Otrexup 25mg/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 (DMARD), Antipsoriatic, Antineoplastic
Pharmacologic Class
Folic acid antagonist, Antimetabolite
Pregnancy Category
Category X
FDA Approved
Sep 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Otrexup (methotrexate) is a medication used to treat severe rheumatoid arthritis, severe psoriasis, and certain types of cancer. It works by slowing down the growth of certain cells in the body, including fast-growing cancer cells, and by reducing inflammation and overactivity of the immune system in conditions like arthritis and psoriasis. It is given as a weekly injection under the skin.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting the medication 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 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.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for 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 the medication at room temperature, protected from light and moisture. Do not store in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor 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 the medication 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 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.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for 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 the medication at room temperature, protected from light and moisture. Do not store in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor 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 due to increased risk of liver damage.
- Avoid excessive sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Maintain good hydration by drinking plenty of fluids.
- Avoid live vaccines while on methotrexate.
- Use effective contraception during treatment and for at least 6 months after stopping for both men and women, as methotrexate can cause severe birth defects or miscarriage.
- Report any signs of infection (fever, chills, sore throat) immediately.
- Report any unusual bleeding or bruising, severe fatigue, yellow skin/eyes, persistent cough, or shortness of breath.
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/Psoriasis: 7.5 mg to 25 mg once weekly, administered subcutaneously. Otrexup 25mg/0.4ml is a single dose pre-filled syringe.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
rheumatoidArthritis:
7.5 mg to 25 mg once weekly, SC. Initial dose often 7.5 mg/week, adjusted based on response and tolerability.
psoriasis:
10 mg to 25 mg once weekly, SC. Initial dose often 10 mg/week, adjusted based on response and tolerability.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, SC. Dosing may be adjusted based on response and tolerability, typically not exceeding 20-30 mg/week.
Adolescent:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, SC. Dosing may be adjusted based on response and tolerability, typically not exceeding 20-30 mg/week.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 51-80 mL/min: Consider 25% dose reduction or increased monitoring.
Moderate:
CrCl 30-50 mL/min: Consider 50% dose reduction or increased monitoring. Use with extreme caution.
Severe:
CrCl <30 mL/min: Contraindicated for non-oncologic use due to significant risk of toxicity.
Dialysis:
Methotrexate is partially dialyzable. Avoid use in patients on dialysis for non-oncologic indications due to prolonged elimination and increased toxicity risk.
Hepatic Impairment:
Mild:
Use with caution; monitor liver function closely. Consider dose reduction.
Moderate:
Avoid or use with extreme caution; significant risk of hepatotoxicity. Consider dose reduction or discontinuation.
Severe:
Contraindicated in patients with severe hepatic impairment (e.g., cirrhosis, fibrosis, or significant elevation of liver enzymes).
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 co-factor in the de novo synthesis of purines and pyrimidines. 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 inhibition of polymorphonuclear leukocyte chemotaxis.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous administration provides good and consistent bioavailability, typically 80-90% compared to intravenous administration. Oral bioavailability is variable and dose-dependent.
Tmax:
Subcutaneous: 1-2 hours.
FoodEffect:
Not applicable for subcutaneous administration.
Distribution:
Vd:
Approximately 0.4-0.8 L/kg (distributes into total body water).
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at lower doses used for RA/psoriasis; higher doses (e.g., for oncology) can achieve therapeutic concentrations in CSF.
Elimination:
HalfLife:
Approximately 3-10 hours (low dose, non-oncologic use); can be prolonged in renal impairment or with drug interactions.
Clearance:
Primarily renal (glomerular filtration and active tubular secretion).
ExcretionRoute:
Renal (approximately 50-90% unchanged within 24 hours); small amount excreted in bile.
Unchanged:
50-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: Clinical improvement typically seen within 3-6 weeks, with full effect potentially taking 3-6 months.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: Peak clinical effect often observed after several months of consistent weekly dosing.
DurationOfAction:
Due to its mechanism of action and cellular effects, the therapeutic effects persist for the duration of weekly dosing.
