Drug Class Description
Cytostatic (antimetabolite)
Generic Name
Capecitabine
Drug Description
Xeloda 150 mg and 500 mg film-coated tablets
Presentation
Film-coated tabletLight peach film-coated tablet of biconvex, oblong shape with the marking '150' on the one side and 'Xeloda' on the other side. Peach film-coated tablet of biconvex, oblong shape with the marking '500' on the one side and 'Xeloda' on the other side.
Indications
Xeloda is indicated for the adjuvant treatment of patients following surgery of stage III (Dukes' stage C) colon cancer. Xeloda is indicated for the treatment of metastatic colorectal cancer. Xeloda is indicated for first-line treatment of advanced gastric cancer in combination with a platinum-based regimen.Xeloda in combination with docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Xeloda is also indicated as monotherapy for the treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline-containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.
Adult Dosage
Xeloda should only be prescribed by a qualified physician experienced in the utilisation of anti-neoplastic agents. Xeloda tablets should be swallowed with water within 30 minutes after a meal. Treatment should be discontinued if progressive disease or intolerable toxicity is observed. Standard and reduced dose calculations according to body surface area for starting doses of Xeloda of 1250 mg/m2 and 1000 mg/m2 are provided in tables 1 and 2, respectively.Recommended posology:MonotherapyColon, colorectal and breast cancer Given as single agent, the recommended starting dose for Xeloda in the adjuvant treatment of colon cancer, in the treatment of metastatic colorectal cancer or of locally advanced or metastatic breast cancer is 1250 mg/m2 administered twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 14 days followed by a 7-day rest period. Adjuvant treatment in patients with stage III colon cancer is recommended for a total of 6 months.Combination therapyColorectal and gastric cancerIn combination treatment, the recommended starting dose of Xeloda should be reduced to 800 – 1000 mg/m2 when administered twice daily for 14 days followed by a 7-day rest period, or to 625 mg/m2 twice daily when administered continuously. The inclusion of biological agents in a combination regimen has no effect on the starting dose of Xeloda. Premedication to maintain adequate hydration and anti-emesis according to the cisplatin summary of product characteristics should be started prior to cisplatin administration for patients receiving the Xeloda plus cisplatin combination.Breast cancerIn combination with docetaxel, the recommended starting dose of Xeloda in the treatment of metastatic breast cancer is 1250 mg/m2 twice daily for 14 days followed by a 7-day rest period, combined with docetaxel at 75 mg/m2 as a 1 hour intravenous infusion every 3 weeks. Pre-medication with an oral corticosteroid such as dexamethasone according to the docetaxel summary of product characteristics should be started prior to docetaxel administration for patients receiving the Xeloda plus docetaxel combination.Dose modifications for toxicity when Xeloda is used as a 3 weekly cycle in combination with other agents: Dose modifications for toxicity when Xeloda is used as a 3 weekly cycle in combination with other agents should be made according to Table 3 above for Xeloda and according to the appropriate summary of product characteristics for the other agent(s).At the beginning of a treatment cycle, if a treatment delay is indicated for either Xeloda or the other agent(s), then administration of all agents should be delayed until the requirements for restarting all drugs are met.During a treatment cycle for those toxicities considered by the treating physician not to be related to Xeloda, Xeloda should be continued and the dose of the other agent should be adjusted according to the appropriate Prescribing Information.If the other agent(s) have to be discontinued permanently, Xeloda treatment can be resumed when the requirements for restarting Xeloda are met.This advice is applicable to all indications and to all special populations.Dose modifications for toxicity when Xeloda is used continuously in combination with other agents: Dose modifications for toxicity when Xeloda is used continuously in combination with other agents should be made according for Xeloda and according to the appropriate summary of product characteristics for the other agent(s).Posology adjustments for special populations:Hepatic impairment: insufficient safety and efficacy data are available in patients with hepatic impairment to provide a dose adjustment recommendation. No information is available on hepatic impairment due to cirrhosis or hepatitis.
