Rasuvo 20mg/0.4ml Pf Inj, 4 Pens
WARNING: Severe side effects like bone marrow problems, liver problems, lung problems, and infections can happen with this drug. Some side effects may not go away and can be deadly. You must talk with the doctor about the risks of this drug. This drug may cause kidney problems in some patients. Talk with the doctor.Regular blood work and other exams will need to be done to check for side effects. Follow what the doctor has told you. Tell your doctor if you have kidney problems or extra fluid around your stomach area or lungs. The chance of side effects may be raised.Talk with your doctor if you are getting radiation. There may be more chance of harm to tissue and bone.New types of cancer have happened in people taking this drug. If you have questions, talk with the doctor.It is common to have diarrhea, upset stomach, throwing up, or mouth sores with this drug. However, sometimes these may be signs of severe and sometimes deadly stomach or bowel problems. Tell your doctor if you get any new or worsening signs. You may need to stop this drug.Severe skin reactions have happened with this drug. These have included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and other severe skin reactions. Sometimes these have been deadly. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin; other skin irritation (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.Very bad and sometimes deadly bone marrow problems and stomach or bowel problems have happened when this drug was taken with nonsteroidal anti-inflammatory drug (NSAIDs) like ibuprofen or naproxen.Not all methotrexate products are used to treat cancer. Talk with the doctor.This drug may cause harm to an unborn baby or loss of an unborn baby. A pregnancy test will be done before you start this drug to show that you are NOT pregnant.If you or your sex partner may become pregnant, you must use birth control while taking this drug and for some time after the last dose. Ask your doctor how long to use birth control. If you or your sex partner gets pregnant, call your doctor right away.Do not take if you are pregnant.This drug must only be used when other drugs cannot be used or have not worked. Talk with your doctor to be sure that the benefits of this drug are more than the risks. @ COMMON USES: It is used to treat some types of arthritis.It is used to treat some types of psoriasis.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antirheumatic, Antineoplastic, Immunosuppressant
Pharmacologic Class
Antimetabolite, Folate Antagonist
Pregnancy Category
Category X
FDA Approved
Jul 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Methotrexate is a medication used to treat certain types of cancer, severe psoriasis, and severe rheumatoid arthritis. For conditions like rheumatoid arthritis and psoriasis, it works by reducing inflammation and slowing down the overactive immune system. It is usually taken once a week, not daily, to prevent serious side effects.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before proceeding with another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other 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 dosage and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use of this medication can lead to serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Your doctor may adjust your dosage based on blood work results, side effects, and the medication's effectiveness.
Handling and Storage
Handle this medication with care. Consult your doctor or pharmacist for guidance on proper handling procedures.
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. Avoid storing in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor for instructions on what to do next.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before proceeding with another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other 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 dosage and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use of this medication can lead to serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Your doctor may adjust your dosage based on blood work results, side effects, and the medication's effectiveness.
Handling and Storage
Handle this medication with care. Consult your doctor or pharmacist for guidance on proper handling procedures.
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. Avoid storing in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor for instructions on what to do next.
Lifestyle & Tips
- Take exactly as prescribed, usually once a week on the same day. Do NOT take daily for rheumatoid arthritis or psoriasis.
- Take folic acid or folinic acid as directed by your doctor to help reduce side effects.
- Avoid alcohol completely while on methotrexate 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 (e.g., MMR, varicella, nasal flu vaccine) while on methotrexate.
- Use effective contraception during treatment and for at least 6 months after stopping for both men and women, as it can cause severe birth defects.
- Inform all healthcare providers, including dentists, that you are taking methotrexate.
Available Forms & Alternatives
Available Strengths:
- Rasuvo 10mg/0.2ml Pf Inj, 4 Pens
- Rasuvo 12.5mg/0.25ml Pf Inj, 4 Pens
- Rasuvo 22.5mg/0.45ml Pf Inj, 4 Pens
- Rasuvo 25mg/0.5ml Pf Inj, 4 Pens
- Rasuvo 15mg/0.3ml Pf Inj, 4 Pens
- Rasuvo 17.5mg/0.35ml Pf Inj, 4 Pens
- Rasuvo 20mg/0.4ml Pf Inj, 4 Pens
- Rasuvo 30mg/0.6ml Pf Inj, 4 Pens
- Rasuvo 7.5mg/0.15ml Pf Inj, 4 Pens
- Rasuvo 15mg Inj, 0.3ml
- Rasuvo 17.5mg Inj, 0.35ml
- Rasuvo 20mg Inj, 0.4ml
- Rasuvo 7.5mg Inj, 0.15ml
Dosing & Administration
Adult Dosing
Standard Dose:
For Rheumatoid Arthritis/Psoriasis: 7.5 mg to 20 mg once weekly, administered subcutaneously.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis (RA):
Initial: 7.5 mg once weekly. May gradually increase to a maximum of 20 mg once weekly. Some patients may require up to 25 mg once weekly.