Safety & Warnings
BLACK BOX WARNING
Methotrexate has been associated with severe toxic reactions, including death. Patients should be closely monitored for bone marrow, liver, lung, and kidney toxicities. Methotrexate can cause severe myelosuppression, hepatotoxicity (including fibrosis and cirrhosis), pneumonitis, and renal damage. Diarrhea and ulcerative stomatitis require interruption of therapy. Methotrexate can cause fetal death or teratogenic effects when administered to pregnant women. It is contraindicated in pregnant women with non-oncologic diseases. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or significant effusions. Concomitant administration of NSAIDs with high-dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity. Methotrexate should be used only by physicians whose knowledge and experience include the use of antimetabolite therapy. Patients should be fully informed of the risks involved and should be under constant supervision.
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 discolored sputum, 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 bruising that worsens, 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 yellowing of the 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 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-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 minimal or no side effects. 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, fatigue, or weakness
Stomach pain
Common cold symptoms
Reporting Side Effects
This is not an exhaustive list of potential 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 discolored sputum, 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 bruising that worsens, 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 yellowing of the 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 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-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 minimal or no side effects. 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, fatigue, or weakness
Stomach pain
Common cold symptoms
Reporting Side Effects
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, sore throat, or other signs of infection
- Unusual bleeding or bruising
- Severe fatigue or weakness
- Yellowing of the skin or eyes (jaundice)
- Dark urine
- Severe abdominal pain
- Persistent cough or shortness of breath
- Severe mouth sores or ulcers
- Severe diarrhea
- Skin rash 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 symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weakened immune system
Additionally, if you are breast-feeding, please note that you should not breast-feed while taking this medication. Your doctor will advise you on whether you need to avoid breast-feeding for a period after your last dose.
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 determine whether it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weakened immune system
Additionally, if you are breast-feeding, please note that you should not breast-feed while taking this medication. Your doctor will advise you on whether you need to avoid breast-feeding for a period after your last dose.
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 determine whether it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without 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.
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's 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-bristled toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult 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 sunburn while taking this medication. To protect yourself, avoid direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear when exposed to the sun. Continue to take these precautions for as long as your doctor advises.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or 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. Elderly patients (65 years and older) should use this medication with caution, as they may be more susceptible to side effects.
This medication may affect fertility, potentially leading to 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's 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-bristled toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult 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 sunburn while taking this medication. To protect yourself, avoid direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear when exposed to the sun. Continue to take these precautions for as long as your doctor advises.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or 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. Elderly patients (65 years and older) should use this medication with caution, as they may be more susceptible to side effects.
This medication may affect fertility, potentially leading to 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, GI ulcers)
- Severe gastrointestinal toxicity (nausea, vomiting, diarrhea)
- Hepatotoxicity
- Nephrotoxicity
What to Do:
Seek immediate medical attention. The antidote for methotrexate overdose is leucovorin (folinic acid), which helps to rescue healthy cells from the effects of methotrexate. Glucarpidase may also be used in severe cases. Call 911 or your local poison control center (1-800-222-1222).
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Trimethoprim/sulfamethoxazole (increased myelosuppression)
- Probenecid (decreased renal elimination 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, use with caution and monitor for toxicity, especially renal)
- Salicylates (low-dose methotrexate, use with caution and monitor for toxicity)
- 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 toxicity)
- Nephrotoxic drugs (e.g., aminoglycosides, cisplatin - impaired methotrexate elimination)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Sulfonylureas (increased hypoglycemic effect)
- Tetracyclines, chloramphenicol (may increase methotrexate levels)
- Folic acid antagonists (e.g., pyrimethamine - increased myelosuppression)
Moderate Interactions
- Theophylline (methotrexate may decrease theophylline clearance)
- Caffeine (may reduce methotrexate efficacy in RA, though clinical significance debated)
- Oral antibiotics (e.g., neomycin, broad-spectrum antibiotics - may alter gut flora, affecting methotrexate absorption/metabolism)
- Corticosteroids (may reduce methotrexate efficacy or increase toxicity depending on timing)
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 myelosuppression.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To establish baseline liver function and detect pre-existing hepatic impairment.
Timing: Prior to initiation of therapy.
Renal Function Tests (RFTs) including serum creatinine, BUN, eGFR
Rationale: To establish baseline renal function and detect pre-existing renal impairment, as methotrexate is primarily renally eliminated.
Timing: Prior to initiation of therapy.
Chest X-ray
Rationale: To establish baseline pulmonary status and rule out pre-existing lung disease, given risk of methotrexate-induced 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 months, then every 1-2 months thereafter.
