Rasuvo 15mg Inj, 0.3ml
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?
Methotrexate is a medication that works by slowing down the growth of certain cells in the body. For conditions like rheumatoid arthritis and psoriasis, it helps to reduce inflammation and suppress the overactive immune system. For cancer, it helps to stop cancer cells from growing.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before using another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions or concerns, consult your doctor or pharmacist.
Dosing and Frequency
Your dose and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use can lead to serious errors. Ensure you understand your dosing schedule and frequency before starting treatment. If you have any doubts, consult your doctor.
Your dosing schedule may be adjusted 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.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
Additional Recommendations
* Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue of the skin, typically on the top of the thigh or in the belly area. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Important Administration Guidelines
Do not inject the medication within 2 inches (5 cm) of the belly button.
Check the solution for cloudiness, leakage, or particles before use. If any of these conditions are present, do not use the medication.
Avoid injecting into skin that is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
If you are unsure whether a dose was injected correctly or experience difficulty administering the dose, consult your doctor or pharmacist before using another dose.
Safe Disposal of Needles and Supplies
Dispose of used needles in a designated needle/sharp disposal box.
Do not reuse needles or other items.
When the disposal box is full, follow local regulations for proper disposal.
If you have any questions or concerns, consult your doctor or pharmacist.
Dosing and Frequency
Your dose and frequency of administration will be determined by your doctor based on the specific health condition being treated.
Important: This medication should never be taken daily unless prescribed for certain types of cancer. Incorrect use can lead to serious errors. Ensure you understand your dosing schedule and frequency before starting treatment. If you have any doubts, consult your doctor.
Your dosing schedule may be adjusted 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.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
Additional Recommendations
* Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Lifestyle & Tips
- Take exactly as prescribed, usually once a week on the same day. Do NOT take daily for arthritis/psoriasis, as this can be fatal.
- Avoid alcohol completely while on methotrexate due to increased risk of liver damage.
- Use effective birth control during treatment and for at least 6 months after stopping for both men and women, as methotrexate can cause severe birth defects or miscarriage.
- Avoid prolonged sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Avoid live vaccines (e.g., MMR, varicella, nasal flu vaccine) while on methotrexate. Discuss all vaccinations with your doctor.
- Stay well-hydrated, especially if taking higher doses.
- Take folic acid or folinic acid (leucovorin) as prescribed by your doctor to reduce side effects, but do not take it on the same day as your methotrexate dose unless specifically instructed.
- Inform your doctor or dentist that you are taking methotrexate before any surgery or dental procedures.
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. Rasuvo 15mg is a specific dose strength.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
rheumatoid_arthritis:
7.5 mg once weekly, adjusted to maximum 20 mg once weekly. Some patients may require up to 25 mg once weekly.
psoriasis:
Initial 10-25 mg once weekly, adjusted based on response and toxicity. Max 30 mg once weekly.
oncology:
Dosing varies significantly by indication (e.g., leukemia, lymphoma, osteosarcoma) and is typically much higher, often requiring leucovorin rescue. Rasuvo is generally not used for high-dose oncology protocols.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Juvenile Idiopathic Arthritis (JIA): 10 mg/m² once weekly, adjusted to maximum 20 mg/m² once weekly or 0.65 mg/kg once weekly (max 25 mg/week). Acute Lymphoblastic Leukemia (ALL): Dosing varies widely based on protocol (e.g., maintenance therapy 20 mg/m² once weekly).
Adolescent:
Similar to child dosing for JIA/ALL, or adult dosing for other indications if applicable.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Use with caution, consider dose reduction (e.g., 75% of dose).
Moderate:
CrCl 31-60 mL/min: Significant dose reduction required (e.g., 50% of dose) or avoid. Monitor closely.
Severe:
CrCl < 30 mL/min: Contraindicated for non-oncologic indications. For oncology, extreme caution, significant dose reduction, or avoid.
Dialysis:
Methotrexate is partially dialyzable. Avoid use in patients on dialysis for non-oncologic indications. For oncology, specific protocols apply, often requiring post-dialysis dosing and leucovorin rescue.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function closely.
Moderate:
Significant caution. Consider dose reduction or avoid, especially if bilirubin > 3-5 mg/dL or AST > 3x ULN. Contraindicated in severe hepatic impairment.
