Alvosuni

Sunitinib

Unresectable &/or metastatic malignant GI stromal tumour (GIST) in adults after failure of imatinib treatment due to resistance or intolerance. Unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours (pNET) w/ disease progression in adults. Advanced/metastatic renal cell carcinoma (MRCC) in adults.

GIST & MRCC 50 mg once daily, for 4 consecutive wk, followed by 2-wk rest period to comprise complete cycle of 6 wk. Daily dose: Not to exceed 75 mg nor decreased <25 mg. pNET 37.5 mg once daily w/o scheduled rest period. Max dose in Phase 3: 50 mg daily. Dose adjustment: May apply 12.5 mg steps based on individual safety & tolerability.

May be taken with or without food.

Hypersensitivity.

Discontinue if signs or symptoms of SJS, TEN, or erythema multiforme (eg, progressive skin rash often w/ blisters or mucosal lesions); hepatic failure; symptoms of pancreatitis; in patients w/ nephrotic syndrome; presence of clinical manifestations of CHF; who develop thrombotic microangiopathy & necrotising fasciitis. Interrupt administration &/or reduced dose in patients w/o clinical evidence of CHF but w/ ejection fraction <50% & >20% below baseline; if fistula; angioedema due to hypersensitivity occurs. Temporary interrupt therapy & resume following intervention in patients undergoing major surgical procedures; w/ seizures & signs/symptoms consistent w/ posterior reversible leukoencephalopathy syndrome eg, HTN, headache, decreased alertness, altered mental functioning & visual loss, including cortical blindness & may be resumed at discretion of treating physician; in case of symptomatic hypoglycaemia; suspend treatment in patients w/ severe uncontrolled HTN & resume once appropriately controlled. Avoid invasive dental procedures in patients who have previously received or are receiving IV bisphosphonates. Allergic to Na; sunset yellow FCF (E110) & tartrazine (E102). Consider occurrence of haemolytic anaemia, thrombocytopenia, fatigue, fluctuating neurological manifestation, renal impairment & fever in the diagnosis of thrombotic microangiopathy including TTP & haemolytic uraemic syndrome, sometimes leading to renal failure or fatal outcome; dental exam & appropriate preventive dentistry prior treatment; close monitoring, clinical treatment & prophylactic hydration in case of tumor lysis syndrome; baseline & periodic evaluations of left ventricular ejection fraction (LVEF) while receiving treatment & in patients w/o cardiac risk factors. Monitor for clinical signs & symptoms of CHF while receiving treatment especially patients w/ cardiac risk factors &/or history of CAD; development of worsening proteinuria. Risk or history of CV events, including heart failure, cardiomyopathy, LVEF decline to below LLN, myocarditis, myocardial ischaemia & MI; HTN or aneurysm; high tumour burden, pre-existing chronic renal insufficiency, oliguria, dehydration, hypotension, & acidic urine; older age, DM, underlying renal impairment, cardiac failure, sepsis, dehydration/hypovolaemia & rhabdomyolysis. Patients w/ known history of QT interval prolongation, taking antiarrhythmics or medicinal products that prolongs QT interval, or w/ relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances; moderate to severe proteinuria. Screen patients for HTN & control as appropriate. Treatment-related venous thromboembolic events including, DVT & pulmonary embolism; cases of arterial thromboembolic events including CVA, transient ischaemic attack & cerebral infarction; hair or skin depigmentation including dryness, thickness or cracking of skin, blisters, or rash on palms of hands & soles of feet; pyoderma gangrenosum; haemorrhagic events including, GI, resp, urinary tract, & brain haemorrhages; tumour haemorrhage associated w/ tumour necrosis; GI adverse reactions including diarrhoea, nausea/vomiting, abdominal pain, dyspepsia & stomatitis/oral pain; oesophagitis; GI perforation in patients w/ intra-abdominal malignancies. Haemorrhage associated w/ thrombocytopenia & neutropenic infections. May occur anaemia & hypothyroidism early as well as late during treatment. Impaired wound healing; osteonecrosis of the jaw. Perform CBC at the beginning of each treatment cycle; baseline urinalysis; lab measurement of thyroid function every 3 mth. Monitor LFTs (ALT, AST, bilirubin levels) before initiation, during each cycle of treatment & as clinically indicated. Regularly check blood glucose levels in diabetic patients. Periodically monitor platelet counts, coagulation factors (prothrombin time/INR) & physical exam in patients receiving concomitantly w/ anticoagulants (eg, warfarin, acenocoumarol). Avoid co-administration w/ potent CYP3A4 inducers & inhibitors. Concomitant use w/ IV bisphosphonates. May affect ability to drive & use machines. Renal impairment, renal failure &/or acute renal failure. Hepatotoxicity. Not recommended w/ severe hepatic impairment. May compromise male & female fertility. Women of childbearing potential should use effective contraception & avoid becoming pregnant. Not to be used during pregnancy or in women not using effective contraception, & lactation. Childn <18 yr.

