Pecaset 150 mg & 500 mg Tablet

Breast cancer: Metastatic breast cancer (combination therapy): PECASET in combination with docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy, which should have included an anthracycline.

Metastatic breast cancer (monotherapy): PECASET is 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.

Colorectal cancer: Colon cancer: PECASET is indicated as adjuvant treatment after surgery, of patients with Dukesu2019 C colon cancer.

Metastatic colorectal cancer: PECASET is indicated as treatment of patients with metastatic colorectal adenocarcinoma. The benefit relates to time to progression, while overall survival was not influenced.

Gastric cancer: PECASET is indicated as first line treatment of patients with advanced gastric adenocarcinoma in combination with other anti-chemotherapeutic regimens. The benefit relates to time to progression, while overall survival was not influenced.

PECASET should only be prescribed by a qualified medical practitioner experienced in the utilisation of antineoplastic medicine. PECASET film-coated tablets should be swallowed with water within 30 minutes after a meal. Treatment should be discontinued if progressive disease or intolerable toxicity is observed.

Adults: Monotherapy: Colon, colorectal and breast cancer: The recommended monotherapy dose of PECASET is 1 250 mg/m2 administered twice daily (morning and evening: equivalent to 2 500 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 maximum of 6 months.

Combination therapy: Colorectal and gastric cancer: In combination treatment, the starting dose of PECASET should be reduced to 1 000 mg/m2 when administered twice daily for 14 days, followed by a 7 day rest period. For the PECASET dose reduction schedule, please refer to Table 1. The inclusion of biological agents in a combination regimen has no effect on the starting dose of PECASET.

Premedication to maintain adequate hydration and anti-emesis, according to the cisplatin prescribing information, should be started prior to cisplatin administration for patients receiving PECASET plus cisplatin combination.

Breast cancer: In combination with docetaxel, for locally advanced or metastatic breast cancer, the recommended dose of PECASET is 1 250 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. Premedication with an oral corticosteroid such as dexamethasone, according to the docetaxel prescribing information, should be started prior to docetaxel administration for patients receiving the PECASET plus docetaxel combination. PECASET dose is calculated according to body surface area.

Hypersensitivity to capecitabine or any of the other ingredients of PECASET (see COMPOSITION). Hypersensitivity to fluorouracil (capecitabine metabolite), or a history of severe and unexpected reactions to fluoropyrimidine treatment. Dihydropyrimidine dehydrogenase (DPD) deficiency. Severe leukopenia, neutropenia or thrombocytopenia. Severe hepatic impairment. Severe renal impairment (creatinine clearance < 30 ml/min). Concomitant administration with sorivudine or its chemically related analogues, such as brivudine (see section 4.5). If contraindications exist for any of the medicines in the combination regimen, that medicine should not be used. Pregnancy and lactation (see PREGNANCY AND LACTATION).

Patients should be carefully monitored for toxicity. Most adverse events are reversible and do not require permanent discontinuation of PECASET, although doses may have to be withheld or reduced.

Coumarin-derivative anticoagulation Warfarin interaction: See boxed warning above.

Brivudine. Brivudine must not be administered concomitantly with capecitabine. Fatal cases have been reported following this drug interaction. There must be at least a 4-week waiting period between end of treatment with brivudine and start of capecitabine therapy. Treatment with brivudine can be started 24 hours after the last dose of capecitabine (see section 4.3 and 4.5). In the event of accidental administration of brivudine to patients being treated with capecitabine, effective measures should be taken to reduce the toxicity of capecitabine. Immediate admission to hospital is recommended. All measures should be initiated to prevent systemic infections and dehydration.

Diarrhoea: PECASET can produce diarrhoea, which can sometimes be severe and lead to dehydration (see SIDE EFFECTS). PECASET should be used with care in patients who are weak or malnourished. Patients with severe diarrhoea should be closely monitored and given fluid and electrolyte replacement if they become dehydrated. Standard antidiarrhoeal treatments (e.g. loperamide) should be instituted immediately. If National Cancer Institute (NCI) Grade 2, 3 or 4 diarrhoea occurs, treatment with PECASET should be interrupted until the diarrhoea resolves or decreases in intensity.

