Otrexup 22.5/0.4ml Inj, 0.4ml
WARNING: Severe side effects like bone marrow problems, liver problems, lung problems, and infections can happen with this drug. Some side effects may not go away and can be deadly. You must talk with the doctor about the risks of this drug. This drug may cause kidney problems in some patients. Talk with the doctor.Regular blood work and other exams will need to be done to check for side effects. Follow what the doctor has told you. Tell your doctor if you have kidney problems or extra fluid around your stomach area or lungs. The chance of side effects may be raised.Talk with your doctor if you are getting radiation. There may be more chance of harm to tissue and bone.New types of cancer have happened in people taking this drug. If you have questions, talk with the doctor.It is common to have diarrhea, upset stomach, throwing up, or mouth sores with this drug. However, sometimes these may be signs of severe and sometimes deadly stomach or bowel problems. Tell your doctor if you get any new or worsening signs. You may need to stop this drug.Severe skin reactions have happened with this drug. These have included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and other severe skin reactions. Sometimes these have been deadly. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin; other skin irritation (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.Very bad and sometimes deadly bone marrow problems and stomach or bowel problems have happened when this drug was taken with nonsteroidal anti-inflammatory drug (NSAIDs) like ibuprofen or naproxen.Not all methotrexate products are used to treat cancer. Talk with the doctor.This drug may cause harm to an unborn baby or loss of an unborn baby. A pregnancy test will be done before you start this drug to show that you are NOT pregnant.If you or your sex partner may become pregnant, you must use birth control while taking this drug and for some time after the last dose. Ask your doctor how long to use birth control. If you or your sex partner gets pregnant, call your doctor right away.Do not take if you are pregnant.This drug must only be used when other drugs cannot be used or have not worked. Talk with your doctor to be sure that the benefits of this drug are more than the risks. @ COMMON USES: It is used to treat some types of arthritis.It is used to treat some types of psoriasis.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antirheumatic; Antipsoriatic; Antineoplastic
Pharmacologic Class
Antimetabolite; Folic Acid Antagonist; Immunosuppressant
Pregnancy Category
Category X
FDA Approved
Oct 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Otrexup contains methotrexate, a medicine used to treat severe rheumatoid arthritis, psoriasis, and a type of juvenile arthritis. It works by reducing inflammation and slowing down the overactive immune system that causes these conditions. It is given as a weekly injection under the skin.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before proceeding with another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions or concerns, consult your doctor or pharmacist.
Dosing and Frequency
Your dosage and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important Safety Note: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use of this medication can lead to serious errors. Ensure you understand your dosage and administration schedule. If you have any doubts, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for specific guidance on handling and storage.
Hydration and Fluid Intake
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light and moisture. Do not store in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor for guidance on what to do next.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before proceeding with another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions or concerns, consult your doctor or pharmacist.
Dosing and Frequency
Your dosage and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important Safety Note: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use of this medication can lead to serious errors. Ensure you understand your dosage and administration schedule. If you have any doubts, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for specific guidance on handling and storage.
Hydration and Fluid Intake
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light and moisture. Do not store in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor for guidance on what to do next.
Lifestyle & Tips
- Take exactly as prescribed, usually once a week. Do NOT take daily.
- Take folic acid supplementation as directed by your doctor to reduce side effects.
- Avoid alcohol completely due to increased risk of liver damage.
- Avoid excessive sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Avoid contact with people who are sick or have infections, as your immune system may be weakened.
- Do not receive live vaccines (e.g., MMR, varicella, nasal flu vaccine) while on methotrexate.
- Report any signs of infection, unusual bleeding/bruising, severe fatigue, yellowing of skin/eyes, persistent cough, or shortness of breath immediately.
Available Forms & Alternatives
Available Strengths:
- Otrexup 10mg/0.4ml Pf Inj 4 X 0.4ml
- Otrexup 15mg/0.4ml Pf Inj 4 X 0.4ml
- Otrexup 20mg/0.4ml Pf Inj 4 X 0.4ml
- Otrexup 25mg/0.4ml Pf Inj 4 X 0.4ml
- Otrexup 10mg/0.4ml Inj, 0.4ml
- Otrexup 17.5mg/0.4ml Pf Injection
- Otrexup 12.5/0.4ml Inj, 0.4ml
- Otrexup 22.5/0.4ml Inj, 0.4ml
- Otrexup 17.5mg/0.4ml Pf Injection
- Otrexup 22.5/0.4ml Inj, 0.4ml
Dosing & Administration
Adult Dosing
Standard Dose:
Rheumatoid Arthritis: 7.5 mg once weekly, administered subcutaneously. Psoriasis: 10-25 mg once weekly, administered subcutaneously.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
7.5 mg once weekly, subcutaneously. May gradually increase to a maximum of 20 mg once weekly if needed.
