Otrexup 20mg/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, Disease-Modifying Antirheumatic Drug (DMARD), Antineoplastic
Pharmacologic Class
Folic acid antagonist, Antimetabolite
Pregnancy Category
Category X
FDA Approved
Apr 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Methotrexate is a medication that works by slowing down the growth of certain cells in the body. For conditions like rheumatoid arthritis and psoriasis, it helps reduce inflammation and overactive immune responses. It is 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 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 items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions, consult your doctor or pharmacist.
Dosing and Frequency
Your dose 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 dosing schedule and frequency before taking this medication. 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 how well the medication is working.
Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling.
Additional Recommendations
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 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 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 items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions, consult your doctor or pharmacist.
Dosing and Frequency
Your dose 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 dosing schedule and frequency before taking this medication. 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 how well the medication is working.
Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling.
Additional Recommendations
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 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
- Take exactly as prescribed, usually once a week on the same day. Do NOT take daily.
- Take folic acid supplementation as directed by your doctor to reduce side effects (e.g., mouth sores, nausea).
- Avoid alcohol completely while on methotrexate due to increased risk of liver damage.
- Avoid prolonged sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Stay well-hydrated.
- Avoid live vaccines while on methotrexate, as your immune system may be weakened.
- Inform your doctor about all other medications, supplements, and herbal products you are taking.
- 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.
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:
7.5 mg to 20 mg once weekly
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
7.5 mg once weekly, adjusted gradually to a maximum of 20 mg once weekly. Doses above 20 mg/week may be associated with increased toxicity.
Psoriasis:
Initial test dose of 5-10 mg orally or parenterally one week prior to therapy. Then, 10-25 mg once weekly as a single dose, or divided into 3 doses given at 12-hour intervals over 36 hours. Max 30 mg/week.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Dosing established for Polyarticular Juvenile Idiopathic Arthritis (pJIA)
Adolescent:
Dosing established for Polyarticular Juvenile Idiopathic Arthritis (pJIA)
Dose Adjustments
Renal Impairment:
Mild:
CrCl 50-80 mL/min: Reduce dose by 25-50% or extend dosing interval. Monitor closely.
Moderate:
CrCl 30-50 mL/min: Reduce dose by 50-75% or extend dosing interval significantly. Avoid if possible.
Severe:
CrCl < 30 mL/min: Contraindicated due to significant risk of toxicity.
Dialysis:
Methotrexate is partially dialyzable. Avoid use in patients on dialysis due to prolonged elimination and increased toxicity risk. If used in life-threatening situations, consider leucovorin rescue and extended dialysis.
Hepatic Impairment:
Mild:
Use with caution. Monitor LFTs closely.
Moderate:
Avoid or use with extreme caution. Significant risk of hepatotoxicity.
Severe:
Contraindicated in patients with severe hepatic impairment (e.g., cirrhosis, fibrosis, significant elevation of LFTs).
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 cofactor for purine and pyrimidine synthesis. This leads to inhibition of DNA, RNA, and protein synthesis, particularly in rapidly proliferating cells. In rheumatoid arthritis and psoriasis, its mechanism is thought to involve immunosuppressive and anti-inflammatory effects, possibly through inhibition of lymphocyte proliferation, induction of adenosine release, and inhibition of polymorphonuclear leukocyte chemotaxis.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80-90% for subcutaneous administration (higher and more consistent than oral).
Tmax:
0.5-1 hour (subcutaneous)
FoodEffect:
Not significant for subcutaneous administration.
Distribution:
Vd:
0.4-0.8 L/kg (initial), 0.2-0.3 L/kg (steady-state)
ProteinBinding:
Approximately 50% (primarily to albumin)
CnssPenetration:
Limited at typical low doses; increases with higher doses and inflammation of meninges.
Elimination:
HalfLife:
3-10 hours (low dose); 8-15 hours (high dose)
Clearance:
Primarily renal clearance (glomerular filtration and active tubular secretion).
ExcretionRoute:
Renal (approximately 80-90% unchanged), minor biliary excretion.
Unchanged:
Approximately 80-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial clinical effects; full effect may take 3-6 months.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 3-6 months.
DurationOfAction:
Weekly dosing maintains therapeutic effect.
