Otrexup 15mg/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
Antirheumatic; Antineoplastic; Immunosuppressant
Pharmacologic Class
Antimetabolite; Folic acid antagonist
Pregnancy Category
Category X
FDA Approved
Oct 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Methotrexate is a medication used to treat certain types of cancer, severe psoriasis, and severe rheumatoid arthritis. It works by slowing down the growth of certain cells in the body, including cancer cells, rapidly growing skin cells in psoriasis, and cells involved in inflammation in rheumatoid arthritis. Otrexup is a pre-filled syringe designed for easy self-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 using 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 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: 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 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 moisture. Do not store in a bathroom.
Hydration
Drink plenty of non-caffeinated liquids unless your doctor advises you to limit fluid intake.
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 using 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 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: 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 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 moisture. Do not store in a bathroom.
Hydration
Drink plenty of non-caffeinated liquids unless your doctor advises you to limit fluid intake.
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 on the same day. Do NOT take daily for rheumatoid arthritis or psoriasis, as this can lead to severe, even fatal, toxicity.
- Take folic acid or folinic acid supplementation as directed by your doctor. This helps reduce side effects without significantly reducing effectiveness.
- Avoid alcohol consumption, as it can increase the risk of liver damage.
- Stay well-hydrated by drinking plenty of fluids.
- Avoid prolonged sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Avoid live vaccines (e.g., measles, mumps, rubella, chickenpox) while on methotrexate due to weakened immune system.
- Report any signs of infection (fever, chills, sore throat), unusual bleeding/bruising, severe diarrhea, mouth sores, yellowing of skin/eyes, or new/worsening cough or shortness of breath immediately to your doctor.
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:
For Rheumatoid Arthritis (RA) or Psoriasis: 15 mg (0.4 mL) subcutaneously once weekly.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
Initial: 7.5 mg subcutaneously once weekly. Adjust to achieve optimal response, not to exceed 20 mg/week (or 25 mg/week in some cases, depending on patient response and tolerability).
Psoriasis:
Initial: 10-25 mg subcutaneously once weekly as a single dose, or 2.5 mg every 12 hours for 3 doses each week (total 7.5 mg/week). Adjust to achieve optimal response, not to exceed 25 mg/week.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For Juvenile Idiopathic Arthritis (JIA): 10 mg/m² subcutaneously once weekly. Dosing may be adjusted based on response and tolerability, typically up to 0.6 mg/kg/week (max 25 mg/week).
Adolescent:
For Juvenile Idiopathic Arthritis (JIA): 10 mg/m² subcutaneously once weekly. Dosing may be adjusted based on response and tolerability, typically up to 0.6 mg/kg/week (max 25 mg/week).
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Consider 25% dose reduction or increased monitoring. Use with caution.
Moderate:
CrCl 31-60 mL/min: Consider 50% dose reduction or increased monitoring. Use with extreme caution. Often contraindicated for non-oncologic indications.
Severe:
CrCl <30 mL/min: Contraindicated for non-oncologic indications due to risk of severe toxicity.
Dialysis:
Methotrexate is dialyzable, but standard hemodialysis is not effective for rapid clearance. High-flux hemodialysis or hemoperfusion may be used in toxicity. Contraindicated for non-oncologic indications.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function closely.
Moderate:
Avoid use or use with extreme caution. Significant dose reduction may be necessary. Often contraindicated for non-oncologic indications.
Severe:
Contraindicated due to risk of severe hepatotoxicity.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that 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 cofactor for purine and pyrimidine synthesis. This leads to inhibition of DNA, RNA, and protein synthesis. In rheumatoid arthritis and psoriasis, its anti-inflammatory and immunosuppressive effects are thought to be due to inhibition of lymphocyte proliferation, induction of adenosine release, and effects on cytokine production.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (similar to intramuscular).
Tmax:
Subcutaneous: 1-2 hours.
FoodEffect:
Not significantly affected by food when administered subcutaneously.
Distribution:
Vd:
0.4-0.8 L/kg (low dose); higher at toxic concentrations due to third-space accumulation.
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited penetration into the CNS at conventional doses; higher concentrations achieved with high-dose intravenous or intrathecal administration.
Elimination:
HalfLife:
3-10 hours (low dose); 8-15 hours (high dose). Prolonged in renal impairment or third-space fluid accumulation.
Clearance:
Primarily renal clearance via glomerular filtration and active tubular secretion.