Target: Maintain 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 (LFTs) including AST, ALT, albumin, bilirubin
Frequency: Every 2-4 weeks for the first 3 months, then every 1-2 months thereafter.
Target: Maintain within normal limits or stable baseline.
Action Threshold: Hold dose for persistent elevation of AST/ALT >2-3 times upper limit of normal (ULN) or significant changes in albumin/bilirubin.
Renal Function Tests (RFTs) including serum creatinine, BUN, eGFR
Frequency: Every 2-4 weeks for the first 3 months, then every 1-2 months thereafter.
Target: Maintain within normal limits or stable baseline.
Action Threshold: Hold dose for significant increase in creatinine or decrease in eGFR.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising
- Fatigue, weakness (signs of myelosuppression)
- Yellowing of skin or eyes, dark urine, abdominal pain (signs of hepatotoxicity)
- Shortness of breath, cough (signs of pneumonitis)
- Mouth sores, painful swallowing, severe diarrhea (signs of mucositis/GI toxicity)
- Skin rash, photosensitivity
- Nausea, vomiting
Special Patient Groups
Pregnancy
Methotrexate is contraindicated in pregnant women with non-oncologic diseases (e.g., RA, psoriasis) due to significant risk of fetal death and severe teratogenic effects (e.g., craniofacial, cardiovascular, and limb abnormalities). Women of childbearing potential must use effective contraception during therapy and for at least 6 months after the last dose. Men should also use effective contraception during therapy and for at least 3 months after the last dose.
Trimester-Specific Risks:
First Trimester:
Highest risk of major congenital malformations and spontaneous abortion.
Second Trimester:
Risk of fetal toxicity, growth restriction, and malformations.
Third Trimester:
Risk of fetal toxicity and complications.
Lactation
Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant. Breastfeeding is contraindicated during methotrexate therapy.
Infant Risk:
High risk of myelosuppression, immunosuppression, and other toxicities in the infant.
Pediatric Use
Used for polyarticular juvenile idiopathic arthritis (pJIA). Dosing is typically weight or body surface area-based. Close monitoring for adverse effects is crucial, similar to adults. Long-term safety and efficacy in children should be carefully considered.
Geriatric Use
Elderly patients may be at increased risk for adverse reactions due to decreased renal function, folate deficiency, and concomitant medications. Close monitoring of renal function, CBC, and LFTs is essential. Lower starting doses or less frequent dosing may be appropriate.
Clinical Information
Clinical Pearls
- Methotrexate for RA/Psoriasis is dosed ONCE WEEKLY, not daily. Daily dosing can be fatal.
- Folic acid supplementation (typically 1-5 mg once daily, or 5 mg once weekly, avoiding the day of methotrexate administration) is crucial to reduce common side effects like mucositis, nausea, and liver enzyme elevations, without significantly impacting efficacy.
- Patients must be well-hydrated to facilitate renal elimination of methotrexate and prevent kidney toxicity.
- Alcohol consumption should be strictly avoided due to the increased risk of hepatotoxicity.
- Monitor for signs of pneumonitis (dry cough, dyspnea, fever), a potentially severe and acute adverse effect.
- Otrexup is a pre-filled syringe designed for subcutaneous self-administration, which can improve patient adherence and convenience compared to oral tablets or vials requiring drawing up.
- Ensure patients understand the importance of regular laboratory monitoring (CBC, LFTs, RFTs).
Alternative Therapies
- Other conventional synthetic DMARDs (csDMARDs): Hydroxychloroquine, Sulfasalazine, Leflunomide
- Biologic DMARDs (bDMARDs): TNF inhibitors (e.g., Adalimumab, Etanercept, Infliximab), IL-6 inhibitors (e.g., Tocilizumab), T-cell costimulation modulators (e.g., Abatacept), B-cell depleting agents (e.g., Rituximab)
- Targeted Synthetic DMARDs (tsDMARDs): JAK inhibitors (e.g., Tofacitinib, Baricitinib, Upadacitinib)
- For Psoriasis: Phototherapy, other systemic agents (e.g., cyclosporine, apremilast), biologics (e.g., ustekinumab, secukinumab, ixekizumab, guselkumab, risankizumab).
Cost & Coverage
Average Cost:
$1,000 - $2,000 per 4 x 0.4ml pre-filled syringes (25mg/0.4ml)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (Specialty Drug)
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 medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.