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 fetal death and congenital abnormalities; therefore, it is contraindicated in pregnant women with non-oncologic diseases. Methotrexate can cause severe skin reactions. Methotrexate can cause tumor lysis syndrome. Methotrexate can cause opportunistic infections, including Pneumocystis jirovecii pneumonia. Methotrexate can cause potentially fatal opportunistic infections. Methotrexate can cause severe, potentially fatal, mucositis. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or pleural effusions. Concomitant administration of NSAIDs with high-dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in severe and fatal toxicities.
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, difficulty breathing, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other Severe 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 Symptoms: Weakness on one side of the body, difficulty speaking or thinking, balance changes, drooping on one side of the face, or blurred vision.
Other Concerning Symptoms: 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 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, difficulty breathing, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other Severe 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 Symptoms: Weakness on one side of the body, difficulty speaking or thinking, balance changes, drooping on one side of the face, or blurred vision.
Other Concerning Symptoms: 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 any signs of infection
- Unusual bleeding or bruising, black or tarry stools
- Severe or persistent diarrhea, nausea, vomiting
- Mouth sores, painful swallowing
- Shortness of breath, dry cough, or new chest pain
- Yellowing of skin or eyes, dark urine, severe fatigue (signs of liver problems)
- Swelling in ankles or feet, decreased urination (signs of kidney problems)
- Severe skin rash, blistering, or peeling
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 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 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. This will help ensure your safety while taking this medication. Do not initiate, stop, or modify 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, 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 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 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. This will help ensure your safety while taking this medication. Do not initiate, stop, or modify 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.
Before operating a vehicle or engaging in any activity that requires your full attention, wait until you understand how this medication affects you. Be aware that 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 individuals who have infections, colds, or flu.
Due to the increased risk of bleeding, exercise caution to avoid injuries. To minimize this risk, use a soft-bristled toothbrush and an electric razor for shaving.
Prior to receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase your risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor before drinking.
You may be more prone to sunburn, so it is vital to limit your exposure to the sun, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to shield yourself from the sun, and continue to take these precautions for the duration recommended by your doctor.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or excessive thirst, notify your doctor promptly. Be aware that 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, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Individuals 65 years or 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.
Before operating a vehicle or engaging in any activity that requires your full attention, wait until you understand how this medication affects you. Be aware that 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 individuals who have infections, colds, or flu.
Due to the increased risk of bleeding, exercise caution to avoid injuries. To minimize this risk, use a soft-bristled toothbrush and an electric razor for shaving.
Prior to receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase your risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor before drinking.
You may be more prone to sunburn, so it is vital to limit your exposure to the sun, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to shield yourself from the sun, and continue to take these precautions for the duration recommended by your doctor.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or excessive thirst, notify your doctor promptly. Be aware that 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, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Individuals 65 years or 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 inflammation)
- Gastrointestinal bleeding
- Renal failure
- Hepatotoxicity
What to Do:
Immediately contact emergency services or poison control (Call 1-800-222-1222). Leucovorin rescue is the primary antidote, administered as soon as possible. Hydration and urinary alkalinization may also be used to enhance methotrexate elimination.
Drug Interactions
Contraindicated Interactions
- Live vaccines (in immunosuppressed patients)
- Trimethoprim/sulfamethoxazole (increased myelosuppression and methotrexate levels)
- Probenecid (decreased renal elimination of methotrexate)
- Non-steroidal anti-inflammatory drugs (NSAIDs) with high-dose methotrexate (severe, sometimes fatal, myelosuppression and nephrotoxicity)
- Salicylates (decreased renal elimination of methotrexate)
- Alcohol (increased risk of hepatotoxicity)
Major Interactions
- NSAIDs (with low-dose methotrexate: use with caution, monitor for toxicity, may increase methotrexate levels)
- Proton pump inhibitors (PPIs) (e.g., omeprazole, pantoprazole: may increase methotrexate levels, especially at higher doses)
- Retinoids (e.g., acitretin, etretinate: increased risk of hepatotoxicity)
- Other hepatotoxic drugs (e.g., azathioprine, leflunomide, sulfasalazine: increased risk of liver damage)
- Nephrotoxic drugs (e.g., aminoglycosides, cisplatin: impaired methotrexate elimination)
- Folic acid antagonists (e.g., pyrimethamine, trimethoprim: increased methotrexate toxicity)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Theophylline (decreased theophylline clearance)
- Ciprofloxacin (may increase methotrexate levels)
Moderate Interactions
- Oral antibiotics (e.g., tetracyclines, chloramphenicol: may alter gut flora, affecting methotrexate absorption/enterohepatic recirculation)
- Penicillins (may decrease renal clearance of methotrexate)
- Sulfonamides (may displace methotrexate from protein binding, increasing free drug)
- Nitrous oxide (may potentiate methotrexate toxicity by inhibiting methionine synthase)
- Cholestyramine (may interfere with methotrexate absorption)
Minor Interactions
- Not typically categorized as minor due to high potential for significant interactions.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status and detect pre-existing cytopenias. Methotrexate can cause myelosuppression.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To establish baseline liver function. Methotrexate is hepatotoxic.