ExcretionRoute:
Renal (primarily), small amount via biliary excretion.
Unchanged:
Approximately 50-90% of the dose is excreted unchanged in the urine within 24 hours.
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial clinical effects; full therapeutic effect may take 3-6 months.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 3-6 months.
DurationOfAction:
Due to its mechanism of action and intracellular polyglutamation, effects persist for the duration of weekly dosing.
Safety & Warnings
BLACK BOX WARNING
Methotrexate has been associated with severe adverse reactions, including:
1. Bone marrow suppression (myelosuppression), aplastic anemia, and pancytopenia.
2. Renal impairment, which can lead to accumulation and increased toxicity.
3. Liver toxicity, including acute liver injury, fibrosis, and cirrhosis.
4. Pulmonary toxicity, including acute or chronic interstitial pneumonitis.
5. Serious dermatologic reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome.
6. Opportunistic infections, including Pneumocystis jirovecii pneumonia.
7. Tumor lysis syndrome.
8. Potentially fatal toxicities when used concomitantly with NSAIDs (especially at high doses).
9. Embryo-fetal toxicity (teratogenicity and fetal death).
10. Gastrointestinal toxicity (e.g., stomatitis, diarrhea, severe mucositis).
11. Malignant lymphomas.
12. Intrathecal administration can be fatal.
1. Bone marrow suppression (myelosuppression), aplastic anemia, and pancytopenia.
2. Renal impairment, which can lead to accumulation and increased toxicity.
3. Liver toxicity, including acute liver injury, fibrosis, and cirrhosis.
4. Pulmonary toxicity, including acute or chronic interstitial pneumonitis.
5. Serious dermatologic reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome.
6. Opportunistic infections, including Pneumocystis jirovecii pneumonia.
7. Tumor lysis syndrome.
8. Potentially fatal toxicities when used concomitantly with NSAIDs (especially at high doses).
9. Embryo-fetal toxicity (teratogenicity and fetal death).
10. Gastrointestinal toxicity (e.g., stomatitis, diarrhea, severe mucositis).
11. Malignant lymphomas.
12. Intrathecal administration can be fatal.
Side Effects
Urgent 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:
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.
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.
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.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or Breathing Problems: Shortness of breath, breathing difficulties, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other Serious Symptoms: Pinpoint red spots on the skin, severe dizziness or fainting, seizures, confusion, excessive sleepiness, changes in vision, bone pain, or swelling, warmth, numbness, color changes, or pain in a leg or arm.
Stroke-Like Symptoms: Weakness on one side of the body, speech or thinking difficulties, balance changes, drooping on one side of the face, or blurred vision.
Other Concerning Symptoms: Headache, neck stiffness.
Common Side Effects
Most people experience no side effects or only mild side effects while taking this medication. However, if you notice any of the following side effects or any other unusual symptoms, contact your doctor for advice:
Decreased appetite
Hair loss
Dizziness, tiredness, or weakness
Stomach pain
Common cold symptoms
Reporting Side Effects
This list is not exhaustive, and you may experience other 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:
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.
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.
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.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or Breathing Problems: Shortness of breath, breathing difficulties, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other Serious Symptoms: Pinpoint red spots on the skin, severe dizziness or fainting, seizures, confusion, excessive sleepiness, changes in vision, bone pain, or swelling, warmth, numbness, color changes, or pain in a leg or arm.
Stroke-Like Symptoms: Weakness on one side of the body, speech or thinking difficulties, balance changes, drooping on one side of the face, or blurred vision.
Other Concerning Symptoms: Headache, neck stiffness.
Common Side Effects
Most people experience no side effects or only mild side effects while taking this medication. However, if you notice any of the following side effects or any other unusual symptoms, contact your doctor for advice:
Decreased appetite
Hair loss
Dizziness, tiredness, or weakness
Stomach pain
Common cold symptoms
Reporting Side Effects
This list is not exhaustive, and you may experience other 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, or other signs of infection
- Unusual bleeding or bruising
- Severe mouth sores or ulcers
- Severe diarrhea or vomiting
- Yellowing of the skin or eyes (jaundice)
- Dark urine or pale stools
- Severe fatigue or weakness
- New or worsening cough, shortness of breath, or difficulty breathing
- Swelling in the legs or ankles
- Severe skin rash or blistering
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.
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 weakened 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. 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 allergic reaction 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 weakened 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. 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.
