Rasuvo 15mg/0.3ml 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, Folic acid antagonist
Pregnancy Category
Category X
FDA Approved
Jul 2014
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 suppress the overactive immune system. For cancer, it helps to stop cancer cells from growing. Rasuvo is a pre-filled pen that you inject under your skin, usually once a week.
How to Use This Medicine
Proper Administration of This Medication
To ensure safe and effective use, follow your doctor's instructions carefully. Read all accompanying information and adhere to the provided guidelines. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the abdominal area.
If you will be self-administering the injection, your doctor or nurse will provide personalized instruction on the proper technique. To avoid complications, do not inject the medication within 2 inches (5 cm) of the navel. Additionally, do not use the solution if it appears cloudy, is leaking, or contains particles.
Choose an injection site with healthy skin, avoiding areas that are irritated, tender, bruised, red, scaly, hard, scarred, or have stretch marks. If you are unsure whether a dose was successfully administered or experience difficulty with injection, consult your doctor or pharmacist before proceeding with another dose.
Safe Disposal and Handling
Dispose of used needles in a designated needle/sharp disposal container. Never reuse needles or other injection equipment. When the container is full, follow local regulations for proper disposal. If you have questions or concerns, consult your doctor or pharmacist.
Dosing and Administration Schedule
Your dosage and frequency of administration will be determined by your doctor, based on the specific health condition being treated. It is crucial to note that this medication should never be taken daily, except in certain cases of cancer treatment, as incorrect use can lead to fatal errors. Ensure you understand your prescribed dosage and administration schedule. If you are unsure, consult your doctor.
The method of administration may be adjusted based on blood work results, side effects, and the medication's efficacy. Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling procedures.
Hydration and Storage
Unless otherwise instructed by your doctor, drink plenty of non-caffeinated liquids. Store the medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Missed Dose
If you miss a dose, contact your doctor for guidance on the appropriate course of action.
To ensure safe and effective use, follow your doctor's instructions carefully. Read all accompanying information and adhere to the provided guidelines. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the abdominal area.
If you will be self-administering the injection, your doctor or nurse will provide personalized instruction on the proper technique. To avoid complications, do not inject the medication within 2 inches (5 cm) of the navel. Additionally, do not use the solution if it appears cloudy, is leaking, or contains particles.
Choose an injection site with healthy skin, avoiding areas that are irritated, tender, bruised, red, scaly, hard, scarred, or have stretch marks. If you are unsure whether a dose was successfully administered or experience difficulty with injection, consult your doctor or pharmacist before proceeding with another dose.
Safe Disposal and Handling
Dispose of used needles in a designated needle/sharp disposal container. Never reuse needles or other injection equipment. When the container is full, follow local regulations for proper disposal. If you have questions or concerns, consult your doctor or pharmacist.
Dosing and Administration Schedule
Your dosage and frequency of administration will be determined by your doctor, based on the specific health condition being treated. It is crucial to note that this medication should never be taken daily, except in certain cases of cancer treatment, as incorrect use can lead to fatal errors. Ensure you understand your prescribed dosage and administration schedule. If you are unsure, consult your doctor.
The method of administration may be adjusted based on blood work results, side effects, and the medication's efficacy. Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling procedures.
Hydration and Storage
Unless otherwise instructed by your doctor, drink plenty of non-caffeinated liquids. Store the medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Missed Dose
If you miss a dose, contact your doctor for guidance on the appropriate course of action.
Lifestyle & Tips
- Take exactly as prescribed, usually once weekly. Do NOT take daily for arthritis or psoriasis, as this can be fatal.
- Avoid alcohol consumption due to increased risk of liver damage.
- Avoid excessive sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Maintain good hydration, especially during and after administration.
- Discuss all other medications, including over-the-counter drugs, supplements, and herbal remedies, with your doctor or pharmacist, especially NSAIDs, aspirin, and certain antibiotics.
- Do not receive live vaccines (e.g., MMR, varicella, yellow fever) 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.
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 once weekly, adjusted to response and tolerability. Max 25 mg once weekly.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
7.5 mg once weekly, adjusted gradually to a maximum of 20 mg/week (or 25 mg/week in some cases) based on response and tolerability. Administered as a single dose or in 3 divided doses given at 12-hour intervals over 36 hours, once weekly.
Psoriasis:
Initial test dose of 5-10 mg parenterally, followed by 2.5 mg at 12-hour intervals for 3 doses, or 7.5 mg once weekly. Adjust to response, not to exceed 30 mg/week. Rasuvo is typically dosed once weekly.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly. Doses up to 30 mg/m² once weekly have been used, not to exceed 25 mg/week.
