Rasuvo 17.5mg/0.35ml 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 (DMARD), Antineoplastic, Immunosuppressant
Pharmacologic Class
Antimetabolite, Folic acid antagonist
Pregnancy Category
Category X
FDA Approved
Jul 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Rasuvo contains methotrexate, a medicine that works by slowing down the growth of certain cells in the body. For conditions like rheumatoid arthritis and psoriasis, it helps reduce inflammation and overactive immune responses. It is given as a once-weekly injection under the skin.
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 have any doubts, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling.
Additional Recommendations
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor 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 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 have any doubts, consult your doctor.
Monitoring and Adjustments
The way you take this medication may change based on blood work results, side effects, and the medication's effectiveness.
Handle this medication with care, and consult your doctor or pharmacist for guidance on proper handling.
Additional Recommendations
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store this medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom.
Missed Dose
* If you miss a dose, contact your doctor 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 completely while on methotrexate due to increased risk of liver damage.
- Avoid prolonged sun exposure and use sunscreen/protective clothing as methotrexate can cause photosensitivity.
- Avoid live vaccines while on methotrexate.
- Report any signs of infection, unusual bleeding/bruising, severe fatigue, shortness of breath, or yellowing of skin/eyes immediately.
- Maintain good hydration.
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 - 25 mg
Condition-Specific Dosing:
Rheumatoid Arthritis:
Initial: 7.5 mg once weekly. May gradually increase to a maximum of 20 mg once weekly. Doses >20 mg/week may be associated with increased toxicity.
Psoriasis:
Initial: 10 mg to 25 mg once weekly as a single dose, or 2.5 mg every 12 hours for 3 doses each week (not to exceed 30 mg/week). Subcutaneous administration is typically once weekly.
Polyarticular Juvenile Idiopathic Arthritis (pJIA):
0.4 mg/kg once weekly (maximum 25 mg/week).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 0.4 mg/kg once weekly (maximum 25 mg/week).
Adolescent:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 0.4 mg/kg once weekly (maximum 25 mg/week).
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Consider 25% dose reduction or close monitoring.
Moderate:
CrCl 51-60 mL/min: Consider 50% dose reduction. CrCl <50 mL/min: Generally not recommended or contraindicated for non-oncologic indications due to risk of severe toxicity.
Severe:
Contraindicated (CrCl <30 mL/min) for non-oncologic indications.
Dialysis:
Methotrexate is poorly dialyzable by standard hemodialysis. High-flux hemodialysis may remove some. Not recommended for patients on dialysis for non-oncologic indications.
Hepatic Impairment:
Mild:
Use with caution; monitor liver function closely.
Moderate:
Significant dose reduction or avoidance. Contraindicated in patients with severe hepatic impairment (e.g., cirrhosis, fibrosis, or significant liver enzyme abnormalities).
Severe:
Contraindicated.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that competitively inhibits dihydrofolate reductase (DHFR), an enzyme responsible for converting dihydrofolate to tetrahydrofolate. Tetrahydrofolate is essential for DNA synthesis, cell replication, and repair. By inhibiting DHFR, methotrexate interferes with DNA, RNA, and protein synthesis, leading to inhibition of cell proliferation. In rheumatoid arthritis and psoriasis, its anti-inflammatory and immunosuppressive effects are thought to be due to inhibition of lymphocyte proliferation, induction of adenosine release, and inhibition of polymorphonuclear leukocyte chemotaxis.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80-90% for subcutaneous administration (compared to oral).
Tmax:
1-2 hours (subcutaneous).
FoodEffect:
Not significantly affected by food when administered subcutaneously.
Distribution:
Vd:
0.4-0.8 L/kg (at low doses).
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at low doses used for RA/Psoriasis; significant penetration at high, oncologic doses.
Elimination:
HalfLife:
3-10 hours (low dose); 8-15 hours (high dose).
Clearance:
Primarily renal tubular secretion and glomerular filtration.
ExcretionRoute:
Renal (approximately 80-90% unchanged within 24 hours at low doses).
