Otrexup 17.5mg/0.4ml Pf Injection
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), Immunosuppressant, Antineoplastic
Pharmacologic Class
Folic acid antagonist, Dihydrofolate reductase inhibitor
Pregnancy Category
Category X
FDA Approved
Oct 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Methotrexate is a medication that works by slowing down the growth of certain cells in the body. For conditions like rheumatoid arthritis and psoriasis, it helps to reduce inflammation and calm down an overactive immune system. It's often taken once a week.
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 or concerns, 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 starting treatment. If you have any questions or concerns, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and treatment response.
Your doctor or pharmacist will provide guidance on handling this medication safely.
General Health Tips
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light and moisture.
Do not store in a bathroom.
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 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 or concerns, 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 starting treatment. If you have any questions or concerns, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and treatment response.
Your doctor or pharmacist will provide guidance on handling this medication safely.
General Health Tips
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light and moisture.
Do not store in a bathroom.
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 arthritis/psoriasis, as this can lead to severe toxicity.
- Take folic acid or leucovorin as prescribed by your doctor to help reduce side effects.
- 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.
- Report any signs of infection (fever, chills, sore throat), unusual bleeding/bruising, severe mouth sores, persistent cough, or yellowing of skin/eyes immediately to your doctor.
- Avoid live vaccines (e.g., MMR, varicella, nasal flu vaccine) while on methotrexate. Discuss all vaccinations with your doctor.
- 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.
- Stay well-hydrated, especially if experiencing nausea or vomiting.
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.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
Initial: 7.5 mg once weekly. Adjust gradually to optimal response, not exceeding 20 mg/week (or 25 mg/week in some cases).
Psoriasis:
Initial: 10 mg to 25 mg once weekly as a single dose, or 2.5 mg every 12 hours for 3 doses each week (total 7.5 mg/week). Adjust gradually to optimal response, not exceeding 25 mg/week.
Oncology (higher doses):
Dosing varies significantly by cancer type and protocol, often administered intravenously at much higher doses (e.g., 20-1000 mg/m2 or higher) with leucovorin rescue. Otrexup is not indicated for oncology uses.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly.
Adolescent:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly. For psoriasis/RA, adult dosing may apply based on weight/BSA.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Use with caution, consider dose reduction (e.g., 75% of dose).
Moderate:
CrCl 31-60 mL/min: Significant dose reduction (e.g., 50% of dose) or extended dosing interval. Close monitoring required. Some sources recommend avoiding use.
Severe:
CrCl < 30 mL/min: Contraindicated due to impaired elimination and increased risk of toxicity.
Dialysis:
Methotrexate is partially dialyzable. However, due to its complex pharmacokinetics and potential for rebound, use is generally contraindicated or requires extreme caution and specialized monitoring. High-flux hemodialysis may remove some drug.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function closely. Consider dose reduction.
Moderate:
Generally contraindicated or requires significant dose reduction and extreme caution due to increased risk of hepatotoxicity. Baseline liver biopsy may be required for psoriasis patients.
Severe:
Contraindicated due to increased risk of severe hepatotoxicity and impaired elimination.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that acts as a folic acid antagonist. It competitively inhibits dihydrofolate reductase (DHFR), an enzyme responsible for converting dihydrofolate to tetrahydrofolate. Tetrahydrofolate is a critical co-factor for purine and pyrimidine synthesis, which are essential for DNA and RNA production. By inhibiting DHFR, methotrexate impairs DNA synthesis, repair, and cellular replication. In rheumatoid arthritis and psoriasis, its anti-inflammatory and immunosuppressive effects are thought to be mediated by inhibition of lymphocyte proliferation, induction of adenosine release (which has anti-inflammatory properties), and inhibition of polymorphonuclear leukocyte chemotaxis.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV). Oral: Variable and dose-dependent (e.g., 30-70% at low doses, decreases at higher doses due to saturation of absorption).
Tmax:
Subcutaneous: 1-2 hours. Oral: 1-5 hours.
FoodEffect:
Oral absorption may be delayed and peak concentrations reduced by food, but overall extent of absorption is generally not significantly affected for low doses. Not relevant for subcutaneous injection.
