What are the commonalities between the metabolism of subcutaneous Methotrexate, Hydrocodone, Actemra (Tocilizumab), Rituximab, and Mycophenolate?

From the Guidelines

The commonalities between the metabolism of subcutaneous methotrexate, hydrocodone, actemra (tocilizumab), rituximab, and mycophenolate are limited, with the primary commonality being the involvement of hepatic processes to some degree for most of these medications, though through different mechanisms, as noted in the 2020 guidelines for the management of psoriasis with systemic nonbiologic therapies 1. The metabolism of these medications varies significantly:

• Methotrexate is primarily eliminated unchanged through the kidneys, with some hepatic metabolism, and its use requires careful monitoring of renal function and liver enzymes, as outlined in the multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders 1.
• Hydrocodone, an opioid, undergoes extensive hepatic metabolism via CYP2D6 and CYP3A4 enzymes.
• Actemra and rituximab are monoclonal antibodies that are cleared through proteolytic degradation rather than traditional drug metabolism pathways.
• Mycophenolate is rapidly converted to its active form mycophenolic acid in the liver and undergoes enterohepatic recirculation. Key considerations for the use of these medications include:
• Renal function affects the clearance of methotrexate and mycophenolate metabolites, highlighting the need for careful dose adjustment in patients with renal impairment, as discussed in the systematic review of the literature on the optimal dosage and route of administration of methotrexate in rheumatoid arthritis 1.
• Hepatic processes are involved in the metabolism of hydrocodone, mycophenolate, and to some extent, methotrexate, necessitating monitoring of liver enzymes and adjustment of doses as needed.
• The distinct metabolic pathways of these medications result in different drug interaction profiles, dosing considerations, and monitoring requirements, emphasizing the importance of understanding these pathways when prescribing these medications together, particularly in patients with hepatic or renal impairment.

From the Research

Metabolism of Subcutaneous Medications

The metabolism of subcutaneous medications such as methotrexate, hydrocodone, actemra (tocilizumab), rituximab, and mycophenolate involves various pathways and mechanisms.

• Methotrexate is an antimetabolite that is useful for treating both benign and malignant proliferative disorders, with its pharmacokinetics and potential toxicity being crucial for understanding treatment regimens 2.
• Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been shown to have a higher absolute PK bioavailability at a dose of 162 mg compared to 81 mg when administered subcutaneously 3.
• Rituximab, a monoclonal anti-CD20 antibody, has been approved for the treatment of rheumatoid arthritis in association with methotrexate, with studies showing its efficacy and safety in combination with methotrexate 4, 5.
• Subcutaneous methotrexate has been shown to be safe and effective in routine clinical practice, with higher continuation rates and lower rates of adverse events compared to oral methotrexate and other disease-modifying antirheumatic drugs (DMARDs) 6.

Commonalities in Metabolism

While the specific metabolism of each medication may differ, there are some commonalities in their metabolism, including:

• The importance of urinary excretion, with factors such as renal function influencing the metabolism of medications like methotrexate 2.
• The role of monoclonal antibodies, such as rituximab and tocilizumab, in targeting specific receptors and pathways to produce their therapeutic effects 3, 4, 5.
• The potential for subcutaneous administration to affect the pharmacokinetics and pharmacodynamics of medications, as seen with tocilizumab and methotrexate 3, 6.