Rasuvo 25mg/0.5ml 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
Antimetabolite, Disease-Modifying Antirheumatic Drug (DMARD), 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 medicine that works by slowing down the growth of certain cells in the body. For conditions like rheumatoid arthritis and psoriasis, it helps reduce inflammation and overactive immune responses. It's given as a weekly injection under the skin.
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.
Prior to injection, inspect the skin for any signs of irritation, tenderness, bruising, redness, scaliness, hardness, scarring, or stretch marks. If you notice any of these conditions, do not proceed with the injection.
If you are unsure whether a dose was successfully administered or experience difficulty with the injection process, consult your doctor or pharmacist before attempting another dose.
Safe Disposal of Needles and Sharps
Dispose of used needles and other sharp objects in a designated needle/sharp disposal container. Never reuse needles or other items, as this can pose a risk of infection or other complications. When the disposal container is full, follow local regulations for proper disposal. If you have any 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 essential 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 dosage and administration schedule may be adjusted based on blood work results, side effects, and the medication's efficacy.
Handling and Storage
Exercise caution when handling this medication. Consult your doctor or pharmacist for guidance on proper handling procedures.
To stay hydrated, drink plenty of non-caffeinated liquids, unless your doctor advises you to restrict fluid intake.
Storage and Disposal
Store this 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.
Prior to injection, inspect the skin for any signs of irritation, tenderness, bruising, redness, scaliness, hardness, scarring, or stretch marks. If you notice any of these conditions, do not proceed with the injection.
If you are unsure whether a dose was successfully administered or experience difficulty with the injection process, consult your doctor or pharmacist before attempting another dose.
Safe Disposal of Needles and Sharps
Dispose of used needles and other sharp objects in a designated needle/sharp disposal container. Never reuse needles or other items, as this can pose a risk of infection or other complications. When the disposal container is full, follow local regulations for proper disposal. If you have any 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 essential 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 dosage and administration schedule may be adjusted based on blood work results, side effects, and the medication's efficacy.
Handling and Storage
Exercise caution when handling this medication. Consult your doctor or pharmacist for guidance on proper handling procedures.
To stay hydrated, drink plenty of non-caffeinated liquids, unless your doctor advises you to restrict fluid intake.
Storage and Disposal
Store this 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 a week. NEVER take daily for arthritis/psoriasis.
- Avoid alcohol completely or limit significantly due to increased risk of liver damage.
- Take folic acid or folinic acid as prescribed by your doctor to reduce side effects.
- Avoid live vaccines while on methotrexate.
- Use effective birth control during treatment and for at least 6 months after stopping for both men and women.
- Stay well-hydrated.
- Avoid excessive sun exposure; use sunscreen and protective clothing.
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:
Rheumatoid Arthritis/Psoriasis: 7.5 mg to 25 mg once weekly, administered subcutaneously.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
Initial: 7.5 mg once weekly. Adjust gradually to optimal response, not exceeding 20 mg/week (or 25 mg/week in some cases for Rasuvo).
Psoriasis:
Initial: 10 mg to 25 mg once weekly as a single dose, or 2.5 mg every 12 hours for 3 doses each week (total 7.5 mg/week). Adjust gradually to optimal response, not exceeding 25 mg/week.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly.
Adolescent:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly. For psoriasis/RA, adult dosing may apply based on weight/BSA.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 51-80 mL/min: Consider 50% reduction in dose or close monitoring.
Moderate:
CrCl 10-50 mL/min: Avoid use or significantly reduce dose (e.g., 70% reduction) and monitor closely. Consult specialist.
Severe:
CrCl <10 mL/min: Contraindicated.
Dialysis:
Not dialyzable by standard hemodialysis. Contraindicated.
Hepatic Impairment:
Mild:
Use with caution; monitor liver function closely.
Moderate:
Avoid or use with extreme caution; significant dose reduction may be necessary. Contraindicated in severe liver disease.
Severe:
Contraindicated (e.g., alcoholic liver disease, cirrhosis, significant fibrosis).
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase (DHFR), an enzyme essential for DNA synthesis, repair, and cellular replication. By inhibiting DHFR, methotrexate prevents the reduction of dihydrofolate to tetrahydrofolate, a critical co-factor in the synthesis of purine nucleotides and thymidylate. In rheumatologic conditions and psoriasis, its mechanism is thought to involve inhibition of lymphocyte proliferation, induction of adenosine release (which has anti-inflammatory properties), and inhibition of polymorphonuclear leukocyte chemotaxis.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV).
Tmax:
Subcutaneous: 1-2 hours.
FoodEffect:
Not applicable for subcutaneous administration.
Distribution:
Vd:
0.4-0.8 L/kg (distributes into body tissues and third spaces like ascites or pleural effusions).
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at typical low-dose systemic therapy; higher doses or intrathecal administration are required for significant CNS levels.
Elimination:
HalfLife:
3-10 hours (low dose); 8-15 hours (high dose).
Clearance:
Primarily renal (glomerular filtration and active tubular secretion).
ExcretionRoute:
Renal (50-90% unchanged), small amount via biliary excretion.
