Otrexup 10mg/0.4ml Pf Inj 4 X 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
Antimetabolite, Antirheumatic, Antineoplastic
Pharmacologic Class
Folic acid antagonist, Dihydrofolate reductase inhibitor
Pregnancy Category
Category X
FDA Approved
Oct 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Methotrexate is a medication that works by interfering with the growth of certain cells in the body. It is used to treat certain types of cancer, severe psoriasis, and severe rheumatoid arthritis. For conditions like arthritis and psoriasis, it helps to reduce inflammation and slow down the overgrowth of skin cells or the immune system's attack on joints. It is often given as a weekly injection.
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 supplies.
When the disposal box is full, follow local regulations for proper disposal.
If you have 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: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use can lead to serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Your doctor may adjust the dosage or administration schedule based on blood work results, side effects, and the medication's effectiveness.
Handling and Storage
Handle this medication with care. Consult your doctor or pharmacist for guidance on proper handling procedures.
Store the medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Hydration
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store the medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
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 supplies.
When the disposal box is full, follow local regulations for proper disposal.
If you have 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: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use can lead to serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Your doctor may adjust the dosage or administration schedule based on blood work results, side effects, and the medication's effectiveness.
Handling and Storage
Handle this medication with care. Consult your doctor or pharmacist for guidance on proper handling procedures.
Store the medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Hydration
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store the medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Avoid alcohol completely due to increased risk of liver damage.
- Use effective birth control during treatment and for at least 6 months after stopping for both men and women, as methotrexate can cause severe birth defects or miscarriage.
- Avoid prolonged sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Stay well-hydrated, especially with high doses, to help prevent kidney problems.
- Avoid live vaccines while on methotrexate therapy.
- Report any signs of infection (fever, sore throat) immediately to your doctor.
- Take folic acid or folinic acid (leucovorin) as prescribed by your doctor to reduce side effects, but do not take it on the same day as your methotrexate dose unless specifically instructed.
- Do not take NSAIDs (like ibuprofen, naproxen) or aspirin without consulting your doctor, as they can increase methotrexate toxicity.
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, given as a single dose or in 3 divided doses of 2.5 mg at 12-hour intervals. Psoriasis: 10-25 mg once weekly, given as a single dose or in 3 divided doses of 2.5 mg at 12-hour intervals. Oncology: Highly variable, depends on specific cancer type and protocol (e.g., 30-40 mg/m2 weekly for maintenance, or high-dose regimens with leucovorin rescue).
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
rheumatoidArthritis:
7.5 mg once weekly, adjusted to maximum 20 mg/week based on response and tolerability.
psoriasis:
Initial test dose 5-10 mg parenterally, then 10-25 mg once weekly, adjusted based on response and tolerability.
oncology:
Highly individualized based on specific cancer type, stage, and protocol (e.g., acute lymphoblastic leukemia, osteosarcoma, breast cancer, etc.). Doses can range from low weekly doses to high-dose regimens requiring leucovorin rescue.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m2 once weekly. Acute Lymphoblastic Leukemia (ALL): Highly variable, often 20 mg/m2 once weekly for maintenance, or high-dose regimens.
Adolescent:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m2 once weekly. Acute Lymphoblastic Leukemia (ALL): Highly variable, often 20 mg/m2 once weekly for maintenance, or high-dose regimens.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 51-80 mL/min: Reduce dose by 25-50% or extend dosing interval. Monitor closely.
Moderate:
CrCl 31-50 mL/min: Reduce dose by 50% or extend dosing interval significantly. Use with extreme caution.
Severe:
CrCl <30 mL/min: Contraindicated for non-oncologic indications. For oncologic use, significant dose reduction or avoidance is necessary, often requiring specialized protocols and close monitoring of methotrexate levels.
Dialysis:
Methotrexate is dialyzable, but clearance is slow. Avoid use in patients on dialysis for non-oncologic indications. For oncologic use, specific protocols are required, and methotrexate levels must be monitored. Leucovorin rescue is critical.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function tests closely.
Moderate:
Significant caution. Consider dose reduction or avoidance, especially if baseline liver enzymes are elevated or there is evidence of liver disease. Methotrexate is associated with hepatotoxicity.
