Rasuvo 10mg/0.2ml Pf Inj, 4 Pens
WARNING: Severe side effects like bone marrow problems, liver problems, lung problems, and infections can happen with this drug. Some side effects may not go away and can be deadly. You must talk with the doctor about the risks of this drug. This drug may cause kidney problems in some patients. Talk with the doctor.Regular blood work and other exams will need to be done to check for side effects. Follow what the doctor has told you. Tell your doctor if you have kidney problems or extra fluid around your stomach area or lungs. The chance of side effects may be raised.Talk with your doctor if you are getting radiation. There may be more chance of harm to tissue and bone.New types of cancer have happened in people taking this drug. If you have questions, talk with the doctor.It is common to have diarrhea, upset stomach, throwing up, or mouth sores with this drug. However, sometimes these may be signs of severe and sometimes deadly stomach or bowel problems. Tell your doctor if you get any new or worsening signs. You may need to stop this drug.Severe skin reactions have happened with this drug. These have included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and other severe skin reactions. Sometimes these have been deadly. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin; other skin irritation (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.Very bad and sometimes deadly bone marrow problems and stomach or bowel problems have happened when this drug was taken with nonsteroidal anti-inflammatory drug (NSAIDs) like ibuprofen or naproxen.Not all methotrexate products are used to treat cancer. Talk with the doctor.This drug may cause harm to an unborn baby or loss of an unborn baby. A pregnancy test will be done before you start this drug to show that you are NOT pregnant.If you or your sex partner may become pregnant, you must use birth control while taking this drug and for some time after the last dose. Ask your doctor how long to use birth control. If you or your sex partner gets pregnant, call your doctor right away.Do not take if you are pregnant.This drug must only be used when other drugs cannot be used or have not worked. Talk with your doctor to be sure that the benefits of this drug are more than the risks. @ COMMON USES: It is used to treat some types of arthritis.It is used to treat some types of psoriasis.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antirheumatic, Antineoplastic, Immunosuppressant
Pharmacologic Class
Antimetabolite, Folic acid antagonist
Pregnancy Category
Category X
FDA Approved
Jul 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Methotrexate is a medication that works by reducing the activity of your immune system. This helps to decrease inflammation and slow down the progression of certain autoimmune diseases like rheumatoid arthritis and psoriasis. It's given as a weekly injection.
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 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 any questions or concerns, consult your doctor or pharmacist.
Dosing and Frequency
Your dosage and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use of this medication can lead to serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, 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 guidance on proper handling procedures.
Store the medication at room temperature, protected from light and moisture. Do not store in a bathroom.
Hydration
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 moisture. Do not store in a bathroom.
Missed Dose
If you miss a dose, contact your doctor for guidance on what to do next.
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 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 any questions or concerns, consult your doctor or pharmacist.
Dosing and Frequency
Your dosage and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use of this medication can lead to serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, 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 guidance on proper handling procedures.
Store the medication at room temperature, protected from light and moisture. Do not store in a bathroom.
Hydration
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 moisture. Do not store in a bathroom.
Missed Dose
If you miss a dose, contact your doctor for guidance on what to do next.
Lifestyle & Tips
- Take exactly as prescribed, usually once a week on the same day. Do NOT take daily.
- Take folic acid supplementation as directed by your doctor to reduce side effects (e.g., mouth sores, nausea).
- Avoid alcohol completely or limit intake significantly due to increased risk of liver damage.
- Avoid prolonged sun exposure and use sunscreen/protective clothing, as methotrexate can increase sun sensitivity.
- Report any signs of infection (fever, chills, sore throat) immediately.
- Report any unusual bleeding or bruising.
- Report any new or worsening cough or shortness of breath.
- 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, as it can cause severe birth defects.
Available Forms & Alternatives
Available Strengths:
- Rasuvo 10mg/0.2ml Pf Inj, 4 Pens
- Rasuvo 12.5mg/0.25ml Pf Inj, 4 Pens
- Rasuvo 22.5mg/0.45ml Pf Inj, 4 Pens
- Rasuvo 25mg/0.5ml Pf Inj, 4 Pens
- Rasuvo 15mg/0.3ml Pf Inj, 4 Pens
- Rasuvo 17.5mg/0.35ml Pf Inj, 4 Pens
- Rasuvo 20mg/0.4ml Pf Inj, 4 Pens
- Rasuvo 30mg/0.6ml Pf Inj, 4 Pens
- Rasuvo 7.5mg/0.15ml Pf Inj, 4 Pens
- Rasuvo 15mg Inj, 0.3ml
- Rasuvo 17.5mg Inj, 0.35ml
- Rasuvo 20mg Inj, 0.4ml
- Rasuvo 7.5mg Inj, 0.15ml
Dosing & Administration
Adult Dosing
Standard Dose:
For Rheumatoid Arthritis/Psoriasis: 7.5 mg to 20 mg once weekly, administered subcutaneously.