Severe:
Contraindicated (e.g., alcoholic liver disease, cirrhosis, or other significant liver impairment).
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that competitively inhibits dihydrofolate reductase (DHFR), an enzyme essential for DNA synthesis, repair, and cellular replication. By inhibiting DHFR, methotrexate prevents the reduction of dihydrofolate to tetrahydrofolate, a critical co-factor for purine and pyrimidine synthesis. This leads to the inhibition of DNA, RNA, and protein synthesis, particularly in rapidly proliferating cells (e.g., cancer cells, immune cells). At lower doses used for autoimmune diseases, its mechanism is thought to involve inhibition of AICAR transformylase and thymidylate synthase, leading to accumulation of adenosine, which has anti-inflammatory properties, and inhibition of T-lymphocyte proliferation.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV). Oral: Highly variable, 23-90% depending on dose (saturable absorption).
Tmax:
Subcutaneous: 1-2 hours. Oral: 1-5 hours.
FoodEffect:
Oral absorption may be delayed by food, but overall extent of absorption is not significantly affected.
Distribution:
Vd:
0.4-0.8 L/kg (at low doses); higher at high doses due to saturation of tissue binding sites.
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at low doses. At high doses, significant penetration occurs, especially with intrathecal administration.
Elimination:
HalfLife:
Low dose (RA/Psoriasis): 3-10 hours. High dose (Oncology): 8-15 hours (prolonged in renal impairment).
Clearance:
Primarily renal clearance via glomerular filtration and active tubular secretion.
ExcretionRoute:
Renal (primary), small amount via bile/feces.
Unchanged:
Approximately 50-90% of dose excreted unchanged in urine within 24 hours.
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial clinical effects, up to 12 weeks for maximal benefit.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 4-12 weeks.
DurationOfAction:
Effects persist as long as therapy is continued; cessation leads to return of disease activity.
Safety & Warnings
BLACK BOX WARNING
Methotrexate has been associated with severe toxic reactions, including death. Patients should be closely monitored for bone marrow, liver, lung, and kidney toxicities. Methotrexate can cause severe myelosuppression, hepatotoxicity (fibrosis and cirrhosis), pulmonary toxicity (acute and chronic interstitial pneumonitis), and renal toxicity. Diarrhea and ulcerative stomatitis require interruption of therapy. Malignant lymphomas may occur. Opportunistic infections, including Pneumocystis jirovecii pneumonia, may occur. Methotrexate can cause fetal death or teratogenic effects and is contraindicated in pregnant women with non-oncologic diseases. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or significant effusions. Concomitant use with NSAIDs is not recommended for high-dose methotrexate and requires extreme caution with low-dose methotrexate.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
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.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
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, difficulty breathing, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other Severe 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, facial drooping, 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're bothered by any of the following side effects or if they persist, contact your doctor:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
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.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
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, difficulty breathing, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other Severe 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, facial drooping, 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're bothered by any of the following side effects or if they persist, contact your doctor:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, or signs of infection (e.g., sore throat, cough)
- Unusual bleeding or bruising (e.g., nosebleeds, bleeding gums, purple spots on skin)
- Severe mouth sores, ulcers, or swelling in the mouth
- Yellowing of the skin or eyes (jaundice), dark urine, or severe stomach pain (signs of liver problems)
- Shortness of breath, dry cough, or difficulty breathing (signs of lung problems)
- Severe nausea, vomiting, or diarrhea
- Severe fatigue or weakness
- Swelling in your ankles or feet
- Skin rash or peeling skin
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult your doctor to determine the necessary duration of breast-feeding avoidance after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication with your other medications and health conditions. Do not initiate, 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 weak immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult your doctor to determine the necessary duration of breast-feeding avoidance after completing the medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you verify that it is safe to take this medication with your other medications and health conditions. Do not initiate, 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.
Until you understand how this drug affects you, avoid driving and other activities that require alertness. Be aware that you may be more susceptible to infections, so it's crucial to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
You may experience an increased risk of bleeding, so it's vital to be cautious and avoid injuries. To minimize this risk, use a soft toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor.
