Kseloda

Kseloda – medicine with antineoplastic action.

Form of release and structure

Kseloda is issued in the form of tablets, film coated: oblong, biconvex, the engraving of "XELODA" is applied on one of the parties; on 150 mg – light - milk-pink (light-peach) color, an engraving on the other side of a tablet – "150"; on 500 mg – milk-pink (peach) color, an engraving on the other side of a tablet – "500" (in blisters on 10 pieces, on 6 or 12 blisters in a cardboard pack; in polyethylene bottles on 60 or 120 pieces, on 1 bottle in a cardboard pack).

Is a part of 1 tablet:

• Active ingredient: капецитабин – 150 or 500 mg;
• Auxiliary components (150/500 mg respectively): magnesium stearate – 2,7/9 mg, lactose – 15,6/52 mg, microcrystallic cellulose – 7,2/24 mg, a gipromelloza (3 мПа.с) – 4,5/15 mg, croscarmellose sodium – 6/20 mg;
• Cover (150/500 mg respectively): Opadry pink 03A14309/Opadry pink 03A14309 (talc, a gipromelloz (6 мПа.с), titanium dioxide (E171), dye iron oxide yellow (E172), dye iron oxide red (E172)) – 8,5/18 mg.

Indications to use

• Breast cancer (metastatic or locally-spread): monotherapy of cancer showing resistance to chemotherapy taxons or medicines of an anthracycline row or in case of existence of contraindications to their use; the combined treatment with dotsetaksely at inefficiency of the chemotherapy including medicine of an anthracycline row;
• Carcinoma of the stomach: therapy of the first line of a widespread carcinoma of the stomach;
• Colorectal cancer: therapy of a metastatic colorectal cancer; adjuvant cancer therapy of a large intestine of the III stage after surgical intervention.

Contraindications

Absolute:

• The diagnosed deficit of DPD (dehydrogenase dihydropyrimidine);
• Initial maintenance of thrombocytes <^{100 × 109/l} and/or neutrophils <^{1,5 × 109/l};
• Heavy renal failure (at clearance of creatinine it is lower than 30 ml in a minute);
• Existence of contraindications to one of medicines as a part of the combined treatment;
• Simultaneous use with sorivudiny and its structural analogs like brivudin;
• Pregnancy and period of a lactation;
• Children's age (for this group of patients data on safety and efficiency of use of Kseloda are absent);
• Hypersensitivity to a ftoruratsil or existence of anamnestic data on development of unexpected or heavy side effects at treatment by derivatives of a ftorpirimidin;
• Hypersensitivity to drug components.

Relative (Kseloda is appointed with care):

• Coronary heart disease;
• Renal failure of moderate severity;
• Liver failure;
• Lactose intolerance, hereditary deficit of lactase, glyukozo-galaktozny malabsorption;
• Combined use with peroral anticoagulants of a coumarinic row;
• Age of 60 years.

Route of administration and dosage

Kseloda should be accepted inside, washing down with water, it is preferable – not later, than in half an hour after meal.

When performing monotherapy of a colorectal cancer, breast cancer and colon cancer of Kselodu usually appoint 2 times a day (in morning and evening) 1250 ^mg/sq.m (2500 ^mg/sq.m a day). 14 days of administration of drug alternate to a 7-day break.

Along with other drugs appoint the following mode of dosing:

• Breast cancer: 2 times a day on 1250 ^{mg/sq.m (}14 days of administration of drug alternate to a 7-day break) along with dotsetaksely (intravenous infusion within 1 hour of 75 ^mg/sq.m of 1 times in 21 days). Before introduction of a dotsetaksel carrying out premedication is shown;
• Colorectal cancer and carcinoma of the stomach: 2 times a day on 800-1000 ^mg/sq.m within 14 days with the subsequent 7-day break, or are continuous on 625 ^mg/sq.m 2 times a day. Use of immunobiological medicines does not render on Kseloda's dose of influence. Before introduction of an oksaliplatin and Cisplatinum appoint premedication and antiemetic drugs for ensuring adequate hydration. The recommended duration of a course of adjuvant therapy of a colon cancer of the III stage makes 6 months (8 courses).

