Long COVID Patterns in the RECOVER-Adult Study
November 21, 2025
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Brand Name :
Jylamvo
(United States) [Available] ,Otrexup
(United States) [Available] ,Rasuvo
(United States) [Available] ,Xatmep
(United States) [Available]Synonyms :
Methotrexate
Class :
Anticancer: antimetabolites: folate antagonists
Brand Name :
Jylamvo
(United States) [Available] ,Otrexup
(United States) [Available] ,Rasuvo
(United States) [Available] ,Xatmep
(United States) [Available]Synonyms :
Methotrexate
Class :
Anticancer: antimetabolites: folate antagonists
DosingÂ
Adult dosageÂ
Injectable Solution:Â
25 mg/mLÂ
Powder for Injection:Â
1 g/vial (25 mg/mL when reconstituted)Â
SC Autoinjector (Otrexup):Â
10 mg/0.4 mLÂ
12.5 mg/0.4 mLÂ
15 mg/0.4 mLÂ
17.5 mg/0.4 mLÂ
20 mg/0.4 mLÂ
22.5 mg/0.4 mLÂ
25 mg/0.4 mLÂ
SC Autoinjector (Rasuvo):Â
2.5 mg/0.05 mL (delivers doses between 7.5 mg and 30 mg in 2.5 mg increments)Â
SC Prefilled Syringe (RediTrex):Â
7.5 mg/0.3 mLÂ
10 mg/0.4 mLÂ
12.5 mg/0.5 mLÂ
15 mg/0.6 mLÂ
17.5 mg/0.7 mLÂ
20 mg/0.8 mLÂ
22.5 mg/0.9 mLÂ
25 mg/mLÂ
Tablet:Â
2.5 mgÂ
5 mgÂ
7.5 mgÂ
10 mgÂ
15 mgÂ
Oral Solution:Â
2.5 mg/mL (Xatmep)Â
2 mg/mL (Jylamvo)Â
Acute Lymphoblastic Leukemia (ALL)Â
IV: 10–5,000 mg/m² based on disease, risk, concurrent drugs, treatment phase, and response; leucovorin rescue required with high doses.
Oral (Jylamvo): 20 mg/m² once weekly; adjust to maintain desired ANC.Â
Meningeal LeukemiaÂ
Treatment: 12 mg intrathecal (max 15 mg), every 2–7 days; give one extra dose after CSF cell count normalizes.Â
Prophylaxis: 12–15 mg intrathecal, no more than once weekly.Â
Non-Hodgkin Lymphoma (NHL)Â
IV Use (Systemic):Â
As part of combination chemotherapy: 1,000–3,000 mg/m² over 24 hours, followed by leucovorin rescue. High-dose regimens (up to 8,000 mg/m²) may be used, especially in CNS involvement.Â
Oral Use (Jylamvo):Â
For relapsed/refractory NHL: 2.5 mg taken 2–4 times weekly (max 10 mg/week). For cutaneous T-cell lymphoma (e.g., mycosis fungoides): 25–75 mg once weekly alone, or 10 mg/m² twice weekly in combination regimens.Â
CNS Involvement:Â
As a single agent: 8,000 mg/m² IV over 4 hours. With immunochemotherapy: 3,000–8,000 mg/m² IV with leucovorin rescue.Â
OsteosarcomaÂ
12 g/m² IV over 4 hours on specific weeks post-surgery (weeks 4–7, 11–12, 15–16, 29–30, 44–45).Â
May increase to 15 g/m² if peak methotrexate levels are <454 mcg/mL; do not exceed 20 g per dose.Â
Breast CancerÂ
40 mg/m² IV as part of a regimen with cyclophosphamide and fluorouracilÂ
Gestational Trophoblastic Neoplasia (GTN)Â
30–200 mg/m² or 0.4–1 mg/kg IV/IM; high-risk GTN: 300 mg/m² IV over 12 hours with other drugs.Â
Rheumatoid Arthritis (RA)Â
Initial Dose: 7.5 mg PO/IV/IM once weekly or 2.5 mg PO every 12 hours for 3 doses/week.Â
Max: 20 mg/week PO.Â
Jylamvo: Start at 7.5 mg PO weekly; titrate.Â
SC (Otrexup/Rasuvo/RediTrex): Start at 7.5–10 mg once weekly; adjust as needed.Â
Psoriasis
Dose: 10–25 mg PO/SC/IM/IV once weekly; max 30 mg/week.Â
Jylamvo/Trexall: orally weekly or in divided doses.Â
SC (Otrexup/Rasuvo/RediTrex): 10–25 mg weekly.Â
Injectable SolutionÂ
25 mg/mLÂ
Powder for Injection (reconstituted to 25 mg/mL)Â
1 g/vialÂ
Â
Subcutaneous (SC) AutoinjectorsÂ
Otrexup:Â
10 mg/0.4 mLÂ
12.5 mg/0.4 mLÂ
15 mg/0.4 mLÂ
17.5 mg/0.4 mLÂ
20 mg/0.4 mLÂ
22.5 mg/0.4 mLÂ
25 mg/0.4 mLÂ
Â
Rasuvo:Â
2.5 mg/0.05 mL (dose range: 7.5–30 mg in 2.5 mg increments)Â
Â
Subcutaneous Prefilled Syringes (RediTrex)Â
7.5 mg/0.3 mLÂ
10 mg/0.4 mLÂ
12.5 mg/0.5 mLÂ
15 mg/0.6 mLÂ
17.5 mg/0.7 mLÂ
20 mg/0.8 mLÂ
22.5 mg/0.9 mLÂ
25 mg/mLÂ
Oral TabletsÂ