Distribution:
Vd:
0.4-0.8 L/kg (initial distribution phase); higher at steady state due to intracellular accumulation.
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at conventional doses due to poor passage across the blood-brain barrier. Higher doses (e.g., intrathecal) are required for therapeutic CNS concentrations.
Elimination:
HalfLife:
Low dose (e.g., RA/psoriasis): 3-10 hours. High dose (e.g., oncology): 8-15 hours (terminal half-life).
Clearance:
Primarily renal (glomerular filtration and active tubular secretion).
ExcretionRoute:
Primarily renal (50-90% unchanged within 24 hours for low doses). A small amount (5-10%) is excreted in bile/feces.
Unchanged:
50-90% (renal excretion for low doses)
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: Clinical improvement typically seen within 3-6 weeks, with maximal benefit often taking 3-6 months.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 3-6 months.
DurationOfAction:
Effects persist as long as treatment is continued. Due to its long intracellular half-life as polyglutamates, effects can linger after discontinuation.
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. Deaths have been reported. Methotrexate has been associated with opportunistic infections, including Pneumocystis jirovecii pneumonia. Diarrhea and ulcerative stomatitis require interruption of therapy. Methotrexate can cause severe dermatologic reactions. Malignant lymphomas may occur. Tumor lysis syndrome may occur. Methotrexate can cause fetal death or teratogenic effects when administered to pregnant women. 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 toxicity. Use with caution with NSAIDs at low doses.
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding
Signs of pancreatitis (pancreas problems): severe abdominal pain, severe back pain, or severe nausea and vomiting
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain
Signs of liver problems: dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellowing of the skin or eyes
Signs of lung or breathing problems: shortness of breath, difficulty breathing, cough, or fever
Signs of nerve problems: abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part)
Pinpoint red spots on the skin
Severe dizziness or fainting
Seizures
Confusion
Excessive sleepiness
Changes in vision
Bone pain
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Weakness on one side of the body, speech or thinking difficulties, balance problems, drooping on one side of the face, or blurred vision
Headache
Neck stiffness
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have 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:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding
Signs of pancreatitis (pancreas problems): severe abdominal pain, severe back pain, or severe nausea and vomiting
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain
Signs of liver problems: dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellowing of the skin or eyes
Signs of lung or breathing problems: shortness of breath, difficulty breathing, cough, or fever
Signs of nerve problems: abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part)
Pinpoint red spots on the skin
Severe dizziness or fainting
Seizures
Confusion
Excessive sleepiness
Changes in vision
Bone pain
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Weakness on one side of the body, speech or thinking difficulties, balance problems, drooping on one side of the face, or blurred vision
Headache
Neck stiffness
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have 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, body aches (signs of infection)
- Unusual bleeding or bruising, black tarry stools, red or dark urine (signs of myelosuppression/bleeding)
- Severe mouth sores, ulcers in the mouth or throat
- Severe nausea, vomiting, diarrhea
- Persistent dry cough, shortness of breath, difficulty breathing (signs of lung toxicity)
- Yellowing of skin or eyes, dark urine, severe abdominal pain (signs of liver toxicity)
- Severe skin rash, blistering, peeling skin
- Swelling in ankles or feet, decreased urination (signs of kidney problems)
- Severe fatigue or weakness
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 weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult with your doctor to determine the necessary duration of breast-feeding avoidance after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Never start, stop, or change the dose 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 weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult with your doctor to determine the necessary duration of breast-feeding avoidance after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Never start, stop, or change the dose 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 activities that require alertness, wait until you understand how this drug 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 prevent 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 the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor.
You may be more prone to sunburn, so it is vital to avoid excessive sun exposure, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to shield yourself from the sun, and continue this protection for the duration recommended by your doctor.
If you experience symptoms such as excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or abnormal thirst, notify your doctor promptly.
Be aware that this medication can cause severe nervous system problems, which may be temporary or long-lasting and potentially life-threatening. If you have concerns or questions, 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 drug 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 experience a missed period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Before operating a vehicle or engaging in activities that require alertness, wait until you understand how this drug 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 prevent 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 the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor.
You may be more prone to sunburn, so it is vital to avoid excessive sun exposure, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to shield yourself from the sun, and continue this protection for the duration recommended by your doctor.