Psoriasis:
Initial: 10 mg to 25 mg once weekly, administered as a single dose or in 3 divided doses given at 12-hour intervals over 36 hours. Doses should be adjusted to achieve optimal clinical response, not to exceed 30 mg per week.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Doses up to 30 mg/m² once weekly have been used in some cases.
Adolescent:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Doses up to 30 mg/m² once weekly have been used in some cases.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 51-80 mL/min: Reduce dose by 25%. Monitor closely.
Moderate:
CrCl 30-50 mL/min: Reduce dose by 50%. Monitor closely. Consider alternative therapy.
Severe:
CrCl <30 mL/min: Contraindicated for non-oncologic indications due to significant risk of toxicity. For oncologic indications, significant dose reduction or avoidance is necessary.
Dialysis:
Methotrexate is poorly dialyzable by standard hemodialysis. High-flux hemodialysis may remove some drug. Avoid use in patients on dialysis for non-oncologic indications. For oncologic indications, specific protocols for post-dialysis dosing and leucovorin rescue are required.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function tests frequently.
Moderate:
Use with extreme caution. Consider dose reduction or avoidance, especially if bilirubin >3-5 mg/dL. Increased risk of hepatotoxicity.
Severe:
Generally contraindicated in patients with significant hepatic impairment (e.g., cirrhosis, ascites, or recent hepatitis).
Confidence:
Medium
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase (DHFR), an enzyme essential for DNA synthesis, repair, and cellular replication. By inhibiting DHFR, methotrexate prevents the reduction of dihydrofolate to tetrahydrofolate, a critical cofactor for purine and pyrimidine synthesis. This leads to inhibition of DNA, RNA, and protein synthesis. In rheumatoid arthritis and psoriasis, its mechanism of action is thought to involve immunosuppressive and anti-inflammatory effects, possibly through inhibition of lymphocyte proliferation, inhibition of polymorphonuclear leukocyte chemotaxis, and adenosine-mediated anti-inflammatory effects.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV).
Tmax:
Subcutaneous: 1-2 hours.
FoodEffect:
Not significantly affected by food when administered subcutaneously.
Distribution:
Vd:
0.4-0.8 L/kg (initial), 0.2-0.6 L/kg (steady state).
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited penetration into the CNS at standard doses; higher doses (e.g., intrathecal) are required for therapeutic CNS concentrations.
Elimination:
HalfLife:
3-10 hours (low dose, non-oncologic); 8-15 hours (high dose, oncologic).
Clearance:
Primarily renal clearance via glomerular filtration and active tubular secretion.
ExcretionRoute:
Approximately 80-90% excreted unchanged in urine within 24 hours.
Unchanged:
80-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial effects, 4-12 weeks for maximal effect.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 4-12 weeks.
DurationOfAction:
Effects persist as long as therapy is continued; cessation leads to gradual loss of effect.
Safety & Warnings
BLACK BOX WARNING
Methotrexate has several Black Box Warnings:
1. **Bone Marrow Suppression:** May occur abruptly and lead to severe or fatal infections. Monitor CBCs frequently.
2. **Renal Impairment:** Excretion is primarily renal. Impaired renal function will increase methotrexate levels and toxicity. Use with extreme caution or avoid in patients with renal impairment.
3. **Hepatotoxicity:** May cause acute and chronic hepatotoxicity, including fibrosis and cirrhosis. Liver biopsies are often recommended for patients with psoriasis on long-term therapy. Monitor LFTs frequently.
4. **Pulmonary Toxicity:** Acute or chronic interstitial pneumonitis, potentially fatal, may occur at any time during therapy. Symptoms include dry cough, fever, dyspnea. Requires immediate discontinuation.
