a causal relationship between a product and event be proven, and reports do not always contain enough detail to properly evaluate an event." The information in these reports "cannot be used to estimate the incidence of these events."

Do not rely on openFDA to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated.

Not medical advice. This site counts what was reported to FDA. Questions about a medicine or device belong with a pharmacist or clinician.

312,274
reports across the class: 1.5% of all reports; 17,704
reports, 12 months to June 2026: 21,141 in the 12 months before; 83.5%
marked serious by the reporter: 57.4% across all reports; 7
drugs with a page: brand and generic names counted separately

Folate analog metabolic inhibitor is a pharmacologic class (an FDA Established Pharmacologic Class) with 7 drug pages on this site. Together those drugs are listed as a suspect or interacting product in 312,274 adverse event reports received by FDA, 1.5% of the database, from January 2004 to June 2026.

17,704 reports arrived in the 12 months to June 2026, down 16% from 21,141 in the 12 months before. FDA releases FAERS data quarterly, so the newest months are incomplete and grow in later releases. 83.5% of the class's reports are marked serious, 10.5% record death among the outcomes and 30.9% record hospitalisation, as reported.

Across the class the reactions recorded most often are drug ineffective (23.9%), rheumatoid arthritis (10%) and off label use (9.2%). The class median share shown beside each term is the middle value across the member drugs; it is the comparison used on every drug page in this class.

The members table is ordered by report count for navigation only. FDA states that adverse event reports "represent a small percentage of total usage numbers of a product", that "common products may have a higher number of adverse events due to the higher total number of people using the product", and that the data "by themselves are not an indicator of the safety profile of the drug or biologic."

Drugs in the class

Drug	Name type	Reports	Latest 12 months	Marked serious	Top term recorded
Methotrexate	generic	207,259	11,503	90.7%	Drug ineffective
Methotrexate sodium	generic	67,497	2,458	61%	Drug ineffective
Pemetrexed	generic	18,409	2,785	98.7%	Malignant neoplasm progression
AlimtaPemetrexed disodium	brand	11,274	432	89.8%	Off label use
RasuvoMethotrexate	brand	2,979	91	14.1%	Drug ineffective
Pemetrexed disodium	generic	2,942	397	98.9%	Myelosuppression
OtrexupMethotrexate	brand	1,914	38	9.8%	Device issue

Ordered by report count for navigation only. FDA states that adverse event reports "represent a small percentage of total usage numbers of a product", that "common products may have a higher number of adverse events due to the higher total number of people using the product", and that the data "by themselves are not an indicator of the safety profile of the drug or biologic."

Reports by month, five years

FDA releases FAERS data quarterly, so the newest months are incomplete and grow in later releases.

Reactions recorded across the class

share of class reports recording the termmedian drug in the class

Drug ineffectivethe medicine did not work as expected23.9%74,524
Rheumatoid arthritisrheumatoid arthritis, an inflammatory joint disease10%31,367
Off label useused for a purpose or in a way not on the label9.2%28,714
Painpain, site not specified8.3%26,066
Drug intolerancethe medicine was not tolerated7.8%24,227
Arthralgiajoint pain7.6%23,755
Fatiguetiredness7.3%22,887
Nauseafeeling sick7.1%22,145
Joint swellinga swollen joint6.2%19,216
Rashskin rash5.8%18,236
Drug hypersensitivityan allergic-type reaction to a medicine5.7%17,839
Condition aggravatedthe condition being treated got worse5.4%16,974
Treatment failurethe treatment did not work5.1%15,872
Alopeciahair loss5%15,691
Diarrhoealoose or frequent stools5%15,586
Abdominal discomfortstomach discomfort4.6%14,410
Contraindicated product administered4.6%14,370
Vomitingbeing sick4.4%13,870
Headachehead pain4.3%13,450
Pyrexiafever4.2%13,248
Synovitis4.1%12,688
Pneumonialung infection4.1%12,649
Arthropathy3.9%12,165
Infectionan infection, type not specified3.9%12,034
Swellingswelling3.8%11,893

Solid bar: share of all class reports. Hollow bar: the median share across the 7 member drugs, the reference used on each member's page. One report can record several terms.

Outcomes, patients and reporters

Outcomes recorded

Death10.5%32,725

Life-threatening7.3%22,931

Hospitalisation (initial or prolonged)30.9%96,384

Disability4.8%14,940

Congenital anomaly1.2%3,786

Other serious62.8%196,002

Not serious16.5%51,376

Patient age

Under 20.5%1,561

2 to 114.2%13,056

12 to 173%9,374

18 to 4413.1%40,802

45 to 6426.7%83,523

65 to 7414.4%45,111

75 and over7.3%22,832

Age not given30.7%96,015

Who reported

Physician35.8%111,656

Pharmacist3.1%9,720

Other health professional41.9%130,826

Lawyer0.1%206

Consumer or non-health professional16.6%51,909

Not given2.5%7,957

Grey bar: all 20,646,523 reports in the database. Outcome flags are as the reporter set them and are not verified by FDA.

Questions about Folate analog metabolic inhibitor reports

Which drugs are in the Folate analog metabolic inhibitor class on this site?

Methotrexate, Methotrexate sodium, Pemetrexed, Alimta, Rasuvo and Pemetrexed disodium and 1 more. Class membership comes from the pharmacologic class (EPC) on the drug's FDA label.

How many reports does the class have?

312,274 reports through June 2026, 17,704 of them in the latest 12 months. A report listing two drugs of the class counts once for each.

What reactions are recorded most often?

drug ineffective (23.9%), rheumatoid arthritis (10%), off label use (9.2%), pain (8.3%) and drug intolerance (7.8%).

Can the members table be used to rank the drugs?

No. FDA states that adverse event reports "represent a small percentage of total usage numbers of a product", that "common products may have a higher number of adverse events due to the higher total number of people using the product", and that the data "by themselves are not an indicator of the safety profile of the drug or biologic." Drugs differ in how many people take them, in the conditions they treat, in time on the market and in how diligently reports are collected.

How do I report an adverse event?

Through FDA MedWatch (Form FDA 3500, or 1-800-FDA-1088) or to the manufacturer. See the guide on how to report.

Where this comes from. Counts are built from the openFDA Drug Adverse Event (FAERS) bulk export released 28 Sep 2026, which holds reports FDA received through 30 Jun 2026. Drug names are as reported, resolved to the brand or generic name on the FDA label where openFDA's harmonisation matched them; classes are the pharmacologic class (EPC) from the label and the National Drug Code Directory of 17 Sep 2026. A class is the Established Pharmacologic Class most often attached to a drug's reports by openFDA's label harmonisation, or from the NDC Directory where reports carry none. No report narrative, lot number, patient detail or reporter identity is published. See the methodology and sources; FDA's record is authoritative, and corrections are handled within five working days.

Drug data (FAERS) through 30 Jun 2026; device data (MAUDE) through 31 Aug 2026. Not medical advice.