To ensure your safety, avoid driving and other activities that require alertness until you understand how this drug 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 you may experience easier bleeding, so it is vital to be cautious and avoid injuries. To minimize the risk of bleeding, 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 to understand any potential risks.
You may be more prone to sunburn, so it is essential to take protective measures such as avoiding direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to prevent sunburn. Continue to follow your doctor's advice on sun protection for the recommended duration.
If you experience fluid loss, excessive 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 any concerns or questions, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor, as this may affect your treatment. Individuals 65 years or older should use this medication with caution, as they may be more susceptible to side effects.
This drug may impact fertility, potentially leading to difficulty conceiving 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.
To ensure your safety, avoid driving and other activities that require alertness until you understand how this drug 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 you may experience easier bleeding, so it is vital to be cautious and avoid injuries. To minimize the risk of bleeding, 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 to understand any potential risks.
You may be more prone to sunburn, so it is essential to take protective measures such as avoiding direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to prevent sunburn. Continue to follow your doctor's advice on sun protection for the recommended duration.
If you experience fluid loss, excessive 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 any concerns or questions, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor, as this may affect your treatment. Individuals 65 years or older should use this medication with caution, as they may be more susceptible to side effects.
This drug may impact fertility, potentially leading to difficulty conceiving 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 bone marrow suppression (low white blood cells, red blood cells, platelets)
- Severe mucositis (mouth sores, GI inflammation)
- Severe liver damage
- Kidney failure
- Pulmonary toxicity
What to Do:
Immediately contact your doctor or go to the nearest emergency room. Leucovorin (folinic acid) is the antidote for methotrexate overdose and should be administered as soon as possible. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live vaccines (e.g., MMR, varicella, rotavirus, yellow fever) due to immunosuppression and risk of disseminated infection.
- Trimethoprim/sulfamethoxazole (Bactrim) due to increased risk of myelosuppression (additive folate antagonism).
- Probenecid (may significantly increase methotrexate levels by inhibiting renal excretion).
- Alcohol (increases risk of hepatotoxicity).
Major Interactions
- NSAIDs (e.g., ibuprofen, naproxen, diclofenac): May increase methotrexate levels and toxicity, especially with high-dose methotrexate. Use with caution and monitor closely with low-dose methotrexate.
- Proton Pump Inhibitors (PPIs) (e.g., omeprazole, pantoprazole): May increase methotrexate levels, particularly with high-dose methotrexate. Monitor closely.
- Salicylates (e.g., aspirin): May decrease renal clearance of methotrexate.
- Retinoids (e.g., acitretin, isotretinoin): Increased risk of hepatotoxicity.
- Phenytoin: May displace methotrexate from protein binding, increasing free methotrexate levels.
- Folic acid antagonists (e.g., pyrimethamine): Increased risk of myelosuppression.
- Other hepatotoxic drugs (e.g., azathioprine, leflunomide, sulfasalazine): Increased risk of hepatotoxicity.
- Nephrotoxic drugs (e.g., aminoglycosides, cisplatin): May impair methotrexate excretion.
- Highly protein-bound drugs (e.g., sulfonamides, tetracyclines, chloramphenicol): May displace methotrexate from protein binding.
Moderate Interactions
- Theophylline: Methotrexate may decrease theophylline clearance.
- Caffeine: High caffeine intake may reduce the efficacy of methotrexate in RA, though clinical significance is debated.
- Oral antibiotics (e.g., tetracyclines, chloramphenicol, broad-spectrum antibiotics): May alter gut flora, potentially interfering with enterohepatic recirculation of methotrexate, leading to increased levels.
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic parameters and detect pre-existing cytopenias. Methotrexate can cause bone marrow suppression.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs) (AST, ALT, albumin, bilirubin)
Rationale: To assess baseline liver function. Methotrexate is hepatotoxic.
Timing: Prior to initiation of therapy.
Renal Function Tests (Serum Creatinine, eGFR, BUN)
Rationale: To assess baseline renal function. Methotrexate is primarily renally excreted, and impaired renal function increases toxicity.
Timing: Prior to initiation of therapy.
Chest X-ray
Rationale: To establish baseline pulmonary status. Methotrexate can cause pulmonary toxicity (pneumonitis).
Timing: Prior to initiation of therapy.
Hepatitis B and C serology
Rationale: To screen for chronic viral hepatitis, which may increase risk of liver toxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Every 2-4 weeks for the first 1-2 months, then monthly or every 1-3 months once stable.