Grade 2 diarrhoea is defined as an increase of 4 to 6 stools per day, or nocturnal stools. Grade 3 diarrhoea is defined as an increase of 7 to 9 stools per day or incontinence and malabsorption. Grade 4 diarrhoea is defined as an increase of u2265 10 stools per day, grossly bloody diarrhoea or the need for parenteral fluid support. Dose reduction should be applied as necessary (see section 4.2).

Dehydration: Dehydration should be prevented or corrected at the onset. Patients with anorexia, asthenia, nausea, vomiting or diarrhoea may rapidly become dehydrated. Dehydration may cause acute renal failure, especially in patients with pre-existing compromised renal function or when capecitabine is given concomitantly with known nephrotoxic medicinal products. Acute renal failure secondary to dehydration might be potentially fatal. If grade 2 (or higher) dehydration occurs, capecitabine 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 (see section 4.2).

Palmar-plantar erythrodysaesthesia (PPE): PECASET can cause a cutaneous toxicity known as palmar-plantar erythrodysaesthesia (hand-foot syndrome or chemotherapy induced acral erythema), with severity range of Grades 1 - 3. This may result in severe discomfort that interferes with the ability of the patient to work or perform daily tasks. Immediate medical attention is required for such reactions. Grade 1 PPE is defined as numbness, dysaesthesia, paraesthesia, tingling erythema of the hands and/or feet and/or discomfort which does not disrupt normal daily activities. Grade 2 PPE is defined as painful erythema and swelling of the hands and/or feet and/or discomfort affecting normal daily activities. Grade 3 PPE is defined as 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 normal daily activities. The use of PECASET should be interrupted if Grade 2 or 3 PPE occurs, until the event resolves or decreases in intensity to Grade 1. Subsequent doses of PECASET should be decreased following Grade 3 hand-foot syndrome (see section 4.2).

Cardiotoxicity: Caution is advised in patients with a history of heart disease. PECASET may cause cardiotoxicity, including myocardial infarction, angina, dysrhythmias, cardiac arrest, cardiac failure and electrocardiographic changes, which may be more common in patients with a history of coronary artery disease. Cardiac arrhythmias (including ventricular fibrillation, torsade de pointes, and bradycardia), angina pectoris, myocardial infarction, heart failure and cardiomyopathy have been reported in patients receiving capecitabine Caution must be exercised in patients with history of significant cardiac disease, arrhythmias and angina pectoris (see section 4.8).

Hypo- or hypercalcaemia: Hypo- or hypercalcaemia has been reported during capecitabine treatment. Caution must be exercised in patients with pre-existing hypo- or hypercalcaemia (see section 4.8).

Immunosuppression, bone marrow depression and infection: Immunosuppression and bone marrow depression are features of PECASET and may be associated with an increased risk of infections due to pathogenic or opportunistic microorganisms and the reduced capability to cope with them. PECASET should not be given to patients with acute infections and a dose reduction or withdrawal of treatment is recommended if an infection develops and until the infection is controlled. Great caution is advised in patients with existing bone marrow depression and dosage adjustments is recommended. Patients with existing bone marrow depression or cancer are predisposed to coagulopathy. Treatment with PECASET can result in anaemia, neutropenia, thrombocytopenia, pancytopenia or thrombocytopenic purpura. Routine measurements of blood cell counts and haemoglobin concentrations should be done to help prevent the onset of bone marrow depression.

Renal impairment: PECASET is contraindicated in patients with severe renal impairment (see section 4.3). Caution is advised in patients with impaired renal function. Grade 3 - 4 adverse events are higher in patients with moderate renal impairment (creatinine clearance 30 - 50 ml/min) and a dose reduction of 75 % of the starting dose is recommended in these patients. The dosage adjustment applies to both PECASET monotherapy and combination treatment. Patients should be carefully monitored and if Grade 2, 3 or 4 adverse events develop during treatment with PECASET, dosage adjustment or treatment interruption is recommended (see section 4.2).

The rapid destruction of large numbers of cells during PECASET treatment and the consequent release of breakdown products may also lead to problems with hyperuricaemia and acute renal failure due to uric acid nephropathy (tumour lysis syndrome).

Hepatic impairment: Caution is recommended in patients with hepatic impairment as blood concentrations and AUC values for capecitabine treatment may be increased. The effect of hepatic impairment not due to liver metastases or severe hepatic impairment on the disposition of PECASET is not known. PECASET has been associated with hepatic failure and cholestatic jaundice.