Severe:
Generally contraindicated due to risk of severe hepatotoxicity. Avoid use.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that competitively inhibits dihydrofolate reductase (DHFR), an enzyme essential for DNA synthesis, repair, and cellular replication. By inhibiting DHFR, methotrexate prevents the reduction of dihydrofolate to tetrahydrofolate, a critical co-factor in the de novo synthesis of purine nucleotides and thymidylate. This leads to the depletion of intracellular folate cofactors, thereby inhibiting DNA, RNA, and protein synthesis, particularly in rapidly proliferating cells (e.g., malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa). In rheumatoid arthritis and psoriasis, its mechanism is thought to involve immunomodulatory and anti-inflammatory effects, possibly by interfering with lymphocyte proliferation, inhibiting polymorphonuclear leukocyte chemotaxis, and increasing adenosine release.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV). Oral: Variable and dose-dependent (23-90%), saturable at doses >15 mg/m2.
Tmax:
Subcutaneous: 1-2 hours. Oral: 1-5 hours.
FoodEffect:
Food delays absorption and reduces peak concentration of oral methotrexate, but overall bioavailability may not be significantly affected.
Distribution:
Vd:
0.4-0.8 L/kg (initial), 0.2-0.6 L/kg (steady state). Increases with ascites or pleural effusions.
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at conventional doses; significant penetration occurs only with high-dose IV administration or intrathecal administration.
Elimination:
HalfLife:
Low dose (RA/psoriasis): 3-10 hours. High dose (oncology): 8-15 hours (terminal phase).
Clearance:
Primarily renal (glomerular filtration and active tubular secretion).
ExcretionRoute:
Renal (50-90% unchanged), small amount via biliary excretion.
Unchanged:
50-90% (renal excretion)
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis: 3-6 weeks for initial effects, up to 12 weeks for full therapeutic effect. Psoriasis: 1-4 weeks.
PeakEffect:
Rheumatoid Arthritis: 4-12 weeks. Psoriasis: 2-6 weeks.
DurationOfAction:
Variable, depends on dose and indication. Effects persist as long as drug is present and intracellular polyglutamates are active.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe toxic reactions, including death. Patients should be closely monitored for bone marrow, liver, lung, and kidney toxicities. Methotrexate has been associated with severe myelosuppression, hepatotoxicity (fibrosis and cirrhosis), pneumonitis, and renal damage. Diarrhea and ulcerative stomatitis require interruption of therapy. Methotrexate can cause fetal death or teratogenic effects and is contraindicated in pregnant women with non-oncologic diseases. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or pleural effusions. Concomitant use with NSAIDs has resulted in severe, sometimes fatal, methotrexate toxicity. Malignant lymphomas may occur. Opportunistic infections, including Pneumocystis jirovecii pneumonia, may occur. Potentially fatal dermatologic reactions have been reported. Tumor lysis syndrome may occur. Severe, acute toxic reactions, including death, have been reported with intrathecal or high-dose intravenous administration.
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 immediately or seek emergency medical attention:
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, difficulty 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, difficulty breathing, 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 problems, 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 notice any of the following side effects or any other unusual symptoms, contact your doctor for advice:
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 immediately or seek emergency medical attention:
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, difficulty 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, difficulty breathing, 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 problems, 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 notice any of the following side effects or any other unusual symptoms, contact your doctor for advice:
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 or chills (signs of infection)
- Sore throat or mouth sores
- Unusual bleeding or bruising
- Extreme tiredness or weakness
- Yellowing of the skin or eyes (jaundice)
- Dark urine
- Severe diarrhea or vomiting
- Shortness of breath or persistent dry cough
- Swelling in the legs or ankles
- Severe skin rash or peeling skin
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 allergic reaction you experienced, including any symptoms that occurred.
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 with your doctor to determine the necessary duration of breast-feeding avoidance 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. This will help ensure your safety while taking this medication. Do not initiate, discontinue, or modify the dose of any medication without first consulting your doctor to confirm that it is safe to do so.
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 allergic reaction you experienced, including any symptoms that occurred.