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 are associated with increased toxicity.
psoriasis:
Initial: 10 mg to 25 mg once weekly, administered as a single dose. Doses >30 mg/week are associated with increased toxicity.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses up to 20 mg/m² once weekly have been used.
Adolescent:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, administered subcutaneously. Doses up to 20 mg/m² once weekly have been used.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 50-80 mL/min: Reduce dose by 25-50% or extend dosing interval. Monitor closely.
Moderate:
CrCl 30-50 mL/min: Reduce dose by 50-75% or extend dosing interval. Consider alternative therapy.
Severe:
CrCl <30 mL/min: Contraindicated.
Dialysis:
Methotrexate is dialyzable. Contraindicated due to prolonged elimination and increased toxicity risk.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function tests closely.
Moderate:
Significant liver disease (e.g., cirrhosis, fibrosis): Contraindicated.
Severe:
Significant liver disease (e.g., cirrhosis, fibrosis): Contraindicated.
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 interferes with the synthesis of purine nucleotides and thymidylate, thereby inhibiting cell proliferation. In rheumatoid arthritis and psoriasis, its mechanism is thought to involve immunosuppressive and anti-inflammatory effects, possibly through inhibition of lymphocyte proliferation, inhibition of polymorphonuclear leukocyte chemotaxis, and inhibition of cytokine production.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous bioavailability is approximately 80-94% (compared to IV).
Tmax:
0.75-3 hours (subcutaneous).
FoodEffect:
Not significantly affected by food when administered subcutaneously.
Distribution:
Vd:
0.4-0.8 L/kg (initial), 0.06-0.17 L/kg (steady state).
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited (poor penetration at conventional doses; higher doses may achieve therapeutic levels).
Elimination:
HalfLife:
3-10 hours (low dose, non-oncologic indications); 8-15 hours (high dose).
Clearance:
Primarily renal clearance via glomerular filtration and active tubular secretion.
ExcretionRoute:
Approximately 40-90% excreted unchanged in urine within 24 hours. Small amount excreted in bile.
Unchanged:
40-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis: 3-6 weeks (initial clinical effect), 8-12 weeks (maximal effect). Psoriasis: 1-2 weeks (initial effect), 2-6 weeks (maximal effect).
PeakEffect:
Rheumatoid Arthritis: 8-12 weeks. Psoriasis: 2-6 weeks.
DurationOfAction:
Weekly dosing maintains therapeutic effect; effects persist as long as therapy is continued.
Confidence:
High
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., stomatitis, diarrhea, hemorrhagic enteritis, perforation), 6) Opportunistic infections, 7) Tumor lysis syndrome, 8) Severe dermatologic reactions, 9) Secondary malignancy. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or pleural effusions. Concomitant administration of NSAIDs with high-dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity. Methotrexate can cause fetal death or teratogenic effects when administered to pregnant women. It is contraindicated in pregnant women with non-oncologic diseases. Methotrexate can cause severe skin reactions. Diarrhea and ulcerative stomatitis require interruption of therapy; otherwise, hemorrhagic enteritis and death from intestinal perforation may occur. Malignant lymphomas may occur in patients receiving low-dose methotrexate; these may regress following withdrawal of methotrexate. Methotrexate should be used with extreme caution in the presence of active infection and is generally contraindicated in patients with overt or laboratory evidence of immunodeficiency syndromes.
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Allergic reactions: Rash, hives, itching, 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.
Infections: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, 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, difficulty breathing, cough, or fever.
Nerve problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other serious symptoms: Pinpoint red spots on the skin, severe dizziness or fainting, seizures, confusion, excessive sleepiness, changes in vision, bone pain, swelling, warmth, numbness, color changes, or pain in a leg or arm, weakness on one side of the body, speech or thinking difficulties, balance problems, drooping on one side of the face, or blurred vision, headache, or neck stiffness.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you notice 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, tiredness, or weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Allergic reactions: 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.
Infections: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, 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, difficulty breathing, cough, or fever.