Dihydropyrimidine dehydrogenase (DPD) deficiency: Patients with DPD deficiency must not take Pecaset (see contraindications, section 4.3). DPD activity is rate limiting in the catabolism of 5-fluorouracil (see Section 5.2). Patients with DPD deficiency are therefore at increased risk of fluoropyrimidines-related toxicity, including for example stomatitis, diarrhoea, mucosal inflammation, neutropenia and neurotoxicity. DPD deficiency related toxicity usually occurs during the first cycle treatment or after dose increase.

Complete DPD deficiency: Complete DPD deficiency is rare (0,01 - 0,5 % of Caucasians). Patients with complete DPD deficiency are at high risk of life-threatening or fatal toxicity and must not be treated with Pecaset (see section 4.3).

Partial DPD deficiency: Partial DPD deficiency is estimated to affect 3 - 9 % of the Caucasian population. Patients with partial DPD deficiency are at increased risk of severe and potentially life-threatening toxicity. A reduced starting dose should be considered to limit this toxicity. DPD deficiency should be considered as a parameter to be taken into account in conjunction with other routine measures for dose reduction. Initial dose reduction may impact the efficacy of treatment. In the absence of serious toxicity, subsequent doses may be increased with careful monitoring.

Testing for DPD deficiency: Phenotype and/or genotype testing prior to the initiation of treatment with Pecaset is recommended despite uncertainties regarding optimal pre-treatment testing methodologies. Consideration should be given to applicable clinical guidelines.

Genotypic characterisation of DPD deficiency: Pre-treatment testing for rare mutations of the DPYD gene can identify patients with DPD deficiency. The four DPYD variants c.1905+1G>A [also known as DPYD*2A], c.1679T>G [DPYD*13], c.2846A>T and c.1236G>A/HapB3 can cause complete absence or reduction of DPD enzymatic activity. Other rare variants may also be associated with an increased risk of severe or life-threatening toxicity. Certain homozygous and compound heterozygous mutations in the DPYD gene locus (e.g. combinations of the four variants with at least one allele of c.1905+1G>A or c.1679T>G) are known to cause complete or near complete absence of DPD enzymatic activity. Patients with certain heterozygous DPYD variants (including c.1905+1G>A, c.1679T>G, c.2846A>T and c.1236G>A/HapB3 variants) have increased risk of severe toxicity when treated with fluoropyrimidines. The frequency of the heterozygous c.1905+1G>A genotype in the DPYD gene in Caucasian patients is around 1 %, 1,1 % for c.2846A>T, 2.6-6.3% for c.1236G>A/HapB3 variants and 0,07 to 0,1 % for c.1679T>G. Data on the frequency of the four DPYD variants in other populations than Caucasian is limited.

At the present, the four DPYD variants (c.1905+1G>A, c.1679T>G, c.2846A>T and c.1236G>A/HapB3) are considered virtually absent in populations of African (-American) or Asian origin.

Phenotypic characterisation of DPD deficiency: For phenotypic characterisation of DPD deficiency, the measurement of pre-therapeutic blood levels of the endogenous DPD substrate uracil (U) in plasma is recommended. Elevated pre-treatment uracil concentrations are associated with an increased risk of toxicity. Despite uncertainties on uracil thresholds defining complete and partial DPD deficiency, a blood uracil level u2265 16 ng/mL and < 150 ng/mL should be considered indicative of partial DPD deficiency and associated with an increased risk for fluoropyrimidine toxicity. A blood uracil level u2265 150 ng/mL should be considered indicative of complete DPD deficiency and associated with a risk for life-threatening or fatal fluoropyrimidine toxicity.

Hyperbilirubinaemia: PECASET can induce hyperbilirubinaemia. The risk of hyperbilirubinaemia with concurrent increases in alkaline phosphatase and/or transaminases is higher in patients with mild to moderate hepatic function impairment due to hepatic metastases. Treatment with PECASET should be interrupted if treatment-related elevations of bilirubin increase > 3,0 x upper limit of normal (ULN) or treatment-related elevations in hepatic aminotransferases (alanine transaminase (ALT), aspartate aminotransferase (AST) increase > 2,5 x ULN. Treatment may be resumed once bilirubin levels decrease u2264 3,0 x ULN or hepatic aminotransferases decrease u2264 2,5 x ULN.

