Rasuvo 17.5mg Inj, 0.35ml
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, Antipsoriatic, Antineoplastic
Pharmacologic Class
Antimetabolite, Dihydrofolate Reductase Inhibitor, Immunosuppressant
Pregnancy Category
Category X
FDA Approved
Jul 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Rasuvo is a medicine that helps reduce inflammation and slow down certain diseases like rheumatoid arthritis and psoriasis. It works by affecting how your body's cells grow and how your immune system works. It's given as a shot 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. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before using another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other supplies.
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 serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and treatment response.
Your doctor or pharmacist will provide guidance on handling this medication safely.
Additional Recommendations
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. Avoid storing in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor to determine the best course of action.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before using another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other supplies.
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 serious errors. Ensure you understand your dosage and administration schedule. If you are unsure, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and treatment response.
Your doctor or pharmacist will provide guidance on handling this medication safely.
Additional Recommendations
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. Avoid storing in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Take exactly as prescribed, usually once a week. Do NOT take daily.
- Take folic acid supplementation as directed by your doctor to reduce side effects.
- Avoid alcohol consumption, as it can increase the risk of liver damage.
- Avoid excessive sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Maintain good hydration.
- Avoid live vaccines while on methotrexate.
- Inform your doctor about all other medications, including over-the-counter drugs, supplements, and herbal products, especially NSAIDs.
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:
7.5 mg to 25 mg once weekly, administered subcutaneously
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
rheumatoidArthritis:
Initial dose 7.5 mg once weekly, adjusted to optimal response, not to exceed 20 mg once weekly for Rasuvo. Max 25 mg once weekly for other formulations.
psoriasis:
Initial dose 10-25 mg once weekly, adjusted to optimal response, not to exceed 20 mg once weekly for Rasuvo. Max 25 mg once weekly for other formulations.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly.
Adolescent:
Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Doses typically range from 0.4 mg/kg to 0.6 mg/kg once weekly.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Use with caution, monitor closely. No specific dose adjustment for low-dose MTX, but increased risk of toxicity.
Moderate:
CrCl 31-60 mL/min: Reduce dose by 50% or avoid. Use with extreme caution and close monitoring.
Severe:
CrCl < 30 mL/min: Contraindicated.
Dialysis:
Methotrexate is dialyzable, but clearance is variable. Avoid use in patients on dialysis due to prolonged exposure and increased toxicity risk.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function tests closely.
Moderate:
Avoid or use with extreme caution. Significant dose reduction may be necessary. Contraindicated in patients with alcoholic liver disease or other chronic liver disease.
Severe:
Contraindicated.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase (DHFR), an enzyme critical for the synthesis of purine nucleotides and thymidylate, essential for DNA synthesis and cell replication. This leads to inhibition of cell proliferation. In low doses used for inflammatory conditions, 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 immunosuppressive effects by inhibiting lymphocyte proliferation and function.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80-90% (subcutaneous) compared to intravenous administration.
Tmax:
1-2 hours (subcutaneous).
FoodEffect:
Not significantly affected by food when administered subcutaneously.
Distribution:
Vd:
0.4-0.8 L/kg (low doses).
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited penetration into the CNS at low doses; higher doses or intrathecal administration are required for therapeutic CNS concentrations.
Elimination:
HalfLife:
3-10 hours (low dose, for RA/psoriasis).
Clearance:
Primarily renal clearance (glomerular filtration and active tubular secretion).
ExcretionRoute:
Renal (approximately 50-90% unchanged), minor biliary excretion.
Unchanged:
50-90%
Pharmacodynamics
OnsetOfAction:
For rheumatoid arthritis and psoriasis, clinical improvement typically begins within 3-6 weeks, with full therapeutic effect often taking 3-6 months.
PeakEffect:
Not applicable for chronic conditions in terms of acute peak effect; refers to maximal clinical response over months.