If you experience symptoms such as excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or abnormal thirst, notify your doctor promptly.
Be aware that this medication can cause severe nervous system problems, which may be temporary or long-lasting and potentially life-threatening. If you have concerns or questions, 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 drug 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 experience a missed period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (very low white blood cell count, platelet count, red blood cell count)
- Severe mucositis (mouth sores, GI ulcers, bleeding)
- Severe liver damage
- Kidney failure
- Severe skin reactions
What to Do:
Seek immediate medical attention. Leucovorin calcium is the primary antidote for methotrexate overdose, administered as soon as possible. Hydration and urinary alkalinization may also be used. Call 1-800-222-1222 (Poison Control) or go to the nearest emergency room.
Drug Interactions
Contraindicated Interactions
- Live vaccines (risk of severe infection)
- Trimethoprim/sulfamethoxazole (increased methotrexate levels and toxicity)
- Probenecid (decreased renal excretion of methotrexate)
- NSAIDs/Salicylates (high-dose methotrexate: increased and prolonged methotrexate levels, severe toxicity; low-dose: use with caution, monitor)
- Retinoids (e.g., acitretin, etretinate: increased risk of hepatotoxicity)
- Alcohol (increased risk of hepatotoxicity)
Major Interactions
- NSAIDs/Salicylates (low-dose methotrexate: increased methotrexate levels, risk of myelosuppression, nephrotoxicity, GI toxicity; monitor closely)
- Proton Pump Inhibitors (PPIs) (e.g., omeprazole, pantoprazole: may increase methotrexate levels, especially at higher doses; monitor)
- Folic acid antagonists (e.g., pyrimethamine, trimetrexate: additive toxicity)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Theophylline (decreased theophylline clearance)
- Chloramphenicol, tetracyclines (may displace methotrexate from protein binding, increasing free methotrexate)
- Sulfonamides, sulfonylureas, furosemide, ciprofloxacin, penicillins (may decrease renal clearance of methotrexate)
- Nitrous oxide (may potentiate methotrexate toxicity by inhibiting methionine synthase)
Moderate Interactions
- Oral antibiotics (e.g., neomycin, broad-spectrum antibiotics: may alter gut flora, affecting enterohepatic recirculation of methotrexate)
- Cholestyramine (may interfere with methotrexate absorption)
- Caffeine (high intake may reduce efficacy in RA, theoretical interaction)
- P-glycoprotein inhibitors (e.g., cyclosporine, verapamil: potential for altered methotrexate transport)
Minor Interactions
- Not specifically categorized as minor, but general caution with any drug affecting renal function or bone marrow.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status and identify pre-existing cytopenias, as methotrexate can cause myelosuppression.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs): AST, ALT, alkaline phosphatase, bilirubin, albumin
Rationale: To assess baseline hepatic function and identify pre-existing liver disease, as methotrexate is hepatotoxic.
Timing: Prior to initiation of therapy.
Renal Function Tests: Serum creatinine, BUN, estimated GFR
Rationale: To assess baseline renal function, as methotrexate is primarily renally eliminated and renal impairment increases toxicity.
Timing: Prior to initiation of therapy.
Chest X-ray
Rationale: To establish baseline pulmonary status and rule out pre-existing lung disease, as 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 be exacerbated by immunosuppression and increase risk of liver damage.
Timing: Prior to initiation of therapy.
Pregnancy test (for females of childbearing potential)
Rationale: Methotrexate is teratogenic (Category X).
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Every 1-2 weeks for the first month, then monthly for 3-6 months, then every 1-2 months or as clinically indicated.
Target: Maintain within normal limits; significant drops (e.g., WBC < 3000/mm³, platelets < 100,000/mm³) require dose interruption.
Action Threshold: Significant cytopenias (e.g., WBC < 3000/mm³, ANC < 1500/mm³, platelets < 100,000/mm³), or a rapid decline in counts, require dose interruption and investigation.
Liver Function Tests (LFTs): AST, ALT, alkaline phosphatase, albumin
Frequency: Every 1-2 weeks for the first month, then monthly for 3-6 months, then every 1-2 months or as clinically indicated.
Target: Maintain within normal limits or stable baseline. Transaminases typically < 2-3x ULN.
