Sunitinib 12.5 Eurodrug

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: 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 treatment if signs or symptoms of SJS, TEN, or erythema multiforme (eg, progressive skin rash often w/ blisters or mucosal lesions) are present; if signs or symptoms of hepatic failure are present; if symptoms of pancreatitis are present; in patients w/ nephrotic syndrome; in the presence of clinical manifestations of CHF; in patients who develop thrombotic microangiopathy (TMA), or necrotising fasciitis. Not to be restarted if diagnosis of SJS or TEN is confirmed. Interrupt administration &/or reduce dose in patients w/o clinical evidence of CHF but w/ ejection fraction <50% & >20% below baseline. Interrupt treatment if fistula occurs; angioedema due to hypersensitivity occurs. Temporarily interrupt therapy in patients undergoing major surgical procedures; in case of symptomatic hypoglycaemia. Suspend temporarily in patients w/ seizures & signs/symptoms consistent w/ posterior reversible leukoencephalopathy syndrome eg, HTN, headache, decreased alertness, altered mental functioning & visual loss, including cortical blindness; severe HTN & resume once appropriately controlled. Not for use in patients w/ lung cancer. Avoid invasive dental procedures in patients who have previously received or are receiving IV bisphosphonates. Hair or skin depigmentation; skin dryness, thickness or cracking, blisters, 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. HTN including severe HTN (>200 mmHg systolic or 110 mmHg diastolic). Haemorrhage associated w/ thrombocytopenia & neutropenic infections; anaemia. CV events, including heart failure, cardiomyopathy, LVEF decline to below LLN, myocarditis, myocardial ischaemia & MI. QT interval prolongation & Torsade de pointes. VTE including DVT & pulmonary embolism. Arterial thromboembolic events eg, CVA, transient ischaemic attack & cerebral infarction. Formation of aneurysms &/or artery dissections. TMA, including TTP & haemolytic uraemic syndrome, leading to renal failure or fatal outcome, in the occurrence of haemolytic anaemia, thrombocytopenia, fatigue, fluctuating neurological manifestation, renal impairment & fever. Hypothyroidism. Increased serum lipase & amylase activities in patients w/ various solid tumours; serious pancreatic events. Hepatotoxicity; hepatic failure. Renal impairment, renal failure &/or acute renal failure; proteinuria, nephrotic syndrome. Impaired wound healing. Osteonecrosis of jaw. Seizures. Tumor lysis syndrome. Serious infections w/ or w/o neutropenia; necrotising fasciitis. Decreased blood glucose. Consider dental exam & appropriate preventive dentistry prior to treatment; prophylactic hydration in case of tumor lysis syndrome; baseline & periodic evaluations of left ventricular ejection fraction (LVEF) while receiving treatment; baseline evaluation of ejection fraction 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. Patients who are at risk for, or who have history of CV events; 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; w/ moderate to severe proteinuria. Screen patients for HTN & control as appropriate. Perform CBC at the beginning of each treatment cycle; baseline urinalysis; routine monitoring 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 concomitant anticoagulants (eg, warfarin, acenocoumarol). Avoid co-administration w/ potent CYP3A4 inducers & inhibitors. Concomitant use w/ IV bisphosphonates. Minor influence on ability to drive & use machines. Not recommended in severe hepatic impairment. May compromise male & female fertility. Women of childbearing potential should use effective contraception & avoid becoming pregnant. Pregnancy. Not to breastfeed while on treatment. Paed <18 yr.

Neutropenia, thrombocytopoenia, anaemia, leukopoenia; hypothyroidism; decreased appetite & anorexia; insomnia; dizziness, headache, taste disturbance (dysgeusia, ageusia); HTN; dyspnoea, epistaxis, cough; stomatitis & aphthous stomatitis, upper & lower abdominal pain, vomiting, diarrhoea, dyspepsia, nausea, constipation; skin discolouration (yellow skin & pigmentation disorder), palmar-plantar erythrodysaesthesia syndrome, rash (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 & asthenia, oedema (face & peripheral), pyrexia. Viral infections (nasopharyngitis & oral herpes), resp infection (bronchitis, lower resp tract infection, pneumonia & resp tract infection), abscess (limb, anal, gingival, liver, pancreatic, perineal, perirectal, rectal, SC & tooth), fungal infections (oesophageal & oral candidiasis), UTI, cellulitis & skin infections, sepsis & septic shock; lymphopoenia; dehydration, hypoglycaemia; depression; peripheral neuropathy, paraesthesia, hypoaesthesia, hyperaesthesia; periorbital & eyelid oedema, increased lacrimation; myocardial ischemia (acute coronary syndrome, angina pectoris, unstable angina, coronary artery occlusion), decreased/abnormal ejection fraction; DVT, hot flush, flushing; pulmonary embolism, pleural effusion, haemoptysis, exertional dyspnoea, oropharyngeal & 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, disorder, hyperpigmentation & lesion, eczema, blister, erythema, alopecia, acne, pruritus, hyperkeratosis, dermatitis, nail disorder & 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_0-∞ w/ potent CYP3A4 inhibitor ketoconazole. Increased conc w/ potent CYP3A4 inhibitors (eg, ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice). Reduced combined (sunitinib + primary metabolite) C_max & AUC_0-∞ w/ CYP3A4 inducer rifampicin. Decreased conc w/ potent CYP3A4 inducers eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb or herbal prep containing St. John's wort (Hypericum perforatum). Possible interaction w/ BCRP inhibitors.

Targeted Cancer Therapy

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

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