The recommended schemes of use of Kseloda as a part of the combined treatment:

• Combination with Cisplatinum: Kseloda – 2 times a day on 1000 ^mg/sq.m (14 days of administration of drug alternate to a 7-day break), appoint the first dose in the evening in the first day of a cycle of therapy, the last – in the morning to the fifteenth day. Cisplatinum – 1 time in 21 days on 80 ^mg/sq.m in the form of intravenous infusion within 2 hours, the first infusion is carried out in the first day of a cycle;
• Combination with bevatsizumaby and/or oksaliplatiny: Kseloda – 2 times a day on 1000 ^mg/sq.m (14 days of administration of drug alternate to a 7-day break), appoint the first dose in the evening in the first day of a cycle of therapy, the last – in the morning to the fifteenth day. Bevatsizumab – 1 time in 21 days on 7,5 mg/kg in the form of intravenous infusion within 30-90 minutes, the first infusion is carried out in the first day of a cycle. Oksaliplatin – 130 ^mg/sq.m in the form of intravenous infusion within 2 hours, administer the drug after a bevatsizumab;
• Combination with epirubitsiny and platinum drug: Kseloda – 2 times a day on 625 ^mg/sq.m are continuous. Epirubitsin – 1 time in 21 days on 50 ^mg/sq.m intravenously bolyusno, since first day of a cycle. Platinum drug – 1 time in 21 days of 130 ^mg/sq.m of an oksaliplatin or 60 ^mg/sq.m of Cisplatinum in the form of intravenous infusion within 2 hours, the first dose is appointed in the first day of a cycle;
• Combination with irinotekany: Kseloda – 2 times a day on 1000 ^mg/sq.m (14 days of administration of drug alternate to a 7-day break). Irinotekan – 1 time in 21 days on 250 ^mg/sq.m in the form of intravenous infusion within 30 minutes, the first infusion is appointed in the first day of a cycle;
• Combination with bevatsizumaby and irinotekany: Kseloda – 2 times a day on 800 ^mg/sq.m (14 days of administration of drug alternate to a 7-day break). Irinotekan – 1 time in 21 days on 200 ^mg/sq.m in the form of intravenous infusion within 30 minutes, the first infusion is appointed in the first day of a cycle. Bevatsizumab – 1 time in 21 days on 7,5 mg/kg in the form of intravenous infusion within 30-90 minutes, the first infusion is appointed in the first day of a cycle.

Toxic action of Kseloda can be eliminated with carrying out a symptomatic treatment and/or dose adjustment of drug (having interrupted a course or having lowered a dose). After a dose decline it is impossible to increase it further.

In cases when the toxic effect does not pose a serious threat for the patient's life, therapy can be continued in an initial dose or without interruption of a course (therapy interrupt 2 and 3 degrees at toxicity). At disappearance of symptoms of toxicity, or its reduction to 1 degree, treatment by drug can be resumed in a full dose or to carry out its correction.

At emergence of signs of toxicity 4 degrees therapy need to be cancelled or to temporarily interrupt before reduction or stopping of symptoms up to 1 degree, then Kseloda's reception can be resumed in 1/2 initial doses.

At development of the undesirable phenomena it is necessary to notify the attending physician on it. At emergence of toxicity of average or heavy severity it is necessary to stop Kseloda's reception immediately.

In case of purpose of the combined treatment at expectation of a delay of use of one of drugs therapy should not be begun.

If when carrying out a combination therapy the toxicity phenomena, not connected, according to the doctor, with Kseloda's reception are observed, carry out correction of the caused disturbance of medicine without change of a dose of Kseloda.

At metastasises in a liver and moderate or easy functional disturbances of a liver change of an initial dose is not required, at the same time such patients need careful observation. Safety and efficiency of use of drug at a heavy liver failure were not studied.

The initial dose is recommended to be lowered to 75% of 1250 ^mg/sq.m at an initial moderate renal failure (at clearance of creatinine of 30-50 ml a minute). At easy severity of a renal failure (at clearance of creatinine of 51-80 ml a minute) correction of an initial dose should not be carried out.

It is necessary to consider that at advanced and senile age the heavy undesirable phenomena 3 and 4 degrees usually develop more often than at young patients. In this regard patients of this age group need careful observation.