2.5 mgÂ
5 mgÂ
7.5 mgÂ
10 mgÂ
15 mgÂ
Â
Oral SolutionsÂ
2.5 mg/mL (Xatmep)Â
2 mg/mL (Jylamvo)Â
Polyarticular Juvenile Idiopathic Arthritis (pJIA)Â
Initial dose: 10 mg/m² orally, IM, or SC once weekly.Â
Â
Note: SC administration (e.g., Otrexup, Rasuvo, RediTrex) offers better absorption than oral.Â
Higher doses (20–30 mg/m²/week) may improve efficacy and reduce GI side effects, but safety beyond 20 mg/m²/week is not well established.Â
Jylamvo: Weekly oral solution, titrate to response (most respond within 3–6 weeks).Â
Meningeal Leukemia (Prophylaxis and Treatment)Â
Intrathecal (IT) using preservative-free methotrexate.Â
Treatment up to twice weekly (≥2-day interval); avoid <1-week intervals due to toxicity.Â
Prophylaxis: No more than once weekly.Â
Dosing by age:Â
Acute Lymphoblastic Leukemia (ALL)Â
IV dose: 10–5,000 mg/m² depending on treatment phase and patient factors.Â
Oral (Xatmep, Jylamvo): 20 mg/m² weekly; adjust to maintain desired neutrophil levels.Â
Non-Hodgkin Lymphoma (NHL)Â
IV dose range: 10–8,000 mg/m², protocol-dependent.Â
Combination regimens: 1,000–3,000 mg/m² over 24 hr with leucovorin rescue.Â
CNS-directed or high-dose therapy:Â
Solo: 8,000 mg/m² IV over 4 hrÂ
With immunochemotherapy: 3,000–8,000 mg/m² IVÂ
Cutaneous NHL (as single agent): 5–75 mg IVÂ
OsteosarcomaÂ
Dose: 12 g/m² IV over 4 hr on weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, and 45 post-surgery.Â
Max single dose: 20 gÂ
may have an increased immunosuppressive effect when combined with upadacitinib
may enhance the serum concentration when combined with methotrexate
may enhance the serum concentration when combined with methotrexate
may enhance the serum concentration when combined with methotrexate
may enhance the serum concentration when combined with methotrexate
may enhance the serum concentration when combined with methotrexate
methotrexate: they may decrease the therapeutic effect of sipuleucel-T
methotrexate: they may decrease the therapeutic effect of vaccines
measles, mumps, rubella, and varicella vaccine, live 
methotrexate: they may decrease the therapeutic effect of vaccines
measles mumps and rubella vaccine, live
methotrexate: they may decrease the therapeutic effect of vaccines
methotrexate: they may decrease the therapeutic effect of vaccines
smallpox (vaccinia) vaccine, live
methotrexate: they may decrease the therapeutic effect of vaccines
it may reduce the therapeutic effect of covid-19 vaccines 
may decrease the therapeutic effect of COVID-19 vaccine
may increase the immunosuppressive effect of tacrolimus
may have an increased neutropenic effect when combined with deferiprone
may have an increased myelosuppressive effect when combined with ropeginterferon alfa-2b
may increase the Myelosuppressive effect of each other when combined
human papillomavirus vaccine, nonavalentÂ
may diminish the pharmacodynamic antagonistic effect of each other when combined
may enhance the hepatotoxic adverse effects of methotrexate
methotrexate may diminish the therapeutic effects of BCG vaccine
interaction with methotrexate may diminish the therapeutic effects of the vaccine, avoid combination
interaction with methotrexate may increase the neutropenic adverse effect of deferiprone
increases the risk of serious infection as a result of the immunosuppressive effect
interaction may increase the serum concentration of methotrexate
take vaccine at least 2 week prior to methotrexate initiation to avoid interaction. The interaction may reduce therapeutic effect of vaccine
interaction with proton pump inhibitors may cause delayed elimination of methotrexate.
