Rasuvo 7.5mg Inj, 0.15ml
WARNING: Severe side effects like bone marrow problems, liver problems, lung problems, and infections can happen with this drug. Some side effects may not go away and can be deadly. You must talk with the doctor about the risks of this drug. This drug may cause kidney problems in some patients. Talk with the doctor.Regular blood work and other exams will need to be done to check for side effects. Follow what the doctor has told you. Tell your doctor if you have kidney problems or extra fluid around your stomach area or lungs. The chance of side effects may be raised.Talk with your doctor if you are getting radiation. There may be more chance of harm to tissue and bone.New types of cancer have happened in people taking this drug. If you have questions, talk with the doctor.It is common to have diarrhea, upset stomach, throwing up, or mouth sores with this drug. However, sometimes these may be signs of severe and sometimes deadly stomach or bowel problems. Tell your doctor if you get any new or worsening signs. You may need to stop this drug.Severe skin reactions have happened with this drug. These have included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and other severe skin reactions. Sometimes these have been deadly. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin; other skin irritation (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.Very bad and sometimes deadly bone marrow problems and stomach or bowel problems have happened when this drug was taken with nonsteroidal anti-inflammatory drug (NSAIDs) like ibuprofen or naproxen.Not all methotrexate products are used to treat cancer. Talk with the doctor.This drug may cause harm to an unborn baby or loss of an unborn baby. A pregnancy test will be done before you start this drug to show that you are NOT pregnant.If you or your sex partner may become pregnant, you must use birth control while taking this drug and for some time after the last dose. Ask your doctor how long to use birth control. If you or your sex partner gets pregnant, call your doctor right away.Do not take if you are pregnant.This drug must only be used when other drugs cannot be used or have not worked. Talk with your doctor to be sure that the benefits of this drug are more than the risks. @ COMMON USES: It is used to treat some types of arthritis.It is used to treat some types of psoriasis.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antimetabolite, Antirheumatic, Antineoplastic
Pharmacologic Class
Folic acid antagonist; Dihydrofolate reductase inhibitor
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. It works by slowing down the growth of certain cells in the body, including cancer cells, and by reducing inflammation in conditions like arthritis and psoriasis. For arthritis and psoriasis, it is typically taken once a week, not daily.
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 you have administered the dose correctly or experience difficulty with injection, 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 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 result in serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling.
Additional Recommendations
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light and moisture. Do not store in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor to determine the best course of action.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether you have administered the dose correctly or experience difficulty with injection, 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 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 result in serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling.
Additional Recommendations
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light and moisture. Do not store in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Take exactly as prescribed, usually once a week on the same day. Do NOT take daily for arthritis or psoriasis.
- Take folic acid supplementation as directed by your doctor to reduce side effects (e.g., mouth sores, nausea).
- Avoid or limit alcohol consumption due to increased risk of liver damage.
- Avoid excessive sun exposure and use sunscreen/protective clothing as methotrexate can increase sun sensitivity.
- Maintain good hydration, especially during high-dose therapy.
- Avoid live vaccines while on methotrexate therapy.
- Report any signs of infection (fever, chills, sore throat) immediately.
- Use effective contraception during and for a specified period after treatment (for both men and women) due to risk of birth defects.
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, administered subcutaneously.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
Initial: 7.5 mg once weekly, subcutaneously. May gradually increase to 20 mg once weekly. Doses >20 mg/week may be associated with increased toxicity.
Psoriasis:
Initial: 10-25 mg once weekly, subcutaneously, as a single dose or divided into 3 doses given at 12-hour intervals over 36 hours. Dosage should be adjusted to achieve optimal clinical response, not to exceed 30 mg/week.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, subcutaneously. Doses up to 30 mg/m² once weekly have been used.
Adolescent:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, subcutaneously. Doses up to 30 mg/m² once weekly have been used. For other indications (e.g., cancer), dosing is highly individualized based on protocol.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 51-80 mL/min: Consider 25% dose reduction or close monitoring.
Moderate:
CrCl 10-50 mL/min: Reduce dose by 50% or avoid use for non-oncologic indications. Close monitoring of methotrexate levels is recommended for oncologic use.
Severe:
CrCl <10 mL/min: Contraindicated for non-oncologic indications. For oncologic use, generally contraindicated or requires significant dose reduction and close monitoring of methotrexate levels.