5. **Gastrointestinal Toxicity:** Diarrhea, stomatitis, mucositis, and ulcerative stomatitis may occur. Severe GI toxicity can lead to hemorrhagic enteritis and death. Discontinue if severe GI symptoms occur.
6. **Malignant Lymphomas:** May occur, often reversible upon discontinuation of methotrexate.
7. **Tumor Lysis Syndrome:** May occur in patients with rapidly growing tumors.
8. **Dermatologic Reactions:** Severe, potentially fatal dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome) have been reported.
9. **Opportunistic Infections:** Increased risk of opportunistic infections, including Pneumocystis jirovecii pneumonia.
10. **Concomitant Use with NSAIDs:** Concomitant administration of NSAIDs with high-dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in severe, sometimes fatal, toxicities. Caution with low-dose methotrexate.
11. **Embryo-Fetal Toxicity:** Methotrexate can cause fetal death or severe birth defects. Contraindicated in pregnant women with non-oncologic diseases. Women of childbearing potential should be advised of the potential risks and use effective contraception.
1. **Bone Marrow Suppression:** May occur abruptly and lead to severe or fatal infections. Monitor CBCs frequently.
2. **Renal Impairment:** Excretion is primarily renal. Impaired renal function will increase methotrexate levels and toxicity. Use with extreme caution or avoid in patients with renal impairment.
3. **Hepatotoxicity:** May cause acute and chronic hepatotoxicity, including fibrosis and cirrhosis. Liver biopsies are often recommended for patients with psoriasis on long-term therapy. Monitor LFTs frequently.
4. **Pulmonary Toxicity:** Acute or chronic interstitial pneumonitis, potentially fatal, may occur at any time during therapy. Symptoms include dry cough, fever, dyspnea. Requires immediate discontinuation.
5. **Gastrointestinal Toxicity:** Diarrhea, stomatitis, mucositis, and ulcerative stomatitis may occur. Severe GI toxicity can lead to hemorrhagic enteritis and death. Discontinue if severe GI symptoms occur.
6. **Malignant Lymphomas:** May occur, often reversible upon discontinuation of methotrexate.
7. **Tumor Lysis Syndrome:** May occur in patients with rapidly growing tumors.
8. **Dermatologic Reactions:** Severe, potentially fatal dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome) have been reported.
9. **Opportunistic Infections:** Increased risk of opportunistic infections, including Pneumocystis jirovecii pneumonia.
10. **Concomitant Use with NSAIDs:** Concomitant administration of NSAIDs with high-dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in severe, sometimes fatal, toxicities. Caution with low-dose methotrexate.
11. **Embryo-Fetal Toxicity:** Methotrexate can cause fetal death or severe birth defects. Contraindicated in pregnant women with non-oncologic diseases. Women of childbearing potential should be advised of the potential risks and use effective contraception.
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 or seek medical attention immediately:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or Breathing Problems: Shortness of breath, breathing difficulties, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other 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, facial drooping, or blurred vision.
Other Concerning Symptoms: Headache, neck stiffness.
Common Side Effects
Most medications can cause side effects, but many people experience none or only mild symptoms. 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
Reporting Side Effects
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 or seek medical attention immediately:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or Breathing Problems: Shortness of breath, breathing difficulties, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other 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, facial drooping, or blurred vision.
Other Concerning Symptoms: Headache, neck stiffness.
Common Side Effects
Most medications can cause side effects, but many people experience none or only mild symptoms. 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
Reporting Side Effects
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:
- Unexplained fever, chills, sore throat, or signs of infection.
- Unusual bleeding or bruising.
- Severe fatigue or weakness.
- Yellowing of skin or eyes (jaundice), dark urine, severe stomach pain (signs of liver problems).
- Shortness of breath, dry cough, chest pain (signs of lung problems).
- Severe mouth sores, painful swallowing, or severe diarrhea.
- Severe skin rash or blistering.
- Swelling in legs or ankles, changes in urination (signs of kidney problems).