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 with your doctor to determine the necessary duration of breast-feeding avoidance 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. This will help ensure your safety while taking this medication. Do not initiate, discontinue, or modify the dose of any medication without first consulting your doctor to confirm that it is safe to do so.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
When starting this medication, avoid driving and other activities that require alertness until you understand how it affects you. You may be more susceptible to infections, so it is crucial to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
Be aware that this medication may increase your risk of bleeding easily. To minimize this risk, be cautious and avoid injuries. 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 direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear when going outside. Continue to take sun protection measures for as long as your doctor advises.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and can worsen over time. In some cases, these problems may not improve and can be life-threatening. If you have concerns, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Older adults (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 difficulty getting 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.
When starting this medication, avoid driving and other activities that require alertness until you understand how it affects you. You may be more susceptible to infections, so it is crucial to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
Be aware that this medication may increase your risk of bleeding easily. To minimize this risk, be cautious and avoid injuries. 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 direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear when going outside. Continue to take sun protection measures for as long as your doctor advises.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and can worsen over time. In some cases, these problems may not improve and can be life-threatening. If you have concerns, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Older adults (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 difficulty getting 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 ulcers)
- Hepatotoxicity (liver damage)
- Nephrotoxicity (kidney damage)
- Nausea, vomiting, diarrhea
What to Do:
Immediately contact emergency services or a poison control center (Call 1-800-222-1222). Leucovorin rescue is the primary antidote for methotrexate overdose, administered as soon as possible. Hydration and urinary alkalinization may also be used to enhance methotrexate excretion. Glucarpidase (Voraxaze) may be used in cases of delayed methotrexate elimination due to impaired renal function.
Drug Interactions
Contraindicated Interactions
- Live vaccines (during methotrexate therapy)
- Trimethoprim/sulfamethoxazole (increased myelosuppression)
- Probenecid (decreased renal excretion of methotrexate)
- NSAIDs (high-dose methotrexate, risk of severe toxicity)
- Salicylates (high-dose methotrexate, risk of severe toxicity)
- Alcohol (increased risk of hepatotoxicity)
Major Interactions
- NSAIDs (low-dose methotrexate, increased methotrexate levels and toxicity)
- Proton Pump Inhibitors (PPIs) (e.g., omeprazole, pantoprazole - may increase methotrexate levels, especially at higher doses)
- Penicillins (e.g., amoxicillin - may decrease renal clearance of methotrexate)
- Cephalosporins (e.g., cephalexin - may decrease renal clearance of methotrexate)
- Folic acid antagonists (e.g., trimethoprim, pyrimethamine - additive myelosuppression)
- Sulfonamides (e.g., sulfasalazine - increased methotrexate levels, additive myelosuppression)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Retinoids (e.g., acitretin - increased risk of hepatotoxicity)
- Azathioprine, mercaptopurine (additive myelosuppression, hepatotoxicity)
- Theophylline (decreased theophylline clearance)
Moderate Interactions
- Oral antibiotics (e.g., tetracyclines, chloramphenicol - may alter gut flora, affecting methotrexate absorption/enterohepatic recirculation)
- Cisplatin (altered methotrexate clearance)
- Nitrous oxide (may exacerbate methotrexate toxicity by inhibiting methionine synthase)
- Amiodarone (potential for increased methotrexate toxicity)
- Leflunomide (increased risk of hepatotoxicity and myelosuppression)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status and detect pre-existing cytopenias. Methotrexate causes myelosuppression.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To assess baseline hepatic function. Methotrexate is hepatotoxic.
Timing: Prior to initiation of therapy
Renal Function Tests (RFTs) including serum creatinine, BUN, eGFR
Rationale: To assess baseline renal function. Methotrexate is primarily renally eliminated, and impaired renal function increases toxicity.
Timing: Prior to initiation of therapy
Chest X-ray
Rationale: To rule out pre-existing pulmonary disease. Methotrexate can cause pneumonitis.
Timing: Prior to initiation of therapy
Hepatitis B and C serology
Rationale: To screen for chronic viral hepatitis, which may increase risk of hepatotoxicity.
Timing: Prior to initiation of therapy
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: Maintain WBC >3,000/mm3, ANC >1,500/mm3, Platelets >100,000/mm3.
Action Threshold: Hold dose for significant cytopenias (e.g., WBC <3,000/mm3, ANC <1,500/mm3, Platelets <100,000/mm3). Consider dose reduction or discontinuation.