Target: Within normal limits; monitor for significant drops in cell counts.
Action Threshold: Hold dose for significant cytopenias (e.g., WBC <3,500/mm³, ANC <1,500/mm³, Platelets <100,000/mm³).
Liver Function Tests (AST, ALT, albumin, bilirubin)
Frequency: Every 2-4 weeks for the first 1-2 months, then monthly or every 1-3 months once stable.
Target: AST/ALT <2x ULN (Upper Limit of Normal); albumin and bilirubin within normal limits.
Action Threshold: Hold dose for persistent elevation of AST/ALT >2-3x ULN, or any significant increase in bilirubin or decrease in albumin. Liver biopsy may be considered for persistent abnormalities.
Renal Function Tests (Serum Creatinine, eGFR)
Frequency: Every 2-4 weeks for the first 1-2 months, then monthly or every 1-3 months once stable.
Target: Within normal limits; stable creatinine.
Action Threshold: Hold dose or reduce dose for significant increase in creatinine or decrease in eGFR.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, cough)
- Signs of bleeding/bruising (petechiae, unusual bleeding)
- Signs of liver toxicity (fatigue, nausea, vomiting, dark urine, yellowing of skin/eyes, abdominal pain)
- Signs of pulmonary toxicity (new or worsening cough, shortness of breath, fever)
- Signs of gastrointestinal toxicity (severe diarrhea, stomatitis, oral ulcers)
- Skin rash or lesions
Special Patient Groups
Pregnancy
Contraindicated in pregnancy for non-oncologic indications (e.g., RA, psoriasis) due to significant risk of embryo-fetal toxicity, including fetal death and severe birth defects. Women of childbearing potential should 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:
High risk of major congenital malformations (e.g., craniofacial, cardiovascular, limb abnormalities) and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, hydrocephalus, and other abnormalities.
Third Trimester:
Risk of fetal toxicity and premature delivery.
Lactation
Contraindicated during lactation. 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 of serious adverse effects including myelosuppression, immunosuppression, and potential long-term developmental effects.
Pediatric Use
Used in pediatric patients for Juvenile Idiopathic Arthritis (JIA) and certain cancers (e.g., acute lymphoblastic leukemia). Dosing is weight or body surface area-based. Close monitoring for toxicity is essential, similar to adults.
Geriatric Use
Use with caution in elderly patients due to increased likelihood of decreased renal and hepatic function, and potential for concomitant diseases or other drug therapies. Close monitoring of renal function, liver function, and blood counts is crucial. Dose adjustments may be necessary.
Clinical Information
Clinical Pearls
- Emphasize the once-weekly dosing schedule for RA/psoriasis to patients; daily dosing can be fatal.
- Folic acid supplementation (typically 1-5 mg once daily, or 5 mg once weekly on a different day than methotrexate) is crucial to reduce common side effects like nausea, oral ulcers, and liver enzyme elevations.
- Patients should be advised to avoid alcohol completely due to the increased risk of hepatotoxicity.
- Ensure patients understand the importance of regular blood tests (CBC, LFTs, renal function) to monitor for toxicity.
- Educate patients on signs and symptoms of serious adverse effects (e.g., infection, bleeding, liver/lung problems) and when to seek immediate medical attention.
- Otrexup is a pre-filled syringe designed for subcutaneous injection; proper injection technique should be demonstrated and confirmed with the patient.
Alternative Therapies
- Other conventional synthetic DMARDs (csDMARDs) for RA/psoriasis: Hydroxychloroquine, Sulfasalazine, Leflunomide.
- Biologic DMARDs (bDMARDs) for RA/psoriasis: 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), IL-12/23 inhibitors (e.g., Ustekinumab), IL-17 inhibitors (e.g., Secukinumab, Ixekizumab).
- Targeted Synthetic DMARDs (tsDMARDs) / JAK inhibitors: Tofacitinib, Baricitinib, Upadacitinib.
Cost & Coverage
Average Cost:
Varies widely by pharmacy and insurance plan. Otrexup 15mg/0.4ml (4 pre-filled syringes) can range from $1,000 - $2,000+. per 4 pre-filled syringes
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (Brand-name specialty drug). Generic methotrexate is typically Tier 1 or 2.
General Drug Facts
If your symptoms or health issues persist or worsen, it's 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 be sure to check with your pharmacist for more information. If you have any questions or concerns about this 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, including the amount taken and the time it happened, to ensure you receive the best possible care.