Dihydropyramidine dehydrogenase (DPD) deficiency: PECASET is contraindicated in patients with DPD deficiency (see section 4.3). PECASET can cause stomatitis, diarrhoea, neutropenia and neurotoxicity, which has been attributed to a deficiency of DPD activity. A link between decreased levels of DPD and increased, potentially fatal toxic effects of 5-fluorouracil can therefore not be excluded.

Cytotoxic medication or radiation therapy: Caution is advised with PECASET treatment in patients who have previously received cytotoxic medication or radiation treatment.

Chicken pox or herpes zoster: Caution is advised with PECASET in patients who have or recently had chicken pox or herpes zoster infections, as they are at risk of developing generalised disease.

Diabetes mellitus or electrolyte disturbances: Caution must be exercised in patients with diabetes mellitus or electrolyte disturbances, as these may be aggravated during PECASET treatment.

Ophthalmologic complications: Patients should be carefully monitored for ophthalmological complications such as keratitis and corneal disorders, especially if they have a prior history of eye disorders. Treatment of eye disorders should be initiated as clinically appropriate.

Severe skin reactions: Capecitabine can induce severe skin reactions such as Stevens-Johnson syndrome and Toxic Epidermal Necrolysis. Capecitabine should be permanently discontinued in patients who experience a severe skin reaction during treatment.

Elderly: Elderly patients should be carefully monitored during treatment with PECASET.

Lactose intolerance: PECASET contains lactose and should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Warfarin: See boxed warning above.

Sorivudine and analogues: Due to the inhibition of DPD by sorivudine, a clinically significant interaction occurs between sorivudine and the capecitabine metabolite 5-FU. This interaction causes increased fluoropyrimidine toxicity and is potentially fatal. PECASET should not be administered with sorivudine or any related analogues such as brivudine (see CONTRAINDICATIONS).

Phenytoin: Formal interaction studies of phenytoin with PECASET have not been conducted. The mechanism of interaction between PECASET and phenytoin is presumed to be inhibition of the CYP2C9 isoenzyme system by capecitabine. Plasma concentration and associated clinical symptoms of toxicity may increase as a result of concomitant use with PECASET. Dose of phenytoin may need to be reduced with concomitant use. Patients should be regularly monitored for increased phenytoin plasma concentrations.

Food: Current safety and efficacy data is based upon the administration of PECASET after food, therefore it is recommended that PECASET be taken after food. Administration of PECASET with food decreases the absorption of capecitabine. See section 5.2.

Antacid: The administration of aluminium and magnesium containing antacids immediately after PECASET produces a small increase in capecitabine blood concentrations and the metabolite 5u2019-DFCR. No effect on other metabolites (5u2019-DFUR, 5-FU and FBAL) was noted.

Leucovorin (folinic acid): Leucovorin has no effect on the pharmacokinetics of capecitabine. However, concurrent use may increase the therapeutic and toxic effects of fluorouracil as a result of increased concentrations. Fatalities as a result of severe enterocolitis, diarrhoea and dehydration have been reported in elderly patients who receive PECASET and leucovorin concomitantly.

Allopurinol: Concomitant use of PECASET with allopurinol should be avoided as an interaction between allopurinol and 5-FU is possible, and may cause decreased efficacy of 5-FU.

Cytochrome P450: Caution is advised during co-administration of PECASET and isoenzymes 1A2, 2C9 and 3A4 due to a possible interaction (see boxed warning above) with CYP2C9 substrate (warfarin).

Interferon alpha: The maximum tolerated dose of PECASET is reduced when used concomitantly with interferon alpha.

Radiation therapy or bone marrow depressants: Additive bone marrow depression can occur, including severe dermatitis and/or mucositis. Dosage reduction is recommended when two or more bone marrow depressants, including radiation therapy, are used concomitantly or consecutively. The maximum tolerated dose (MTD) of PECASET is reduced during radiotherapy for the treatment of rectal cancer, using either a continuous schedule or given daily Monday to Friday during a 6 week course of radiotherapy.