Adolescent:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly. Doses up to 30 mg/m² once weekly have been used, not to exceed 25 mg/week.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Consider 25% dose reduction or increased monitoring. Use with caution.
Moderate:
CrCl 51-60 mL/min: Consider 50% dose reduction. CrCl <50 mL/min: Generally contraindicated for non-oncologic indications due to risk of severe toxicity.
Severe:
CrCl <30 mL/min: Contraindicated for non-oncologic indications.
Dialysis:
Methotrexate is poorly dialyzable by standard hemodialysis. High-flux dialysis may remove some. Contraindicated for non-oncologic indications in patients requiring dialysis.
Hepatic Impairment:
Mild:
Use with extreme caution. Monitor liver function closely. Consider dose reduction.
Moderate:
Generally contraindicated for non-oncologic indications due to risk of severe hepatotoxicity.
Severe:
Contraindicated for non-oncologic indications.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase (DHFR). DHFR catalyzes the reduction of dihydrofolate to tetrahydrofolate, a critical step in DNA synthesis, repair, and cellular replication. By inhibiting DHFR, methotrexate interferes with the synthesis of purine nucleotides and thymidylate, thereby inhibiting DNA and RNA synthesis and cell proliferation. In rheumatoid arthritis and psoriasis, its mechanism is thought to involve immunosuppressive and anti-inflammatory effects, possibly through inhibition of lymphocyte proliferation, inhibition of polymorphonuclear leukocyte chemotaxis, and effects on adenosine metabolism.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80-90% (subcutaneous), variable with oral doses >15 mg/m².
Tmax:
1-2 hours (subcutaneous).
FoodEffect:
Not applicable for subcutaneous administration; oral absorption may be delayed by food.
Distribution:
Vd:
0.4-0.8 L/kg (initial phase); higher with high doses.
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at conventional doses; significant at high doses (e.g., for CNS malignancies).
Elimination:
HalfLife:
3-10 hours (low dose); 8-15 hours (high dose). Prolonged in renal impairment or third-space fluid accumulation.
Clearance:
Primarily renal clearance.
ExcretionRoute:
Renal (50-90% unchanged), small amount via biliary excretion.
Unchanged:
50-90% (renal excretion).
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial effects, up to 12 weeks for maximal benefit.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 4-12 weeks.
DurationOfAction:
Effects persist as long as therapy is continued; cessation leads to return of disease activity.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe or fatal toxic reactions. Patients should be closely monitored. Deaths have been reported.
1. Bone Marrow Suppression: May occur abruptly.
2. Renal Toxicity: Excretion is primarily renal; impaired renal function will increase methotrexate levels and toxicity.
3. Hepatotoxicity: Liver fibrosis and cirrhosis may occur.
4. Pulmonary Toxicity: Acute or chronic interstitial pneumonitis, potentially fatal, may occur at any time during therapy.
5. Gastrointestinal Toxicity: Diarrhea, stomatitis, mucositis, and hemorrhagic enteritis may occur.
6. Dermatologic Reactions: Severe, potentially fatal, dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome) have been reported.
7. Opportunistic Infections: Increased risk of opportunistic infections, including Pneumocystis jirovecii pneumonia.
8. Tumor Lysis Syndrome: May occur in patients with rapidly growing tumors.
9. Secondary Malignancy: Lymphoma and other malignancies have been reported.
10. Embryo-Fetal Toxicity: Methotrexate can cause fetal death or teratogenic effects when administered to a pregnant woman. Contraindicated in pregnant women with non-oncologic diseases.
11. 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 methotrexate toxicity. Use with caution with low-dose methotrexate.
1. Bone Marrow Suppression: May occur abruptly.
2. Renal Toxicity: Excretion is primarily renal; impaired renal function will increase methotrexate levels and toxicity.
3. Hepatotoxicity: Liver fibrosis and cirrhosis may occur.
4. Pulmonary Toxicity: Acute or chronic interstitial pneumonitis, potentially fatal, may occur at any time during therapy.
5. Gastrointestinal Toxicity: Diarrhea, stomatitis, mucositis, and hemorrhagic enteritis may occur.
6. Dermatologic Reactions: Severe, potentially fatal, dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome) have been reported.
7. Opportunistic Infections: Increased risk of opportunistic infections, including Pneumocystis jirovecii pneumonia.
8. Tumor Lysis Syndrome: May occur in patients with rapidly growing tumors.
9. Secondary Malignancy: Lymphoma and other malignancies have been reported.
10. Embryo-Fetal Toxicity: Methotrexate can cause fetal death or teratogenic effects when administered to a pregnant woman. Contraindicated in pregnant women with non-oncologic diseases.