Child Dosage
Children (under 18 years): The safety and efficacy of Xeloda in children has not been studied.
Elderly Dosage
During Xeloda monotherapy, no adjustment of the starting dose is needed. However, grade 3 or 4 treatment-related adverse reactions were more frequent in patients 60 years of age compared to younger patients.When Xeloda was used in combination with other agents, elderly patients (65 years) experienced more grade 3 and grade 4 adverse drug reactions, including those leading to discontinuation, compared to younger patients. Careful monitoring of patients 60 years of age is advisable.- In combination with docetaxel: an increased incidence of grade 3 or 4 treatment-related adverse reactions and treatment-related serious adverse reactions were observed in patients 60 years of age or more (see section 5.1). For patients 60 years of age or more, a starting dose reduction of Xeloda to 75% (950 mg/m2 twice daily) is recommended. If no toxicity is observed in patients 60 years of age treated with a reduced Xeloda starting dose in combination with docetaxel, the dose of Xeloda may be cautiously escalated to 1250 mg/m2 twice daily.- In combination with irinotecan: for patients 65 years of age or more, a starting dose reduction of Xeloda to 800 mg/m2 twice daily is recommended.
Contra Indications
History of severe and unexpected reactions to fluoropyrimidine therapy,Hypersensitivity to capecitabine or to any of the excipients or fluorouracil,In patients with known dihydropyrimidine dehydrogenase (DPD) deficiency, During pregnancy and lactation,In patients with severe leucopenia, neutropenia, or thrombocytopenia, In patients with severe hepatic impairment, In patients with severe renal impairment (creatinine clearance below 30 ml/min),Treatment with sorivudine or its chemically related analogues, such as brivudine (see section 4.5),If contraindications exist to any of the agents in the combination regimen, that agent should not be used.
Special Precautions
Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and hand-foot syndrome (hand-foot skin reaction, palmar-plantar erythrodysaesthesia). Most adverse reactions are reversible and do not require permanent discontinuation of therapy, although doses may need to be withheld or reduced.Diarrhoea. Patients with severe diarrhoea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated. Standard antidiarrhoeal treatments (e.g. loperamide) may be used. NCIC CTC grade 2 diarrhoea is defined as an increase of 4 to 6 stools/day or nocturnal stools, grade 3 diarrhoea as an increase of 7 to 9 stools/day or incontinence and malabsorption. Grade 4 diarrhoea is an increase of 10 stools/day or grossly bloody diarrhoea or the need for parenteral support. Dose reduction should be applied as necessary.Dehydration. Dehydration should be prevented or corrected at the onset. Patients with anorexia, asthenia, nausea, vomiting or diarrhoea may rapidly become dehydrated. If Grade 2 (or higher) dehydration occurs, Xeloda treatment should be immediately interrupted and the dehydration corrected. Treatment should not be restarted until the patient is rehydrated and any precipitating causes have been corrected or controlled. Dose modifications applied should be applied for the precipitating adverse event as necessary.Hand-foot syndrome (also known as hand-foot skin reaction or palmar-plantar erythrodysaesthesia or chemotherapy induced acral erythema). Grade 1 hand- foot syndrome is defined as numbness, dysaesthesia/paraesthesia, tingling, painless swelling or erythema of the hands and/or feet and/or discomfort which does not disrupt the patient's normal activities.Grade 2 hand- foot syndrome is painful erythema and swelling of the hands and/or feet and/or discomfort affecting the patient's activities of daily living.Grade 3 hand- foot syndrome is moist desquamation, ulceration, blistering and severe pain of the hands and/or feet and/or severe discomfort that causes the patient to be unable to work or perform activities of daily living. If grade 2 or 3 hand- foot syndrome occurs, administration of Xeloda should be interrupted until the event resolves or decreases in intensity to grade 1. Following grade 3 hand- foot syndrome, subsequent doses of Xeloda should be decreased. When Xeloda and cisplatin are used in combination, the use of vitamin B6 (pyridoxine) is not advised for symptomatic or secondary prophylactic treatment of hand–foot syndrome, because of published reports that it may decrease the efficacy of cisplatin.Cardiotoxicity. Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, dysrhythmias, cardiogenic shock, sudden death and electrocardiographic changes. These adverse reactions may be more common in patients with a prior history of coronary artery disease. Cardiac arrhythmias, angina pectoris, myocardial infarction, heart failure and cardiomyopathy have been reported in patients receiving Xeloda. Caution must be exercised in patients with history of significant cardiac disease, arrhythmias and angina pectoris.Hypo- or hypercalcaemia. Hypo- or hypercalcaemia has been reported during Xeloda treatment. Caution must be exercised in patients with pre-existing hypo- or hypercalcaemia.Central or peripheral nervous system disease. Caution must be exercised in patients with central or peripheral nervous system disease, e.g. brain metastasis or neuropathy.Diabetes mellitus or electrolyte disturbances. Caution must be exercised in patients with diabetes mellitus or electrolyte disturbances, as these may be aggravated during Xeloda treatment.Coumarin-derivative anticoagulation. In a drug interaction study with single-dose warfarin administration, there was a significant increase in the mean AUC (+57%) of S-warfarin. These results suggest an interaction, probably due to an inhibition of the cytochrome P450 2C9 isoenzyme system by capecitabine. Patients receiving concomitant Xeloda and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely and the anticoagulant dose adjusted accordingly.Hepatic impairment. In the absence of safety and efficacy data in patients with hepatic impairment, Xeloda use should be carefully monitored in patients with mild to moderate liver dysfunction, regardless of the presence or absence of liver metastasis. Administration of Xeloda should be interrupted if treatment-related elevations in bilirubin of >3.0 x ULN or treatment-related elevations in hepatic aminotransferases (ALT, AST) of >2.5 x ULN occur. Treatment with Xeloda monotherapy may be resumed when bilirubin decreases to 3.0 x ULN or hepatic aminotransferases decrease to 2.5 x ULN.Renal impairment. The incidence of grade 3 or 4 adverse reactions in patients with moderate renal impairment (creatinine clearance 30-50 ml/min) is increased compared to the overall population.As this medicinal product contains anhydrous lactose as an excipient, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Interactions
Interaction studies have only been performed in adults.Interaction with other medicinal products:Coumarin-derivative anticoagulants: altered coagulation parameters and/or bleeding have been reported in patients taking Xeloda concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. These reactions occurred within several days and up to several months after initiating Xeloda therapy and, in a few cases, within one month after stopping Xeloda. In a clinical pharmacokinetic interaction study, after a single 20 mg dose of warfarin, Xeloda treatment increased the AUC of S-warfarin by 57% with a 91% increase in INR value. Since metabolism of R-warfarin was not affected, these results indicate that capecitabine down-regulates isozyme 2C9, but has no effect on isozymes 1A2 and 3A4. Patients taking coumarin-derivative anticoagulants concomitantly with Xeloda should be monitored regularly for alterations in their coagulation parameters (PT or INR) and the anti-coagulant dose adjusted accordingly.Phenytoin: increased phenytoin plasma concentrations resulting in symptoms of phenytoin intoxication in single cases have been reported during concomitant use of Xeloda with phenytoin. Patients taking phenytoin concomitantly with Xeloda should be regularly monitored for increased phenytoin plasma concentrations.Folinic acid: a combination study with Xeloda and