Timing: Prior to initiation of therapy
Renal Function Tests (serum creatinine, BUN, eGFR)
Rationale: To establish 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 establish baseline pulmonary status. Methotrexate can cause pulmonary toxicity.
Timing: Prior to initiation of therapy
Hepatitis B and C serology
Rationale: To screen for chronic viral hepatitis, which can increase risk of methotrexate-induced hepatotoxicity.
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 as clinically indicated.
Target: Maintain WBC > 3,000/mm³, ANC > 1,500/mm³, Platelets > 100,000/mm³.
Action Threshold: Hold dose for significant drops (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 2 months, then monthly or as clinically indicated.
Target: AST/ALT < 2x upper limit of normal (ULN).
Action Threshold: Hold dose for persistent or significant elevations (e.g., AST/ALT > 2x ULN). Consider liver biopsy for persistent elevations or cumulative dose concerns.
Renal Function Tests (serum creatinine, BUN)
Frequency: Monthly or as clinically indicated.
Target: Stable creatinine, within normal limits for patient.
Action Threshold: Hold dose for significant increase in creatinine (> 50% increase from baseline or above ULN). Adjust dose or discontinue.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising (petechiae, purpura)
- Severe or persistent diarrhea
- Oral ulcers or stomatitis (mouth sores)
- Shortness of breath, cough, or new onset dyspnea (signs of pulmonary toxicity)
- Yellowing of skin or eyes, dark urine (signs of hepatotoxicity)
- Severe skin reactions (rash, blistering)
- Nausea, vomiting, abdominal pain
- Fatigue, weakness
Special Patient Groups
Pregnancy
Contraindicated in pregnant women with non-oncologic diseases due to high risk of fetal death and severe congenital abnormalities. Category X.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, limb, cardiovascular defects) and spontaneous abortion.
Second Trimester:
Risk of fetal death and growth restriction.
Third Trimester:
Risk of fetal death and growth restriction.
Lactation
Contraindicated. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant.
Infant Risk:
High risk of myelosuppression, immunosuppression, and other toxicities in the infant.
Pediatric Use
Approved for polyarticular juvenile idiopathic arthritis (pJIA). Close monitoring for toxicity is essential. Long-term effects on growth and development should be considered.
Geriatric Use
Use with caution. Elderly patients may have decreased renal function, which can lead to increased methotrexate levels and toxicity. More susceptible to myelosuppression and hepatotoxicity. Lower doses or extended dosing intervals may be necessary.
Clinical Information
Clinical Pearls
- Methotrexate is dosed WEEKLY, not daily. Accidental 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 mucositis, nausea, and liver enzyme elevations, without significantly reducing efficacy.
- Ensure adequate hydration to prevent renal toxicity.
- Strictly avoid alcohol due to the risk of severe hepatotoxicity.
- Patients must be educated on the signs and symptoms of toxicity and when to seek immediate medical attention.
- Regular and frequent monitoring of CBC, LFTs, and renal function is mandatory.
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: Systemic therapies (e.g., cyclosporine, apremilast), biologics, phototherapy.
Cost & Coverage
Average Cost:
$1,000 - $2,000+ per 4 x 0.4ml (20mg/0.4ml) prefilled syringes
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization)
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 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 emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.