Unchanged:
80-90%
Pharmacodynamics
OnsetOfAction:
Rheumatoid Arthritis/Psoriasis: 3-6 weeks for initial clinical effects; full effect may take 8-12 weeks.
PeakEffect:
Rheumatoid Arthritis/Psoriasis: 8-12 weeks.
DurationOfAction:
Effects persist as long as therapy is continued; cessation leads to gradual loss of effect.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe toxic reactions, including death. Patients should be closely monitored. Deaths have been reported with low-dose methotrexate. Methotrexate has been associated with: 1. Bone marrow suppression (myelosuppression), 2. Renal toxicity, 3. Liver toxicity (hepatotoxicity), 4. Pulmonary toxicity (pneumonitis), 5. Gastrointestinal toxicity (e.g., stomatitis, diarrhea, hemorrhagic enteritis), 6. Opportunistic infections, 7. Tumor lysis syndrome, 8. Dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome). Methotrexate can cause fetal death or teratogenic effects and is contraindicated in pregnancy. Concomitant administration with NSAIDs is not recommended for high-dose methotrexate. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or significant effusions.
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 experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of infection, including:
+ Fever
+ Chills
+ Severe sore throat
+ Ear or sinus pain
+ Cough
+ Increased or changed sputum production
+ Pain while urinating
+ Mouth sores
+ Wounds that won't heal
Signs of bleeding, such as:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that get bigger
+ Uncontrollable bleeding
Signs of pancreatitis (pancreas problems), including:
+ Severe stomach pain
+ Severe back pain
+ Severe upset stomach or vomiting
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine production
+ Blood in the urine
+ Sudden weight gain
Signs of liver problems, including:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of lung or breathing problems, such as:
+ Shortness of breath or other breathing difficulties
+ Cough
+ Fever
Signs of nerve problems, including:
+ Burning, numbness, or tingling sensations
+ Weakness
+ 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
Trouble speaking or thinking
Balance changes
Drooping on one side of the face
Blurred vision
Headache
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 experience any of the following side effects or any other symptoms that bother you or don't go away, contact your doctor:
Decreased appetite
Hair loss
Dizziness
Fatigue
Weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of infection, including:
+ Fever
+ Chills
+ Severe sore throat
+ Ear or sinus pain
+ Cough
+ Increased or changed sputum production
+ Pain while urinating
+ Mouth sores
+ Wounds that won't heal
Signs of bleeding, such as:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that get bigger
+ Uncontrollable bleeding
Signs of pancreatitis (pancreas problems), including:
+ Severe stomach pain
+ Severe back pain
+ Severe upset stomach or vomiting
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine production
+ Blood in the urine
+ Sudden weight gain
Signs of liver problems, including:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of lung or breathing problems, such as:
+ Shortness of breath or other breathing difficulties
+ Cough
+ Fever
Signs of nerve problems, including:
+ Burning, numbness, or tingling sensations
+ Weakness
+ 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
Trouble speaking or thinking
Balance changes
Drooping on one side of the face
Blurred vision
Headache
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 experience any of the following side effects or any other symptoms that bother you or don't go away, contact your doctor:
Decreased appetite
Hair loss
Dizziness
Fatigue
Weakness
Stomach pain
Common cold symptoms
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, sore throat, or other signs of infection.
- Unusual bleeding or bruising.
- Severe fatigue or weakness.
- Shortness of breath, dry cough, or new respiratory symptoms.
- Yellowing of skin or eyes (jaundice), dark urine, or severe abdominal pain (signs of liver problems).
- Severe mouth sores, painful swallowing, or severe diarrhea.
- New or worsening skin rash.
- Swelling in ankles or feet, or significant decrease in urination.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weakened immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult your doctor to determine the necessary duration 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.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weakened immune system
If you are breast-feeding, please note that you should not breast-feed while taking this medication. Additionally, you may need to avoid breast-feeding for a period after your last dose. Consult your doctor to determine the necessary duration 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.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
When starting this medication, be cautious and avoid driving or engaging in activities that require alertness until you understand how it affects you.