Unchanged:
50-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial clinical effects; maximal benefit may take 3-6 months.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 3-6 months.
DurationOfAction:
Effects persist as long as therapy is continued; cessation leads to gradual loss of benefit.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe toxic reactions including death. Patients should be closely monitored. Deaths have been reported with low-dose methotrexate. Methotrexate has been associated with: 1) Bone marrow suppression (myelosuppression), 2) Renal toxicity, 3) Liver toxicity (hepatotoxicity, fibrosis, cirrhosis), 4) Pulmonary toxicity (pneumonitis), 5) Gastrointestinal toxicity (diarrhea, stomatitis, mucositis, hemorrhagic enteritis, perforation), 6) Opportunistic infections, 7) Tumor lysis syndrome, 8) Severe skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), 9) Secondary malignancy (lymphoma), 10) Teratogenicity (fetal death or congenital anomalies). Methotrexate should be used only by physicians experienced in antimetabolite chemotherapy. Patients should be fully informed of the risks. Accidental daily use instead of weekly use has led to fatal toxicity. Folic acid supplementation is recommended to reduce some toxicities.
Side Effects
Serious Side Effects: Seek Medical Help Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical attention right away:
Allergic reactions: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infections: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that get bigger, or uncontrollable bleeding.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or breathing problems: Shortness of breath, breathing difficulties, cough, or fever.
Nerve problems: Abnormal burning, numbness, or tingling sensations, weakness, or paralysis.
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 changes, facial drooping, blurred vision, headache, or neck stiffness.
Other Side Effects
Most people experience few or no side effects while taking this medication. However, if you experience any of the following side effects or any other symptoms that bother you or don't go away, 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, contact 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 experience any of the following symptoms, contact your doctor or seek medical attention right away:
Allergic reactions: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infections: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that get bigger, or uncontrollable bleeding.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or breathing problems: Shortness of breath, breathing difficulties, cough, or fever.
Nerve problems: Abnormal burning, numbness, or tingling sensations, weakness, or paralysis.
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 changes, facial drooping, blurred vision, headache, or neck stiffness.
Other Side Effects
Most people experience few or no side effects while taking this medication. However, if you experience any of the following side effects or any other symptoms that bother you or don't go away, 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, contact 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 any signs of infection
- Unusual bleeding or bruising
- Extreme tiredness or weakness
- Shortness of breath, dry cough
- Severe nausea, vomiting, diarrhea
- Sores in the mouth or throat
- Yellowing of skin or eyes, dark urine, severe stomach pain
- Severe skin rash, blistering, or peeling
- Swelling in legs or ankles
- Changes in urination (less frequent or painful)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult 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. They will help you verify that it is safe to take this medication in conjunction with your other medications and health conditions. Do not initiate, discontinue, 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 allergic reaction you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult 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. They will help you verify that it is safe to take this medication in conjunction with your other medications and health conditions. Do not initiate, discontinue, 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.
When starting this medication, avoid driving and other activities that require alertness until you understand how it affects you. You may be more susceptible to infections, so it's 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 this medication may increase your risk of bleeding easily. To minimize this risk, be cautious and avoid injuries. Use a soft toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult 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.
You may be more prone to sunburns while taking this medication. To protect yourself, avoid direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear when going outside. Continue to take these precautions for as long as your doctor advises.
If you experience excessive fluid loss, unusual 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 any concerns or questions, 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 susceptible to side effects.
This medication 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.
When starting this medication, avoid driving and other activities that require alertness until you understand how it affects you. You may be more susceptible to infections, so it's 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 this medication may increase your risk of bleeding easily. To minimize this risk, be cautious and avoid injuries. Use a soft toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult 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.
You may be more prone to sunburns while taking this medication. To protect yourself, avoid direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear when going outside. Continue to take these precautions for as long as your doctor advises.
If you experience excessive fluid loss, unusual 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 any concerns or questions, 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 susceptible to side effects.
This medication 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 inflammation)
- Severe liver damage
- Renal failure
What to Do:
Immediately contact your doctor or go to the nearest emergency room. Leucovorin rescue is the primary antidote for methotrexate overdose. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live vaccines (during methotrexate therapy)
- Trimethoprim/sulfamethoxazole (increased myelosuppression)
- Probenecid (decreased renal clearance of methotrexate)
- Aspirin (high dose) and NSAIDs (high dose) in patients receiving high-dose methotrexate (can increase methotrexate levels and toxicity)
- Alcohol (increased hepatotoxicity)
Major Interactions
- NSAIDs (non-steroidal anti-inflammatory drugs) - can increase methotrexate levels and toxicity, especially with higher methotrexate doses or renal impairment.
- Proton Pump Inhibitors (PPIs) - omeprazole, pantoprazole, etc. (may increase methotrexate levels, particularly with high-dose methotrexate).
- Penicillins (e.g., amoxicillin, penicillin G) - may decrease renal clearance of methotrexate.
- Sulfonamides (e.g., sulfasalazine) - may displace methotrexate from protein binding or inhibit renal tubular secretion, increasing toxicity.
- Folic acid antagonists (e.g., trimetrexate, pyrimethamine) - additive antifolate effects, increased toxicity.
