Drug Class Description
Antineoplastic agents - Protein-tyrosine kinase inhibitor
Generic Name
Sunitinib
Drug Description
SUTENT® 12.5 mg hard capsulesSUTENT® 25 mg hard capsulesSUTENT® 50 mg hard capsules
Presentation
SUTENT® 12.5 mgHard capsules.Gelatin capsules with orange cap and orange body, printed with white ink “Pfizer” on the cap, “STN 12.5 mg” on the body, and containing yellow to orange granules.SUTENT® 25 mgHard CapsulesGelatin capsule with caramel cap and orange body, printed with white ink “Pfizer” on the cap and “STN 25 mg ” on the body and containing yellow to orange granules.SUTENT® 50 mgHard capsulesGelatin capsules with caramel cap and caramel body, printed with white ink “Pfizer” on the cap and “STN 50 mg” on the body and containing yellow to orange granules.
Indications
Gastrointestinal Stromal Tumour (GIST) SUTENT is indicated for the treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST) after failure of imatinib mesylate treatment due to resistance or intolerance.Metastatic Renal Cell Carcinoma (MRCC) SUTENT is indicated for the treatment of advanced and/ormetastatic renal cell carcinoma (MRCC).
Adult Dosage
Therapy should be initiated by a physician experienced in the treatment of renal cell carcinoma or GIST.The recommended dose of SUTENT is one 50 mg dose orally, taken daily for 4 consecutive weeks, followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks.Dose adjustmentsSafety and Tolerability Dose modifications in 12.5-mg steps may be applied based on individual safety and tolerability. Daily dose should not exceed 75 mg nor be decreased below 25 mg.CYP3A4 Inhibitors/Inducers Co-administration of potent CYP3A4 inducers such as rifampin, should be avoided. If this is not possible, the dose of SUTENT may need to be increased in 12.5 mg increments (up to 87.5 mg per day) based on careful monitoring of tolerability.Co-administration of SUTENT with potent CYP3A4 inhibitors, such as ketoconazole, should be avoided. If this is not possible the doses of SUTENT may need to be reduced to a minimum of 37.5 mg daily, based on careful monitoring of the tolerability.Selection of an alternate concomitant medication with no, or minimal potential to induce or inhibit CYP3A4 should be considered.Paediatric use: The safety and efficacy of SUTENT in paediatric patients have not been established.SUTENT should not be used in paediatric population until further data become available.Elderly patients use: Approximately 34% of the subjects in clinical studies of SUTENT were 65 or over. No significant differences in safety or effectiveness were observed between younger and older patients.Hepatic Insufficiency: No dose adjustment is recommended when administering SUTENT to patients with mild or moderate (Child-Pugh Class A and B) hepatic impairment. SUTENT has not been studied in subjects with Child-Pugh Class C hepatic impairment.Renal Insufficiency: No clinical studies have been performed in patients with impaired renal function.SUTENT may be taken with or without food.If a dose is missed the patient should not be given an additional dose. The patient should take the usual prescribed dose on the following day.
Child Dosage
Paediatric use: The safety and efficacy of SUTENT in paediatric patients have not been established. SUTENT should not be used in paediatric population until further data become available.
Elderly Dosage
Elderly patients use: Approximately 25% of the subjects in clinical studies of SUTENT were 65 or over. No significant differences in safety or effectiveness were observed between younger and older patients.
Contra Indications
Hypersensitivity to sunitinib malate or to any of the excipients.
