Otrexup 12.5/0.4ml Inj, 0.4ml
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
Antineoplastic, Antirheumatic, Immunosuppressant
Pharmacologic Class
Antimetabolite, Folic acid antagonist
Pregnancy Category
Category X
FDA Approved
Oct 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Otrexup 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 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 questions or concerns, 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.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store the medication at room temperature, protected from light and moisture.
Keep the medication out of the 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 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 questions or concerns, 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.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit fluid intake.
Storage and Disposal
Store the medication at room temperature, protected from light and moisture.
Keep the medication out of the bathroom.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Take exactly as prescribed, usually once a week. Do NOT take daily.
- Take folic acid or folinic acid supplementation as directed by your doctor to reduce side effects.
- Avoid alcohol completely while on methotrexate, as it can significantly increase the risk of liver damage.
- Stay well-hydrated, especially during the first few days after your weekly dose.
- Avoid prolonged sun exposure and use sunscreen, as methotrexate can increase sun sensitivity.
- Report any signs of infection (fever, chills, sore throat) immediately.
- Avoid live vaccines while on methotrexate.
- Discuss all other medications, including over-the-counter drugs, supplements, and herbal remedies, with your doctor or pharmacist before taking them.
Available Forms & Alternatives
Available Strengths:
- Otrexup 10mg/0.4ml Pf Inj 4 X 0.4ml
- Otrexup 15mg/0.4ml Pf Inj 4 X 0.4ml
- Otrexup 20mg/0.4ml Pf Inj 4 X 0.4ml
- Otrexup 25mg/0.4ml Pf Inj 4 X 0.4ml
- Otrexup 10mg/0.4ml Inj, 0.4ml
- Otrexup 17.5mg/0.4ml Pf Injection
- Otrexup 12.5/0.4ml Inj, 0.4ml
- Otrexup 22.5/0.4ml Inj, 0.4ml
- Otrexup 17.5mg/0.4ml Pf Injection
- Otrexup 22.5/0.4ml Inj, 0.4ml
Dosing & Administration
Adult Dosing
Standard Dose:
For Rheumatoid Arthritis/Psoriasis: 7.5 mg to 25 mg once weekly, administered subcutaneously. Otrexup 12.5 mg/0.4 mL is a specific pre-filled syringe strength.
Dose Range:
7.5 - 25 mg
Condition-Specific Dosing:
rheumatoid_arthritis:
7.5 mg to 25 mg once weekly, adjusted to achieve optimal response.
psoriasis:
10 mg to 25 mg once weekly, adjusted based on response and tolerability. Initial dose may be 2.5 mg three times at 12-hour intervals for a total of 7.5 mg/week.
Pediatric Dosing
Neonatal:
Not established for RA/Psoriasis. Used in oncology with specific protocols.
Infant:
Not established for RA/Psoriasis. Used in oncology with specific protocols.
Child:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Max 20 mg/week.
Adolescent:
For Polyarticular Juvenile Idiopathic Arthritis (pJIA): 10 mg/m² once weekly, administered subcutaneously. Max 20 mg/week. For Psoriasis/RA, adult dosing may apply based on weight/BSA.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 61-80 mL/min: Consider 25% dose reduction or increased monitoring.
Moderate:
CrCl 51-60 mL/min: Consider 50% dose reduction. CrCl <50 mL/min: Generally not recommended or significantly reduced dose with extreme caution.
Severe:
CrCl <30 mL/min: Contraindicated due to risk of severe toxicity.
Dialysis:
Methotrexate is partially dialyzable. Dosing in patients on dialysis is complex and generally contraindicated for non-oncologic indications due to prolonged elimination and toxicity risk. Consult specialist.
Hepatic Impairment:
Mild:
Use with caution. Monitor liver function closely.
Moderate:
Significant caution, dose reduction may be necessary. Avoid if significant liver disease (e.g., cirrhosis, fibrosis).
Severe:
Contraindicated in patients with severe hepatic impairment, including alcoholic liver disease, cirrhosis, or significant fibrosis.
