Rinvoq Disease Interactions

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers; patients who are current or past smokers are at additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, and pacritinib. Before starting or continuing therapy, the benefits and risks for the individual patient should be considered, especially in patients with other cardiovascular risk factors and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur. Tofacitinib, baricitinib, and upadacitinib are indicated for patients with inadequate response or intolerance to 1 or more TNF blockers, but should be discontinued in patients who have experienced a myocardial infarction or stroke. The dosage recommended for tofacitinib should not be exceeded; for the treatment of ulcerative colitis, tofacitinib should be used at the lowest effective dose and for the shortest duration needed to achieve and/or maintain therapeutic response.

Malignancies (including lymphomas and solid tumors) have been reported in patients treated with tofacitinib and other Janus kinase (JAK) inhibitors used to treat inflammatory conditions; lymphomas and other malignancies have been seen in patients treated with baricitinib or upadacitinib. Patients who are current or past smokers are at additional increased risk of malignancies. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, pacritinib, and fedratinib. Before starting or continuing therapy, the benefits and risks for the individual patient should be considered, especially in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer), patients who develop a malignancy during therapy, and patients who are current or past smokers. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Thrombosis (including deep venous thrombosis, pulmonary embolism, and arterial thrombosis) has occurred in patients treated for inflammatory conditions with Janus kinase (JAK) inhibitors, including baricitinib, tofacitinib, and upadacitinib; many of these adverse events were serious and some resulted in death. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, fedratinib, and pacritinib. Baricitinib, pacritinib, tofacitinib, and upadacitinib should be avoided in patients who may be at increased risk of thrombosis; for the treatment of ulcerative colitis, tofacitinib should be used at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response. If symptoms of thrombosis occur, baricitinib, pacritinib, tofacitinib, and upadacitinib should be discontinued and patients should be evaluated promptly and treated appropriately.

Serious and sometimes fatal infections, including opportunistic and reactivation of infections have been reported in patients receiving upadacitinib treatment. It is recommended to avoid the use of upadacitinib in patients with an active, serious infection, including localized infections. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with upadacitinib. Interrupt therapy if a patient develops a new infection or an opportunistic infection and appropriate antimicrobial therapy should be initiated. Treatment with upadacitinib may be resumed once the infection is controlled.

The use of upadacitinib is associated with an increase incidence of neutropenia, lymphopenia, and anemia. Avoid initiation or interrupt treatment with upadacitinib in patients with low neutrophil counts (i.e., ANC less than 1000 cells/mm3), lymphocyte counts (i.e., less than 500 cells/mm3) and low hemoglobin levels (i.e., less than 8 g/dL). It is recommended to evaluate patients for abnormal blood cell counts at baseline and thereafter according to routine patient management.

Gastrointestinal perforation has been reported with the use of upadacitinib. This agent should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs). It is recommended to monitor for new onset abdominal symptoms for early identification of gastrointestinal perforation.

The use of upadacitinib is not recommended in patients with severe hepatic impairment. No dose adjustment is required in patients with mild or moderate hepatic impairment. Treatment with upadacitinib is associated with increased incidence of liver enzyme elevation. Evaluate baseline liver function and thereafter according to routine patient management. Treatment should be interrupted if drug-induced liver injury is suspected.

Treatment with upadacitinib is associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Care should be exercised when using this agent in patients with hyperlipidemia. It is recommended to monitor patients after initiation of treatment, and thereafter according to the clinical guidelines and to manage patients accordingly.

Use of live, attenuated vaccines during, or immediately prior to, upadacitinib therapy is not recommended. Prior to initiating treatment with upadacitinib, it is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, in agreement with current immunization guidelines.