Vonjo 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.

Severe diarrhea, sometimes requiring discontinuation of treatment, has occurred in patients treated with pacritinib. Preexisting diarrhea should be controlled prior to starting treatment with pacritinib. Antidiarrheal agents should be promptly used to treat diarrhea at the first onset of symptoms. Antidiarrheal agents, fluid replacement, and/or dose modification should be used to manage diarrhea. Reducing or interrupting pacritinib should be considered in patients with significant diarrhea (despite optimal supportive care).

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving pacritinib. It is recommended to avoid the use of pacritinib in patients with an active, serious infection, including localized infections and to consider the risks and benefits before starting treatment. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment. Treatment should be interrupted if a patient develops a serious infection, an opportunistic infection, or sepsis and appropriate therapy should be instituted according to clinical guidelines. Close monitoring is recommended.

Serious episodes of bleeding, including those requiring transfusion/invasive intervention, and some leading to fatal bleeding events have been reported in patients treated with pacritinib. Platelet counts should be periodically assessed, monitoring for signs of bleeding (when indicated); hemorrhage should be managed with medical intervention, dose reductions, intermittent interruptions, and/or permanent treatment discontinuations. It is recommended to withhold pacritinib for 7 days prior to planned surgery/invasive procedure.

Pacritinib can cause a QT prolongation of greater than 500 msec, and patients receiving this drug were more likely to develop a QT prolongation of at least 60 msec from baseline (compared to the control group) in clinical trials. This agent should be avoided in patients with QT intervals greater than 480 msec at baseline, and/or in those who are taking medications known to prolong the QTc interval. Hypokalemia should be corrected before initiating and during therapy with this agent. QT prolongation occurring during treatment should be managed with treatment interruption and electrolyte management. Periodic monitoring of ECGs and electrolytes is recommended in these patients.