DurationOfAction:
Effects persist as long as treatment is continued; cessation leads to gradual loss of therapeutic benefit.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe or fatal toxic reactions. Patients should be closely monitored for bone marrow, liver, lung, and kidney toxicities. Methotrexate has been associated with fetal death and congenital anomalies; it is contraindicated in pregnant women with non-neoplastic disease. Methotrexate can cause severe dermatologic reactions. Methotrexate can cause opportunistic infections. Malignant lymphomas may occur. Diarrhea and ulcerative stomatitis require interruption of therapy. Concomitant use with NSAIDs has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal 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 notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding.
Signs of pancreatitis (pancreas problems): severe stomach pain, severe back pain, or severe nausea and vomiting.
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Signs of liver problems: dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Signs of lung or breathing problems: shortness of breath, difficulty breathing, cough, or fever.
Signs of nerve problems: abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Pinpoint red spots on the skin.
Severe dizziness or fainting.
Seizures.
Confusion.
Excessive sleepiness.
Changes in vision.
Bone pain.
Swelling, warmth, numbness, color changes, or pain in a leg or arm.
Weakness on one side of the body, speech or thinking difficulties, balance changes, facial drooping, or blurred vision.
Headache.
Neck stiffness.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you're bothered by any of the following side effects or if they persist, contact your doctor or seek medical help:
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, 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 or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding.
Signs of pancreatitis (pancreas problems): severe stomach pain, severe back pain, or severe nausea and vomiting.
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Signs of liver problems: dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Signs of lung or breathing problems: shortness of breath, difficulty breathing, cough, or fever.
Signs of nerve problems: abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Pinpoint red spots on the skin.
Severe dizziness or fainting.
Seizures.
Confusion.
Excessive sleepiness.
Changes in vision.
Bone pain.
Swelling, warmth, numbness, color changes, or pain in a leg or arm.
Weakness on one side of the body, speech or thinking difficulties, balance changes, facial drooping, or blurred vision.
Headache.
Neck stiffness.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you're bothered by any of the following side effects or if they persist, contact your doctor or seek medical help:
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, 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:
- Unexplained fever, chills, or signs of infection (e.g., sore throat, cough)
- Unusual bleeding or bruising, extreme fatigue, or paleness (signs of low blood counts)
- Yellowing of skin or eyes, dark urine, severe abdominal pain, or persistent nausea/vomiting (signs of liver problems)
- New or worsening cough, shortness of breath, or chest pain (signs of lung problems)
- Severe diarrhea, mouth sores, or ulcers in the mouth
- Severe skin rash, blistering, or peeling
- Swelling in the legs or ankles, or significant decrease in urination (signs of kidney problems)
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 breastfeeding, please note that you should not breastfeed while taking this medication. Additionally, you may need to avoid breastfeeding for a period after your last dose. Consult your doctor to determine the necessary timeframe.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weakened immune system
If you are breastfeeding, please note that you should not breastfeed while taking this medication. Additionally, you may need to avoid breastfeeding for a period after your last dose. Consult your doctor to determine the necessary timeframe.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before operating a vehicle or engaging in any activity that requires your full attention, make sure you understand how this drug 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 individuals who have infections, colds, or the flu.
Be aware that you may experience easier bleeding, so it is vital to exercise caution and avoid injuries. To minimize the risk of bleeding, use a soft-bristled toothbrush and an electric razor for shaving.
Prior to receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor before drinking.
You may be more prone to sunburn, so it is recommended to avoid direct sunlight, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to shield yourself from the sun, and continue to take these precautions for the duration advised by your doctor.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or abnormal thirst, notify your doctor promptly. This medication may cause severe nervous system problems, which can be temporary or long-lasting and may worsen over time. In some cases, these problems may not be reversible and can be fatal. If you have any concerns or questions, consult with your doctor.
If you have undergone radiation therapy, inform your doctor. Elderly patients (65 years and older) should use this medication with caution, as they may be more susceptible to side effects.
This drug may affect fertility, potentially leading to infertility. 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 any activity that requires your full attention, make sure you understand how this drug 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 individuals who have infections, colds, or the flu.
