Rasuvo 20mg Inj, 0.4ml
WARNING: Severe side effects like bone marrow problems, liver problems, lung problems, and infections can happen with this drug. Some side effects may not go away and can be deadly. You must talk with the doctor about the risks of this drug. This drug may cause kidney problems in some patients. Talk with the doctor.Regular blood work and other exams will need to be done to check for side effects. Follow what the doctor has told you. Tell your doctor if you have kidney problems or extra fluid around your stomach area or lungs. The chance of side effects may be raised.Talk with your doctor if you are getting radiation. There may be more chance of harm to tissue and bone.New types of cancer have happened in people taking this drug. If you have questions, talk with the doctor.It is common to have diarrhea, upset stomach, throwing up, or mouth sores with this drug. However, sometimes these may be signs of severe and sometimes deadly stomach or bowel problems. Tell your doctor if you get any new or worsening signs. You may need to stop this drug.Severe skin reactions have happened with this drug. These have included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and other severe skin reactions. Sometimes these have been deadly. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin; other skin irritation (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.Very bad and sometimes deadly bone marrow problems and stomach or bowel problems have happened when this drug was taken with nonsteroidal anti-inflammatory drug (NSAIDs) like ibuprofen or naproxen.Not all methotrexate products are used to treat cancer. Talk with the doctor.This drug may cause harm to an unborn baby or loss of an unborn baby. A pregnancy test will be done before you start this drug to show that you are NOT pregnant.If you or your sex partner may become pregnant, you must use birth control while taking this drug and for some time after the last dose. Ask your doctor how long to use birth control. If you or your sex partner gets pregnant, call your doctor right away.Do not take if you are pregnant.This drug must only be used when other drugs cannot be used or have not worked. Talk with your doctor to be sure that the benefits of this drug are more than the risks. @ COMMON USES: It is used to treat some types of arthritis.It is used to treat some types of psoriasis.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antineoplastic, Antirheumatic, Immunosuppressant
Pharmacologic Class
Antimetabolite, Folic acid antagonist
Pregnancy Category
Category X
FDA Approved
Jul 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Rasuvo is a medication containing methotrexate, which 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 certain cancers, it helps to stop cancer cells from growing.
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 using another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions, consult your doctor or pharmacist.
Dosing and Frequency
Your dose and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use can lead to fatal errors. Ensure you understand your dosing schedule and frequency before starting treatment. If you have any doubts, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and treatment response.
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 a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before using another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions, consult your doctor or pharmacist.
Dosing and Frequency
Your dose and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use can lead to fatal errors. Ensure you understand your dosing schedule and frequency before starting treatment. If you have any doubts, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and treatment response.
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. Do NOT take daily.
- Take folic acid supplementation as directed by your doctor (usually 1 mg daily, or 5 mg once weekly, given at least 24 hours after your methotrexate dose) to reduce side effects.
- Avoid alcohol completely due to increased risk of liver damage.
- Avoid excessive sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Maintain good hydration by drinking plenty of fluids.
- Avoid live vaccines while on methotrexate.
- Use effective contraception during treatment and for at least 6 months after stopping for both men and women, as methotrexate can cause severe birth defects or miscarriage.
- Report any signs of infection (fever, chills, sore throat), unusual bleeding or bruising, severe mouth sores, persistent cough or shortness of breath, or yellowing of skin/eyes immediately to your doctor.
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 (RA) and Psoriasis: 7.5 mg to 20 mg once weekly, administered subcutaneously. Doses should be adjusted to achieve optimal response with acceptable toxicity.
Dose Range:
7.5 - 20 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
Initial: 7.5 mg once weekly. May gradually increase to 20 mg once weekly. Doses >20 mg/week have been associated with increased toxicity.
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 >30 mg/week are not recommended.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly.
Adolescent:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Consider 25% dose reduction or close monitoring.
Moderate:
CrCl 51-60 mL/min: Consider 50% dose reduction. CrCl <50 mL/min: Generally contraindicated or significant dose reduction (e.g., 75%) and extreme caution.
Severe:
CrCl <30 mL/min: Contraindicated due to risk of severe toxicity.
Dialysis:
Methotrexate is poorly dialyzable by standard hemodialysis. High-flux dialysis may remove some. Generally contraindicated or used with extreme caution and significant dose reduction, with close monitoring of methotrexate levels.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function closely.
Moderate:
Significant liver disease (e.g., cirrhosis, fibrosis): Generally contraindicated due to increased risk of hepatotoxicity.
Severe:
Bilirubin >5 mg/dL or significant liver impairment: Contraindicated.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that acts as a folic acid antagonist. It competitively inhibits dihydrofolate reductase (DHFR), an enzyme that catalyzes the reduction of 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, leading to inhibition of DNA, RNA, and protein synthesis. In autoimmune diseases like RA and psoriasis, its mechanism is thought to involve immunosuppressive and anti-inflammatory effects, possibly through inhibition of lymphocyte proliferation, induction of adenosine release, and effects on cytokine production.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV). Oral bioavailability is variable and dose-dependent.