Psoriasis:
Initial test dose of 5-10 mg orally or parenterally one week prior to therapy. Then, 10-25 mg once weekly, subcutaneously. Doses usually not exceeding 30 mg/week.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly, not to exceed 25 mg/week.
Adolescent:
Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly, not to exceed 25 mg/week.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Reduce dose by 25%.
Moderate:
CrCl 51-60 mL/min: Reduce dose by 50%.
Severe:
CrCl <50 mL/min: Contraindicated.
Dialysis:
Methotrexate is dialyzable, but use is generally contraindicated due to prolonged elimination and increased toxicity risk. Consult nephrologist.
Hepatic Impairment:
Mild:
Use with extreme caution. Monitor liver function closely.
Moderate:
Generally contraindicated due to increased risk of hepatotoxicity.
Severe:
Contraindicated.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that competitively inhibits dihydrofolate reductase (DHFR), an enzyme responsible for converting dihydrofolate to tetrahydrofolate. Tetrahydrofolate is essential for DNA synthesis, cell replication, and repair. By inhibiting DHFR, methotrexate interferes with DNA synthesis, repair, and cellular replication. In rheumatoid arthritis and psoriasis, its mechanism is thought to involve immunosuppressive and anti-inflammatory effects, possibly by inhibiting lymphocyte proliferation, affecting cytokine production, and inducing adenosine release.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80-90% (subcutaneous)
Tmax:
1-2 hours (subcutaneous)
FoodEffect:
Not significant for subcutaneous administration.
Distribution:
Vd:
0.4-0.8 L/kg
ProteinBinding:
Approximately 50% (primarily to albumin)
CnssPenetration:
Limited at typical low doses; can accumulate in CNS with high doses or repeated administration.
Elimination:
HalfLife:
3-10 hours (low dose); 8-15 hours (high dose)
Clearance:
Primarily renal clearance via glomerular filtration and active tubular secretion.
ExcretionRoute:
Renal (primarily), small amount via bile/feces.
Unchanged:
Approximately 50-90% (renal)
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial effects, up to 12 weeks for maximal benefit.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 8-12 weeks.
DurationOfAction:
Effects persist as long as therapy is continued; requires weekly dosing.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe or fatal toxic reactions. Patients should be closely monitored for bone marrow, liver, lung, and kidney toxicities. Methotrexate has been associated with severe myelosuppression, hepatotoxicity (including fibrosis and cirrhosis), pneumonitis, and renal damage. Diarrhea and ulcerative stomatitis require interruption of therapy. Concomitant use with NSAIDs is not recommended, especially with high-dose methotrexate. Methotrexate can cause embryo-fetal toxicity and fetal death; it is contraindicated in pregnant women with non-oncologic diseases. Methotrexate can cause severe dermatologic reactions. Opportunistic infections, including Pneumocystis jirovecii pneumonia, may occur. Tumor lysis syndrome and neurotoxicity have been reported.
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding
Signs of pancreatitis (pancreas problems): severe stomach pain, severe back pain, or severe nausea and vomiting
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain
Signs of liver problems: dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes
Signs of lung or breathing problems: shortness of breath, breathing difficulties, cough, or fever
Signs of nerve problems: abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part)
Pinpoint red spots on the skin
Severe dizziness or fainting
Seizures
Confusion
Excessive sleepiness
Changes in vision
Bone pain
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Weakness on one side of the body, speech or thinking difficulties, balance changes, facial drooping, or blurred vision
Headache
Neck stiffness
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding
Signs of pancreatitis (pancreas problems): severe stomach pain, severe back pain, or severe nausea and vomiting
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain
Signs of liver problems: dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes
Signs of lung or breathing problems: shortness of breath, breathing difficulties, cough, or fever
Signs of nerve problems: abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part)
Pinpoint red spots on the skin
Severe dizziness or fainting
Seizures
Confusion
Excessive sleepiness
Changes in vision
Bone pain
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Weakness on one side of the body, speech or thinking difficulties, balance changes, facial drooping, or blurred vision
Headache
Neck stiffness
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, sore throat, or other signs of infection
- Unusual bleeding or bruising, black tarry stools, blood in urine or stools
- Yellowing of the skin or eyes (jaundice), dark urine, severe fatigue, abdominal pain (signs of liver problems)
- New or worsening cough, shortness of breath, chest pain (signs of lung problems)
- Severe mouth sores, ulcers, or painful swallowing
- Severe nausea, vomiting, or diarrhea
- Severe skin rash, peeling skin, or blisters
- Swelling in the legs or ankles
- Confusion, seizures, or severe headache (rare with low dose)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult your doctor to determine the necessary duration for avoiding breast-feeding after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult your doctor to determine the necessary duration for avoiding breast-feeding after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Until you understand how this drug affects you, avoid driving and other activities that require alertness. Be aware that you may be more susceptible to infections, so it's crucial to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
As this medication may increase your risk of bleeding, be cautious to avoid injuries. To minimize this risk, use a soft toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult with your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor.