Special Precautions
Co--administration of potent CYP3A4 inducers such as rifampin, may decrease sunitinib plasma concentrations. Combination with inducers should therefore be avoided. If this is not possible, the dosage of SUTENT may need to be increasedCo-administration of strong CYP3A4 inhibitor such as ketoconazole may increase sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential is recommended. If this is not possible, the dosage of SUTENT may need to be reduced.Skin and tissues Skin discolouration, possibly due to the active substance colour (yellow) is a common treatment-related adverse event occurring in approximately 30% of patients. Patients should be advised that depigmentation of the hair or skin may also occur during treatment with SUTENT. Other possible dermatologic effects may include dryness, thickness or cracking of the skin, blisters or occasional rash on the palms of the hands and soles of the feet.Mouth pain/irritation was reported in approximately 14% of patients. Dysgeusia (taste disturbance) was reported in approximately 28% of patients.The above events were not cumulative, were typically reversible and generally did not result in treatment discontinuation.HaemorrhageHaemorrhagic events, some of which were fatal, reported through post-marketing experience, have included GI, respiratory, tumour, urinary tract and brain haemorrhages. In clinical trials treatment-related tumour haemorrhage occurred in approximately 2% of patients with GIST. These events may occur suddenly, and in the case of pulmonary tumours, may present as severe and life-threatening haemoptysis or pulmonary haemorrhage. Fatal pulmonary haemorrhage occurred in 2 patients receiving SUTENT on a clinical trial of patients with metastatic non-small cell lung cancer (NSCLC). Both patients had squamous cell histology. SUTENT is not approved for use in patients with NSCLC. Bleeding events occurred in 18% of patients receiving SUTENT in a phase 3 GIST Study compared to 17% of patients receiving placebo. In patients receiving SUTENT for treatment-naïve MRCC, 28% had bleeding events compared to 7% of patients receiving IFN- α. Seven (1.9%) patients on sunitinib malate versus 0% of patients on IFN-α experienced Grade 3 or greater treatment-related bleeding events. Of patients receiving sunitinib malate for cytokine-refractory MRCC, 26% experienced bleeding. Routine assessment of this event should include complete blood counts and physical examination.Epistaxis was the most common treatment-related haemorrhagic adverse event, having been reported for approximately half of the patients with solid tumours who experienced haemorrhagic events. Some of these events were severe, but very rarely fatal.Gastrointestinal events Nausea, diarrhoea, stomatitis, dyspepsia and vomiting were the most commonly reported treatment-related gastrointestinal events.Supportive care for gastrointestinal adverse events requiring treatment may include medication with an anti-emetic or anti-diarrhoeal medication.Gastrointestinal tractSerious, sometimes fatal gastrointestinal complications including gastrointestinal perforation have occurred rarely in patients with intra-abdominal malignancies treated with SUTENT. Treatment-related fatal gastrointestinal bleeding occurred in 0.5% of patients receiving placebo in the GIST Phase 3 study.HypertensionTreatment-related hypertension was reported in approximately 16% of patients with solid tumours. SUTENT dosing was reduced or temporarily delayed in approximately 2.7% of this patient population. None of these patients were discontinued from treatment with SUTENT. Severe hypertension >200 mmHg systolic or 110 mmHg diastolic) occurred in 4.7% of this patient population. Treatment-related hypertension was reported in approximately 24% of patients receiving sunitinib malate for treatment-naïve MRCC compared to 1% of patients receiving IFN-α. Severe hypertension occurred in 5% of treatment-naïve patients on sunitinib malate and 1% of patients on IFN-α. Patients should be screened for hypertension and controlled as appropriate. Temporary suspension is recommended in patients with severe hypertension that is not controlled with medical management. Treatment may be resumed once hypertension is appropriately controlled.HaematologicalDecreased absolute neutrophil counts of grade 3 and 4 severity were reported in 10% and 1.7% of patients on the phase 3 GIST study, respectively, and in 16% and 1.6% of patients on the phase 3 MRCC study, respectively. Decreased platelet counts of grade 3 and 4 severity were reported in 3.7% and 0.4% of patients on the phase 3 GIST study, respectively, and in 8.2% and 1.1% of patients on the phase 3 MRCC study, respectively. The above events were not cumulative, were typically reversible and generally did not result in treatment discontinuation. None of these events in the phase 3 studies were fatal, but rare fatal haematological events have been reported through post-marketing experience.Complete blood counts should be performed at the beginning of each treatment cycle for patients receiving treatment with SUTENT.CardiovascularCardiovascular events, some of which were fatal, reported through