11. 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 methotrexate toxicity. Use with caution with low-dose methotrexate.
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:
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 stomach 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 yellow skin and 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, facial drooping, or blurred vision.
Headache.
Neck stiffness.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Decreased appetite.
Hair loss.
Dizziness, fatigue, or weakness.
Stomach pain.
Common cold symptoms.
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
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 stomach 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 yellow skin and 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, facial drooping, or blurred vision.
Headache.
Neck stiffness.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Decreased appetite.
Hair loss.
Dizziness, fatigue, or weakness.
Stomach pain.
Common cold symptoms.
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, sore throat, or other signs of infection.
- Unusual bleeding or bruising.
- Extreme tiredness or weakness.
- Shortness of breath, dry cough, or chest pain.
- Severe nausea, vomiting, diarrhea, or mouth sores.
- Yellowing of the skin or eyes (jaundice).
- Severe skin rash, blistering, or peeling.
- Swelling in the legs or ankles.
- Dark urine or pale stools.
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 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 your doctor to determine the necessary duration for avoiding breast-feeding after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Do not initiate, stop, or modify the dose 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 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 your doctor to determine the necessary duration for avoiding breast-feeding after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Do not initiate, stop, or modify the dose 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 operating a vehicle or engaging in activities that require alertness, wait until you understand how this drug affects you. Be aware that you may have a higher risk of developing an infection. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Due to the potential for increased bleeding, exercise caution to prevent 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 the risk of infection when taken with this medication. Additionally, discuss the consumption of alcohol with your doctor.
You may be more susceptible to sunburn; therefore, avoid exposure to direct sunlight, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to shield yourself from the sun. Continue sun protection as advised by your doctor.
Notify your doctor if you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or abnormal thirst. 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, 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 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 operating a vehicle or engaging in activities that require alertness, wait until you understand how this drug affects you. Be aware that you may have a higher risk of developing an infection. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Due to the potential for increased bleeding, exercise caution to prevent 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 the risk of infection when taken with this medication. Additionally, discuss the consumption of alcohol with your doctor.
You may be more susceptible to sunburn; therefore, avoid exposure to direct sunlight, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to shield yourself from the sun. Continue sun protection as advised by your doctor.
Notify your doctor if you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or abnormal thirst. 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, 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 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, leading to infection, bleeding, fatigue)
- Severe mucositis (mouth sores, GI inflammation)
- Severe liver damage
- Kidney failure
What to Do:
Seek immediate medical attention. The antidote is leucovorin (folinic acid), which helps to reverse the toxic effects of methotrexate. Call 1-800-222-1222 (Poison Control Center) or go to the nearest emergency room.
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Trimethoprim/sulfamethoxazole (increased methotrexate levels and toxicity)
- Probenecid (decreased renal excretion of methotrexate)
- NSAIDs/Salicylates (high-dose methotrexate; may increase methotrexate levels and toxicity)
- Retinoids (e.g., acitretin, etretinate) (increased risk of hepatotoxicity)
Major Interactions
- NSAIDs/Salicylates (low-dose methotrexate; increased methotrexate levels and toxicity, especially myelosuppression and nephrotoxicity)
- Proton Pump Inhibitors (PPIs) (e.g., omeprazole, pantoprazole) (may increase methotrexate levels, especially at higher methotrexate doses)
- Folic acid antagonists (e.g., pyrimethamine, trimethoprim) (additive antifolate effects, increased toxicity)
- Sulfonamides (e.g., sulfasalazine) (increased methotrexate levels and toxicity)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Theophylline (decreased theophylline clearance)
- Other hepatotoxic drugs (e.g., azathioprine, leflunomide, retinoids, alcohol) (additive hepatotoxicity)
- Nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, cisplatin) (increased risk of methotrexate toxicity due to impaired renal clearance)
- Penicillins (decreased renal clearance of methotrexate)
- Ciprofloxacin (decreased renal clearance of methotrexate)
Moderate Interactions
- Oral antibiotics (e.g., tetracyclines, chloramphenicol) (may alter gut flora, affecting methotrexate absorption/enterohepatic recirculation)
- Cholestyramine (may interfere with methotrexate absorption)
- L-asparaginase (antagonizes methotrexate effect if given concurrently)
- Nitrous oxide (may potentiate methotrexate toxicity by inhibiting methionine synthase)
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 cytopenias. Methotrexate can cause severe myelosuppression.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To establish baseline liver function. Methotrexate is hepatotoxic and can cause fibrosis and cirrhosis.
Timing: Prior to initiation of therapy.
Renal Function Tests (serum creatinine, BUN, estimated GFR)
Rationale: To establish baseline renal function. Methotrexate is primarily renally eliminated, and impaired renal function increases toxicity.