Nerve problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other serious symptoms: Pinpoint red spots on the skin, severe dizziness or fainting, seizures, confusion, excessive sleepiness, changes in vision, bone pain, swelling, warmth, numbness, color changes, or pain in a leg or arm, weakness on one side of the body, speech or thinking difficulties, balance problems, drooping on one side of the face, or blurred vision, headache, or neck stiffness.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you notice 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, tiredness, or weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, or other signs of infection
- Unusual bleeding or bruising
- Severe fatigue or weakness
- Yellowing of skin or eyes (jaundice)
- Dark urine or pale stools
- Severe nausea, vomiting, or diarrhea
- Mouth sores or ulcers
- New or worsening cough, shortness of breath
- Severe skin rash or peeling
- Swelling in ankles or feet
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 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 for avoiding breast-feeding after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Never start, stop, or change the dose of any medication without first consulting your doctor to confirm it is safe to do so.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
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 for avoiding breast-feeding after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. This will help ensure your safety while taking this medication. Never start, stop, or change the dose of any medication without first consulting your doctor to confirm it is safe to do so.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before operating a vehicle or engaging in activities that require alertness, wait until you understand how this drug affects you. Be aware that you may have a higher risk of developing infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Due to the potential for increased bleeding, exercise caution to avoid injuries. For personal grooming, use a soft-bristled toothbrush and an electric razor to reduce the risk of bleeding.
Prior to receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss the consumption of alcohol with your doctor.
You may be more susceptible to sunburn; therefore, limit your exposure to the sun, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to safeguard against the sun's harmful effects. Continue to protect yourself from sunburn for the duration recommended by your doctor.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or abnormal thirst, notify your doctor promptly. This medication has been associated with severe nervous system problems, which can be temporary or long-lasting and may worsen over time. In some cases, these problems may not resolve and can be fatal. If you have concerns, consult with your doctor.
If you have undergone radiation therapy, inform your doctor. Individuals aged 65 and older should use this medication with caution, as they may be more prone to side effects.
This drug may impact fertility, potentially leading to difficulties in becoming pregnant or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Before operating a vehicle or engaging in activities that require alertness, wait until you understand how this drug affects you. Be aware that you may have a higher risk of developing infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Due to the potential for increased bleeding, exercise caution to avoid injuries. For personal grooming, use a soft-bristled toothbrush and an electric razor to reduce the risk of bleeding.
Prior to receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss the consumption of alcohol with your doctor.
You may be more susceptible to sunburn; therefore, limit your exposure to the sun, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to safeguard against the sun's harmful effects. Continue to protect yourself from sunburn for the duration recommended by your doctor.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or abnormal thirst, notify your doctor promptly. This medication has been associated with severe nervous system problems, which can be temporary or long-lasting and may worsen over time. In some cases, these problems may not resolve and can be fatal. If you have concerns, consult with your doctor.
If you have undergone radiation therapy, inform your doctor. Individuals aged 65 and older should use this medication with caution, as they may be more prone to side effects.
This drug may impact fertility, potentially leading to difficulties in becoming pregnant or fathering a child. It is unclear whether fertility will return to normal if this occurs. If you miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe bone marrow suppression (low blood counts)
- Severe mucositis (mouth sores)
- Gastrointestinal bleeding
- Liver damage
- Kidney failure
What to Do:
Seek immediate medical attention. The antidote is leucovorin (folinic acid), which helps to counteract the effects of methotrexate. Glucarpidase may be used in cases of delayed methotrexate clearance due to renal impairment. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Trimethoprim/sulfamethoxazole (increased methotrexate levels and toxicity)
- Probenecid (decreased renal excretion of methotrexate)
- Salicylates (high dose) (decreased renal excretion of methotrexate)
- Non-steroidal anti-inflammatory drugs (NSAIDs) (caution, especially with high-dose methotrexate; can increase methotrexate levels and toxicity)
- Alcohol (increased risk of hepatotoxicity)
- Hepatotoxic agents (e.g., retinoids, azathioprine, sulfasalazine, leflunomide) (increased risk of hepatotoxicity)
- Nephrotoxic agents (e.g., cisplatin, aminoglycosides) (increased risk of methotrexate toxicity due to impaired renal clearance)
Major Interactions
- Folic acid antagonists (e.g., trimethoprim, pyrimethamine) (additive antifolate effects, increased toxicity)
- Proton pump inhibitors (PPIs) (e.g., omeprazole, pantoprazole) (may increase methotrexate levels, especially at high doses, by inhibiting renal elimination)
- Penicillins (e.g., amoxicillin, penicillin G) (may decrease renal clearance of methotrexate)
- Ciprofloxacin (may decrease renal clearance of methotrexate)
- Oral antibiotics (e.g., tetracyclines, chloramphenicol) (may alter gut flora, affecting methotrexate absorption/enterohepatic recirculation)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Theophylline (decreased theophylline clearance)
- Sulfonamides (increased methotrexate toxicity)
Moderate Interactions
- Oral contraceptives (may decrease methotrexate levels)
- Cholestyramine (may decrease methotrexate absorption)
- L-asparaginase (antagonizes methotrexate effect)
- Nitrous oxide (may potentiate methotrexate toxicity by inhibiting methionine synthase)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status and detect myelosuppression.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To establish baseline liver function and detect hepatotoxicity.