folinic acid indicated that folinic acid has no major effect on the pharmacokinetics of Xeloda and its metabolites. However, folinic acid has an effect on the pharmacodynamics of Xeloda and its toxicity may be enhanced by folinic acid: the maximum tolerated dose (MTD) of Xeloda alone using the intermittent regimen is 3000 mg/m2 per day whereas it is only 2000 mg/m2 per day when Xeloda was combined with folinic acid (30 mg orally bid).Sorivudine and analogues: a clinically significant drug-drug interaction between sorivudine and 5-FU, resulting from the inhibition of dihydropyrimidine dehydrogenase by sorivudine, has been described. This interaction, which leads to increased fluoropyrimidine toxicity, is potentially fatal. Therefore, Xeloda must not be administered concomitantly with sorivudine or its chemically related analogues, such as brivudine. There must be at least a 4-week waiting period between end of treatment with sorivudine or its chemically related analogues such as brivudine and start of Xeloda therapy.Antacid: the effect of an aluminum hydroxide and magnesium hydroxide-containing antacid on the pharmacokinetics of capecitabine was investigated. There was a small increase in plasma concentrations of capecitabine and one metabolite (5'-DFCR); there was no effect on the 3 major metabolites (5'-DFUR, 5-FU and FBAL).Allopurinol: interactions with allopurinol have been observed for 5-FU; with possible decreased efficacy of 5-FU. Concomitant use of allopurinol with Xeloda should be avoided.Interaction with cytochrome P-450: For potential interactions with isozymes 1A2, 2C9 and 3A4, see interactions with coumarin-derivative anticoagulation.Interferon alpha: the MTD of Xeloda was 2000 mg/m2 per day when combined with interferon alpha-2a (3 MIU/m2 per day) compared to 3000 mg/m2 per day when Xeloda was used alone.Radiotherapy: the MTD of Xeloda alone using the intermittent regimen is 3000 mg/m2 per day, whereas, when combined with radiotherapy for rectal cancer, the MTD of Xeloda is 2000 mg/m2 per day using either a continuous schedule or given daily Monday through Friday during a 6-week course of radiotherapy.Oxaliplatin: no clinically significant differences in exposure to capecitabine or its metabolites, free platinum or total platinum occurred when capecitabine was administered in combination with oxaliplatin or in combination with oxaliplatin and bevacizumab.Bevacizumab: there was no clinically significant effect of bevacizumab on the pharmacokinetic parameters of capecitabine or its metabolites in the presence of oxaliplatin.Food interaction: In all clinical trials, patients were instructed to administer Xeloda within 30 minutes after a meal. Since current safety and efficacy data are based upon administration with food, it is recommended that Xeloda be administered with food. Administration with food decreases the rate of capecitabine absorption.
Adverse Reactions
a. Summary of the safety profileThe overall safety profile of Xeloda is based on data from over 3000 patients treated with Xeloda as monotherapy or Xeloda in combination with different chemotherapy regimens in multiple indications. The safety profiles of Xeloda monotherapy for the metastatic breast cancer, metastatic colorectal cancer and adjuvant colon cancer populations are comparable.The most commonly reported and/or clinically relevant treatment-related adverse drug reactions (ADRs) were gastrointestinal disorders (especially diarrhoea, nausea, vomiting, abdominal pain, stomatitis), hand-foot syndrome (palmar-plantar erythrodysaesthesia), fatigue, asthenia, anorexia, cardiotoxicity, increased renal dysfunction in those with preexisting compromised renal function, and thrombosis/embolism.b. Tabulated summary of adverse reactionsADRs considered by the investigator to be possibly, probably, or remotely related to the administration of Xeloda are listed in Table1 for Xeloda given as a single agent and in Table2 for Xeloda given in combination with different chemotherapy regimens in multiple indications. The following headings are used to rank the ADRs by frequency: very common ( 1/10), common ( 1/100, < 1/10) and