You may be more prone to sunburns while taking this medication. To protect yourself, avoid exposure to direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear when going outside. Continue to take these precautions for as long as your doctor advises.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or excessive thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and potentially life-threatening. If you have any concerns or questions, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Elderly patients (65 years and older) should use this medication with caution, as they may be more susceptible to side effects.
This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Until you understand how this drug affects you, avoid driving and other activities that require alertness. Be aware that you may be more susceptible to infections, so it's crucial to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
As this medication may increase your risk of bleeding, be cautious to avoid injuries. To minimize this risk, use a soft toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult with your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor.
You may be more prone to sunburns while taking this medication. To protect yourself, avoid exposure to direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear when going outside. Continue to take these precautions for as long as your doctor advises.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or excessive thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and potentially life-threatening. If you have any concerns or questions, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Elderly patients (65 years and older) should use this medication with caution, as they may be more susceptible to side effects.
This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (low white blood cells, red blood cells, platelets)
- Severe mucositis (mouth sores)
- Gastrointestinal toxicity (severe nausea, vomiting, diarrhea)
- Hepatotoxicity (liver damage)
- Nephrotoxicity (kidney damage)
What to Do:
Immediately contact your doctor or go to the nearest emergency room. Leucovorin rescue (folinic acid) is the primary antidote for methotrexate overdose. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Trimethoprim/sulfamethoxazole (increased myelosuppression due to additive folate antagonism)
- Probenecid (decreased renal elimination of methotrexate)
- NSAIDs (high-dose methotrexate, can increase methotrexate levels and toxicity)
- Salicylates (can decrease renal elimination of methotrexate)
- Other hepatotoxic agents (e.g., retinoids, azathioprine, sulfasalazine, alcohol) - increased risk of hepatotoxicity
- Other myelosuppressive agents (e.g., azathioprine, chloramphenicol, pyrimethamine) - increased risk of hematologic toxicity
Major Interactions
- NSAIDs (low-dose methotrexate, use with caution and monitor for toxicity)
- Penicillins (can decrease renal elimination of methotrexate)
- Proton pump inhibitors (e.g., omeprazole, pantoprazole) - can increase methotrexate levels, especially at higher doses
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Folic acid antagonists (e.g., pyrimethamine, triamterene) - increased risk of myelosuppression
- Nitrous oxide (can potentiate methotrexate toxicity by inhibiting methionine synthase)
Moderate Interactions
- Folic acid/folinic acid supplements (can reduce methotrexate efficacy if not appropriately timed or dosed)
- Cholestyramine (can interfere with methotrexate absorption)
- Tetracyclines (can increase methotrexate levels)
- Chloral hydrate (can displace methotrexate from protein binding)
Minor Interactions
- Not many specific minor interactions; general caution with drugs affecting renal function or protein binding.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status and detect myelosuppression.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To establish baseline liver function and detect hepatotoxicity.
Timing: Prior to initiation of therapy.
Renal Function Tests (serum creatinine, BUN, estimated GFR)
Rationale: To establish baseline renal function, as methotrexate is primarily renally cleared.
Timing: Prior to initiation of therapy.
Chest X-ray
Rationale: To establish baseline pulmonary status and rule out pre-existing lung disease.
Timing: Prior to initiation of therapy.
Hepatitis B and C serology
Rationale: To screen for viral hepatitis, which can increase risk of liver toxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Weekly for the first month, then every 2-4 weeks for the next 2 months, then monthly or every 1-2 months thereafter.