post-marketing experience, have included left ventricular ejection fraction (LVEF) decrease and cardiac failure. In clinical trials, decreases in LVEF of 20% and below the lower limit of normal occurred in approximately 2% of SUTENT-treated GIST patients, 4% of cytokine-refractory MRCC patients, 2% of placebo-treated patients. These LVEF declines do not appear to have been progressive and often improved as treatment continued. In the treatment-naïve MRCC study, 21% patients on SUTENT and 12% of patients on interferon-α (IFN-α), had an LVEF value below the lower limit of normal. One (<1%) patient who received SUTENT was diagnosed with congestive heart failure (CHF).Treatment-related adverse events of 'cardiac failure', 'cardiac failure congestive' or 'left ventricular failure' were reported in 0.7% of patients with solid tumours and 1% of patients treated with placebo. All patients had GIST. In the phase 3 GIST study (n=312), treatment-related fatal cardiac events occurred in 1% of patients on each arm of the study (i.e. SUTENT and placebo arms). In a phase 2 study in cytokine-refractory MRCC patients, 0.9% of patients experienced treatment-related fatal myocardial infarction and in the phase 3 study in treatment-naïve MRCC patients, 0.6% of patients on the IFN-α arm and 0 patients on the SUTENT arm experienced fatal cardiac events. The relationship, if any, between receptor tyrosine kinase (RTK) inhibition and cardiac function remains unclear.Patients who presented with cardiac events within 12 months prior to SUTENT administration, such as myocardial infarction (including severe/unstable angina), coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF), cerebrovascular accident or transient ischemic attack, or pulmonary embolism were excluded from SUTENT clinical studies.Close monitoring for clinical signs and symptoms of CHF should be performed, especially in patients with cardiac risk factors and/or history of coronary artery disease.Physicians are advised to weigh this risk against the potential benefits of the drug. These patients should be carefully monitored for clinical signs and symptoms of CHF while receiving SUTENT. Baseline and periodic eva luations of LVEF should also be considered while the patient is receiving SUTENT. In patients without cardiac risk factors, a baseline eva luation of ejection fraction should be considered.In the presence of clinical manifestations of CHF, discontinuation of SUTENT is recommended. The dose of SUTENT should be interrupted and/or reduced in patients without clinical evidence of CHF but with an ejection fraction <50% and >20% below baseline.QT Interval prolongationData from non-clinical (in vitro and in vivo) studies, at doses higher than the recommended human dose, indicate that sunitinib has the potential to inhibit the cardiac action potential repolarization process (e.g. prolongation of QT interval).Increases in the QTc interval to over 500 msec occurred in 0.5% and changes from baseline in excess of 60 msec occurred in 1.1% of the 450 solid tumours patients; both these parameters are recognized as potentially significant changes. At approximately twice therapeutic concentrations, SUTENT has been shown to prolong the QTcF Inteva l (Frederica's Correction).QT interval prolongation was investigated in a trial in 24 patients, aged 20-87 years, with advanced malignancies. The results of this study demonstrated that sunitinib had an effect on QTc (defined as a mean placebo-adjusted change of > 10 msec with a 90% CI upper limit > 15 msec) at therapeutic concentration (day 3) using the within-day baseline correction method, and at greater than therapeutic concentration (Day 9) using both baseline correction methods. No patients had a QTc value >500 msec. Although an effect on QTcF was observed on Day 3 at 24 hours post-dose (i.e. at therapeutic plasma concentration expected after the recommended starting dose of 50 mg) with the within-day baseline correction method, the clinical significance of this finding is unclear.Using comprehensive serial ECG assessments at times corresponding to either therapeutic or greater than therapeutic exposures, none of the patients in the eva luable or ITT populations were observed to develop QTc prolongation considered as “severe” (i.e. equal to or greater than Grade 3 by CTCAE version 3.0).At therapeutic plasma concentrations, the maximum QTcF (Frederica's correction) mean change from baseline was 9.6 msec (90% CI 15.1msec). At approximately twice therapeutic concentrations, the maximum QTcF change from baseline was 15.4 msec (90% CI 22.4 msec). Moxifloxacin (400 mg) used as a positive control showed a 5.6 msec maximum mean QTcF change from baseline. No subjects experienced an effect on the QTc inteva l greater than Grade 2 (CTCAE version 3.0). No patient presented with a cardiac arrhythmia.QT interval prolongation may lead to an increased risk of ventricular arrhythmias including Torsade de pointes. Torsade de pointes has been observed in <0.1% of SUTENT-exposed patients. SUTENT should be used with caution in patients with a known history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances. Concomitant treatment with potent CYP3A4 