Targeted Synthetic DMARDs and Tofacitinib

• Targeted synthetic (ts) DMARDs are the newest group of DMARDs.

Prototype and Other Medications

• Tofacitinib is the prototype tsDMARD, a Janus kinase (JAK) inhibitor.
• Other JAK inhibitors include baricitinib and upadacitinib.

Expected Pharmacologic Action

• Tofacitinib and other JAK inhibitors disrupt the signaling pathways involved in inflammatory and immune responses.

Adverse Drug Reactions

• Risk of upper respiratory and urinary tract infections.
• Potential for serious infections like tuberculosis, pneumonia, cellulitis, and herpes zoster.
• May cause neutropenia, elevated liver enzymes, serum creatinine, and lipids.
• Reports of lymphoma, other cancers, myocardial infarction, and thrombosis with tofacitinib use.
• Increased risk of gastrointestinal perforation, especially with NSAID use or diverticulitis.

Interventions

• Monitor for infection manifestations: fever, chills, fatigue, cough.
• Assess baseline CBC, WBC, and liver enzymes before treatment, then every 3 months.
• Assess baseline lipid profile, then monitor within 4 to 8 weeks after starting treatment.

Safety Information

• Do not administer tofacitinib to clients with anemia, neutropenia, or leukopenia.
• Concurrent use of methotrexate or corticosteroids with tofacitinib increases the risk of serious infections.
• Clients should be up to date on all vaccines prior to tofacitinib and avoid live vaccines while taking it.

Administration

• Administer tablet or oral solution twice daily or extended-release tablet once daily.
• Do not chew, crush, or split the extended-release tablet.

Client Instructions

• Report any signs of infection to the provider immediately.
• Immediately report chest pain, dyspnea, edema, extremity discoloration, tenderness, or swelling, abdominal pain, or changes in stool.
• Pregnant clients should enroll in the pregnancy exposure registry.
• Breastfeeding is not recommended during treatment.

Contraindications and Precautions

• Contraindicated in clients with active infection, leukopenia, neutropenia, or anemia.
• Use caution in clients with a history of serious infections or tuberculosis exposure.
• Exercise caution in clients at increased risk for gastrointestinal perforation or with a history of lymphoma or other malignancies.

Interactions

• Some anti-infectives can have additive or inhibitory effects on tofacitinib.
• Avoid or adjust dosage when prescribing ketoconazole, fluconazole, and rifampin concurrently.
• Biologic DMARDs and other immunosuppressants (e.g., cyclosporine) can increase immunosuppressive effects.