Rasuvo 30mg/0.6ml 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, 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?
Rasuvo contains methotrexate, 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. For cancer, it helps stop cancer cells from growing. It is given as an injection under the skin, usually once a week.
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; do not use if any of these issues are present.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before proceeding with another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have 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 can lead to fatal errors. Ensure you understand your dosage and administration schedule; if unclear, consult your doctor.
Your doctor may adjust the dosage or administration schedule based on blood work results, side effects, and the medication's effectiveness.
Handling and Storage
Handle this medication with care; consult your doctor or pharmacist for specific guidance.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store the medication at room temperature, protected from light, and in a dry place.
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; do not use if any of these issues are present.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before proceeding with another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have 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 can lead to fatal errors. Ensure you understand your dosage and administration schedule; if unclear, consult your doctor.
Your doctor may adjust the dosage or administration schedule based on blood work results, side effects, and the medication's effectiveness.
Handling and Storage
Handle this medication with care; consult your doctor or pharmacist for specific guidance.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store the medication at room temperature, protected from light, and in a dry place.
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 or leucovorin as prescribed by your doctor 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.
- Use effective contraception during treatment and for at least 6 months after stopping for both men and women, as it can cause birth defects.
- Avoid live vaccines while on methotrexate.
- Stay well-hydrated.
- Report any signs of infection, unusual bleeding/bruising, severe fatigue, shortness of breath, or yellowing of skin/eyes immediately.
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:
Varies by indication. For Rheumatoid Arthritis/Psoriasis: 7.5 mg to 25 mg once weekly, administered subcutaneously.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
7.5 mg once weekly, adjusted gradually to a maximum of 20 mg once weekly. Some patients may require up to 25 mg once weekly.
Psoriasis:
Initial dose of 10-25 mg once weekly, adjusted based on response and toxicity. Doses usually do not exceed 30 mg per 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 to 0.6 mg/kg/week (max 25 mg/week).
Adolescent:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 to 0.6 mg/kg/week (max 25 mg/week).
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Consider 25% dose reduction or increased monitoring. CrCl 51-60 mL/min: Consider 50% dose reduction or increased monitoring.
Moderate:
CrCl 30-50 mL/min: Avoid use or significantly reduce dose (e.g., 50-75% reduction) and monitor closely. Increased risk of toxicity.
Severe:
CrCl <30 mL/min: Contraindicated.
Dialysis:
Methotrexate is dialyzable, but standard hemodialysis is not effective for rapid removal. High-flux dialysis may be more effective. Contraindicated in patients requiring dialysis due to severe renal impairment.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function closely.
Moderate:
Avoid or use with extreme caution. Significant dose reduction may be necessary. Increased risk of hepatotoxicity.
Severe:
Contraindicated in patients with severe hepatic impairment (e.g., cirrhosis, significant fibrosis, or elevated bilirubin).
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, cell replication, and repair. By inhibiting DHFR, methotrexate impairs purine and pyrimidine synthesis, leading to inhibition of DNA, RNA, and protein synthesis. In low doses used for inflammatory conditions (e.g., RA, psoriasis), its mechanism is thought to involve inhibition of AICAR transformylase and thymidylate synthase, leading to accumulation of adenosine, which has anti-inflammatory properties. It also has immunomodulatory effects.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV). Oral bioavailability is variable and dose-dependent.
Tmax:
Subcutaneous: 1-2 hours
FoodEffect:
Not significant for subcutaneous administration.
Distribution:
Vd:
0.4-0.8 L/kg (at low doses); increases with higher doses due to saturation of tissue binding sites.
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at low doses; higher doses or intrathecal administration are required for therapeutic CNS concentrations.
Elimination:
HalfLife:
Low dose (RA/Psoriasis): 3-10 hours (terminal half-life can be longer due to polyglutamation and enterohepatic recirculation).
Clearance:
Primarily renal clearance via glomerular filtration and active tubular secretion.
ExcretionRoute:
Renal (50-90% unchanged), small amount via bile/feces (5-10%).
Unchanged:
50-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial clinical effects; full effect may take 3-6 months.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 3-6 months.