Tmax:
Subcutaneous: 1-2 hours
FoodEffect:
Not applicable for subcutaneous injection.
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 at conventional doses; significant penetration at high doses (e.g., intrathecal administration).
Elimination:
HalfLife:
3-10 hours (low dose); 8-15 hours (high dose)
Clearance:
Primarily renal clearance via glomerular filtration and active tubular secretion.
ExcretionRoute:
Renal (primary), biliary (minor)
Unchanged:
Approximately 50-90% (renal excretion)
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial clinical effects, up to 12 weeks for maximal effect.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 4-12 weeks.
DurationOfAction:
Effects persist as long as treatment is continued; cessation leads to gradual loss of effect.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe toxic reactions, including death. Patients should be closely monitored for bone marrow, liver, lung, and kidney toxicities. Methotrexate has been associated with severe myelosuppression, hepatotoxicity (including fibrosis and cirrhosis), pneumonitis, and renal damage. Diarrhea and ulcerative stomatitis require interruption of therapy. Methotrexate can cause fetal death or teratogenic effects and is contraindicated in pregnant women with non-oncologic diseases. Concomitant use with NSAIDs has been reported to cause severe, sometimes fatal, methotrexate toxicity. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or significant effusions. Lymphoma and other malignancies have been reported. Opportunistic infections, including Pneumocystis jirovecii pneumonia, may occur. Tumor lysis syndrome may occur. Severe skin reactions have been reported.
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 problem): 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, drooping facial muscles, or blurred vision.
Headache.
Neck stiffness.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild ones. If you're 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:
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 problem): 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, drooping facial muscles, or blurred vision.
Headache.
Neck stiffness.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild ones. If you're 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, signs of infection
- Unusual bleeding or bruising
- Severe mouth sores or ulcers
- Persistent cough, shortness of breath, or difficulty breathing
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Severe nausea, vomiting, or diarrhea
- Severe skin rash or peeling skin
- Swelling in ankles or feet
- Severe fatigue or weakness
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the 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 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 your last dose.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication with your existing medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the 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 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 your last dose.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication with your existing medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Until you understand how this drug affects you, avoid driving and other activities that require alertness. 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 people who have infections, colds, or flu.
Be aware that you may experience easier bleeding, so it is vital to be cautious and avoid injuries. To minimize the risk of bleeding, use a soft toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult with your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor before drinking.
You may be more prone to sunburn, so it is essential to avoid excessive sun exposure, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to safeguard yourself against the sun. Continue to take sun protection measures for as long as your doctor advises.
If you experience fluid loss, excessive sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and can worsen over time. In some cases, these problems may not improve and can be life-threatening. If you have concerns, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Older adults (65 years and above) should use this medication with caution, as they may be more susceptible to side effects.
This drug may affect fertility, potentially leading to difficulty getting pregnant or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Until you understand how this drug affects you, avoid driving and other activities that require alertness. 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 people who have infections, colds, or flu.
Be aware that you may experience easier bleeding, so it is vital to be cautious and avoid injuries. To minimize the risk of bleeding, use a soft toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult with your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor before drinking.
You may be more prone to sunburn, so it is essential to avoid excessive sun exposure, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to safeguard yourself against the sun. Continue to take sun protection measures for as long as your doctor advises.
If you experience fluid loss, excessive sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and can worsen over time. In some cases, these problems may not improve and can be life-threatening. If you have concerns, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Older adults (65 years and above) should use this medication with caution, as they may be more susceptible to side effects.
This drug may affect fertility, potentially leading to difficulty getting pregnant or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (low white blood cells, red blood cells, platelets)
- Severe mucositis (mouth sores, GI ulcers)
- Nausea, vomiting, diarrhea
- Renal failure
- Hepatotoxicity
What to Do:
Immediately contact your doctor or go to an emergency room. Leucovorin rescue is the primary antidote for methotrexate overdose, administered as soon as possible. Hydration and urinary alkalinization may also be used to promote methotrexate excretion. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Trimethoprim/sulfamethoxazole (increased myelosuppression)
- Probenecid (decreased renal excretion of methotrexate)
- Salicylates (high dose) (decreased renal excretion of methotrexate)
- Non-steroidal anti-inflammatory drugs (NSAIDs) (concomitant use with high-dose methotrexate; for low-dose, use with caution and monitor)
- Alcohol (increased risk of hepatotoxicity)
- Hepatotoxic agents (e.g., retinoids, azathioprine, sulfasalazine) (increased risk of hepatotoxicity)
- Folic acid antagonists (e.g., pyrimethamine, triamterene) (increased risk of methotrexate toxicity)
Major Interactions
- NSAIDs (for low-dose methotrexate, use with caution and monitor for toxicity, especially renal)
- Proton pump inhibitors (PPIs) (e.g., omeprazole, pantoprazole) (may increase methotrexate levels, especially at higher doses)
- Penicillins (e.g., amoxicillin) (may decrease renal clearance of methotrexate)
- Ciprofloxacin (may decrease renal clearance of methotrexate)
- Phenytoin (decreased protein binding of phenytoin, increased methotrexate levels)
- Theophylline (decreased clearance of theophylline)
- Chloramphenicol, tetracyclines (may interfere with enterohepatic recirculation of methotrexate)
- Oral retinoids (e.g., acitretin, etretinate) (increased risk of hepatotoxicity)
Moderate Interactions
- Folic acid supplements (may reduce efficacy if given at same time as methotrexate; should be given at least 24 hours after methotrexate dose)
- Colchicine (increased risk of myelosuppression)
- Sulfonylureas (increased hypoglycemic effect)
- Digoxin (decreased digoxin absorption)
- P-glycoprotein inhibitors (may alter methotrexate transport)
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 assess baseline liver function. Methotrexate is hepatotoxic and can cause liver fibrosis/cirrhosis.