uncommon ( 1/1,000, < 1/100). Within each frequency grouping, ADRs are presented in order of decreasing seriousness.Xeloda Monotherapy: Table 4 lists ADRs associated with the use of Xeloda monotherapy based on a pooled analysis of safety data from three major studies including over 1900 patients (studies M66001, SO14695, and SO14796). ADRs are added to the appropriate frequency grouping according to the overall incidence from the pooled analysis.Table1 Summary of related ADRs reported in patients treated with Xeloda monotherapyBody SystemVery CommonAll gradesCommonAll gradesUncommonSevere and/or Life-threatening (grade 3-4) or considered medically relevantInfections and infestationsHerpes viral infection, Nasopharyngitis, Lower respiratory tract infectionSepsis, Urinary tract infection, Cellulitis, Tonsillitis, Pharyngitis, Oral candidiasis, Influenza, Gastroenteritis, Fungal infection, Infection, Tooth abscessNeoplasm benign, malignant and unspecifiedLipomaBlood and lymphatic system disordersNeutropenia, AnaemiaFebrile neutropenia, Pancytopenia, Granulocytopenia, Thrombocytopenia, Leucopenia, Haemolytic anaemia, International normalised Ratio (INR) increased/Prothrombin time prolongedImmune system disordersHypersensitivityMetabolism and nutrition disordersAnorexiaDehydration, Decreased appetite, Weight decreasedDiabetes, Hypokalaemia, Appetite disorder, Malnutrition, HypertriglyceridaemiaPsychiatric disordersInsomnia, DepressionConfusional state, Panic attack, Depressed mood, Libido decreasedNervous system disordersHeadache, Lethargy, Dizziness, Paraesthesia, DysgeusiaAphasia, Memory impairment, Ataxia, Syncope, Balance disorder, Sensory disorder, Neuropathy peripheralEye disordersLacrimation increased, Conjunctivitis, Eye irritationVisual acuity reduced, DiplopiaEar and labyrinth disordersVertigo, Ear painCardiac disordersAngina unstable, Angina pectoris, Myocardial ischaemia, Atrial fibrillation, Arrhythmia, Tachycardia, Sinus tachycardia, PalpitationsVascular disordersThrombophlebitisDeep vein thrombosis, Hypertension, Petechiae, Hypotension, Hot flush, Peripheral coldnessRespiratory, thoracic and mediastinal disordersDyspnoea, Epistaxis, Cough, RhinorrhoeaPulmonary embolism, Pneumothorax, Haemoptysis, Asthma, Dyspnoea exertionalGastrointestinal disordersHepatobiliary DisordersDiarrhoea, Vomiting, Nausea, Stomatitis, Abdominal painGastrointestinal haemorrhage, Constipation, Upper abdominal pain, Dyspepsia, Flatulence, Dry mouthIntestinal obstruction, Ascites, Enteritis, Gastritis, Dysphagia, Abdominal pain lower, Oesophagitis, Abdominal discomfort, Gastrooesophageal reflux disease, Colitis, Blood in stoolSkin and subcutaneous tissue disordersPalmar-plantar erythrodysaesthesia syndromeRash, Alopecia, Erythema, Dry skin, Pruritus, Skin hyper-pigmentation, Rash macular, Skin desquamation, Dermatitis, Pigmentation disorder, Nail disorderSkin ulcer, Rash, Urticaria, Photosensitivity reaction, Palmar erythema, Swelling face, PurpuraMuskuloskeletal and connective tissue disordersPain in extremity, Back pain, ArthralgiaJoint swelling, Bone pain, Facial pain, Musculoskeletal stiffness, Muscular weaknessRenal and urinary disordersHydronephrosis, Urinary incontinence, Haematuria, Nocturia, Blood creatinine increasedReproductive system and breast disordersVaginal haemorrhageGeneral disorders and administration site conditionsFatigue, AstheniaPyrexia, Lethargy, Oedema peripheral, Malaise, Chest painOedema, Chills, Influenza like illness, Rigors, Body temperature increasedInjury, poisoning and procedural complicationsBlister, OverdoseHepatobiliary DisordersHyperbilirubinaemia , Liver function test abnormalitiesJaundiceXeloda in combination therapy: Table2 lists ADRs associated with the use of Xeloda in combination with different chemotherapy regimens in multiple indications based on safety data from over 1400 patients. ADRs are added to the appropriate frequency grouping (Very common or Common) according to the highest incidence seen in any of the major clinical trials and are only added when they were seen in addition to those seen with Xeloda monotherapy or seen at a higher frequency grouping