From the Guidelines
The starting dose of methotrexate should be 10-15 mg/week, with escalation of 5 mg every 2-4 weeks up to 20-30 mg/week, depending on clinical response and tolerability, as recommended by the most recent guidelines 1. When initiating methotrexate therapy, it is essential to consider the patient's individual risk factors, such as alcohol intake, and to perform baseline laboratory tests, including complete blood count, liver function, and kidney function, as suggested by the multinational evidence-based recommendations 1.
- Key considerations for methotrexate therapy include:
- Starting dose: 10-15 mg/week, with the possibility of escalation based on clinical response and tolerability
- Dose escalation: 5 mg every 2-4 weeks, up to a maximum of 20-30 mg/week
- Administration: oral or parenteral, with the oral route preferred, according to the 2021 American College of Rheumatology guideline 1
- Folic acid supplementation: 1 mg daily or 5 mg weekly, taken 24-48 hours after methotrexate, to reduce side effects, as recommended by the multinational evidence-based recommendations 1
- Monitoring: regular laboratory tests, including complete blood count, liver function, and kidney function, every 4-8 weeks, to assess for toxicity, as suggested by the joint American Academy of Dermatology-National Psoriasis Foundation guidelines 1 The most recent and highest quality study, the 2021 American College of Rheumatology guideline, provides the basis for these recommendations, prioritizing morbidity, mortality, and quality of life as the primary outcomes 1.
From the FDA Drug Label
The recommended starting dosage of Methotrexate Injection is 7.5 mg once weekly, administered intramuscularly with escalation to achieve optimal response. The recommended starting dosage of Methotrexate Injection is 10 mg/m2 once weekly administered subcutaneously or intramuscularly, with escalation to achieve optimal response. The recommended dosage of Methotrexate Injection is 10 mg to 25 mg intramuscularly or intravenously once weekly until adequate response is achieved.
The starting dose of methotrexate is:
- 7.5 mg once weekly for Rheumatoid Arthritis
- 10 mg/m2 once weekly for Polyarticular Juvenile Idiopathic Arthritis
- 10 mg to 25 mg once weekly for Psoriasis 2 2
From the Research
Starting Dose of Methotrexate
- The initial dose of methotrexate should not be less than 10mg/week, preferably orally 3
- A linear dose-response relationship for starting dose was found between 5 mg/m2/week (7.5-10 mg/week) and 10 mg/m2/week (15-22 mg/week), without toxicity correlation 4
- A higher initial dose of MTX (25 mg vs. 15 mg) was more effective, resulting in fewer dose increases due to ineffectiveness and more dose reductions due to higher remission rates 4
Route of Administration
- The parenteral route, most often performed subcutaneously, has some additional benefits over the oral route 5
- Subcutaneous MTX showed a statistically higher ACR20 response (85%) in comparison with oral MTX (77%) (p < 0.05) 4
- Changing to a parenteral administration is proposed when the oral route is not effective enough, gastrointestinal toxicity appears, there is non-compliance or due to cost-effectiveness reasons before using more expensive drugs 3
Dose Escalation and Reduction
- Rapid dose escalation is recommended if inadequate responses occur up to 15-20 or even 25mg/week in about 8 weeks, with increments of 2.5-5mg 3
- The reduction will be carried out according to the dose the patient had, with decreases of 2.5-5mg every 3-6 months 3
- In RA patients who have failed the initial treatment with MTX, the stepwise increase in MTX doses is associated with a higher ACR20 response and sustained remission rate than other strategies 4