Be aware that you may experience easier bleeding, so it is vital to exercise caution and avoid injuries. To minimize the risk of bleeding, use a soft-bristled toothbrush and an electric razor for shaving.
Prior to receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor before drinking.
You may be more prone to sunburn, so it is recommended to avoid direct sunlight, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to shield yourself from the sun, and continue to take these precautions for the duration advised by your doctor.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or abnormal thirst, notify your doctor promptly. This medication may cause severe nervous system problems, which can be temporary or long-lasting and may worsen over time. In some cases, these problems may not be reversible and can be fatal. If you have any concerns or questions, consult with your doctor.
If you have undergone radiation therapy, inform your doctor. Elderly patients (65 years and older) should use this medication with caution, as they may be more susceptible to side effects.
This drug may affect fertility, potentially leading to infertility. 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 (e.g., severe leukopenia, thrombocytopenia, anemia)
- Severe mucositis (mouth sores, GI ulcers)
- Severe liver damage
- Acute kidney injury
What to Do:
Immediately seek emergency medical attention. Leucovorin rescue is the primary antidote for methotrexate overdose. Glucarpidase may be used in cases of delayed methotrexate clearance due to impaired renal function. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Trimethoprim/sulfamethoxazole (increased methotrexate toxicity)
- Nitrous oxide (functional folate deficiency, increased methotrexate toxicity)
- Probenecid (decreased methotrexate renal clearance)
- NSAIDs (with high-dose methotrexate, risk of severe myelosuppression and nephrotoxicity)
Major Interactions
- NSAIDs and salicylates (increased methotrexate levels and toxicity, especially with higher methotrexate doses or in patients with renal impairment; use with caution and monitor closely with low-dose methotrexate)
- Proton pump inhibitors (e.g., omeprazole, pantoprazole - may increase methotrexate levels, especially at higher doses)
- Penicillins (e.g., amoxicillin, penicillin G - may decrease methotrexate renal clearance)
- Sulfonamides (e.g., sulfasalazine - may displace methotrexate from protein binding or inhibit renal excretion)
- Phenytoin (may displace methotrexate from protein binding)
- Retinoids (e.g., acitretin - increased risk of hepatotoxicity)
- Other hepatotoxic agents (e.g., azathioprine, leflunomide, alcohol - increased risk of liver toxicity)
- Nephrotoxic agents (e.g., aminoglycosides, cisplatin - increased risk of methotrexate toxicity due to impaired renal clearance)
- Folic acid antagonists (e.g., pyrimethamine - increased methotrexate toxicity)
- Theophylline (methotrexate may decrease theophylline clearance)
Moderate Interactions
- Chloramphenicol (may decrease methotrexate absorption)
- Oral antibiotics (e.g., tetracyclines, chloramphenicol - may alter gut flora, affecting methotrexate enterohepatic recirculation)
- Ciprofloxacin (may decrease methotrexate renal clearance)
- Colchicine (increased risk of myelosuppression)
- Hydroxychloroquine (may increase intracellular methotrexate levels)
- P-glycoprotein inhibitors (potential for altered methotrexate transport)
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, albumin, bilirubin
Rationale: To assess baseline liver function. Methotrexate is hepatotoxic.
Timing: Prior to initiation of therapy.
Renal Function Tests: Serum creatinine, BUN, estimated GFR/CrCl
Rationale: To assess baseline renal function. Methotrexate is primarily renally eliminated, and impaired renal function increases toxicity.
Timing: Prior to initiation of therapy.
Chest X-ray
Rationale: To establish baseline pulmonary status. Methotrexate can cause pulmonary toxicity (pneumonitis).
Timing: Prior to initiation of therapy.
Hepatitis B and C serology
Rationale: To screen for chronic viral hepatitis, which may increase the risk of methotrexate-induced hepatotoxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Monthly for the first 6 months, then every 1-2 months or as clinically indicated.
Target: Within normal limits; maintain neutrophil count >1500/mm³, platelet count >75,000/mm³.
Action Threshold: Significant drop in cell counts (e.g., WBC <3000/mm³, platelets <50,000/mm³), requiring dose reduction or temporary discontinuation.