- Retinoids (e.g., acitretin) - increased hepatotoxicity.
- Phenytoin - decreased phenytoin levels, increased methotrexate toxicity.
- Theophylline - decreased theophylline clearance.
- Azathioprine, mercaptopurine - increased risk of myelosuppression and hepatotoxicity.
Moderate Interactions
- Oral antibiotics (e.g., tetracyclines, chloramphenicol) - may alter gut flora, affecting methotrexate absorption or enterohepatic recirculation.
- Caffeine - may reduce efficacy of methotrexate in RA (theoretical, clinical significance debated).
- Cholestyramine - may interfere with methotrexate absorption.
- Cisplatin - increased methotrexate toxicity.
- 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 parameters and detect pre-existing cytopenias. Methotrexate can cause myelosuppression.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs) - AST, ALT, alkaline phosphatase, bilirubin, albumin
Rationale: To establish baseline liver function. Methotrexate is hepatotoxic.
Timing: Prior to initiation of therapy
Renal Function Tests - Serum creatinine, BUN, estimated GFR
Rationale: To establish 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 establish baseline pulmonary status and rule out pre-existing lung disease. Methotrexate can cause 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: Every 2-4 weeks for the first 3 months, then every 1-2 months (or as clinically indicated)
Target: WBC >3.5 x 10^9/L, Neutrophils >1.5 x 10^9/L, Platelets >100 x 10^9/L, Hemoglobin >10 g/dL
Action Threshold: Hold dose for significant drops (e.g., WBC <3.0, ANC <1.5, Platelets <100) or persistent abnormalities. Consider dose reduction or discontinuation.
Liver Function Tests (LFTs) - AST, ALT, alkaline phosphatase, bilirubin
Frequency: Every 2-4 weeks for the first 3 months, then every 1-2 months (or as clinically indicated)
Target: AST/ALT <2x ULN (Upper Limit of Normal)
Action Threshold: Hold dose for persistent elevation of AST/ALT >2x ULN or any elevation >3x ULN. Consider liver biopsy for persistent elevations or cumulative dose concerns.
Renal Function Tests - Serum creatinine, BUN
Frequency: Every 2-4 weeks for the first 3 months, then every 1-2 months (or as clinically indicated)
Target: Within normal limits, stable baseline
Action Threshold: Hold dose for significant increase in creatinine or decrease in GFR. Adjust dose or discontinue.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising
- Fatigue, weakness, pallor (anemia)
- Shortness of breath, dry cough, chest pain (pneumonitis)
- Nausea, vomiting, diarrhea, oral sores (mucositis)
- Yellowing of skin or eyes, dark urine, abdominal pain (hepatotoxicity)
- Skin rash, 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 congenital anomalies.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, limb, skeletal abnormalities) and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, bone marrow suppression, and other adverse effects.
Third Trimester:
Risk of fetal growth restriction, bone marrow suppression, and other adverse effects.
Lactation
Contraindicated. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant, including myelosuppression.
Infant Risk:
High risk of serious adverse effects (e.g., myelosuppression, growth inhibition).
Pediatric Use
Used in Juvenile Idiopathic Arthritis (JIA) and certain pediatric cancers. Dosing is weight or body surface area (BSA) based. Close monitoring for toxicity is essential, similar to adults. Rasuvo is approved for JIA in patients 2 years of age and older.
Geriatric Use
Use with caution. Elderly patients may have reduced renal and hepatic function, increasing the risk of methotrexate toxicity. Close monitoring of renal function, CBC, and LFTs is crucial. Dose adjustments may be necessary.
Clinical Information
Clinical Pearls
- Methotrexate for RA/psoriasis is dosed WEEKLY, not daily. Accidental daily dosing is a common and potentially fatal error.
- Folic acid supplementation (e.g., 1-5 mg once daily or 5 mg once weekly, taken on a different day than methotrexate) is highly recommended to reduce common side effects like nausea, oral ulcers, and liver enzyme elevations, without significantly impacting efficacy.
- Patients should be educated on the importance of avoiding alcohol due to the risk of hepatotoxicity.
- Subcutaneous administration may offer better bioavailability and reduced GI side effects compared to oral administration, especially at higher doses.
- Monitor for signs of pneumonitis (dry cough, dyspnea), which can occur acutely at any time during therapy and requires immediate discontinuation.
- Ensure patients are up-to-date on non-live vaccinations before starting methotrexate, as live vaccines are contraindicated during therapy.
Alternative Therapies
- Other conventional synthetic DMARDs (csDMARDs): Hydroxychloroquine, Sulfasalazine, Leflunomide.
- Biologic DMARDs (bDMARDs): TNF inhibitors (e.g., Adalimumab, Etanercept, Infliximab), IL-6 inhibitors (e.g., Tocilizumab), T-cell costimulation inhibitors (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 (e.g., Tofacitinib, Baricitinib, Upadacitinib).
- Other immunosuppressants (for severe cases or specific indications): Cyclosporine, Azathioprine.
Cost & Coverage
Average Cost:
Varies widely, typically $500-$1500 per 4 pens (25mg/0.5ml)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (Specialty drug, may require prior authorization)
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.