You may be more susceptible to infections due to this medication. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
This medication can increase your risk of bleeding. Be mindful of this and take steps to prevent injuries. For example, use a soft-bristled toothbrush and an electric razor for shaving.
Before 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.
It is also important to discuss alcohol consumption with your doctor before drinking.
Your skin may be more sensitive to the sun, increasing the risk of sunburn. To protect yourself, avoid direct sunlight, sunlamps, and tanning beds. Use sunscreen with a suitable SPF and wear protective clothing and eyewear when going outside. Continue to take these precautions for as long as your doctor advises.
If you experience symptoms such as excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or excessive 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 any concerns or questions, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor, as this may impact your treatment.
Individuals aged 65 and older should use this medication with caution, as they may be more prone to side effects.
This medication may affect 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 experience any changes in your menstrual cycle, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
When starting this medication, be cautious and avoid driving or engaging in activities that require alertness until you understand how it affects you.
You may be more susceptible to infections due to this medication. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
This medication can increase your risk of bleeding. Be mindful of this and take steps to prevent injuries. For example, use a soft-bristled toothbrush and an electric razor for shaving.
Before 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.
It is also important to discuss alcohol consumption with your doctor before drinking.
Your skin may be more sensitive to the sun, increasing the risk of sunburn. To protect yourself, avoid direct sunlight, sunlamps, and tanning beds. Use sunscreen with a suitable SPF and wear protective clothing and eyewear when going outside. Continue to take these precautions for as long as your doctor advises.
If you experience symptoms such as excessive fluid loss, unusual sweating, vomiting, diarrhea, decreased appetite, or excessive 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 any concerns or questions, discuss them with your doctor.
If you have undergone radiation therapy, inform your doctor, as this may impact your treatment.
Individuals aged 65 and older should use this medication with caution, as they may be more prone to side effects.
This medication may affect 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 experience any changes in your menstrual cycle, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe bone marrow suppression (e.g., severe neutropenia, thrombocytopenia, anemia)
- Severe mucositis (mouth sores, GI ulceration)
- Severe liver damage
- Renal failure
What to Do:
Immediately contact your doctor or go to the nearest emergency room. Leucovorin calcium is the antidote for methotrexate overdose and should be administered as soon as possible. Hydration and urinary alkalinization may also be used to enhance methotrexate excretion. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Live vaccines (during methotrexate therapy)
- Trimethoprim/sulfamethoxazole (increased myelosuppression)
- Probenecid (decreased renal elimination of methotrexate)
- Nitrous oxide (functional folate deficiency)
Major Interactions
- NSAIDs (e.g., ibuprofen, naproxen, diclofenac) - increased methotrexate levels and toxicity, especially at higher MTX doses or in patients with renal impairment.
- Salicylates (e.g., aspirin) - increased methotrexate levels and toxicity.
- Proton pump inhibitors (e.g., omeprazole, pantoprazole) - increased methotrexate levels, particularly at high doses.
- Penicillins (e.g., amoxicillin, penicillin G) - decreased renal clearance of methotrexate.
- Sulfonamides (e.g., sulfasalazine) - increased methotrexate levels and toxicity.
- Retinoids (e.g., acitretin) - increased risk of hepatotoxicity.
- Other hepatotoxic agents (e.g., azathioprine, leflunomide) - increased risk of liver toxicity.
- Folic acid antagonists (e.g., pyrimethamine) - increased toxicity.
Moderate Interactions
- Theophylline (methotrexate may decrease theophylline clearance).
- Chloramphenicol, tetracyclines (may interfere with enterohepatic recirculation of methotrexate).
- Phenytoin (methotrexate may increase phenytoin levels).
- Oral antibiotics (may alter gut flora, affecting methotrexate absorption/metabolism).
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status and identify 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 identify pre-existing liver disease.
Timing: Prior to initiation of therapy.