Timing: Prior to initiation of therapy
Renal Function Tests (RFTs) including serum creatinine, BUN, estimated GFR
Rationale: To assess baseline renal function. Methotrexate is primarily renally excreted, 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 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 liver toxicity.
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: WBC >3,000/mm³, Platelets >100,000/mm³, Hemoglobin >9 g/dL
Action Threshold: Hold dose if WBC <3,000/mm³, Platelets <100,000/mm³, or significant drop in any cell line. Re-evaluate therapy.
Liver Function Tests (LFTs) including AST, ALT, albumin
Frequency: Every 2-4 weeks for the first 2 months, then monthly or every 1-2 months thereafter.
Target: AST/ALT <2x upper limit of normal (ULN)
Action Threshold: Hold dose if AST/ALT >2x ULN (persistent or significant elevation). Consider liver biopsy if persistent elevations or cumulative dose concerns.
Renal Function Tests (RFTs) including serum creatinine
Frequency: Monthly or every 1-2 months thereafter, or more frequently if clinically indicated or with concomitant nephrotoxic drugs.
Target: Creatinine within normal limits, stable
Action Threshold: Hold dose or reduce dose if creatinine increases by >50% from baseline or if GFR significantly declines.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising (petechiae, purpura)
- Fatigue, weakness, pallor (anemia)
- Shortness of breath, cough, dyspnea (pulmonary toxicity)
- Nausea, vomiting, diarrhea, abdominal pain
- Oral ulcers, stomatitis, mucositis
- Yellowing of skin or eyes, dark urine (liver toxicity)
- Skin rash, photosensitivity
- Hair loss
- Neurological symptoms (headache, confusion, seizures - rare with low dose)
Special Patient Groups
Pregnancy
Contraindicated. Methotrexate is a potent teratogen and abortifacient. It can cause fetal death or severe birth defects.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, limb, cardiovascular defects) and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, skeletal abnormalities, and central nervous system effects.
Third Trimester:
Risk of fetal growth restriction, bone marrow suppression, and other systemic effects.
Lactation
Contraindicated. 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) - significant risk of adverse effects due to high concentrations in milk and potential for toxicity.
Pediatric Use
Approved for polyarticular juvenile idiopathic arthritis (pJIA). Dosing is weight or body surface area-based. Close monitoring for toxicity is essential, similar to adults. Used off-label for various pediatric cancers.
Geriatric Use
Use with caution. Elderly patients may have decreased renal function, which can lead to increased methotrexate levels and toxicity. Increased risk of myelosuppression and other adverse effects. Close monitoring of renal function, CBC, and LFTs is crucial.
Clinical Information
Clinical Pearls
- Methotrexate for RA/psoriasis/pJIA is dosed ONCE WEEKLY. Daily dosing (except for specific oncology protocols) can be fatal.
- Folic acid supplementation is crucial to reduce common side effects (e.g., mucositis, GI upset, myelosuppression) without significantly reducing efficacy for autoimmune conditions. It should be taken at least 24 hours after the weekly methotrexate dose.
- Patients must be educated on the importance of avoiding alcohol due to the risk of severe hepatotoxicity.
- Regular monitoring of CBC, LFTs, and renal function is mandatory due to the potential for severe toxicities.
- Any signs of infection, unexplained bleeding/bruising, severe mouth sores, or new onset cough/shortness of breath warrant immediate medical attention.
- Leucovorin is the antidote for methotrexate overdose or severe toxicity; it should be readily available in clinical settings where high-dose methotrexate is used.
Alternative Therapies
- For Rheumatoid Arthritis: Hydroxychloroquine, Sulfasalazine, Leflunomide, Biologic DMARDs (e.g., TNF inhibitors like adalimumab, etanercept; IL-6 inhibitors like tocilizumab; T-cell costimulation modulators like abatacept; JAK inhibitors like tofacitinib).
- For Psoriasis: Biologic DMARDs (e.g., TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors), Oral systemic agents (e.g., apremilast, cyclosporine, acitretin), Phototherapy.
- For Juvenile Idiopathic Arthritis: Other DMARDs, Biologic DMARDs.
Cost & Coverage
Average Cost:
Varies, typically $100-$500+ per 4 prefilled syringes (20mg/0.4ml)
Generic Available:
Yes
Insurance Coverage:
Tier 3 or 4 (Specialty Drug)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea 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.