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 your doctor to determine the necessary duration of breast-feeding avoidance after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Do not initiate, stop, or modify the dosage of any medication without first consulting your doctor to confirm that it is safe to do so.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A 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 your doctor to determine the necessary duration of breast-feeding avoidance after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Do not initiate, stop, or modify the dosage of any medication without first consulting your doctor to confirm that it is safe to do so.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before engaging in activities that require your full attention, such as driving, wait until you understand how this drug affects you. Be aware that you may have a higher risk of developing infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or the flu.
Due to the potential for increased bleeding, exercise caution to avoid injuries. Use a soft-bristled toothbrush and an electric razor for shaving.
Consult your doctor before receiving any vaccinations, 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.
You may be more susceptible to sunburn; therefore, 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. 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. This medication has been associated with severe nervous system problems, which can be temporary or long-lasting and may worsen over time. In some cases, these problems may not resolve and can be fatal. If you have 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 prone to side effects.
This drug may impact 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 engaging in activities that require your full attention, such as driving, wait until you understand how this drug affects you. Be aware that you may have a higher risk of developing infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or the flu.
Due to the potential for increased bleeding, exercise caution to avoid injuries. Use a soft-bristled toothbrush and an electric razor for shaving.
Consult your doctor before receiving any vaccinations, 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.
You may be more susceptible to sunburn; therefore, 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. 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. This medication has been associated with severe nervous system problems, which can be temporary or long-lasting and may worsen over time. In some cases, these problems may not resolve and can be fatal. If you have 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 prone to side effects.
This drug may impact 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 bone marrow suppression (low blood counts, infection, bleeding)
- Severe mucositis (mouth sores, GI ulcers)
- Severe liver damage
- Kidney failure
What to Do:
Immediately contact emergency services or a poison control center (1-800-222-1222). Leucovorin rescue is the primary antidote and must be administered promptly. Glucarpidase may be used in cases of delayed methotrexate clearance despite leucovorin.
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Trimethoprim/Sulfamethoxazole (increased myelosuppression)
- Probenecid (decreased renal excretion of methotrexate)
- NSAIDs (high-dose methotrexate, risk of severe toxicity)
- Salicylates (high-dose methotrexate, risk of severe toxicity)
Major Interactions
- NSAIDs (low-dose methotrexate, increased methotrexate levels and toxicity)
- Salicylates (low-dose methotrexate, increased methotrexate levels and toxicity)
- Proton Pump Inhibitors (PPIs) (e.g., omeprazole, pantoprazole - may increase methotrexate levels)
- Penicillins (e.g., amoxicillin - may decrease renal clearance of methotrexate)
- Sulfonamides (e.g., sulfasalazine - increased risk of myelosuppression)
- Folic acid antagonists (e.g., pyrimethamine - increased toxicity)
- Other hepatotoxic agents (e.g., azathioprine, retinoids, alcohol - increased risk of hepatotoxicity)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Theophylline (decreased theophylline clearance)
- Cisplatin (increased methotrexate toxicity)
Moderate Interactions
- Oral antibiotics (e.g., tetracyclines, chloramphenicol - may alter gut flora, affecting methotrexate absorption/metabolism)
- Colchicine (increased risk of myelosuppression)
- Hydroxychloroquine (may increase methotrexate levels)
- Cyclosporine (may increase methotrexate levels and cyclosporine levels)
- Leflunomide (increased risk of hepatotoxicity and myelosuppression)
- Nitrous oxide (may potentiate methotrexate toxicity by inhibiting methionine synthase)
Minor Interactions
- Not specifically categorized as minor for significant clinical impact, but caution with any new medication.
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, alkaline phosphatase, bilirubin, albumin
Rationale: To establish baseline hepatic function and detect pre-existing liver disease.
Timing: Prior to initiation of therapy.
Renal Function Tests (RFTs) including serum creatinine, BUN, eGFR
Rationale: To establish baseline renal function, as methotrexate is primarily renally eliminated.
Timing: Prior to initiation of therapy.
Chest X-ray
Rationale: To rule out pre-existing pulmonary disease, especially if there are respiratory symptoms, due to risk of methotrexate pneumonitis.
Timing: Prior to initiation of therapy.
Hepatitis B and C serology
Rationale: To screen for chronic viral hepatitis, which can increase risk of hepatotoxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: Within normal limits; Platelets >100,000/mm³, WBC >3,000/mm³.
Action Threshold: Hold dose if significant drop in cell counts (e.g., WBC <3,000/mm³, platelets <100,000/mm³), investigate cause, consider dose reduction or discontinuation.