Dialysis:
Methotrexate is poorly dialyzable by standard hemodialysis. High-flux hemodialysis may remove some. Avoid use or use with extreme caution and close monitoring of levels.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function tests closely.
Moderate:
Use with caution. Consider dose reduction. Avoid if significant liver disease (e.g., cirrhosis, fibrosis) is present.
Severe:
Generally contraindicated due to risk of hepatotoxicity. Avoid use in patients with pre-existing severe liver disease.
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 essential for DNA synthesis, repair, and cellular replication. By inhibiting DHFR, methotrexate interferes with the synthesis of purine nucleotides and thymidylate, thereby inhibiting DNA, RNA, and protein synthesis. In autoimmune diseases like rheumatoid arthritis and psoriasis, its mechanism is thought to involve immunosuppressive and anti-inflammatory effects, possibly by inhibiting lymphocyte proliferation, affecting adenosine metabolism, and inducing apoptosis in inflammatory cells.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV). Oral bioavailability is variable and dose-dependent.
Tmax:
Subcutaneous: 1-2 hours
FoodEffect:
Not significantly affected by food when administered subcutaneously.
Distribution:
Vd:
0.4-0.8 L/kg (at low doses); higher at high doses due to saturation of binding sites.
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at low doses (e.g., for RA/psoriasis). At high doses, it can penetrate the CNS, but levels are variable and often require intrathecal administration for therapeutic CNS concentrations.
Elimination:
HalfLife:
Low dose (RA/psoriasis): 3-10 hours; High dose (oncology): 8-15 hours (can be prolonged in renal impairment or third-space fluid accumulation).
Clearance:
Primarily renal (glomerular filtration and active tubular secretion).
ExcretionRoute:
Renal (approximately 50-90% unchanged within 24 hours), small amount via biliary excretion.
Unchanged:
50-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial therapeutic effects; full effect may take 3-6 months.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 3-6 months.
DurationOfAction:
Varies based on indication and dose; effects persist as long as drug is present and intracellular polyglutamates are active.
Safety & Warnings
BLACK BOX WARNING
Methotrexate has multiple Black Box Warnings:
1. **Severe Toxicity:** Methotrexate can cause severe, life-threatening, or fatal toxic reactions, including myelosuppression, aplastic anemia, gastrointestinal toxicity (e.g., mucositis, diarrhea, hemorrhagic enteritis, intestinal perforation), hepatotoxicity (e.g., acute liver damage, chronic fibrosis, cirrhosis), nephrotoxicity, and pulmonary toxicity (e.g., acute pneumonitis, chronic interstitial fibrosis).
2. **Myelosuppression:** Severe myelosuppression, including aplastic anemia, may occur. Patients should be closely monitored for signs of infection and bleeding.
3. **Hepatotoxicity:** Liver toxicity, including acute hepatitis and chronic fibrosis and cirrhosis, can occur. Liver biopsies are recommended for patients with psoriasis on long-term therapy.
4. **Pulmonary Toxicity:** Acute or chronic interstitial pneumonitis, potentially fatal, may occur at any time during therapy.
5. **Gastrointestinal Toxicity:** Diarrhea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy; otherwise, hemorrhagic enteritis and death from intestinal perforation may occur.
6. **Renal Toxicity:** Methotrexate elimination is reduced in patients with impaired renal function, increasing the risk of toxicity. Use with extreme caution in patients with renal impairment.
7. **Concomitant Medications:** Concomitant administration of NSAIDs, salicylates, or other drugs that reduce methotrexate elimination may result in elevated methotrexate levels and severe toxicity.
8. **Third-Space Accumulation:** Accumulation of methotrexate in third-space fluids (e.g., ascites, pleural effusions) may prolong elimination half-life and increase toxicity.
9. **Dermatologic Reactions:** Severe, potentially fatal, dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome) have been reported.
10. **Opportunistic Infections:** Methotrexate can cause immunosuppression, leading to potentially fatal opportunistic infections.
11. **Tumor Lysis Syndrome:** Methotrexate can induce tumor lysis syndrome in patients with rapidly growing tumors.
12. **Radiation Recall Dermatitis/Esophagitis:** Radiation-induced dermatitis and esophagitis may recur with methotrexate therapy.