At simultaneous use with dotsetaksely for patients of 60 years 3 and 4 degrees are noted increase in frequency of development of the undesirable phenomena. For this group of patients about 75% are recommended to lower an initial dose of Kseloda (2 times a day on 950 ^mg/sq.m).

At the combined use with irinotekany the patient aged from 65 years recommends to reduce an initial dose of Kseloda about 800 ^mg/sq.m 2 times a day.

Side effects

During Kseloda's use development of disturbances from various systems of an organism which are shown with various frequency is possible: ≥1/10 – very often, from ≥1/100 to <1/10 – it is frequent, from ≥1/1000 to <1/100 – infrequently.

Side effects when performing monotherapy:

• Nervous system: often – paresthesias, dizziness (except вертиго), a headache, a food faddism (dysgeusia);
• Hypodermic fabrics and skin: very often – dermatitis, a palmar and bottom syndrome (in the form of hypostasis, paresthesias, a peeling of skin, a hyperemia, blistering); often – a hair loss (full or partial), rash, a xeroderma, a limited dermahemia; perhaps – skin cracks (are presumably connected with Kseloda's reception);
• Alimentary system: very often – abdominal pains, vomiting, diarrhea, nausea, stomatitis (including ulcer); often – pains in epigastric area, a lock, dispepsichesky disturbances;
• Laboratory indicators: often – increase in bilirubin (hyperbilirubinemia);
• Organ of sight: often – a conjunctiva inflammation, the raised slezootdeleniye;
• Metabolism and food: very often – anorexia; often – a loss of appetite, dehydration;
• General disturbances: very often – drowsiness, fatigue; often – weakness, fever, an adynamy.

The disturbances connected with toxicity manifestations (there is, at least, an indirect communication between development of such side effects and Kseloda's use):

• Cardiovascular system: cardialgias (including stenocardia), hypostases of the lower extremities, tachycardia, a cardiomyopathy, a myocardial infarction, myocardium ischemia, heart failure, supraventricular arrhythmias (including fibrillation of auricles, ventricular extrasystoles), sudden death;
• Alimentary system: dryness in a mouth, the meteorism, disturbances connected with an ulceration/inflammation of mucous membranes (in the form of gastritis, an esophagitis, colitis, a duodenitis, gastrointestinal bleedings);
• Respiratory system: cough, short wind;
• Nervous system: sleeplessness, taste disturbance, encephalopathy, confusion of consciousness, symptoms of cerebellar disturbances (in the form of an ataxy, a dysarthtia, a lack of coordination and balance);
• Connecting fabric and musculoskeletal system: mialgiya, joint pains (one or several) and to back;
• Mentality: depression;
• Organ of sight: irritation of eyes;
• Hypodermic fabrics and skin: reactions of a photosensitization, change of nails, a focal peeling of skin, an itch, the strengthened xanthopathy, the syndrome similar to beam dermatitis;
• Lymphatic system and blood: low maintenance of all uniform elements of blood, anemia, miyelosupressiya;
• Parasitic and infectious diseases: the infectious complications connected with a miyelosupressiya, disturbances of integrity of mucous membranes and/or easing of immunity in the form of local and fatal system infections (a bacterial, fungal or virus etiology) and sepsis;
• General disturbances: the increased drowsiness, an adynamy, extremity pains, a stethalgia (not cardial etiology).

At Kseloda's use along with other drugs the safety profile at appointment according to various indications and in various combinations did not differ, however in this case the disturbances characteristic of monotherapy can develop more often.

Some side effects are often observed when carrying out chemotherapy (for example, peripheral touch neuropathy at use of a dotsetaksel or oksaliplatin, increase in arterial pressure at therapy bevatsizumaby), but at Kseloda's reception it is impossible to exclude their deteriorations.

When performing the combined treatment the following disturbances in addition to those can develop at monotherapy:

• Nervous system: very often – a dizesteziya, a peripheral touch neuropathy, a peripheral neuropathy;
• Respiratory system: very often – a pharyngalgia, a perversion of sensitivity of a throat; often – a dysphonia, nasal bleeding, a rhinorrhea;
• Cardiovascular system: very often – embolism/thrombosis, increase in arterial pressure;
• Connecting fabric and musculoskeletal system: very often – gnathalgias;
• Lymphatic system and blood: very often – a febrile neutropenia, a leukopenia;
• Food and metabolism: very often – decrease in body weight;
• Parasitic and infectious diseases: often – candidiasis of an oral cavity;
• General disturbances: very often – temperature intolerance; often – pain, fever.