Liver Function Tests (LFTs) including AST, ALT, alkaline phosphatase, bilirubin, albumin
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: Within normal limits or stable.
Action Threshold: Hold dose if AST/ALT >2-3 times upper limit of normal (ULN) on two consecutive measurements, or if albumin drops significantly. Consider liver biopsy if persistent abnormalities or cumulative dose concerns.
Renal Function Tests (RFTs) including serum creatinine, BUN, eGFR
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: Within normal limits or stable.
Action Threshold: Hold dose if creatinine increases by >50% from baseline or if eGFR drops significantly. Adjust dose or discontinue based on severity.
Symptom Monitoring
- Fever, chills, sore throat, easy bruising or bleeding (myelosuppression)
- Unusual fatigue, weakness, yellowing of skin/eyes, dark urine, abdominal pain (hepatotoxicity)
- Shortness of breath, dry cough, chest pain (pneumonitis)
- Mouth sores, painful swallowing, diarrhea (mucositis, GI toxicity)
- Skin rash, hair loss
- Nausea, vomiting, abdominal discomfort
Special Patient Groups
Pregnancy
Methotrexate is contraindicated in pregnant women with non-oncologic diseases (e.g., RA, psoriasis) due to its teratogenic effects. It can cause fetal death or severe birth defects.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, limb, and skeletal abnormalities) and fetal death.
Second Trimester:
Risk of fetal growth restriction and other abnormalities.
Third Trimester:
Risk of fetal growth restriction and other abnormalities.
Lactation
Methotrexate is excreted into breast milk and is contraindicated during breastfeeding due to the potential for serious adverse reactions in the breastfed infant, including myelosuppression and growth inhibition.
Infant Risk:
High risk of serious adverse effects.
Pediatric Use
Methotrexate is used in pediatric patients for polyarticular juvenile idiopathic arthritis (pJIA) and certain cancers. Dosing is typically weight- or body surface area-based. Close monitoring for toxicity is essential, similar to adults. Long-term effects on growth and development should be considered.
Geriatric Use
Elderly patients may have reduced renal function, which can lead to increased methotrexate levels and a higher risk of toxicity (e.g., myelosuppression, hepatotoxicity). Dose adjustments based on renal function are often necessary. Close monitoring is crucial.
Clinical Information
Clinical Pearls
- Methotrexate for RA/psoriasis is dosed **once weekly**, not daily. Daily dosing for these indications can be fatal.
- Folic acid supplementation (e.g., 1-5 mg once weekly, 24-48 hours after methotrexate dose) is commonly used to reduce side effects like mucositis, GI upset, and liver enzyme elevations, without significantly compromising efficacy.
- Ensure patients are well-hydrated to promote renal excretion and reduce the risk of nephrotoxicity.
- Patients should be educated on the importance of avoiding alcohol due to the risk of hepatotoxicity.
- Regular and diligent monitoring of CBC, LFTs, and renal function is paramount due to the narrow therapeutic index and potential for severe toxicities.
- Prompt recognition and management of methotrexate toxicity (e.g., with leucovorin rescue) are critical.
- Counsel patients on the need for effective contraception for both males and females during and for a specified period after treatment.
Alternative Therapies
- Other conventional synthetic DMARDs (csDMARDs) for RA/psoriasis: Hydroxychloroquine, Sulfasalazine, Leflunomide.
- Biologic DMARDs (bDMARDs) for RA/psoriasis: TNF inhibitors (e.g., Adalimumab, Etanercept, Infliximab), IL-6 inhibitors (e.g., Tocilizumab), T-cell costimulation modulators (e.g., Abatacept), B-cell depleting agents (e.g., Rituximab), IL-17 inhibitors (e.g., Secukinumab), IL-12/23 inhibitors (e.g., Ustekinumab).
- Targeted Synthetic DMARDs (tsDMARDs) / JAK inhibitors for RA/psoriasis: Tofacitinib, Baricitinib, Upadacitinib.
- Other systemic agents for psoriasis: Cyclosporine, Acitretin.
Cost & Coverage
Average Cost:
Varies widely, typically $100-$500 for 4 pens (20mg/0.4ml) per 4 pens
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (Brand-name), Tier 1 (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 this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it occurred.