Liver Function Tests (LFTs) including AST, ALT, albumin
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: AST/ALT <2-3 times upper limit of normal (ULN).
Action Threshold: Hold dose if AST/ALT >3 times ULN. Consider liver biopsy if persistent elevation or cumulative dose concerns. Discontinue if persistent or severe abnormalities.
Serum Creatinine and eGFR
Frequency: Every 1-2 months or as clinically indicated.
Target: Stable, within normal limits.
Action Threshold: Hold dose or reduce if creatinine increases by >50% or eGFR decreases significantly. Adjust dose based on renal function.
Serum Albumin
Frequency: Every 1-2 months or as clinically indicated.
Target: Normal range.
Action Threshold: Low albumin can increase free methotrexate levels and toxicity; monitor closely.
Symptom Monitoring
- Fever
- Sore throat
- Unusual bleeding or bruising
- Fatigue
- Shortness of breath
- Dry cough
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Severe diarrhea
- Mouth sores (stomatitis, mucositis)
- Nausea
- Vomiting
- Abdominal pain
- Skin rash
- Hair loss
Special Patient Groups
Pregnancy
Contraindicated in pregnant women with non-oncologic diseases due to high risk of fetal death and severe teratogenic effects. For oncologic indications, the benefits may outweigh the risks in life-threatening situations, but careful counseling is essential.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, limb, and skeletal abnormalities) and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, hydrocephalus, and other abnormalities.
Third Trimester:
Risk of fetal growth restriction and other adverse effects.
Lactation
Contraindicated. 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)
Pediatric Use
Used for Juvenile Idiopathic Arthritis (JIA) and various pediatric cancers (e.g., Acute Lymphoblastic Leukemia). Dosing is weight or body surface area-based. Close monitoring for toxicity is essential, similar to adults. Long-term effects on growth and development should be considered.
Geriatric Use
Increased risk of toxicity (especially myelosuppression, hepatotoxicity, and nephrotoxicity) due to age-related decline in renal function, decreased folate stores, and potential for polypharmacy. Lower doses or extended dosing intervals may be necessary. Close monitoring of renal function, CBC, and LFTs is crucial.
Clinical Information
Clinical Pearls
- Methotrexate is typically dosed ONCE WEEKLY for rheumatoid arthritis and psoriasis, not daily. Daily dosing for these indications can be fatal.
- Folic acid supplementation (e.g., 1 mg daily, except on methotrexate day) is often prescribed to reduce common side effects like nausea, mucositis, and liver enzyme elevations, without compromising efficacy for RA/psoriasis.
- Patients must be educated on the importance of weekly dosing and the potential for severe toxicities if taken incorrectly.
- Renal function is critical for methotrexate elimination; even mild impairment can lead to significant toxicity. Hydration is important, especially with higher doses.
- Alcohol consumption is strictly prohibited due to the increased risk of severe hepatotoxicity.
- Concomitant use of NSAIDs, even at low doses, can increase methotrexate levels and toxicity; caution and close monitoring are required.
- Leucovorin rescue is essential for high-dose methotrexate regimens and in cases of overdose or delayed elimination.
Alternative Therapies
- For Rheumatoid Arthritis: Other DMARDs (e.g., hydroxychloroquine, sulfasalazine, leflunomide), Biologic DMARDs (e.g., TNF inhibitors like adalimumab, etanercept; IL-6 inhibitors, JAK inhibitors), Corticosteroids.
- For Psoriasis: Other systemic agents (e.g., cyclosporine, acitretin), Biologic agents (e.g., TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors), Phototherapy, Topical agents.
- For Oncology: Varies widely by cancer type; other chemotherapeutic agents, targeted therapies, immunotherapies, radiation therapy, surgery.
Cost & Coverage
Average Cost:
Varies significantly by dose and quantity (e.g., $100-$500+ for a month's supply of Otrexup) per 4 x 0.4ml prefilled syringes (10mg/0.4ml)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (Specialty drug, may require prior authorization)
General Drug Facts
If your symptoms or health condition do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may have additional patient information leaflets, so it is a good idea to consult with your pharmacist for more information. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.