Can sunitinib (Sunitinib Malate) cause multiple organ failure?

From the Guidelines

Sunitinib gali sukelti dauginis organų disfunkcijos sindromą (DODS) retais atvejais. Tai siejama su sunitinibo sukeltu širdies toksiniškumu, kepenų pažeidimu, inkstų funkcijos sutrikimu ir kraujo ligomis, kurios gali pasireikšti kartu ir sukelti daugelio organų disfunkciją. Šis rizika yra didesnė pacientams su ankstesne organų pažeidimu, vyresniems pacientams ar tiems, kurie vartoja daug vaistų [ 1 ]. Sunitinibas yra tirozino kinazės inhibitorius, naudojamas kai kurių vėžių, įskaitant inkstų ląstelių karcinomą ir gastrointestinalinių stromos tumorų, gydymui, paprastai 50 mg per dieną 4 savaites, paskui 2 savaites pertrauka.

Pacientai, gausantys sunitinibą, turėtų būti artimai stebėti, atliekant reguliarius kraujo tyrimus, širdies funkcijos įvertinimus ir kepenų/inkstų funkcijos tyrimus, ir turėtų nedelsiant pranešti apie simptomus, kaip stiprų nuovargį, oro trūkumą, sumažėjusį šlapimo kiekį ar odos geltonimą [ 1 ]. Sunitinibo sukelta širdies toksiniškumo rizika yra 4,1 % [ 1 ], o ši rizika yra didesnė pacientams, gausantiems aukštesnes sunitinibo dozes [ 1 ].

Vis dėlto, sunitinibo sukeltos daugelio organų disfunkcijos sindromo rizika yra maža, ir šis vaistas gali būti naudojamas saugiai, jei pacientai yra artimai stebėti ir jei vaisto dozė yra tinkamai parinkta [ 1 ].

From the FDA Drug Label

Sunitinib can cause severe hepatotoxicity, resulting in liver failure or death. Liver failure include jaundiced, elevated transaminases and/or hyperbilirubinemia in conjunction with encephalopathy, coagulopathy, and/or renal failure Cardiovascular events, including heart failure, cardiomyopathy, myocardial ischemia, and myocardial infarction, some of which were fatal, have been reported. In pooled safety population, 3% of patients experienced heart failure; 71% of the patients with heart failure were reported as recovered. Fatal cardiac failure was reported in < 1% of patients Renal and urinary disorders: renal impairment and/or failure* The most frequent events included cerebrovascular accident, transient ischemic attack, and cerebral infarction General disorders and administration site conditions: impaired wound healing. including some fatalities Vascular disorders: arterial (including aortic) aneurysms, dissections, and rupture*; arterial thromboembolic events*.

Multiple organ failure can be caused by sunitinib, as it can lead to:

• Liver failure
• Heart failure
• Renal failure
• Other organ failures due to various adverse reactions, such as cardiovascular events, thromboembolic events, and impaired wound healing. It is essential to carefully monitor patients for signs and symptoms of organ failure and adjust the dose or discontinue sunitinib as necessary 2, 2, 2.

From the Research

Sunitinib and Multiple Organ Failure

• Sunitinib, a tyrosine kinase inhibitor, has been associated with various adverse events, including cardiac toxicities, renal damage, and hemostatic complications 3.
• A case report described a patient who developed multi-organ failure after commencing sunitinib treatment, which ultimately led to the patient's death 3.
• Another study found that sunitinib can cause severe renal injury, leading to acute-on-chronic renal failure, and that reducing the dosage or stopping the medication may be necessary to prevent further damage 4.
• Sunitinib-induced nephrotoxicity can lead to irreversible renal dysfunction, emphasizing the need for close monitoring of patients receiving this treatment 5, 6.

Renal Impairment and Sunitinib Treatment

• Patients with severe renal impairment or those undergoing haemodialysis can be safely treated with sunitinib at doses of 25-50 mg daily for 4 weeks, followed by a 2-week break 7.
• However, these patients may experience more frequent adverse events, such as diarrhea, hand-foot skin reaction, and neutropenia, compared to non-dialysis-dependent patients 7.
• The efficacy of sunitinib in patients with severe renal impairment or end-stage renal disease is similar to that reported in patients with normal renal function 7.

Mechanism of Sunitinib-Induced Nephrotoxicity

• Sunitinib can inhibit the survival of human tubule epithelial cells in a dose- and time-dependent manner, leading to apoptosis and renal damage 4.
• The activation of apoptotic signaling pathways by sunitinib in renal tubular epithelial cells may contribute to the development of nephrotoxicity 4.
• Natural compounds, such as oxypeucedanin, may have a protective effect against sunitinib-induced nephrotoxicity by alleviating apoptosis in renal tubular epithelial cells 4.