Oxaliplatin and bevacizumab: No clinical significant difference in the exposure of PECASET or its metabolites, free platinum or total platinum occurred during concomitant treatment with oxaliplatin or in combination with oxaliplatin and bevacizumab. Bevacizumab does not alter the pharmacokinetics of PECASET or its metabolites in the presence of oxaliplatin.

Vaccines: PECASET may reduce the response to vaccines and there is a possibility of generalised infection with live vaccines. Use with live vaccines is generally not recommended. An estimation of the interval between the discontinuation of PECASET and restoration of the ability of the patient to respond to a vaccine depends on the intensity of treatment and is estimated to vary from 3 months to 1 year. Vaccination of people in close contact with the patient is also not recommended and should be postponed if possible.

Erlotinib: Exposure to erlotinib may be increased by concomitant PECASET use.

Women of childbearing potential / Contraception in males and females: Male patients treated with PECASET should be advised to use highly effective contraception, until the end of relevant systemic exposure to the genotoxic compound including potential genotoxic metabolites plus an additional 3 months after exposure (i.e. five half-lives after the last dose, plus 60-75 days for sperm production plus 10-14 days for the transport to epididymis). Female patients and female sexual partners of male patients receiving PECASET, should be advised to avoid becoming pregnant and to use highly effective contraception, until the end of relevant systemic exposure to the genotoxic compound including potential genotoxic metabolites plus an additional 6 months after exposure (i.e. five half-lives after the last dose, plus 6 months which covers the growth and maturation phase of folliculogenesis).

PECASET is contraindicated in pregnancy and lactation. Pregnancy: PECASET may be mutagenic and teratogenic, and use during pregnancy, especially the first trimester, may lead to foetal abortion, stunting or malformation. Lactation: It is not known if PECASET is excreted into breast milk and should not be taken during breastfeeding, due to the potential risk to the nursing infant.

PECASET can cause side effects such as dizziness, syncope, confusion or vision problems. Patients should be advised not to drive a vehicle or operate machinery until they know how PECASET affects them.