Pharmacology
Mechanism of Action
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase (DHFR), an enzyme essential for DNA synthesis, repair, and cellular replication. By inhibiting DHFR, methotrexate prevents the reduction of dihydrofolate to tetrahydrofolate, a critical cofactor in the synthesis of purine nucleotides and thymidylate. This leads to inhibition of DNA, RNA, and protein synthesis. In rheumatoid arthritis and psoriasis, its anti-inflammatory and immunosuppressive effects are thought to be mediated by inhibition of lymphocyte proliferation, induction of adenosine release (which has anti-inflammatory properties), and inhibition of polymorphonuclear leukocyte chemotaxis.
Pharmacokinetics
Absorption:
Bioavailability:
Subcutaneous: Approximately 80-90% (compared to IV). Oral bioavailability is variable and dose-dependent (e.g., 30-50% at doses >30 mg/m²).
Tmax:
Subcutaneous: 1-2 hours.
FoodEffect:
Not significant for subcutaneous administration. Oral absorption may be delayed by food.
Distribution:
Vd:
Approximately 0.4-0.8 L/kg (initial phase), 0.2-0.3 L/kg (steady state).
ProteinBinding:
Approximately 50% (primarily to albumin).
CnssPenetration:
Limited at conventional doses; significant penetration only occurs with high-dose intravenous administration followed by leucovorin rescue, or intrathecal administration.
Elimination:
HalfLife:
Low dose (e.g., for RA/Psoriasis): 3-10 hours. High dose (e.g., for oncology): 8-15 hours.
Clearance:
Primarily renal clearance via glomerular filtration and active tubular secretion.
ExcretionRoute:
Renal (approximately 50-90% unchanged), small amount via biliary excretion (5-10%).
Unchanged:
50-90% (renal excretion).
Pharmacodynamics
OnsetOfAction:
For RA/Psoriasis: Clinical improvement typically seen within 3-6 weeks, with maximal benefit often taking 3-6 months.
PeakEffect:
Not applicable for chronic conditions; refers to sustained therapeutic effect.
DurationOfAction:
Weekly dosing maintains therapeutic effect for chronic conditions.
Safety & Warnings
BLACK BOX WARNING
Methotrexate can cause severe toxic reactions, including death. Patients should be closely monitored for bone marrow, liver, lung, and kidney toxicities. Methotrexate has been associated with severe myelosuppression, hepatotoxicity, nephrotoxicity, pulmonary toxicity, and gastrointestinal toxicity. Methotrexate can cause fetal death or teratogenic effects when administered to pregnant women. Methotrexate can cause severe skin reactions. Methotrexate can cause tumor lysis syndrome. Methotrexate can cause opportunistic infections. Methotrexate elimination is reduced in patients with impaired renal function, ascites, or pleural effusions. Concomitant administration of NSAIDs with high-dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity. Methotrexate should be used only by physicians whose knowledge and experience include the use of antimetabolite therapy. Patients should be fully informed of the risks involved and be under constant supervision.
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 changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that get bigger, or uncontrollable bleeding.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or Breathing Problems: Shortness of breath, difficulty breathing, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other Serious Symptoms: Pinpoint red spots on the skin, severe dizziness or fainting, seizures, confusion, excessive sleepiness, changes in vision, bone pain, swelling, warmth, numbness, color changes, or pain in a leg or arm, weakness on one side of the body, speech or thinking difficulties, balance changes, facial drooping, blurred vision, headache, or neck stiffness.
Common Side Effects
Most people experience few or no side effects. However, if you notice any of the following symptoms, contact your doctor if they bother you or don't go away:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
Reporting Side Effects
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 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 changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruises that get bigger, or uncontrollable bleeding.
Pancreatitis: Severe stomach pain, severe back pain, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, nausea or stomach pain, light-colored stools, vomiting, or yellow skin and eyes.
Lung or Breathing Problems: Shortness of breath, difficulty breathing, cough, or fever.
Nerve Problems: Abnormal burning, numbness, or tingling sensations; weakness; or paralysis (inability to move a body part).
Other Serious Symptoms: Pinpoint red spots on the skin, severe dizziness or fainting, seizures, confusion, excessive sleepiness, changes in vision, bone pain, swelling, warmth, numbness, color changes, or pain in a leg or arm, weakness on one side of the body, speech or thinking difficulties, balance changes, facial drooping, blurred vision, headache, or neck stiffness.