DurationOfAction:
Weekly dosing maintains therapeutic effects.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe toxic reactions including death. Patients should be closely monitored. Methotrexate has been associated with: 1. Bone marrow suppression (myelosuppression), 2. Renal toxicity, 3. Liver toxicity (hepatotoxicity), 4. Pulmonary toxicity (pneumonitis), 5. Gastrointestinal toxicity (e.g., mucositis, diarrhea, ulcerative stomatitis), 6. Opportunistic infections, 7. Tumor lysis syndrome, 8. Dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome). Methotrexate can cause fetal death or teratogenic effects and is contraindicated in pregnant women. Concomitant use with NSAIDs is not recommended with high-dose methotrexate. Accidental daily use instead of weekly use has led to fatal toxicity.
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 experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or Breathing Problems: Shortness of breath, breathing difficulties, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations, weakness, or paralysis.
Other Severe Symptoms: Pinpoint red spots on the skin, severe dizziness or fainting, seizures, confusion, excessive sleepiness, changes in vision, bone pain, or swelling, warmth, numbness, color changes, or pain in a leg or arm.
Stroke-Like Symptoms: Weakness on one side of the body, speech or thinking difficulties, balance changes, facial drooping, or blurred vision.
Other Concerning Symptoms: Headache, neck stiffness.
Common Side Effects
Most people experience minimal or no side effects. However, if you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
Reporting Side Effects
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or Breathing Problems: Shortness of breath, breathing difficulties, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations, weakness, or paralysis.
Other Severe Symptoms: Pinpoint red spots on the skin, severe dizziness or fainting, seizures, confusion, excessive sleepiness, changes in vision, bone pain, or swelling, warmth, numbness, color changes, or pain in a leg or arm.
Stroke-Like Symptoms: Weakness on one side of the body, speech or thinking difficulties, balance changes, facial drooping, or blurred vision.
Other Concerning Symptoms: Headache, neck stiffness.
Common Side Effects
Most people experience minimal or no side effects. However, if you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
Reporting Side Effects
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, sore throat, or other signs of infection
- Unusual bleeding or bruising
- Severe fatigue or weakness
- Shortness of breath or persistent dry cough
- Yellowing of skin or eyes (jaundice)
- Dark urine or pale stools
- Severe nausea, vomiting, or diarrhea
- Mouth sores or ulcers
- Severe skin rash or blistering
- 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. This will help ensure that it is safe to take this medication with your other 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 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. This will help ensure that it is safe to take this medication with your other 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.
When starting this drug, be cautious and avoid driving or engaging in activities that require alertness until you understand how it affects you. 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 careful and avoid injuries. To minimize the risk of bleeding, 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 before drinking.
You may be more prone to sunburn, so it is recommended to avoid direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to safeguard yourself against the sun's harmful effects. Continue to take sun protection measures for as long as advised by your doctor.
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 concerns, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor, as this may affect your treatment. Elderly patients (65 years or older) should use this medication with caution, as they may be more susceptible to side effects.
This drug may impact 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.
When starting this drug, be cautious and avoid driving or engaging in activities that require alertness until you understand how it affects you. 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 careful and avoid injuries. To minimize the risk of bleeding, 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 before drinking.
You may be more prone to sunburn, so it is recommended to avoid direct sunlight, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to safeguard yourself against the sun's harmful effects. Continue to take sun protection measures for as long as advised by your doctor.
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 concerns, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor, as this may affect your treatment. Elderly patients (65 years or older) should use this medication with caution, as they may be more susceptible to side effects.
This drug may impact 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 bone marrow suppression (low white blood cells, red blood cells, platelets)
- Severe mucositis (mouth sores, GI ulcers)
- Severe liver damage
- Kidney failure
What to Do:
Immediately contact your doctor or go to the nearest emergency room. Leucovorin rescue is the primary antidote, administered as soon as possible. Glucarpidase may be used in cases of delayed methotrexate clearance due to renal impairment.