Neutropenia, thrombocytopoenia, anaemia, leukopoenia; hypothyroidism; decreased appetite (including, anorexia); insomnia; dizziness, headache, taste disturbance (including, dysgeusia, ageusia); HTN; dyspnoea, epistaxis, cough; stomatitis (including, aphthous stomatitis), upper & lower abdominal pain, vomiting, diarrhoea, dyspepsia, nausea, constipation; skin discolouration (including, yellow skin, pigmentation disorder), palmar-plantar erythrodysaesthesia syndrome, rash (including dermatitis psoriasiform, exfoliative, erythematous, follicular, generalised, macular, maculo-papular, papular & pruritic rash), hair colour changes, dry skin; pain in extremity, arthralgia, back pain; mucosal inflammation, fatigue (including asthenia), oedema (including face & peripheral), pyrexia. Viral infections (including, nasopharyngitis & oral herpes), resp infections (including bronchitis, lower resp tract infection, pneumonia & resp tract infection), abscess (including, limb, anal, gingival, liver, pancreatic, perineal, perirectal, rectal, SC & tooth abscess), fungal infections (including oesophageal & oral candidiasis), UTI, skin infections (including cellulitis), sepsis (including sepsis shock); lymphopoenia; dehydration, hypoglycaemia; depression; peripheral neuropathy, paraesthesia, hypoaesthesia, hyperaesthesia; periorbital & eyelid oedema, increased lacrimation; myocardial ischemia (including acute coronary syndrome, angina pectoris & unstable, coronary artery occlusion), decreased/abnormal ejection fraction; DVT, hot flush, flushing; pulmonary embolism, pleural effusion, haemoptysis, dyspnoea, exertional, oropharyngeal pain (including pharyngolaryngeal pain), nasal congestion & dryness; GERD, dysphagia, GI haemorrhage, oesophagitis, abdominal distension & discomfort, rectal haemorrhage, gingival bleeding, mouth ulceration, proctalgia, cheilitis, haemorrhoids, glossodynia, oral pain & discomfort, dry mouth, flatulence, eructation; skin exfoliation & reaction (including skin disorder), eczema, blister, erythema, alopecia, acne, pruritus, skin hyperpigmentation & lesion, hyperkeratosis, dermatitis, nail disorder (including discolouration); musculoskeletal pain, muscle spasms, myalgia, muscular weakness; renal failure, acute renal failure, chromaturia, proteinuria; chest pain, pain, flu-like illness, chills; decreased wt, WBC, & platelet count, Hb, increased lipase, amylase, AST, ALT, blood creatinine, uric acid, & BP. SJS, TEN.

Increased combined (sunitinib + primary metabolite) C_max & AUC w/ potent CYP3A4 inhibitor eg, ketoconazole. Increased conc w/ potent CYP3A4 inhibitors (eg, ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice). Reduced combined (sunitinib + primary metabolite) C_max & AUC w/ CYP3A4 inducer eg, rifampicin. Decreased conc w/ potent CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb or herbal prep containing St. John's Wort/Hypericum perforatum).

Targeted Cancer Therapy

L01EX01 - sunitinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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