Timing: Prior to initiation of therapy.
Chest X-ray
Rationale: To establish baseline pulmonary status and rule out pre-existing lung disease. Methotrexate can cause acute or chronic interstitial pneumonitis.
Timing: Prior to initiation of therapy.
Hepatitis B and C serology
Rationale: To screen for chronic viral hepatitis, which may increase risk of methotrexate-induced hepatotoxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Weekly for the first month, then every 2-4 weeks for the next 2 months, then monthly or every 1-2 months thereafter.
Target: Maintain within normal limits; monitor for significant drops.
Action Threshold: Hold methotrexate if WBC <3,000/mm³, ANC <1,500/mm³, or platelets <100,000/mm³.
Liver Function Tests (AST, ALT, albumin)
Frequency: Every 2-4 weeks for the first 2-3 months, then monthly or every 1-2 months thereafter.
Target: Maintain within normal limits or stable baseline.
Action Threshold: Hold methotrexate if AST/ALT persistently >2-3 times ULN, or if albumin drops significantly.
Renal Function Tests (serum creatinine, BUN)
Frequency: Monthly or every 1-2 months, or more frequently if clinically indicated.
Target: Maintain within normal limits or stable baseline.
Action Threshold: Hold methotrexate if creatinine increases significantly or GFR decreases.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising (petechiae, purpura)
- Fatigue, weakness, pallor (anemia)
- Shortness of breath, cough (especially dry, non-productive), chest pain (pneumonitis)
- Nausea, vomiting, diarrhea, abdominal pain
- Oral sores, mucositis
- Yellowing of skin or eyes, dark urine (hepatotoxicity)
- Skin rash, itching, peeling skin
- Hair loss
- Neurological symptoms (headache, confusion, seizures - rare with low dose)
Special Patient Groups
Pregnancy
Contraindicated in pregnant women with non-oncologic diseases (e.g., rheumatoid arthritis, psoriasis) due to significant risk of fetal death or severe teratogenic effects. For oncologic indications, the benefits may outweigh the risks in life-threatening situations, but careful counseling is essential.
Trimester-Specific Risks:
First Trimester:
Highest risk of major congenital malformations (e.g., craniofacial, limb, and skeletal abnormalities) and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, hydrocephalus, and other abnormalities.
Third Trimester:
Risk of fetal growth restriction and potential for neonatal toxicity if exposed near term.
Lactation
Contraindicated during breastfeeding. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant, including myelosuppression and growth inhibition.
Infant Risk:
High risk (L5).
Pediatric Use
Used for polyarticular juvenile idiopathic arthritis (pJIA). Dosing is weight/surface area-based. Close monitoring for toxicity is essential, similar to adults. Risk of hepatotoxicity and myelosuppression is present.
Geriatric Use
Use with caution in elderly patients due to increased likelihood of decreased renal and hepatic function, and potential for concomitant medications that may interact. Dose adjustments may be necessary based on renal function. Increased susceptibility to myelosuppression and other toxicities.
Clinical Information
Clinical Pearls
- Methotrexate is a once-weekly medication for RA/psoriasis/pJIA. Taking it daily for these conditions can be fatal due to cumulative toxicity.
- Folic acid supplementation (e.g., 1-5 mg once weekly, taken 24-48 hours after methotrexate dose) is often prescribed to reduce common side effects like nausea, mucositis, and liver enzyme elevations, without significantly reducing efficacy.
- Subcutaneous administration (like Rasuvo) often has better bioavailability and may cause less gastrointestinal upset compared to oral methotrexate, especially at higher doses.
- Patients must be educated on the importance of regular blood tests (CBC, LFTs, renal function) and reporting any new symptoms immediately.
- Avoid alcohol completely while on methotrexate due to the significant risk of liver damage.
- Ensure patients understand the severe risks of pregnancy and the need for strict contraception for both male and female patients.
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-23 inhibitors (e.g., guselkumab).
- Targeted Synthetic DMARDs (tsDMARDs) / JAK inhibitors: Tofacitinib, Baricitinib, Upadacitinib.
- Systemic retinoids (e.g., acitretin) for psoriasis.
- Phototherapy for psoriasis.
Cost & Coverage
Average Cost:
Varies significantly by pharmacy and insurance plan. Rasuvo 15mg/0.3ml 4-pack can range from $1,000 - $2,000+. per 4 pens
Generic Available:
Yes
Insurance Coverage:
Specialty Tier or Non-Preferred Brand Tier for brand-name Rasuvo; often Preferred Brand or Generic Tier for generic methotrexate.
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, including the amount taken and the time it happened, to ensure you receive the best possible care.