Target: Maintain within normal limits; adjust dose or hold if significant drops (e.g., WBC <3000/mm³, platelet <100,000/mm³).
Action Threshold: Significant drop in cell counts (e.g., WBC <3000/mm³, platelet <100,000/mm³), or persistent neutropenia/thrombocytopenia.
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Frequency: Weekly for the first month, then every 2-4 weeks for the next 2 months, then monthly or every 1-2 months thereafter.
Target: Maintain within normal limits or stable baseline; AST/ALT <2x ULN.
Action Threshold: Persistent elevation of AST/ALT >2-3 times upper limit of normal, or significant decrease in albumin.
Renal Function Tests (serum creatinine, BUN)
Frequency: Monthly or every 1-2 months, or more frequently if risk factors for renal impairment.
Target: Maintain within normal limits or stable baseline.
Action Threshold: Significant increase in serum creatinine or BUN.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, cough)
- Signs of bleeding/bruising (petechiae, unusual bleeding)
- Signs of liver toxicity (jaundice, dark urine, fatigue, abdominal pain)
- Signs of lung toxicity (new or worsening cough, shortness of breath, fever)
- Oral mucositis/stomatitis (sore mouth, ulcers)
- Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain)
- Skin reactions (rash, itching, peeling skin)
- Neurological symptoms (headache, confusion, seizures - rare with low dose)
Special Patient Groups
Pregnancy
Contraindicated in pregnant women with non-oncologic diseases due to significant risk of embryo-fetal toxicity, fetal death, and teratogenic effects (e.g., craniofacial, cardiovascular, and limb abnormalities). Women of childbearing potential must use effective contraception during and for at least 6 months after therapy. Men should use effective contraception during and for at least 3 months after therapy.
Trimester-Specific Risks:
First Trimester:
Highest risk of major congenital malformations and fetal death.
Second Trimester:
Significant risk of fetal toxicity and death.
Third Trimester:
Significant risk of fetal toxicity and death.
Lactation
Contraindicated during breastfeeding. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant, including myelosuppression and growth inhibition.
Infant Risk:
High risk (L5 - Contraindicated)
Pediatric Use
Approved for polyarticular juvenile idiopathic arthritis (pJIA). Dosing is weight or body surface area-based. Close monitoring for toxicity is essential, similar to adults. Long-term safety data in children is available.
Geriatric Use
Increased risk of adverse reactions, particularly myelosuppression, hepatotoxicity, and renal impairment, due to decreased organ function and concomitant medications. Renal function should be carefully assessed. Lower doses or less frequent monitoring may be necessary.
Clinical Information
Clinical Pearls
- Methotrexate for RA/Psoriasis/JIA is dosed WEEKLY, not daily. Daily dosing for non-oncologic indications can be fatal.
- Folic acid supplementation (typically 1-5 mg once weekly, 24-48 hours after methotrexate dose) is crucial to reduce common side effects like mucositis, GI upset, and myelosuppression, without significantly impacting efficacy.
- Patients must be educated on the importance of weekly dosing and the severe consequences of daily dosing.
- Strict avoidance of alcohol is paramount due to the risk of hepatotoxicity.
- Close monitoring of CBC, LFTs, and renal function is essential due to the narrow therapeutic index and potential for severe toxicities.
- Patients should be advised to report any signs of infection, bleeding, or respiratory symptoms immediately.
- Leucovorin (folinic acid) is the antidote for methotrexate overdose or severe toxicity.
Alternative Therapies
- Other conventional synthetic DMARDs (csDMARDs): Hydroxychloroquine, Sulfasalazine, Leflunomide
- Biologic DMARDs (bDMARDs): TNF inhibitors (e.g., Adalimumab, Etanercept, Infliximab), IL-6 inhibitors (e.g., Tocilizumab), T-cell costimulation modulators (e.g., Abatacept), B-cell depleting agents (e.g., Rituximab)
- Targeted synthetic DMARDs (tsDMARDs): JAK inhibitors (e.g., Tofacitinib, Baricitinib, Upadacitinib)
- For Psoriasis: Phototherapy, other systemic agents (e.g., Cyclosporine, Acitretin), biologics (e.g., Ustekinumab, Secukinumab, Ixekizumab, Guselkumab, Risankizumab)
Cost & Coverage
Average Cost:
Varies widely by dose and pharmacy, typically $300-$1000+ per 4 pre-filled syringes
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.