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Pemetrexed (concurrent use may increase methotrexate toxicity)
- Probenecid (decreases renal excretion of methotrexate)
- NSAIDs/Salicylates (high dose methotrexate, risk of severe toxicity)
- Trimethoprim/Sulfamethoxazole (increased risk of bone marrow suppression)
- Alcohol (increased risk of hepatotoxicity)
Major Interactions
- NSAIDs/Salicylates (low dose methotrexate, increased risk of toxicity, monitor closely)
- Proton Pump Inhibitors (PPIs) (e.g., omeprazole, esomeprazole - may increase methotrexate levels, especially at higher doses)
- Penicillins (e.g., amoxicillin, penicillin G - may decrease renal clearance of methotrexate)
- Sulfonamides (e.g., sulfasalazine - may displace methotrexate from protein binding, increase free methotrexate)
- Folic acid antagonists (e.g., trimethoprim, pyrimethamine - additive bone marrow suppression)
- Retinoids (e.g., acitretin - increased risk of hepatotoxicity)
- Phenytoin (may decrease phenytoin levels, or methotrexate toxicity may be increased)
- Theophylline (methotrexate may decrease theophylline clearance)
- Chloramphenicol, tetracyclines (may interfere with enterohepatic recirculation, increasing methotrexate levels)
Moderate Interactions
- Ciprofloxacin (may decrease methotrexate clearance)
- Oral antibiotics (may alter gut flora, affecting enterohepatic recirculation)
- Colchicine (increased risk of myelosuppression)
- Hydroxychloroquine (may increase intracellular methotrexate levels)
- Leflunomide (increased risk of hepatotoxicity and myelosuppression)
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 myelosuppression.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs) - AST, ALT, albumin, bilirubin
Rationale: To establish baseline hepatic function. Methotrexate is hepatotoxic.
Timing: Prior to initiation of therapy
Renal Function Tests - Serum creatinine, BUN, eGFR
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 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.
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 if WBC <3.5 x 10^9/L, Neutrophils <1.5 x 10^9/L, Platelets <100 x 10^9/L, or significant drop in hemoglobin. Re-evaluate and consider dose reduction or discontinuation.
Liver Function Tests (LFTs) - AST, ALT, albumin
Frequency: Every 2-4 weeks for the first 3 months, then every 1-2 months.
Target: AST/ALT <2x upper limit of normal (ULN)
Action Threshold: Hold dose if AST/ALT >2x ULN on two consecutive measurements, or if albumin decreases significantly. Consider liver biopsy if persistent elevation or cumulative dose concerns.
Serum creatinine and eGFR
Frequency: Every 2-4 weeks for the first 3 months, then every 1-2 months.
Target: Within normal limits, stable from baseline.
Action Threshold: Hold dose if creatinine increases by >50% from baseline or if eGFR drops significantly. Re-evaluate and consider dose reduction or discontinuation.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising
- Fatigue, weakness, pallor (anemia)
- Shortness of breath, dry cough (pulmonary toxicity)
- Nausea, vomiting, diarrhea, oral sores/mucositis
- Yellowing of skin or eyes, dark urine (hepatotoxicity)
- Skin rash, itching
- Hair loss
- Headache, dizziness
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. Methotrexate is a known human 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, and skeletal abnormalities) and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, skeletal abnormalities, and other developmental issues.
Third Trimester:
Risk of fetal growth restriction and other developmental issues. May also cause fetal toxicity.
Lactation
Contraindicated during breastfeeding. 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, including bone marrow suppression, growth inhibition, and potential long-term developmental issues.
Pediatric Use
Used for Juvenile Idiopathic Arthritis (JIA) and certain pediatric 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
Use with caution. Elderly patients may have decreased renal and hepatic function, increasing the risk of methotrexate toxicity. More frequent monitoring of CBC, LFTs, and renal function is recommended. Start with lower doses and titrate carefully.
Clinical Information
Clinical Pearls
- Methotrexate is typically dosed ONCE WEEKLY for rheumatoid arthritis and psoriasis. Accidental daily dosing has led to fatal outcomes. Emphasize this to patients.
- Folic acid supplementation (usually 1-5 mg once daily, or 5 mg once weekly, taken on a different day than methotrexate) is crucial to reduce common side effects like nausea, mucositis, and liver enzyme elevations, without significantly impacting efficacy for inflammatory conditions.
- Ensure patients are adequately hydrated to minimize renal toxicity.
- Patients should be advised to avoid alcohol completely due to the risk of additive hepatotoxicity.
- Regular and diligent monitoring of CBC, LFTs, and renal function is paramount to detect and manage toxicity early.
- Subcutaneous administration often has better bioavailability and less GI side effects compared to oral administration, especially at higher doses.
- Counsel patients on the importance of contraception for both males and females during and for a significant period after treatment.
Alternative Therapies
- For Rheumatoid Arthritis: Other conventional 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), JAK inhibitors (e.g., tofacitinib, baricitinib).
- 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).
- For Oncology: Varies widely by cancer type and stage; other chemotherapeutic agents, targeted therapies, immunotherapies.
Cost & Coverage
Average Cost:
Approximately $1,000 - $2,000 per 4-pen pack (30mg/0.6ml)
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (Tier 3 or 4) for brand-name products; generic methotrexate injection may be covered at a lower tier.
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to ensure you receive the best possible care.