may reduce the time of elimination and increase the serum concentration of methotrexate
the interaction may enhance hepatotoxic and haematotoxic effects of methotrexate
methotrexate may decrease the therapeutic effects of lenograstim, avoid within 24 hours of administration of antineoplastic agents
may diminish the therapeutic effects of lipegfilgrastim
may enhance the severity of oral mucositis
avoid interaction, as it may increase hepatotoxicity and serum concentration of methotrexate
interaction may lead to bone marrow suppression, avoid interaction with sulfonamide antibiotics
high risk of serious infection due to immunosuppressive effects
may enhance the toxic effect of methotrexate, avoid combination
risk of severe infection due to immunosuppressive effects, avoid combination
it increases the toxicity of varicella or rubella-containing live vaccines
measles, mumps, rubella, and varicella vaccine, live (Rx)
may enhance the adverse/toxic effect of rubella, and varicella vaccine, live 
measles mumps and rubella vaccine, live
may enhance the adverse/toxic effect of rubella, and varicella vaccine, live 
may enhance the adverse/toxic effect of rubella, and varicella vaccine, live 
vaccinia immune globulin intravenous (Rx)
may enhance the adverse/toxic effect of rubella, and varicella vaccine, live 
may enhance the adverse/toxic effect of rubella, and varicella vaccine, live 
methotrexate can also enhance the immunosuppressive effect of tacrolimus (Topical)
methotrexate can also enhance the immunosuppressive effect of tacrolimus (Topical)
methotrexate can also enhance the immunosuppressive effect of tacrolimus (Topical)
methotrexate can also enhance the immunosuppressive effect of tacrolimus (Topical)
methotrexate can also enhance the immunosuppressive effect of tacrolimus (Topical)
may have an increasingly adverse effect when combined with BCG products
myelosuppressive agents may diminish the therapeutic effect of BCG
measles, mumps, rubella and varicella vaccine, liveÂ
may increase the toxic effects of varicella virus containing vaccine
may increase the immunosuppressive effects
may have an increased myelosuppressive effect when combined with fexinidazole
may increase the immunosuppressive effect of tacrolimus
may enhance the serum concentration of tafamidis
may have an increasingly adverse effect when combined with talimogene laherparepvec
may enhance the concentration of serum when combined with OAT1/3 substrates
abiraterone acetate and niraparibÂ
may increase the neutropenic effect of myelosuppressive agents
the level of methotrexate may be increased by aspirin rectal by reducing renal clearance
dipyridamole: it may decrease the therapeutic effect of myelosuppressive agents
olopatadine: it may decrease the therapeutic effect of myelosuppressive agents
paraldehyde: it may decrease the therapeutic effect of myelosuppressive agents
may enhance the risk of serious infection by increasing immunosuppressive effect of methotrexate
may enhance the risk of serious infection by increasing the immunosuppressive effect of methotrexate
may enhance the hepatotoxic effect of methotrexate
methotrexate may diminish the therapeutic effect of brincidofovir
may diminish the therapeutic effect of methotrexate
may enhance the adverse myelosuppressive effects of chloramphenicol
may increase the serum concentration of methotrexate
may enhance the adverse myelosuppressive effects of clozapine
may diminish the therapeutic effect of the covid-19 vaccine
may increase the hepatotoxic adverse effects of methotrexate by enhancing the serum concentration
may increase the serum concentration of methotrexate
may enhance the adverse toxic effects of methotrexate
the interaction may decrease the serum concentration of fosphenytoin by increasing the unbound protein metabolites. It also increases the serum concentration of methotrexate
may increase the serum concentration of methotrexate
methotrexate may enhance the immunosuppressive effect of inebilizumab
may increase the serum concentration of methotrexate
methotrexate may increase the serum concentration of mercaptopurine
may enhance the hepatotoxic effect of methotrexate