compared to Xeloda monotherapy (see Table 4). Uncommon ADRs reported for Xeloda in combination therapy are consistent with the ADRs reported for Xeloda monotherapy or reported for monotherapy with the combination agent (in literature and/or respective summary of product characteristics).Some of the ADRs are reactions commonly seen with the combination agent (e.g. peripheral sensory neuropathy with docetaxel or oxaliplatin, hypertension seen with bevacizumab); however an exacerbation by Xeloda therapy can not be excluded.Table2 Summary of related ADRs reported in patients treated with Xeloda in combination treatment in addition to those seen with Xeloda monotherapy or seen at a higher frequency grouping compared to Xeloda monotherapy.Body SystemVery commonAll gradesCommonAll gradesInfections and infestationsHerpes zoster, Urinary tract infection, Oral candidiasis, Upper respiratory tract infection , Rhinitis, Influenza,+InfectionBlood and lymphatic system disorders+Neutropenia, +Leucopenia, +Anaemia, +Neutropenic fever, ThrombocytopeniaBone marrow depression, +Febrile NeutropeniaImmune system disordersHypersensitivityMetabolism and nutrition disordersAppetite decreasedHypokalaemia, Hyponatraemia, Hypomagnesaemia, Hypocalcaemia, HyperglycaemiaPsychiatric disordersSleep disorder, AnxietyNervous system disordersTaste disturbance, Paraesthesia and dysaesthesia, Peripheral neuropathy, Dysgeusia, HeadacheNeurotoxicity, Tremor, Neuralgia, Hypersensitivity reactionEye disordersLacrimation increasedVisual disorders, Dry eyeEar and labyrinth disordersTinnitus, HypoacusisCardiac disordersAtrial fibrillation, Cardiac ischaemia/infarctionVascular disordersLower limb oedema, Hypertension, +Embolism and thrombosisFlushing, Hypotension, Hypertensive crisisRespiratory, thoracic and mediastinal system disordersSore throat, Dysaesthesia pharynxHiccups, Pharyngolaryngeal pain, DysphoniaGastrointestinal disordersConstipation, DyspepsiaUpper gastrointestinal haemorrhage, Mouth ulceration, Gastritis, Abdominal distension, Gastroesophageal reflux disease, Oral pain, Dysphagia, Rectal haemorrhage, Abdominal pain lowerHepatobiliary disordersHepatic function abnormalSkin and subcutaneous tissue disordersAlopecia, Nail disorderHyperhidrosis, Rash erythematous, Urticaria, Night sweatsMusculoskeletal and connective tissue disordersMyalgia, Arthralgia, Pain in extremityPain in jaw , Muscle spasms, Trismus, Muscular weaknessRenal and urinary disorderHaematuria, Proteinuria, Creatinine renal clearance decreasedGeneral disorders and administration site conditionsPyrexia, Weakness, +LethargyMucosal inflammation, Pain in limb, Pain, Temperature intolerance, Chills, Chest pain, Influenza-like illness, +FeverInjury, poisoning and procedural complicationsContusion+ For each term, the frequency count was based on ADRs of all grades. For terms marked with a “+”, the frequency count was based on grade 3-4 ADRs. ADRs are added according to the highest incidence seen in any of the major combination trials.Post-Marketing Experience:The following additional serious adverse reactions have been identified during post-marketing exposure:- Very rare: lacrimal duct stenosis- Very rare: hepatic failure and cholestatic hepatitis have been reported during clinical trials and post-marketing exposurec. Description of selected adverse reactionsHand-foot syndrome:For the capecitabine dose of 1250 mg/m2 twice daily on days 1 to 14 every 3 weeks, a frequency of 53% to 60% of all-grades HFS was observed in capecitabine monotherapy trials (comprising studies in adjuvant therapy in colon cancer, treatment of metastatic colorectal cancer, and treatment of breast cancer) and a frequency of 63% was observed in the capecitabine/docetaxel arm for the treatment of metastatic breast cancer. For the capecitabine dose of 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks, a frequency of 22% to 30% of all-grade HFS was observed in capecitabine combination therapyA meta-analysis of 13 clinical trials with data from over 3800 patients treated with capecitabine monotherapy or capecitabine in combination with different chemotherapy regimens in multiple