Liver Function Tests (LFTs): AST, ALT, albumin
Frequency: Monthly for the first 6 months, then every 1-2 months or as clinically indicated.
Target: AST/ALT <2-3 times upper limit of normal (ULN).
Action Threshold: Persistent elevation of AST/ALT >3 times ULN, or significant drop in albumin, requiring dose reduction, temporary discontinuation, or liver biopsy.
Renal Function Tests: Serum creatinine, estimated GFR/CrCl
Frequency: Periodically (e.g., every 3-6 months) or as clinically indicated, especially if risk factors for renal impairment are present.
Target: Within normal limits; stable creatinine.
Action Threshold: Significant increase in serum creatinine or decrease in GFR, requiring dose adjustment or discontinuation.
Symptom Monitoring
- Signs of myelosuppression (e.g., fever, sore throat, unusual bleeding or bruising, fatigue)
- Signs of hepatotoxicity (e.g., jaundice, dark urine, persistent nausea/vomiting, abdominal pain, fatigue)
- Signs of pulmonary toxicity (e.g., new or worsening cough, dyspnea, fever, chest pain)
- Signs of gastrointestinal toxicity (e.g., severe diarrhea, stomatitis, oral ulcers, vomiting)
- Signs of dermatologic reactions (e.g., severe rash, blistering, desquamation)
- Signs of infection (e.g., fever, chills, malaise)
Special Patient Groups
Pregnancy
Contraindicated in pregnant women with non-neoplastic diseases due to significant risk of fetal death and congenital anomalies (Category X). Effective contraception must be used by both male and female patients during and for a specified period after treatment.
Trimester-Specific Risks:
First Trimester:
Highest risk of major congenital malformations (e.g., craniofacial, limb, cardiovascular defects) and fetal death.
Second Trimester:
Risk of fetal growth restriction and other adverse outcomes.
Third Trimester:
Risk of fetal growth restriction and other adverse outcomes.
Lactation
Contraindicated. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant.
Infant Risk:
High risk of serious adverse effects including myelosuppression, immunosuppression, and growth inhibition.
Pediatric Use
Approved for polyarticular juvenile idiopathic arthritis (pJIA). Close monitoring for adverse effects is crucial, similar to adults. Dosage is based on body surface area.
Geriatric Use
Use with caution. Elderly patients may have decreased renal function, increased susceptibility to liver toxicity, and increased risk of myelosuppression. Close monitoring of renal, hepatic, and hematologic parameters is essential. Dose adjustments may be necessary.
Clinical Information
Clinical Pearls
- Methotrexate for inflammatory conditions is dosed ONCE WEEKLY, not daily. Daily dosing can be fatal.
- Folic acid supplementation (typically 1-5 mg once weekly, 24-48 hours after methotrexate dose) is crucial to reduce common side effects like nausea, stomatitis, and liver enzyme elevations, without significantly compromising efficacy.
- Patients should be educated on the importance of avoiding alcohol due to increased risk of hepatotoxicity.
- Regular monitoring of CBC, LFTs, and renal function is mandatory due to the potential for severe toxicities.
- Patients should be advised to report any signs of infection, unusual bleeding/bruising, persistent cough, or jaundice immediately.
- Ensure patients understand the subcutaneous injection technique if self-administering.
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 modulators (e.g., abatacept), B-cell depleting agents (e.g., rituximab)
- Targeted Synthetic DMARDs (tsDMARDs): JAK inhibitors (e.g., tofacitinib, baricitinib, upadacitinib)
- For psoriasis: Phototherapy, other systemic agents (e.g., cyclosporine, apremilast), biologics (e.g., ustekinumab, secukinumab, ixekizumab)
Cost & Coverage
Average Cost:
Varies widely, typically $100-$500+ per month (for weekly injections)
Generic Available:
Yes
Insurance Coverage:
Often Tier 2 or 3, may require prior authorization. Coverage varies by insurance plan.
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 taken, the amount, and the time it happened.