Action Threshold: Persistent elevation of AST/ALT > 2-3 times ULN, or significant decline in albumin, requires dose reduction or interruption. Liver biopsy may be considered for persistent abnormalities in psoriasis patients.
Renal Function Tests: Serum creatinine, BUN
Frequency: Monthly for 3-6 months, then every 1-2 months or as clinically indicated.
Target: Maintain within normal limits or stable baseline.
Action Threshold: Significant increase in serum creatinine (> 50% increase from baseline or above ULN) requires dose reduction or interruption.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, cough)
- Unusual bleeding or bruising (petechiae, purpura)
- Severe fatigue or weakness
- Shortness of breath, persistent dry cough, new or worsening dyspnea (signs of pulmonary toxicity)
- Severe nausea, vomiting, diarrhea, stomatitis, oral ulcers (signs of GI toxicity)
- Yellowing of skin or eyes, dark urine, abdominal pain (signs of hepatotoxicity)
- Skin rash, itching, peeling skin (severe dermatologic reactions)
- New or worsening neurological symptoms (headache, confusion, seizures - rare with low dose)
- Hair loss
Special Patient Groups
Pregnancy
Contraindicated in pregnancy (Pregnancy Category X). Methotrexate is a potent teratogen and abortifacient. It can cause severe birth defects (e.g., craniofacial, cardiovascular, limb abnormalities) and fetal death.
Trimester-Specific Risks:
First Trimester:
Highest risk of major congenital malformations and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, oligohydramnios, and other abnormalities.
Third Trimester:
Risk of fetal growth restriction, bone marrow suppression, and other adverse effects. May induce premature labor.
Lactation
Contraindicated during breastfeeding (Lactation Risk L5). Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant, including myelosuppression and growth inhibition. Discontinue nursing or discontinue the drug.
Infant Risk:
High risk of serious adverse effects (e.g., myelosuppression, immunosuppression, growth inhibition).
Pediatric Use
Used in pediatric patients for Juvenile Idiopathic Arthritis (JIA) and certain cancers. Dosing is weight or body surface area (BSA) based. Close monitoring for toxicity is essential, similar to adults. Long-term effects on growth and development should be considered.
Geriatric Use
Use with caution in elderly patients due to increased likelihood of decreased renal function, hepatic impairment, and concomitant diseases or medications. Dose adjustments may be necessary based on renal function. Elderly patients may be more susceptible to adverse effects, particularly myelosuppression and hepatotoxicity.
Clinical Information
Clinical Pearls
- Emphasize weekly dosing for RA/psoriasis; daily dosing is a common and potentially fatal error.
- Folic acid supplementation (e.g., 1 mg daily, or 5 mg once weekly 24 hours after methotrexate) is crucial to reduce common side effects like nausea, stomatitis, and liver enzyme elevations, without significantly impacting efficacy.
- Patients should be educated on the importance of avoiding alcohol due to the risk of hepatotoxicity.
- Regular monitoring of CBC, LFTs, and renal function is non-negotiable due to the narrow therapeutic index and potential for severe toxicities.
- Counsel patients on signs of infection and myelosuppression, and to report them immediately.
- Ensure patients understand the teratogenic risk and the need for strict contraception for both male and female patients of reproductive potential.
- Subcutaneous administration may improve bioavailability and reduce GI side effects compared to oral administration, especially at higher doses used in RA/psoriasis.
Alternative Therapies
- For Rheumatoid Arthritis: Hydroxychloroquine, Sulfasalazine, Leflunomide, Azathioprine, Cyclosporine, Biologic DMARDs (e.g., Adalimumab, Etanercept, Infliximab, Rituximab, Abatacept, Tocilizumab), Tofacitinib, Baricitinib, Upadacitinib.
- For Psoriasis: Cyclosporine, Acitretin, Biologic agents (e.g., Adalimumab, Etanercept, Infliximab, Ustekinumab, Secukinumab, Ixekizumab, Guselkumab), Apremilast, Phototherapy.
Cost & Coverage
Average Cost:
Varies widely, typically $100-$500+ per 4-pack of 17.5mg/0.4ml pre-filled syringes
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (Specialty/Non-Preferred Brand) for brand; Tier 1 or 2 for generic.
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.