You may be more prone to sunburn, so it's essential to limit your exposure to the sun, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to safeguard against the sun's harmful effects. Continue to take these precautions for as long as your doctor advises.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and can worsen over time. In some cases, these problems may not improve and can be life-threatening. If you have concerns, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Elderly patients (65 years or older) should use this medication with caution, as they may be more susceptible to side effects.
This drug may affect 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.
Until you understand how this drug affects you, avoid driving and other activities that require alertness. Be aware that you may be more susceptible to infections, so it's crucial to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
You may experience an increased risk of bleeding, so it's vital to be cautious and avoid injuries. To minimize this risk, use a soft toothbrush and an electric razor for shaving.
Before receiving any vaccinations, consult your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss your alcohol consumption with your doctor.
You may be more prone to sunburn, so it's essential to limit your exposure to the sun, sunlamps, and tanning beds. Use sunscreen and wear protective clothing and eyewear to safeguard against the sun's harmful effects. Continue to take these precautions for as long as your doctor advises.
If you experience excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or unusual thirst, notify your doctor promptly. This medication can cause severe nervous system problems, which may be temporary or long-lasting and can worsen over time. In some cases, these problems may not improve and can be life-threatening. If you have concerns, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor. Elderly patients (65 years or older) should use this medication with caution, as they may be more susceptible to side effects.
This drug may affect 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 myelosuppression (low white blood cells, red blood cells, platelets)
- Severe mucositis (mouth sores, gastrointestinal ulcers)
- Severe liver damage
- Kidney failure
- Nausea, vomiting, diarrhea
What to Do:
Immediately contact emergency services or a poison control center (Call 1-800-222-1222). Leucovorin (folinic acid) is the antidote for methotrexate overdose and should be 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 (risk of severe infection in immunosuppressed patients)
- Alcohol (increased risk of hepatotoxicity)
- NSAIDs (high-dose methotrexate, risk of severe myelosuppression and nephrotoxicity)
- Probenecid (decreased renal clearance of methotrexate, increased toxicity)
- Salicylates (decreased renal clearance of methotrexate, increased toxicity)
- Trimethoprim/Sulfamethoxazole (increased antifolate effect, increased toxicity)
Major Interactions
- NSAIDs (low-dose methotrexate, increased methotrexate levels and toxicity, monitor closely)
- Proton Pump Inhibitors (e.g., omeprazole, pantoprazole - may increase methotrexate levels, especially at high doses)
- Penicillins (e.g., amoxicillin, piperacillin - may decrease renal clearance of methotrexate, increased toxicity)
- Ciprofloxacin (may decrease renal clearance of methotrexate, increased toxicity)
- Folic acid antagonists (e.g., trimethoprim, pyrimethamine - increased antifolate effect, increased toxicity)
- Phenytoin (decreased phenytoin levels, increased methotrexate toxicity)
- Theophylline (decreased theophylline clearance)
- Retinoids (e.g., acitretin - increased risk of hepatotoxicity)
- Azathioprine, Mercaptopurine (increased risk of myelosuppression)
Moderate Interactions
- Oral antibiotics (e.g., tetracyclines, chloramphenicol - may alter gut flora, affecting methotrexate absorption/enterohepatic recirculation)
- Sulfonamides (may displace methotrexate from protein binding, increasing free drug)
- Barbiturates (may increase methotrexate metabolism)
- Oral contraceptives (potential for decreased contraceptive efficacy)
- Cholestyramine (may interfere with methotrexate absorption)
- P-glycoprotein inhibitors (potential to increase methotrexate levels)
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.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs) including AST, ALT, albumin, bilirubin
Rationale: To assess baseline hepatic function and detect pre-existing liver disease.
Timing: Prior to initiation of therapy
Renal Function Tests (RFTs) including serum creatinine, BUN, eGFR
Rationale: To assess baseline renal function, as methotrexate is primarily renally cleared.
Timing: Prior to initiation of therapy
Chest X-ray
Rationale: To rule out pre-existing pulmonary disease, as methotrexate can cause pulmonary toxicity.
Timing: Prior to initiation of therapy
Hepatitis B and C serology
Rationale: To screen for chronic viral hepatitis, which can be exacerbated by immunosuppression.
Timing: Prior to initiation of therapy
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: WBC > 3.5 x 10^9/L, Platelets > 100 x 10^9/L, Hemoglobin within normal limits.