Common Side Effects
Most people experience few or no side effects. However, if you notice any of the following symptoms, contact your doctor if they bother you or don't go away:
Decreased appetite
Hair loss
Dizziness, fatigue, or weakness
Stomach pain
Common cold symptoms
Reporting Side Effects
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:
- Unexplained fever or chills
- Sore throat or mouth sores
- Unusual bleeding or bruising
- Extreme tiredness or weakness
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Severe nausea, vomiting, or diarrhea
- Shortness of breath or persistent dry cough
- Severe skin rash or peeling skin
- Swelling in ankles or feet
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the 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
Additionally, if you are breast-feeding, please note that you should not breast-feed while taking this medication. Your doctor will advise you on whether you need to avoid breast-feeding for a period after your last dose.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins
Any health problems you have
This information will help your doctor determine whether it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Alcohol use disorder
+ Bone marrow disease, such as low white blood cell count, low platelet count, or anemia
+ Kidney disease
+ Liver disease
+ A weak immune system
Additionally, if you are breast-feeding, please note that you should not breast-feed while taking this medication. Your doctor will advise you on whether you need to avoid breast-feeding for a period after your last dose.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins
Any health problems you have
This information will help your doctor determine whether it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before engaging in activities that require alertness, such as driving, wait until you understand how this drug affects you. Be aware that you may have a higher risk of developing infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Due to the potential for increased bleeding, exercise caution to avoid injuries. Use a soft-bristled toothbrush and an electric razor for shaving.
Consult your doctor before receiving any vaccinations, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss the consumption of alcohol with your doctor.
You may be more susceptible to sunburn; therefore, limit your exposure to the sun, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to prevent sunburn. Continue to protect yourself from the sun as advised by your doctor.
If you experience fluid loss, excessive 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 potentially life-threatening. If you have concerns or questions, 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 prone to side effects.
This drug 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 miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Before engaging in activities that require alertness, such as driving, wait until you understand how this drug affects you. Be aware that you may have a higher risk of developing infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Due to the potential for increased bleeding, exercise caution to avoid injuries. Use a soft-bristled toothbrush and an electric razor for shaving.
Consult your doctor before receiving any vaccinations, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication. Additionally, discuss the consumption of alcohol with your doctor.
You may be more susceptible to sunburn; therefore, limit your exposure to the sun, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to prevent sunburn. Continue to protect yourself from the sun as advised by your doctor.
If you experience fluid loss, excessive 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 potentially life-threatening. If you have concerns or questions, 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 prone to side effects.
This drug 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 miss a menstrual period, have unprotected sex, or suspect that your birth control has failed, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe bone marrow suppression (low white blood cells, red blood cells, platelets)
- Severe mucositis (mouth sores, gastrointestinal inflammation)
- Liver damage
- Kidney failure
- Nausea, vomiting, diarrhea
What to Do:
Seek immediate medical attention. The antidote is leucovorin (folinic acid), which can counteract the toxic effects of methotrexate. Glucarpidase may be used in cases of very high methotrexate levels with renal dysfunction. Call 911 or your local emergency number, or the Poison Control Center at 1-800-222-1222.
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Trimethoprim/sulfamethoxazole (increased methotrexate levels and toxicity)
- Probenecid (decreased renal excretion of methotrexate)
- Salicylates (high dose methotrexate, decreased renal excretion)
- Phenytoin (increased methotrexate levels and toxicity)
- Retinoids (e.g., acitretin, etretinate - increased risk of hepatotoxicity)
- Nitrous oxide (functional folate deficiency, myelosuppression)
Major Interactions
- NSAIDs (non-steroidal anti-inflammatory drugs) - concurrent use with low-dose methotrexate requires caution and close monitoring due to potential for increased methotrexate levels and toxicity (especially renal, hematologic). Avoid with high-dose methotrexate.
- Proton Pump Inhibitors (PPIs) - may increase methotrexate levels, especially at high doses.
- Penicillins, Sulfonamides, Tetracyclines, Chloramphenicol - may decrease renal clearance of methotrexate, increasing toxicity.
- Folic acid antagonists (e.g., pyrimethamine, triamterene) - additive folate antagonism, increased toxicity.
Moderate Interactions
- Theophylline (methotrexate may increase theophylline levels)
- Cyclosporine (may increase methotrexate levels and vice versa, increased risk of nephrotoxicity)
- Other hepatotoxic drugs (e.g., azathioprine, leflunomide, sulfasalazine) - increased risk of liver toxicity.