13. **Embryo-Fetal Toxicity:** Methotrexate can cause embryo-fetal toxicity, fetal death, or teratogenic effects. It is contraindicated in pregnant women with non-oncologic diseases. Women of childbearing potential should be advised to use effective contraception during and for a specified period after therapy. Men should be advised about potential effects on spermatogenesis and to use effective contraception.
1. **Severe Toxicity:** Methotrexate can cause severe, life-threatening, or fatal toxic reactions, including myelosuppression, aplastic anemia, gastrointestinal toxicity (e.g., mucositis, diarrhea, hemorrhagic enteritis, intestinal perforation), hepatotoxicity (e.g., acute liver damage, chronic fibrosis, cirrhosis), nephrotoxicity, and pulmonary toxicity (e.g., acute pneumonitis, chronic interstitial fibrosis).
2. **Myelosuppression:** Severe myelosuppression, including aplastic anemia, may occur. Patients should be closely monitored for signs of infection and bleeding.
3. **Hepatotoxicity:** Liver toxicity, including acute hepatitis and chronic fibrosis and cirrhosis, can occur. Liver biopsies are recommended for patients with psoriasis on long-term therapy.
4. **Pulmonary Toxicity:** Acute or chronic interstitial pneumonitis, potentially fatal, may occur at any time during therapy.
5. **Gastrointestinal Toxicity:** Diarrhea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy; otherwise, hemorrhagic enteritis and death from intestinal perforation may occur.
6. **Renal Toxicity:** Methotrexate elimination is reduced in patients with impaired renal function, increasing the risk of toxicity. Use with extreme caution in patients with renal impairment.
7. **Concomitant Medications:** Concomitant administration of NSAIDs, salicylates, or other drugs that reduce methotrexate elimination may result in elevated methotrexate levels and severe toxicity.
8. **Third-Space Accumulation:** Accumulation of methotrexate in third-space fluids (e.g., ascites, pleural effusions) may prolong elimination half-life and increase toxicity.
9. **Dermatologic Reactions:** Severe, potentially fatal, dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome) have been reported.
10. **Opportunistic Infections:** Methotrexate can cause immunosuppression, leading to potentially fatal opportunistic infections.
11. **Tumor Lysis Syndrome:** Methotrexate can induce tumor lysis syndrome in patients with rapidly growing tumors.
12. **Radiation Recall Dermatitis/Esophagitis:** Radiation-induced dermatitis and esophagitis may recur with methotrexate therapy.
13. **Embryo-Fetal Toxicity:** Methotrexate can cause embryo-fetal toxicity, fetal death, or teratogenic effects. It is contraindicated in pregnant women with non-oncologic diseases. Women of childbearing potential should be advised to use effective contraception during and for a specified period after therapy. Men should be advised about potential effects on spermatogenesis and to use effective contraception.
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:
Allergic reactions: Rash, hives, itching, redness, swelling, blistering, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or speaking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infections: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or 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, stomach pain, light-colored stools, vomiting, or yellowing of the skin and eyes.
Lung or breathing problems: Shortness of breath, difficulty breathing, cough, or fever.
Nerve problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other serious symptoms: 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, or neck stiffness.
Other Possible Side Effects
Most medications can cause side effects, but many people experience none or only mild symptoms. If you're concerned about 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, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Allergic reactions: Rash, hives, itching, redness, swelling, blistering, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or speaking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infections: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or 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, stomach pain, light-colored stools, vomiting, or yellowing of the skin and eyes.
Lung or breathing problems: Shortness of breath, difficulty breathing, cough, or fever.
Nerve problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other serious symptoms: 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, or neck stiffness.
Other Possible Side Effects
Most medications can cause side effects, but many people experience none or only mild symptoms. If you're concerned about 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, 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, or other signs of infection
- Unusual bleeding or bruising, black/tarry stools, blood in urine or stools
- Severe fatigue, weakness, or dizziness
- Yellowing of skin or eyes (jaundice), dark urine, pale stools
- Shortness of breath, persistent cough, or chest pain
- Severe mouth sores, painful swallowing, or diarrhea
- Severe skin rash, blistering, or peeling
- Swelling in ankles or feet
- Severe headache or confusion
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weakened immune system
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.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication in conjunction with your other medications and health conditions. Never start, stop, or modify the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weakened immune system
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.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication in conjunction with your other medications and health conditions. Never start, stop, or modify the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before operating a vehicle or engaging in 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 excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. Be aware that this medication can cause severe nervous system problems, which may be temporary or long-lasting and can worsen over time. In some cases, these problems may not improve and can be fatal. If you have concerns, consult with your doctor.