inhibitors, which may increase sunitinib plasma concentrations, should be used with caution and the dose of SUTENT reduced.Venous Thromboembolic EventsTreatment-related venous thromboembolic events were reported in approximately 1.0% of patients with solid tumours who received SUTENT on clinical trials, including GIST and MRCC.Seven patients (3%) on SUTENT and none on placebo in a phase 3 GIST study experienced venous thromboembolic events; five of the seven were Grade 3 deep venous thromboses (DVT), and two were Grade 1 or 2. Four of these seven GIST patients discontinued treatment following first observation of DVT.Seven patients (1.9%) receiving SUTENT in the phase 3 for treatment-naïve MRCC study and four patients (2%) on the two cytokine-refractory MRCC studies had treatment-related venous thromboembolic events reported. Six of these patients had pulmonary embolisms, one was Grade 3 and five were Grade 4, and five of these patients had DVT, one each with Grade 1 and 2, and three with Grade 3. Dose interruption occurred in one.In treatment-naïve MRCC patients receiving IFN-α, six (2%) venous thromboembolic events occurred; one patient (<1%) experienced a Grade 3 DVT and five patients (1%) had pulmonary embolism, one Grade 1 and four with Grade 4.No cases with fatal outcome were reported in GIST and MRCC registrational studies. Cases with fatal out-come had been observed in post-marketing setting.Respiratory eventsPatients who presented with pulmonary embolism within the previous 12 months were excluded from SUTENT clinical studies.In patients who received SUTENT in Phase 3 registrational studies, treatment-related pulmonary events (i.e. dyspnoea, pleural effusion, pulmonary embolism or pulmonary oedema)were reported in approximately 5% of patients with GIST and in approximately 14% of patients with MRCC. Rare cases with fatal outcome were reported.Approximately 8% of patients with solid tumours, including GIST and MRCC, who received SUTENT in clinical trials experienced treatment-related pulmonary events.Cases of Pulmonary embolism were observed in approximately 1.3% of patients with GIST and in approximately 0.8% of patients with MRCC, who received Sutent in Phase 3 studies.Thyroid DysfunctionBaseline laboratory measurement of thyroid function is recommended and patients with hypothyroidism or hyperthyroidism should be treated as per standard medical practice prior to the start of sunitinib treatment. All patients should be observed closely for signs and symptoms of thyroid dysfunction on sunitinib treatment. Patients with signs and/or symptoms suggestive of thyroid dysfunction should have laboratory monitoring of thyroid function performed and be treated as per standard medical practice.Hypothyroidism was reported as an adverse event in 7 patients (4%) across the two cytokine-refractory MRCC studies in nine patients (2%) on SUTENT and one patient (<1%) in the IFN-α arm in the treatment-naïve MRCC study. Additionally, TSH elevations were reported in 4 cytokine-refractory MRCC patients (2%). Overall, 7% of the MRCC population had either clinical or laboratory evidence of treatment-emergent hypothyroidism. Treatment-emergent acquired hypothyroidism was noted in 8 GIST patients (4%) on SUTENT versus 1 (1%) on placebo.Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.Pancreatitis Increases in serum lipase and amylase activities were observed in patients with various solid tumours who received SUTENT. Increases in lipase activities were transient and were generally not accompanied by signs or symptoms of pancreatitis in subjects with various solid tumours. Pancreatitis has been observed rarely (<1%) in patients receiving SUTENT for GIST or MRCC.Cases of serious pancreatic events, some with fatal outcome, have been reported. If symptoms of pancreatitis are present, patients should have SUTENT discontinued and be provided with appropriate supportive care.Hepatic FunctionSerious cases of SUTENT-related hepatobiliary events have been reported in patients with solid tumours; hepatic failure was observed in <1% of these patients. Cases of hepatobiliary events some with fatal outcome, have been reported. If signs or symptoms of hepatic failure are present, SUTENT should be discontinued and appropriate supportive care should be provided.Renal functionThe safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically eva luated.Cases of proteinuria and rare cases of nephrotic syndrome have been reported. Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria. Discontinue SUTENT in patients with nephrotic syndrome.SeizuresIn clinical studies of SUTENT and from post-marketing experience, seizures have been observed in subjects with or without radiological evidence of brain metastases. In addition, there have been rare (<1%) reports of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS). Patients with seizures and signs/symptoms consistent with RPLS, such as hypertension, headache, decreased alertness, altered mental functioning and visual loss, including cortical blindness should be controlled with medical management including control of hypertension. Temporary suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.