- Other myelosuppressive drugs (e.g., azathioprine, chloramphenicol) - increased risk of bone marrow suppression.
Minor Interactions
- Not many specific minor interactions; general caution with drugs that affect renal function or are highly protein-bound.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status and detect pre-existing myelosuppression.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs) - 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 - Serum creatinine, BUN, eGFR
Rationale: To assess baseline renal function, as methotrexate is primarily renally eliminated.
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 increase risk of liver toxicity.
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 1-3 months or as clinically indicated.
Target: WBC >3,500/mm³, Platelets >100,000/mm³, Hemoglobin stable.
Action Threshold: Hold dose if WBC <3,000/mm³, Platelets <100,000/mm³, or significant drop in hemoglobin. Investigate and consider dose adjustment or discontinuation.
Liver Function Tests (LFTs) - AST, ALT, albumin
Frequency: Monthly for the first 6 months, then every 1-3 months or as clinically indicated.
Target: AST/ALT <2x upper limit of normal (ULN).
Action Threshold: Hold dose if AST/ALT >2x ULN. If persistent, consider liver biopsy or discontinuation. Avoid if AST/ALT >3x ULN at baseline.
Renal Function Tests - Serum creatinine, eGFR
Frequency: Monthly for the first 6 months, then every 1-3 months or as clinically indicated.
Target: Creatinine stable, eGFR within normal limits for age.
Action Threshold: Hold dose or reduce if creatinine increases significantly or eGFR declines. Avoid if CrCl <30 mL/min.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising
- Fatigue, weakness (signs of anemia)
- Shortness of breath, cough (signs of pulmonary toxicity)
- Oral sores, mucositis
- Nausea, vomiting, diarrhea
- Yellowing of skin or eyes, dark urine (signs of liver toxicity)
- Skin rash, itching
Special Patient Groups
Pregnancy
Contraindicated. Methotrexate is a known human teratogen and abortifacient. It can cause fetal death or severe birth defects.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations (e.g., craniofacial, limb, cardiovascular defects) and spontaneous abortion.
Second Trimester:
Risk of fetal growth restriction, skeletal abnormalities, and other developmental issues.
Third Trimester:
Risk of fetal growth restriction, bone marrow suppression in the neonate, and other adverse effects.
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 due to systemic exposure to methotrexate.
Pediatric Use
Used for polyarticular juvenile idiopathic arthritis (pJIA) and certain pediatric cancers. Dosing is typically weight or body surface area (BSA) based. Close monitoring for toxicity is essential. Not for use in children under 2 years of age for pJIA.
Geriatric Use
Use with caution. Elderly patients may have reduced renal function, which can lead to decreased methotrexate clearance and increased risk of toxicity. Close monitoring of renal function, CBC, and LFTs is crucial. Lower doses or less frequent administration may be necessary.
Clinical Information
Clinical Pearls
- Methotrexate for RA/Psoriasis is dosed ONCE WEEKLY, not daily. Daily dosing can be fatal.
- Folic acid supplementation (typically 1-5 mg once daily, or 5 mg once weekly on a non-methotrexate day) is crucial to reduce common side effects like mucositis, nausea, and liver enzyme elevations, without significantly reducing efficacy.
- Patients must be educated on the importance of avoiding alcohol due to the increased risk of hepatotoxicity.
- Ensure patients understand proper subcutaneous injection technique if self-administering.
- Monitor for signs of pulmonary toxicity (e.g., new or worsening cough, dyspnea), which can occur acutely or chronically and may be fatal.
- Patients should carry a card or wear a medical alert bracelet indicating they are on methotrexate, especially for weekly dosing, to prevent accidental overdose in emergency situations.
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), IL-17 inhibitors (e.g., Secukinumab), IL-23 inhibitors (e.g., Guselkumab)
- Targeted Synthetic DMARDs (tsDMARDs): JAK inhibitors (e.g., Tofacitinib, Baricitinib, Upadacitinib)
- Phototherapy (for psoriasis)
Cost & Coverage
Average Cost:
Varies widely by strength and pharmacy. For Otrexup 12.5 mg/0.4 mL, typically $500-$1000+ per month (4 syringes). per 4 pre-filled syringes
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'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 this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.