PECASET monotherapy: The safety profiles for metastatic breast cancer, metastatic colorectal cancer and colon cancer are comparable. Infections and infestations: Frequent: Herpes simplex, nasopharyngitis, lower respiratory tract infection. Less frequent: Sepsis, cellulitis, oral candidiasis, influenza, fungal infection, herpes infection, infection, tooth abscess, bronchitis, bronchopneumonia, pneumonia, viral infection. Neoplasms benign and malignant (including cysts and polyps): Less frequent: Lipoma. Blood and the lymphatic system disorders: Frequent: Neutropenia, anaemia, lymphopenia, thrombocytopenia. Less frequent: Febrile neutropenia, pancytopenia, granulocytopenia, leukopenia, haemolytic anaemia, thrombocytopenic purpura, lymphoedema. Immune system disorders: Less frequent: Hypersensitivity, anaphylaxis. Metabolism and nutrition disorders: Frequent: Anorexia, dehydration, decreased appetite. Less frequent: Diabetes mellitus, hypokalaemia, appetite disorder, malnutrition, hypertriglyceridaemia, hypomagnesaemia, cachexia, thirst. Psychiatric disorders: Frequent: Insomnia, depression. Less frequent: Confusional state, panic attack, dysarthria, hoarseness, irritability. Nervous system disorders: Frequent: Headache, dizziness, paraesthesia, dysgeusia. Less frequent: Aphasia, memory impairment, ataxia, balance disorder, sensory disorder, peripheral neuropathy, cerebrovascular incident, encephalopathy, loss of consciousness, abnormal coordination, sedation, tremor, difficulty walking. Eye disorders: Frequent: Increased lacrimation, increased conjunctivitis, eye irritation. Less frequent: Reduced visual acuity, diplopia, keratoconjunctivitis, ocular toxicity, dacryostenosis, photophobia. Ear and labyrinth disorders: Less frequent: Vertigo, ear pain. Cardiac disorders: Less frequent: Unstable angina, angina pectoris, myocardial ischaemia, atrial fibrillation, dysrhythmia, tachycardia, sinus tachycardia, palpitations, bradycardia, cardiomyopathy, cardiotoxicity, extrasystoles, myocarditis, ventricular extrasystoles, pericardial effusion, chest pain, electrocardiogram (ECG) changes. Vascular disorders: Frequent: Thrombophlebitis, epistaxis. Less frequent: Syncope, deep vein thrombosis, hypertension, hypotension, hot flushes, peripheral coldness, coagulation disorder, collapse, haemorrhage. Respiratory, thoracic and mediastinal disorders: Frequent: Nasopharyngitis, dyspnoea, cough, rhinorrhoea. Less frequent: Tonsillitis, pharyngitis, pulmonary embolism, pneumothorax, haemoptysis, asthma, exertional dyspnoea, bronchospasm, respiratory distress, laryngitis. Gastrointestinal disorders: Frequent: Diarrhoea, nausea, vomiting, stomatitis, abdominal pain, gastrointestinal haemorrhage, constipation, upper abdominal pain, dyspepsia, flatulence, dry mouth, loose stools. Less frequent: Gastroenteritis, intestinal obstruction, ascites, gastritis, enteritis, dysphagia, lower abdominal pain, oesophagitis, abdominal discomfort, gastro-oesophageal reflux disease, colitis, gastric ulcer, gastrointestinal tract toxicity, ileus, toxic dilation of intestines, abdominal distension, gastrointestinal motility disorder, proctalgia, mucositis, oral ulceration. Hepatobiliary disorders: Frequent: Hyperbilirubinaemia. Less frequent: Jaundice, cholestatic hepatitis, hepatic fibrosis, hepatitis. Frequency unknown: Hepatic failure. Skin and subcutaneous tissue disorders: Frequent: Palmar-plantar erythrodysaesthesia, rash, alopecia, erythema, dry skin, pruritus, skin hyperpigmentation, macular rash, skin desquamation, dermatitis, pigmentation disorder, nail disorder. Less frequent: Petechiae, skin ulcer, urticaria, photosensitivity reaction, palmar erythema, purpura, facial oedema, increased sweating, erythema multiforme. Musculoskeletal, connective tissue and bone disorders: Frequent: Pain in extremity, back pain, arthralgia. Less frequent: Joint swelling, bone pain, facial pain, musculoskeletal stiffness, muscular weakness, arthritis, myalgia. Renal and urinary disorders: Less frequent: Urinary tract infection, hydronephrosis, urinary incontinence, haematuria, nocturia, renal impairment. Reproductive system and breast disorders: Less frequent: Decreased libido, vaginal haemorrhage. General disorders and administrative site conditions: Frequent: Lethargy, fatigue, asthenia, pyrexia, peripheral oedema, malaise, non-cardiac chest pain. Less frequent: Oedema, chills, influenza-like illness, rigors, chest mass, fibrosis. Investigations: Frequent: Decreased weight, liver function test abnormalities, decreased haemoglobin. Less frequent: Blood in stools, increased INR, increased blood creatinine, increased body temperature, increased weight. Injury and poisoning: Less frequent: Blister, overdose, radiation recall syndrome. Laboratory abnormalities: Patients with Grade 1 u2013 4 abnormality: Frequent: Decreased haemoglobin, decreased neutrophils/granulocytes, decreased platelets, decreased lymphocytes, decreased sodium, decreased potassium, decreased calcium, increased bilirubin, increased alkaline phosphatase, increased ALT (SGPT), increased AST (SGOT). Patients with Grade 3 or 4 abnormality: Frequent: Decreased lymphocytes, increased bilirubin, decreased haemoglobin, decreased neutrophils/granulocytes, decreased platelets, decreased calcium, increased alkaline phosphatase, increased ALT (SGPT). Less frequent: Decreased sodium, decreased potassium, increased calcium, increased AST (SGOT). Patients with Grade 4 abnormality: Frequent: Decreased neutrophils/granulocytes, decreased lymphocytes, decreased calcium, increased bilirubin. Less frequent: Decreased haemoglobin, decreased platelets, decreased sodium, decreased potassium, increased calcium, increased alkaline phosphatase, increased ALT (SGPT), increased AST (SGOT).

In the event of overdose, side effects such as nausea, vomiting, diarrhoea, mucositis, gastrointestinal irritation and bleeding, and bone marrow depression can occur. Treatment is symptomatic and supportive. Dialysis may be effective to remove circulating 5u2019-DFUR, the metabolite that is the immediate precursor of fluorouracil.