may decrease the serum concentration of methotrexate
may increase serum concentration of OAT1/3 substrates
may enhance the immunosuppressive effects of ocrelizumab
may enhance immunosuppressive effects of methotrexate
myelosuppressive agents may enhance adverse myelosuppressive effects of Olaparib
may increase serum concentration of methotrexate
methotrexate may diminish the therapeutic effects of pidotimod
may enhance adverse myelosuppressive effects
may enhance adverse toxic effects of methotrexate
may decrease serum concentration of sapropterin
may enhance hepatotoxic adverse effects of methotrexate
may increase the serum concentration of methotrexate
methotrexate may increase the photosensitizing effects of methotrexate
It may enhance and diminish the immunosuppressive effects when combined with maitake
It may diminish the absorption when combined with bile acid sequestrants
It may enhance the serum concentration when combined with pegloticase
It may enhance the effect when combined with tafamidis meglumine
When loracarbef is used together with methotrexate, the risk or seriousness of nephrotoxicity is enhanced
When methotrexate is used together with ouabain, this leads to reduction in methotrexate excretion
When methotrexate is used in combination with rabies vaccine, this leads to a reduction in the rabies vaccine effects through the process of pharmacodynamic antagonism
methotrexate leads to a reduction in the rate of excretion of nitric oxide, which leads to an increased level of serum
When methotrexate is used together with ridaforolimus, this leads to enhanced concentration serum of methotrexate
methotrexate: it may enhance the toxic effect of Anti-Inflammatory Agents
methotrexate: it may enhance the toxic effect of Anti-Inflammatory Agents
aspirin, chlorpheniramine, and phenylephrine
methotrexate: it may enhance the toxic effect of Anti-Inflammatory Agents
methotrexate: it may enhance the toxic effect of Anti-Inflammatory Agents
methotrexate: it may enhance the toxic effect of Anti-Inflammatory Agents
willow bark may increase the levels or effects of methotrexate due to acidic (anionic) drug competition for renal tubular clearance
tetracycline reduces the therapeutic effects of methotrexate by suppressing GI metabolism by intestinal flora
tetracycline reduces the therapeutic effects of methotrexate by suppressing GI metabolism by intestinal flora
it decreases the effect of brincidofovir
lansoprazole amoxicillin and clarithromycin
when amoxicillin combines with methotrexate it decreases the effects of the action of drug by decreasing renal clearance
amoxicillin and clavulanate potassium
when amoxicillin combines with methotrexate it decreases the effects of the action of drug by decreasing renal clearance
omeprazole amoxicillin and clarithromycin
when both drugs are combined, there may be a decreased effect of the drug's action by decreasing renal clearance
when both drugs are combined, there may be a decreased effect of the drug's action by decreasing renal clearance
Interaction with pivmecillinam may enhance the serum concentration of methotrexate
myelosuppressive Agents may enhance the adverse/toxic effect of clozapine
myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib
myelosuppressive Agents may enhance the neutropenic effect of deferiprone
may enhance the effect of myelosuppressive agents
may enhance the effect of myelosuppressive agents
may increase the serum concentration of OAT1/3 substrates
may have an increased myelosuppressive effect when combined with myelosuppressive agents
may have an increased myelosuppressive effect when combined with olaparib
may have an increased adverse effect when combined with clozapine
may have an increased adverse effect when comb
may decrease the therapeutic effect when combined with BCG vaccine
may have an increased myelosuppressive effect when combined with myelosuppressive agents
may result in a significant increase in zavegepant exposure
may increase the toxic effect of myelosuppressive agents
may diminish the serum concentration of each other when combined
It may enhance the risk of adverse effects when combined with Hormone Antagonists