If you have undergone radiation therapy, inform your doctor. Elderly patients (65 years and older) should use this medication with caution, as they may be more susceptible to side effects.
This medication may affect fertility, potentially leading to difficulty conceiving 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 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 excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. Be aware that this medication can cause severe nervous system problems, which may be temporary or long-lasting and can worsen over time. In some cases, these problems may not improve and can be fatal. If you have concerns, consult with your doctor.
If you have undergone radiation therapy, inform your doctor. Elderly patients (65 years and older) should use this medication with caution, as they may be more susceptible to side effects.
This medication may affect fertility, potentially leading to difficulty conceiving or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (low white blood cells, red blood cells, platelets)
- Severe mucositis (mouth sores, gastrointestinal ulceration)
- Severe nausea, vomiting, diarrhea
- Acute renal failure
- Hepatotoxicity
What to Do:
Seek immediate medical attention. The antidote is leucovorin (folinic acid), which can rescue normal cells from methotrexate toxicity. Glucarpidase may be used in cases of delayed methotrexate clearance due to impaired renal function. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live vaccines (during methotrexate therapy)
- Trimethoprim/sulfamethoxazole (increased risk of myelosuppression)
- Probenecid (decreased renal elimination of methotrexate)
- NSAIDs (high-dose methotrexate; may increase methotrexate levels and toxicity)
- Salicylates (high-dose methotrexate; may increase methotrexate levels and toxicity)
- Alcohol (increased risk of hepatotoxicity)
Major Interactions
- NSAIDs (low-dose methotrexate; use with caution, monitor for toxicity)
- Salicylates (low-dose methotrexate; use with caution, monitor for toxicity)
- Proton pump inhibitors (e.g., omeprazole, pantoprazole; may increase methotrexate levels, especially at high doses)
- Penicillins (e.g., amoxicillin; may decrease renal clearance of methotrexate)
- Ciprofloxacin (may decrease renal clearance of methotrexate)
- Folic acid antagonists (e.g., pyrimethamine, triamterene; increased risk of myelosuppression)
- Hepatotoxic agents (e.g., azathioprine, retinoids, sulfasalazine; increased risk of hepatotoxicity)
- Nephrotoxic agents (e.g., aminoglycosides, cisplatin; increased risk of renal toxicity)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Theophylline (decreased theophylline clearance)
- Chloramphenicol, tetracyclines (may displace methotrexate from protein binding, increasing free drug)
Moderate Interactions
- Oral antibiotics (e.g., neomycin, tetracyclines; may alter gut flora, affecting methotrexate absorption)
- Colchicine (increased risk of myelosuppression)
- Hydroxychloroquine (may increase methotrexate levels slightly)
- Leflunomide (increased risk of hepatotoxicity and myelosuppression)
- Nitrous oxide (may exacerbate methotrexate toxicity by inhibiting methionine synthase)
Minor Interactions
- Cholestyramine (may interfere with methotrexate absorption)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status and detect pre-existing cytopenias. Methotrexate can cause myelosuppression.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To assess baseline hepatic function. Methotrexate is hepatotoxic.
Timing: Prior to initiation of therapy
Renal Function Tests (Serum Creatinine, BUN, eGFR)
Rationale: To assess 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 rule out pre-existing pulmonary disease. Methotrexate can cause pulmonary toxicity.
Timing: Prior to initiation of therapy
Hepatitis B and C serology
Rationale: To screen for chronic viral hepatitis, which may increase risk of hepatotoxicity.
Timing: Prior to initiation of therapy
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Every 2-4 weeks for the first 3 months, then every 1-2 months or as clinically indicated.
Target: Maintain WBC >3,000/mm³, ANC >1,500/mm³, Platelets >100,000/mm³.
Action Threshold: Hold dose if significant drop in any cell line (e.g., WBC <3,000/mm³, ANC <1,500/mm³, Platelets <100,000/mm³). Consider dose reduction or discontinuation.
Liver Function Tests (AST, ALT, albumin)
Frequency: Every 2-4 weeks for the first 3 months, then every 1-2 months or as clinically indicated.