indications (colon, colorectal, gastric and breast cancer) showed that HFS (all grades) occurred in 1788 (47%) patients after a median time of 155 [95% CI 135, 187] days after starting treatment with capecitabine. In all studies combined, the following covariates were statistically significantly associated with an increased risk of developing HFS: increasing capecitabine starting dose (gram), decreasing cumulative capecitabine dose (0.1*kg), increasing relative dose intensity in the first six weeks, increasing duration of study treatment (weeks), increasing age (by 10 year increments), female gender, and good ECOG performance status at baseline (0 versus 1).Diarrhoea:Xeloda can induce the occurrence of diarrhoea, which has been observed in up to 50% of patients.The results of a meta-analysis of 13 clinical trials with data from over 3800 patients treated with capecitabine showed that in all studies combined, the following covariates were statistically significantly associated with an increased risk of developing diarrhoea: increasing capecitabine starting dose (gram), increasing duration of study treatment (weeks), increasing age (by 10 year increments), and female gender. The following covariates were statistically significantly associated with a decreased risk of developing diarrhoea: increasing cumulative capecitabine dose (0.1*kg) and increasing relative dose intensity in the first six weeks.Cardiotoxicity:In addition to the ADRs described in Tables 4 and 5, the following ADRs with an incidence of less than 0.1% were associated with the use of Xeloda monotherapy based on a pooled analysis from clinical safety data from 7 clinical trials including 949 patients (2 phase III and 5 phase II clinical trials in metastatic colorectal cancer and metastatic breast cancer): cardiomyopathy, cardiac failure, sudden death, and ventricular extrasystoles.Encephalopathy:In addition to the ADRs described in Tables 4 and 5, and based on the above pooled analysis from clinical safety data from 7 clinical trials, encephalopathy was also associated with the use of Xeloda monotherapy with an incidence of less than 0.1%.d. Special populationsElderly patients:An analysis of safety data in patients 60 years of age treated with Xeloda monotherapy and an analysis of patients treated with Xeloda plus docetaxel combination therapy showed an increase in the incidence of treatment-related grade 3 and 4 adverse reactions and treatment-related serious adverse reactions compared to patients <60 years of age. Patients 60 years of age treated with Xeloda plus docetaxel also had more early withdrawals from treatment due to adverse reactions compared to patients <60 years of age.The results of a meta-analysis of 13 clinical trials with data from over 3800 patients treated with capecitabine showed that in all studies combined, increasing age (by 10 year increments) was statistically significantly associated with an increased risk of developing HFS and diarrhoea and with a decreased risk of developing neutropenia.GenderThe results of a meta-analysis of 13 clinical trials with data from over 3800 patients treated with capecitabine showed that in all studies combined, female gender was statistically significantly associated with an increased risk of developing HFS and diarrhoea and with a decreased risk of developing neutropenia.Patients with renal impairment:An analysis of safety data in patients treated with Xeloda monotherapy (colorectal cancer) with baseline renal impairment showed an increase in the incidence of treatment-related grade 3 and 4 adverse reactions compared to patients with normal renal function (36% in patients without renal impairment n=268, vs. 41% in mild n=257 and 54% in moderate n=59, respectively) (see section 5.2). Patients with moderately impaired renal function show an increased rate of dose reduction (44%) vs. 33% and 32% in patients with no or mild renal impairment and an increase in early withdrawals from treatment (21% withdrawals during the first two cycles) vs. 5% and 8% in patients with no or mild renal impairment.
Manufacturer
Roche
Drug Availability
(POM)
Updated
12 August 2009