Interactions
Drugs that may increase sunitinib plasma concentrations.Concomitant administration of sunitinib malate with the potent CYP3A4 inhibitor, ketoconazole, resulted in a 49% and 51% increase of the complex [sunitinib + primary metabolite] Cmax and AUC0- values, respectively, after a single dose of sunitinib malate in healthy volunteers.Administration of SUTENT with potent inhibitors of the CYP3A4 family (e.g. ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice) may increase sunitinib concentrationsCombination with inhibitors should therefore be avoided, or the selection of an alternate concomitant medication with no, or minimal potential to inhibit CYP3A4 should be considered.If this is not possible, the dosage of SUTENT may need to be reduced to a minimum of 37.5 mg daily, based on careful monitoring of the tolerability.Drugs that may decrease sunitinib plasma concentrations:Concomitant use of SUTENT with the CYP3A4 inducer, rifampin, resulted in a 23% and 46% reduction of the complex [sunitinib + primary metabolite] Cmax and AUC0- values, respectively, after a single dose of SUTENT in healthy volunteers.Administration of SUTENT with potent inducers of the CYP3A4 family (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital or Hypericum perforatum known also as St. John's Wort) may decrease sunitinib concentrations. Combination with inducers should therefore be avoided, or selection of an alternate concomitant medication with no, or minimal potential to induce CYP3A4 should be considered. If this is not possible, the dosage of SUTENT may need to be increased in 12.5 mg increments (up to 87.5 mg per day) based on careful monitoring of tolerability.To maintain sunitinib target concentrations, selection of co-medications with less enzyme induction potential, should be considered. If this is not possible, dose-adjustments of SUTENT may be necessary..Haemorrhage has been observed rarely in patients treated with SUTENT. Patients receiving concomitant treatment with anti-coagulants (e.g. warfarin; acenocumarole) may be periodically monitored by complete blood counts (platelets), coagulation factors (PT/INR), and physical examination
Adverse Reactions
The most important treatment-related serious adverse events associated with SUTENT treatment of patients with solid tumours were pulmonary embolism (1%), thrombocytopoenia (1%), tumour haemorrhage (0.9%), febrile neutropoenia (0.4%), and hypertension (0.4%). The most common treatment-related adverse events (experienced by at least 20% of the patients) of any grade included: fatigue; gastrointestinal disorders, such as diarrhoea, nausea, stomatitis, dyspepsia and vomiting; skin discolouration; dysgeusia and anorexia. Fatigue, hypertension and neutropoenia were the most common treatment-related adverse events of Grade 3 maximum severity and increased lipase was the most frequently occurring treatment-related adverse event of Grade 4 maximum severity in patients with solid tumours. Hepatitis and hepatic failure occurred in <1% of patients and prolonged QT interval in < 0.1%.Fatal events that were considered possibly related to SUTENT included multi-system organ failure, disseminated intravascular coagulation, peritonoeal haemorrhage, rhabdomyolysis, cerebrovascular accident, dehydration, adrenal insufficiency, renal failure, respiratory failure, pleural effusion, pneumothorax, shock, and sudden death.Treatment-related adverse reactions that were reported in >2% of solid tumour patients are listed below, by system organ class, frequency and grade of severity. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.Frequencies are defined as: Very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000).Treatment-Related Adverse Reactions reported in GIST studiesSystem Organ ClassFrequencyAdverse ReactionsAll Gradesn (%)Grade 3n (%)Grade 4n (%)Blood and the lymphatic system disordersVery commonAnaemia86 (19.5%)24 (5.5%)3 (0.7%)Very commonNeutropoenia81 (18.4%)39 (8.9%)5 (1.1%)Very commonThrombocytopoenia67 (15.2%)19 (4.3%)6 (1.4%)CommonLeukopoenia26 (5.9%)9 (2.0%)1 (0.2%)CommonLymphopoenia10 (2.3%)3 (0.7%)1 (0.2%)Endocrine disorders Very commonHypothyroidism59 (13.4%)5 (1.1%)1 (0.2%)Metabolism and nutrition disordersVery commonDecreased appetite a117 (26.6%)8 (1.8%)0 (0.0%)Nervous system disordersVery commonTaste disturbance b105 (23.9%)1 (0.2%)0 (0.0%)Very commonHeadache76 (17.3%)5 (1.1%)0 (0.0%)CommonParaesthesia27 (6.1%)1 (0.2%)0 (0.0%)CommonDizziness18 (4.1%)1 (0.2%)0 (0.0%)CommonNeuropathy peripheral11 (2.5%)0 (0.0%)0 (0.0%)CommonHypoaesthesia10 (2.3%)0 (0.0%)0 (0.0%)Vascular disordersVery commonHypertension101 (23.0%)43 (9.8%)0 (0.0%)Respiratory, thoracic and mediastinal disordersCommonEpistaxis28 (6.4%)1 (0.2%)0 (0.0%)CommonDyspnoea16 (3.6%)2 (0.5%)0 (0.0%)Renal and urinary disordersCommonChromaturia18 (4.1%)0 (0.0%)0 (0.0%)Gastrointestinal disordersVery commonDiarrhoea187 (42.5%)24 (5.5%)0 (0.0%)Very commonNausea161 (36.6%)15 (3.4%)0 (0.0%)Very commonVomiting98 (22.2%)7 (1.6%)0 (0.0%)Very commonStomatitis90 (20.5%)7 (1.6%)0 (0.0%)Very commonDyspepsia80 (18.2%)4 (0.9%)0 (0.0%)Very commonAbdominal pain C / distension77 (17.5%)15 (3.4%)2 (0.5%)Very commonFlatulence46 (10.5%)0 (0.0%)0 (0.0%)Very commonOral pain44 (10.0%)2 (0.5%)0 (0.0%)CommonConstipation37 (8.4%)2 (0.5%)0 (0.0%)CommonGlossodynia37 (8.4%)0 (0.0%)0 (0.0%)CommonDry mouth31 (7.0%)0 (0.0%)0 (0.0%)CommonGastro-oesophageal reflux disease12 (2.7%)1 (0.2%)0 (0.0%)CommonMouth ulceration11 (2.5%)0 (0.0%)0 (0.0%)CommonOral discomfort11 (2.5%)0 (0.0%)0 (0.0%)Skin and subcutaneous tissue disordersVery commonYellow skin/Skin discolouration146 (33.2%)0 (0.0%)0 (0.0%)Very commonPalmar-plantar erythrodysaesthesia syndrome106 (24.1%)27 (6.1%)0 (0.0%)Very commonHair colour changes67 (15.2%)0 (0.0%)0 (0.0%)Very commonRash64 (14.5%)3 (0.7%)0 (0.0%)CommonDry skin41 (9.3%)0 (0.0%)0 (0.0%)CommonAlopecia33 (7.5%)0 (0.0%)0 (0.0%)CommonDermatitis29 (6.6%)1 (0.2%)0 (0.0%)CommonPeriorbital oedema20 (4.5%)0 (0.0%)0 (0.0%)CommonSkin Reaction20 (4.5%)3 (0.7%)0 (0.0%)CommonErythema18 (4.1%)0 (0.0%)0 (0.0%)CommonEczema16 (3.6%)1 (0.2%)0 (0.0%)CommonPruritus16 (3.6%)0 (0.0%)0 (0.0%)CommonSkin hyperpigmentation15 (3.4%)0 (0.0%)0 (0.0%)CommonSkin exfoliation12 (2.7%)0 (0.0%)0 (0.0%)CommonBlister10 (2.3%)1 (0.2%)0 (0.0%)CommonSkin lesion10 (2.3%)1 (0.2%)0 (0.0%)Muscoloskeletal, connective tissue and bone disordersVery CommonPain in extremity/limb54 (12.3%)5 (1.1%)0 (0.0%)CommonArthralgia39 (8.9%)3 (0.7%)0 (0.0%)CommonMyalgia29 (6.6%)0 (0.0%)0 (0.0%)CommonMuscle spasm21 (4.8%)1 (0.2%)0 (0.0%)CommonBack pain11 (2.5%)2 (0.5%)0 (0.0%)CommonMuscular weakness10 (2.3%)1 (0.2%)0 (0.0%)General disorders and administration site conditionsVery commonFatigue/Asthenia287 (65.2%)64 (14.5%)5 (1.1%)Very commonMucosal inflammation70 (15.9%)6 (1.4%)1 (0.2%)Very commonOedema d 59 (13.4%)1 (0.2%)0 (0.0%)CommonPyrexia26 (5.9%)2 (0.5%)0 (0.0%)Psychiatric disordersCommonInsomnia14 (3.2%)0 (0.0%)0 (0.0%)InvestigationsCommonLipase increase35 (8.0%)12 (2.7%)7 (1.6%)CommonWhite blood cell count decreased e 33 (7.5%)15 (3.4%)0 (0.0%)CommonEjection fraction decreased27 (6.1%)5 (1.2%)0 (0.0%)CommonHaemoglobin decreased27 (6.1%)6 (1.4%)0 (0.0%)CommonBlood creatinine phosphokinase increased22 (5.0%)1 (0.2%)1 (0.2%)CommonPlatelet count decrease25 (5.7%)4 (0.9%)1 (0.2%)CommonWeight decreased23 (5.2%)1 (0.2%)0 (0.0%)CommonAmylase increased21 (4.8%)8 (1.8%)0 (0.0%)CommonAspartate aminotransferase increased18 (4.1%)2 (0.5%)1 (0.2%)CommonAlanine aminotransferase increased12 (2.7%)1 (0.2%)0 (0.0%)Any adverse event414 (94.1%)204 (46.4%)53 (12.0%)The following terms have been combined:a Anorexia and decreased appetiteb Dysgeusia, ageusia and taste disturbancec Abdominal pain and abdominal pain upperd Oedema, oedema peripheral and oedema facee White blood cell count decreased, neutrophil count decreased, and leukocyte count decreasedTreatment-Related Adverse Reactions reported in cytokine-refractory and treatment-naïve MRCC studiesSystem Organ ClassFrequencyAdverse ReactionsAll Gradesn (%)Grade 3n (%)Grade 4n (%)Blood and lymphatic system disordersVery commonNeutropoenia89 (16.4%)46 (8.5%)5 (0.9%)Very commonThrombocytopoenia86 (15.8%)37 (6.8%)5 (0.9%)Very commonAnaemia67 (12.3%)20 (3.7%)3 (0.6%)CommonLeukopoenia45 (8.3%)16 (2.9%)0 (0%)CommonLymphopenia21 (3.9%)12 (2.2%)1 (0.2%)Endocrine disordersVery commonHypothyroidism67 (12.3%)7 (1.3%)0 (0%)Eye disordersCommonLacrimation increased39 (7.2%)0 (0%)0 (0%)CommonEyelid oedema12 (2.2%)0 (0%)0 (0%)Metabolism and nutrition disordersCommonDecreased appetite a205 (37.7%)9 (1.7%)0 (0%)CommonDehydration33 (6.1%)7 (1.3%)1 (0.2%)Nervous system disordersVery commonTaste disturbance b250 (46.0%)1 (0.2%)0 (0%)Very commonHeadache82 (15.1%)3 (0.6%)0 (0%)CommonDizziness38 (7.0%)2 (0.4%)0 (0%)CommonParaesthesia36 (5.9%)0 (0%)0 (0%)CommonNeuropathy peripheral33 (6.1%)1 (0.2%)0 (0%)CommonHypoaesthesia20 (3.7%)0 (0%)0 (0%)CommonHyperaesthesia17 (3.1%)0 (0%)0 (0%)Vascular disordersVery commonHypertension143 (26.3%)55 (10.1%)0 (0%)CommonFlushing17 (3.1%)0 (0%)0 (0%)CommonHot flush12 (2.2%)0 (0%)0 (0%)Respiratory, thoracic and mediastinal disordersVery commonEpistaxis86 (15.8%)3 (0.6%)0 (0%)CommonDyspnoea45 (8.3%)6 (1.1%)<
Manufacturer
Pfizer Ltd
Drug Availability
(POM)
Updated
12 August 2009