combinational side effects will increase when methotrexate is used in combination with sulfisoxazole
may have a decrease in excretion when combined with methotrexate
metronidazole/tetracycline/bismuth subsalicylateÂ
by reducing elimination, the levels of methotrexate may be increased with tetracycline
ozanimod: it may decrease the therapeutic effect of myelosuppressive agents
tofacitinib: it may decrease the therapeutic effect of myelosuppressive agents
decreases renal elimination of methotrexate may lead to renal toxicity
may lead to increased myelosuppression
increased serum concentration of methotrexate may lead to toxic effects
high risk o severe infection due to immunosuppression
increase hepatotoxicity due to decreased elimination
increase the metabolism of methotrexate
choline magnesium trisalicylate
salicylates may also lead to an elevation in the concentration of methotrexate
The immunosuppressive effect of immunosuppressants (cytotoxic chemotherapy) may be increased by denosumab
Methotrexate works through multiple mechanisms, making it versatile for treating cancer and autoimmune diseases. In cancer therapy, it functions as an antifolate antimetabolite. It enters cells via folate transporters and converts into methotrexate-polyglutamate, which blocks dihydrofolate reductase—an enzyme needed to produce tetrahydrofolate, essential for DNA and RNA nucleotide synthesis. It also inhibits enzymes involved in purine and thymidylate synthesis, disrupting DNA production and causing cancer cell death.Â
For autoimmune conditions, methotrexate acts differently by inhibiting AICAR transformylase, leading to increased adenosine levels. This suppresses immune cell activity, reducing inflammation by downregulating T-cell and B-cell responses and interfering with inflammatory signalling pathways like interleukin-1β. These combined effects contribute to its anti-inflammatory properties.Â
Frequency defined:Â
>10%:Â Â
FeverÂ
Nausea (11%)Â
Vomiting (11%)Â
Weight lossÂ
Increased liver enzymes (14%)Â
MucositisÂ
MyelosuppressionÂ
1% to 10%Â
Alopecia (10%)Â
Dermatitis (3%)Â
Burning sensation of the skinÂ
Skin photosensitivityÂ
Gastrointestinal ulcer (10%)Â
PruritisÂ
LeukopeniaÂ
PancytopeniaÂ
ThrombocytopeniaÂ
DizzinessÂ
Frequency not defined:Â
Cerebral thrombosisÂ
Arterial thrombosisÂ
HypotensionÂ
Decreased libidoÂ
Menstrual diseasesÂ
PancreatitisÂ
Hepatic failureÂ
Nonimmune anaphylaxisÂ
HaematuriaÂ
InfertilityÂ
Vaginal dischargeÂ
Bone fractureÂ
OsteoporosisÂ
Methotrexate is contraindicated in patients with a history of severe hypersensitivity, including anaphylaxis. It poses a significant risk of embryofetal harm and should not be used for non-cancer conditions during pregnancy. Both men and women of reproductive age should use effective contraception during and after treatment. Formulations containing benzyl alcohol may cause serious central nervous system toxicity or metabolic acidosis, so preservative-free methotrexate is recommended for neonates, low-birth-weight infants, and intrathecal use. Benzyl alcohol-containing products should be avoided in high-dose regimens unless no preservative-free options are available and immediate treatment is necessary. Methotrexate can cause severe adverse effects, including fatal outcomes, so patients must be closely monitored for infections and toxicities affecting bone marrow, kidneys, liver, nervous system, gastrointestinal tract, lungs, and skin.Â
ContraindicationÂ
HypersensitivityÂ
CautionÂ
Embryofetal Risk: Causes fetal harm and death; contraindicated in pregnancy for non-cancer conditions. Effective contraception is essential for men and women during and after treatment.Â
Hypersensitivity: Severe allergic reactions, including anaphylaxis, may occur. Discontinue immediately if symptoms arise.Â
Myelosuppression: Can cause dangerous bone marrow suppression leading to low blood counts. Regular blood monitoring is necessary, and dosage adjustments or discontinuation may be required.Â
Gastrointestinal Toxicity: Risks include severe diarrhea, vomiting, and life-threatening intestinal damage, especially in patients with existing GI diseases. Treatment should be paused or stopped if severe symptoms develop.Â