Renal Function Tests (serum creatinine, BUN, eGFR)
Rationale: To assess baseline renal function, as methotrexate is primarily renally cleared.
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.
Chest X-ray
Rationale: To establish baseline pulmonary status, especially if patient has pre-existing lung disease or symptoms.
Timing: Prior to initiation of therapy (consider).
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: Maintain within normal limits; monitor for significant drops.
Action Threshold: Hold dose for significant cytopenias (e.g., WBC <3,000/mm³, ANC <1,500/mm³, platelets <100,000/mm³).
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: Maintain within normal limits or stable baseline.
Action Threshold: Hold dose if AST/ALT >2-3 times upper limit of normal (ULN) persistently, or if albumin drops significantly. Consider liver biopsy if persistent abnormalities.
Renal Function Tests (serum creatinine, BUN)
Frequency: Every 2-4 weeks for the first 3-6 months, then every 1-2 months or as clinically indicated.
Target: Maintain within normal limits or stable baseline.
Action Threshold: Hold dose or reduce if creatinine increases by >50% from baseline or if eGFR drops significantly.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising
- Fatigue, weakness, pallor (anemia)
- Shortness of breath, cough (pulmonary toxicity)
- Nausea, vomiting, diarrhea, abdominal pain
- Oral sores, mucositis
- Yellowing of skin or eyes, dark urine (liver toxicity)
- Skin rash, photosensitivity
- Hair loss
- Neurological changes (rare at low doses)
Special Patient Groups
Pregnancy
Contraindicated. Methotrexate is a potent teratogen and abortifacient. It can cause fetal death or severe birth defects.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, skeletal, CNS abnormalities) and spontaneous abortion.
Second Trimester:
Risk of fetal toxicity, growth restriction, and malformations.
Third Trimester:
Risk of fetal toxicity and adverse neonatal outcomes.
Lactation
Contraindicated. Methotrexate is excreted into breast milk and can cause serious adverse reactions in a breastfed infant, including myelosuppression.
Infant Risk:
High risk (L5).
Pediatric Use
Approved for polyarticular Juvenile Idiopathic Arthritis (pJIA). Close monitoring for toxicity is essential. Dosing is weight-based. Safety and efficacy in pediatric patients for other indications (e.g., psoriasis) are not fully established for subcutaneous formulations.
Geriatric Use
Use with caution. Elderly patients may have reduced renal function, increased susceptibility to liver toxicity, and increased risk of myelosuppression and other adverse effects. Close monitoring of renal, hepatic, and hematologic parameters is crucial. Lower doses or less frequent administration may be necessary.
Clinical Information
Clinical Pearls
- Methotrexate is a once-weekly medication. Emphasize this to patients to prevent accidental daily dosing, which can be fatal.
- Folic acid supplementation is crucial to mitigate common side effects like mucositis, GI upset, and myelosuppression, but should be taken at least 24 hours after the methotrexate dose.
- Strict avoidance of alcohol is paramount due to the risk of hepatotoxicity.
- Patients should be educated on signs of infection, bleeding, and organ toxicity and instructed to report them immediately.
- Renal function is critical for methotrexate elimination; ensure adequate hydration and avoid nephrotoxic drugs.
- Subcutaneous administration often improves bioavailability and reduces GI side effects compared to oral administration.
Alternative Therapies
- Other conventional DMARDs (e.g., sulfasalazine, hydroxychloroquine, leflunomide)
- Biologic DMARDs (e.g., TNF inhibitors like adalimumab, etanercept; IL-6 inhibitors, T-cell costimulation modulators)
- Targeted Synthetic DMARDs (tsDMARDs, e.g., JAK inhibitors)
- Phototherapy (for psoriasis)
- Systemic corticosteroids (for acute flares, not long-term)
Cost & Coverage
Average Cost:
Varies widely, typically $500-$1500+ per 4 pens (17.5mg/0.35ml)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (Brand name), Tier 1 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is 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 it's a good idea to check with your pharmacist. 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 detailed information about the overdose, including the medication taken, the amount, and the time it occurred.