Timing: Prior to initiation of therapy.
Renal Function Tests (serum creatinine, BUN, estimated GFR)
Rationale: To establish baseline renal function, as methotrexate is primarily renally cleared.
Timing: Prior to initiation of therapy.
Chest X-ray
Rationale: To establish baseline pulmonary status and rule out pre-existing lung disease, given risk of pneumonitis.
Timing: Prior to initiation of therapy.
Hepatitis B and C serology
Rationale: To screen for viral hepatitis, which can increase risk of hepatotoxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Weekly for the first month, then every 2-4 weeks for the next 2 months, then monthly or every 1-2 months thereafter.
Target: Maintain WBC >3,000/mm³, ANC >1,500/mm³, Platelets >100,000/mm³.
Action Threshold: Hold dose if significant drop in counts (e.g., WBC <3,000/mm³, ANC <1,500/mm³, Platelets <100,000/mm³). Consider dose reduction or discontinuation.
Liver Function Tests (AST, ALT, albumin, bilirubin)
Frequency: Every 2-4 weeks for the first 2 months, then monthly or every 1-2 months thereafter.
Target: AST/ALT <2-3 times upper limit of normal (ULN).
Action Threshold: Hold dose if AST/ALT >3 times ULN. Consider liver biopsy if persistent elevations or cumulative dose concerns.
Renal Function Tests (serum creatinine, BUN)
Frequency: Monthly or every 1-2 months.
Target: Within normal limits or stable baseline.
Action Threshold: Hold dose or reduce dose if creatinine increases by >50% or significantly above baseline.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising (petechiae, purpura)
- Fatigue, weakness, pallor (anemia)
- Oral ulcers, stomatitis, gingivitis
- Nausea, vomiting, diarrhea, abdominal pain
- Yellowing of skin or eyes (jaundice), dark urine, light-colored stools
- Shortness of breath, cough (especially dry, non-productive), chest pain
- Skin rash, itching
- Hair loss
- Headache, dizziness, confusion (rare, CNS toxicity)
Special Patient Groups
Pregnancy
Contraindicated in pregnant women with non-oncologic diseases due to significant risk of fetal death and severe birth defects (teratogenic effects).
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, limb, skeletal abnormalities) and fetal death.
Second Trimester:
Risk of fetal death and growth restriction.
Third Trimester:
Risk of fetal death and growth restriction.
Lactation
Contraindicated. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant.
Infant Risk:
High risk of myelosuppression, immunosuppression, and other toxicities.
Pediatric Use
Used in pediatric patients for Juvenile Idiopathic Arthritis (JIA) and certain oncologic indications. Dosing is typically weight or body surface area-based. Close monitoring for adverse effects is crucial, similar to adults.
Geriatric Use
Use with caution. Elderly patients may have reduced renal function, which can lead to increased methotrexate levels and toxicity. Close monitoring of renal function and blood counts is essential. Lower starting doses or less frequent dosing may be appropriate.
Clinical Information
Clinical Pearls
- Methotrexate is a weekly dose medication. Emphasize this to patients to prevent accidental daily dosing, which can be fatal.
- Folic acid supplementation (usually 1-5 mg once weekly, taken on a different day than methotrexate) is crucial to reduce common side effects like nausea, stomatitis, and liver enzyme elevations, without significantly compromising efficacy.
- Patients should be well-hydrated to promote renal excretion of methotrexate.
- Avoid concomitant use of NSAIDs, salicylates, and PPIs, especially with higher methotrexate doses, or use with extreme caution and close monitoring due to potential for increased methotrexate levels and toxicity.
- Educate patients on the importance of reporting any signs of infection, bleeding, or respiratory symptoms immediately.
- Liver biopsy may be considered for patients with persistent or progressive liver enzyme elevations, or after a certain cumulative dose, especially in psoriasis patients, though this practice is less common now with improved monitoring.
Alternative Therapies
- Other conventional synthetic DMARDs (e.g., sulfasalazine, hydroxychloroquine, leflunomide)
- Biologic DMARDs (e.g., TNF inhibitors like adalimumab, etanercept, infliximab; IL-6 inhibitors like tocilizumab; T-cell costimulation modulators like abatacept; B-cell depleting agents like rituximab)
- Targeted Synthetic DMARDs (tsDMARDs) / JAK inhibitors (e.g., tofacitinib, baricitinib, upadacitinib)
- Phototherapy (for psoriasis)
- Systemic corticosteroids (for acute flares, not long-term management)
Cost & Coverage
Average Cost:
Varies widely by pharmacy and insurance plan per 4 pens
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (Brand), Tier 1 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.