Pulmonary Toxicity: Methotrexate may cause lung inflammation (interstitial pneumonitis), potentially fatal, at any dose. Respiratory symptoms warrant prompt evaluation and possible treatment interruption.Â
Secondary Malignancies: Risk of developing new cancers exists; some lymphomas may regress after stopping methotrexate.Â
Tumor Lysis Syndrome: Risk with rapidly growing tumors; preventive treatment should be considered.Â
Fertility: May impair fertility in both sexes; discuss reproductive risks beforehand.Â
Third-Space Accumulation: Methotrexate clearance may be delayed in fluid collections; these should be drained before dosing.Â
Pregnancy consideration: Methotrexate falls under pregnancy category X. methotrexate can cross the placenta and can cause fetal harm followed by the death of the child and pregnant woman. Â
Lactation: limited reports available describing the presence of methotrexate in breastmilk. Because of potential adverse effects, it is advised to avoid breastfeeding during methotrexate therapy.Â
 Pregnancy category:Â
Methotrexate is an antimetabolite and immunosuppressant that inhibits dihydrofolate reductase, interfering with DNA synthesis, repair, and cell replication. In rheumatoid arthritis, it reduces immune system overactivity, thereby decreasing inflammation, pain, and joint damage. In psoriasis, it slows the rapid turnover of skin cells, reducing scaling and plaque formation. Its immunomodulatory effects are also linked to increased extracellular adenosine levels, which help mediate anti-inflammatory responses.Â
PharmacodynamicsÂ
Methotrexate works by inhibiting enzymes involved in nucleotide synthesis, blocking cell division and producing anti-inflammatory effects. It has a long duration of action and is typically administered once weekly. Due to its narrow therapeutic index, it should never be taken daily.Â
PharmacokineticsÂ
AbsorptionÂ
Oral bioavailability: ~60% at doses <30 mg/m²; significantly reduced at doses >80 mg/m².Â
Subcutaneous (SC) bioavailability:Â
Otrexup: 17%–36% higher than PO at doses of 10–25 mg.Â
Rasuvo: 35%–68% higher than PO at doses of 7.5–30 mg.Â
Time to peak plasma concentration:Â
Oral: 1–2 hoursÂ
Intramuscular (IM): 30–60 minutesÂ
DistributionÂ
Protein binding: ~50%Â
Volume of distribution (Vd):Â
Initial: 0.18 L/kgÂ
Steady-state: 0.4–0.8 L/kgÂ
MetabolismÂ
Site: Hepatic and intracellularÂ
Metabolites: Primarily polyglutamated methotrexate derivativesÂ
Elimination/ExcretionÂ
Half-life:Â
Psoriasis, RA, low-dose cancer: 3–10 hoursÂ
High-dose cancer therapy: 8–15 hoursÂ
Routes:Â
Renal (urine): 80%–100% within 24 hoursÂ
Fecal: minimalÂ
Methotrexate has IV incompatibilities with several drugs, notably bleomycin and others like droperidol and propofol. For IV/IM use, it is reconstituted in D5W or saline and administered via IV push (10 mg/min) or infusion, with high doses requiring leucovorin rescue. Intrathecal use demands a preservative-free form and CSF checks. Subcutaneous options (Otrexup, Rasuvo, RediTrex) are weekly, prefilled injectors for abdominal or thigh use, suitable for self-injection with training. Oral forms like Xatmep and Jylamvo must be taken weekly with precise measuring devices to prevent fatal overdosing.Â
Pronunciation: METH-oh-TREX-ate
Methotrexate is an anticancer that belongs to antimetabolites class of medications.
It also treats psoriasis and rheumatoid arthritis.
Take the tablet once weekly.
Side effects of methotrexate include, nausea, vomiting, hair loss or thinning, mouth ulcers.
Tell your doctor about the allergies if you have against methotrexate. Brief the doctor about any other sort of allergies to other food or drug products.
This drug may reduce the bone marrow count in the body; may also cause liver damage.
If you miss a dose, consume it as soon as you remember it, but do not take the missed one nearby to the next one. Avoid doubling the dose.
If you are pregnant, planning for pregnancy or lactating, consult your doctor before starting the treatment.
Pregnancy and breastfeeding are not safe with methotrexate treatment.
Store the medication below 25°C in original container away from light.
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