When carrying out clinical and post-market researches cases of cholestatic hepatitis and liver failure were registered (relationship of cause and effect is not established with performing therapy by Kseloda).

During performing the combined treatment with other chemotherapeutic drugs it was reported about frequent development of a heart attack of myocardium/ischemia and reactions of hypersensitivity.

Changes of laboratory indicators at Kseloda's use are shown as a hyperbilirubinemia, a hypopotassemia, a hyponatremia, a hyperglycemia, a giperkreatininemiya, гипер-/a hypocalcemia, decrease in hemoglobin, reduction of number of neutrophils, granulocytes, thrombocytes, lymphocytes, increase in activity of alaninaminotranspherase, aspartate aminotransferase, an alkaline phosphatase.

During post-marketing use of Kseloda not specified stenosis of the lacrimal tubule was seldom or never recorded. With the same frequency in clinical and post-market researches cases of cholestatic hepatitis and liver failure were registered.

Special instructions

During therapy it is necessary to exercise careful control of patients of toxicity manifestations.

The majority of disturbances have reversible character and do not demand full cancellation of Kseloda though dose adjustment or temporary drug withdrawal can be required.

At treatment development of diarrhea, sometimes heavy is possible. Patients with heavy diarrhea need to be observed carefully, and at development of dehydration it is necessary to carry out a regidratation and to compensate loss of electrolytes. On medical indications it is necessary to appoint standard antidiarrheal medicines as soon as possible. In case of need the dose of drug needs to be lowered.

Dehydration it is necessary to eliminate or warn at the very beginning of emergence. It can quickly develop against the background of anorexia, an adynamy, nausea, vomiting or diarrhea. At dehydration 2 degrees need to be interrupted immediately therapy above and to carry out a regidratation. Before its end and correction or elimination of factors which led to its development administration of drug cannot be resumed.

The range of cardiotoxicity of Kseloda includes heart failure, stenocardia, a myocardial infarction, a cardiac standstill, arrhythmias and changes on the electrocardiogram. These disturbances at patients with coronary heart disease in the anamnesis are most characteristic.

The palmar and bottom syndrome can be manifestation of skin toxicity. At its development to 2 or 3 degrees therapy needs to be interrupted before disappearance of symptoms or their reduction to 1 degree. At development of a syndrome 3 degrees the subsequent doses of Kseloda have to be lowered. B6 vitamin (pyridoxine) is not recommended to be applied to symptomatic or secondary preventive therapy of a palmar and bottom syndrome.

Kseloda can lead to development of a hyperbilirubinemia. Treatment should be interrupted at a hyperbilirubinemia> 3 × UBN (upper bound of norm) or increase in activity of hepatic aminotransferases (alaninaminotranspherase, aspartate aminotransferase)> 2,5 × VGN.

It is possible to resume therapy at lowering of the level of bilirubin and activity of hepatic aminotransferases below the specified limits.

Kseloda has moderate or small influence on ability to manage motor transport and mechanisms. It is necessary to consider that during therapy such undesirable phenomena as dizziness, nausea or weakness can develop.

Medicinal interaction

At co-administration of Kseloda with some drugs there can be following effects:

• Anticoagulants of a coumarinic row: disturbances of indicators of coagulation and/or bleeding during therapy or after its termination (it is necessary to control carefully indicators of coagulation and depending on them to adjust anticoagulant doses);
• _{P450 cytochrome} substrates: the combination was not investigated, at joint appointment it is necessary to be careful;
• Antacids: increase in concentration of a kapetsitabin and one of metabolites (5 '-DFTsT) in a blood plasma;
• Phenytoinum: increase in its concentration in plasma;
• Sorivudin and his analogs: fatal strengthening of toxicity of a kapetsitabin (the combination is not recommended; Kselodu can appoint in 4 days after the end of therapy sorivudiny or its structural analogs);
• Leykovorin (calcium фолинат): strengthening of toxic action of a kapetsitabin.

Terms and storage conditions

To store in the place, unavailable to children, at a temperature up to 30 °C.

Period of validity – 3 years.