Action Threshold: Hold dose if WBC < 3.5 x 10^9/L, ANC < 1.5 x 10^9/L, or Platelets < 100 x 10^9/L. Consider dose reduction or discontinuation.
Liver Function Tests (LFTs) including AST, ALT, albumin
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: AST/ALT < 2x Upper Limit of Normal (ULN).
Action Threshold: Hold dose if AST/ALT > 3x ULN. Consider liver biopsy if persistent elevation or if AST/ALT > 2x ULN on multiple occasions.
Serum Creatinine and eGFR
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: Within normal limits, stable.
Action Threshold: Hold dose or reduce if creatinine increases by > 50% from baseline or if eGFR significantly decreases.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising (petechiae, purpura)
- Severe mouth sores or ulcers (stomatitis, mucositis)
- Yellowing of skin or eyes (jaundice)
- Severe fatigue or weakness
- Shortness of breath, cough, or new onset dyspnea (signs of pulmonary toxicity)
- Severe nausea, vomiting, or diarrhea
- Skin rash or lesions
- Hair loss
Special Patient Groups
Pregnancy
Contraindicated in pregnant women with non-oncologic diseases due to high risk of fetal death and severe birth defects. For oncologic indications, the benefits may outweigh the risks in life-threatening situations, but careful counseling is essential.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, limb, skeletal abnormalities) and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, oligohydramnios, and other adverse outcomes.
Third Trimester:
Risk of fetal growth restriction, oligohydramnios, and other adverse outcomes.
Lactation
Contraindicated. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant, including myelosuppression and growth inhibition.
Infant Risk:
High risk of serious adverse effects.
Pediatric Use
Used in pediatric patients for Juvenile Idiopathic Arthritis (JIA) and certain cancers (e.g., Acute Lymphoblastic Leukemia). Dosing is weight or body surface area-based. Close monitoring for toxicity is crucial, similar to adults.
Geriatric Use
Use with caution in elderly patients due to increased risk of adverse reactions, particularly myelosuppression, renal impairment, and hepatotoxicity. Age-related decline in renal function may necessitate dose adjustments. Close monitoring is essential.
Clinical Information
Clinical Pearls
- Methotrexate for RA/Psoriasis is dosed ONCE WEEKLY. Daily dosing for these indications is a common and potentially fatal medication error.
- Folic acid supplementation (e.g., 1-5 mg once daily, avoiding the methotrexate dosing day) is often prescribed to reduce common side effects like nausea, mucositis, and liver enzyme elevations, without significantly compromising efficacy.
- Subcutaneous administration (like Rasuvo) often has better bioavailability and less GI side effects compared to oral methotrexate, especially at higher doses.
- Patients must be educated on the signs and symptoms of serious toxicities (myelosuppression, hepatotoxicity, pulmonary toxicity) and instructed to seek immediate medical attention if they occur.
- Alcohol consumption is strictly prohibited due to the increased risk of severe hepatotoxicity.
- Renal function is critical for methotrexate elimination; even mild impairment can lead to significant toxicity. Dose adjustments or discontinuation may be necessary.
- Patients should carry a 'methotrexate alert card' or similar identification, especially for high-dose therapy or if there's a risk of overdose.
Alternative Therapies
- Other conventional synthetic DMARDs (csDMARDs) for RA/Psoriasis: Hydroxychloroquine, Sulfasalazine, Leflunomide.
- Biologic DMARDs (bDMARDs) for RA/Psoriasis: 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), IL-17 inhibitors (e.g., Secukinumab), IL-23 inhibitors (e.g., Guselkumab).
- Targeted Synthetic DMARDs (tsDMARDs) / JAK inhibitors: Tofacitinib, Baricitinib, Upadacitinib.
- Other immunosuppressants for severe psoriasis: Cyclosporine, Acitretin.
- For oncology indications, alternatives vary widely based on cancer type and stage.
Cost & Coverage
Average Cost:
Varies widely by pharmacy and insurance plan. Rasuvo 15mg/0.3ml single-dose prefilled syringe can range from $500-$1000+ per syringe without insurance. per single-dose prefilled syringe
Generic Available:
Yes
Insurance Coverage:
Tier 3 or 4 (Specialty drug), often requires prior authorization.
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to discuss them with 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.