Target: AST/ALT <2-3 times upper limit of normal (ULN).
Action Threshold: Hold dose if AST/ALT >3 times ULN. Consider liver biopsy if persistent elevations or cumulative dose is high.
Renal Function Tests (Serum Creatinine, BUN)
Frequency: Every 1-2 months or as clinically indicated.
Target: Within normal limits or stable baseline.
Action Threshold: Hold dose if creatinine increases by >50% from baseline or is significantly elevated. Adjust dose based on CrCl.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising (petechiae, purpura)
- Severe fatigue or weakness
- Shortness of breath, cough, or new onset dyspnea (signs of pulmonary toxicity)
- Yellowing of skin or eyes, dark urine (signs of hepatotoxicity)
- Severe mouth sores, painful swallowing (mucositis)
- Nausea, vomiting, diarrhea
- Skin rash or lesions (psoriasis worsening or drug reaction)
- Hair loss
Special Patient Groups
Pregnancy
Methotrexate is contraindicated in pregnant women with non-oncologic diseases (e.g., psoriasis, rheumatoid arthritis) due to significant risk of embryo-fetal toxicity, fetal death, and teratogenic effects (e.g., craniofacial abnormalities, limb defects, CNS abnormalities). It is a Pregnancy Category X drug. For oncologic indications, the benefits may outweigh the risks in certain life-threatening situations, but careful counseling is essential.
Trimester-Specific Risks:
First Trimester:
Highest risk of major congenital malformations and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, hydrocephalus, and other abnormalities.
Third Trimester:
Risk of fetal growth restriction, bone marrow suppression, and other adverse effects.
Lactation
Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant, including myelosuppression. Breastfeeding is contraindicated during methotrexate therapy and for at least one week after the last dose.
Infant Risk:
High risk (L5) - significant potential for adverse effects in the infant.
Pediatric Use
Methotrexate is used in pediatric patients for juvenile idiopathic arthritis (JIA) and various childhood cancers (e.g., acute lymphoblastic leukemia). Dosing is weight- or body surface area-based. Close monitoring for toxicity is essential, similar to adults.
Geriatric Use
Elderly patients may be at increased risk for methotrexate toxicity due to age-related decreases in renal function, bone marrow reserve, and hepatic function. Close monitoring of renal function, CBC, and LFTs is crucial. Dose adjustments may be necessary, and lower starting doses should be considered.
Clinical Information
Clinical Pearls
- Methotrexate for RA/psoriasis is a *weekly* dose, not daily. Emphasize this to patients to prevent fatal overdose.
- Folic acid supplementation (typically 1-5 mg once daily, or 1 mg daily except on methotrexate day) is crucial to reduce common side effects like mucositis, nausea, and liver enzyme elevations, without significantly impacting efficacy for RA/psoriasis.
- Patients should be well-hydrated, especially during high-dose methotrexate therapy, to promote renal elimination and prevent nephrotoxicity.
- Avoid alcohol completely due to the significant risk of hepatotoxicity.
- Monitor for signs of pulmonary toxicity (new cough, dyspnea) as it can occur acutely or chronically and be fatal.
- Patients should report any signs of infection, bleeding, or severe gastrointestinal symptoms immediately.
- NSAIDs and PPIs can increase methotrexate levels; use with caution and monitor closely, especially with higher methotrexate doses.
Alternative Therapies
- For Rheumatoid Arthritis: Other conventional synthetic DMARDs (e.g., sulfasalazine, hydroxychloroquine, leflunomide), Biologic DMARDs (e.g., TNF inhibitors like adalimumab, etanercept; IL-6 inhibitors like tocilizumab; T-cell costimulation modulators like abatacept; B-cell depleting agents like rituximab), Targeted Synthetic DMARDs (e.g., JAK inhibitors like tofacitinib, baricitinib, upadacitinib).
- For Psoriasis: Other systemic agents (e.g., cyclosporine, acitretin), Biologic agents (e.g., TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors), Oral small molecules (e.g., apremilast), Phototherapy.
Cost & Coverage
Average Cost:
Highly variable, typically $100-$500+ per month depending on dose and specific brand/formulation. Rasuvo 7.5mg Inj may range from $300-$600+ per month. per 4 pre-filled syringes (monthly supply)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (preferred brand or non-preferred brand). Generic methotrexate injection is often Tier 1 or 2.
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.