Capecitabine - Instructions For Use, Reviews, Price, 500 Mg Tablets

Capecitabine

Capecitabine: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood

1. 11. In case of impaired renal function
2. 12. In case of impaired liver function
3. 13. Use in the elderly
4. 14. Drug interactions
5. 15. Analogs
6. 16. Terms and conditions of storage
7. 17. Terms of dispensing from pharmacies
8. 18. Reviews
9. 19. Price in pharmacies

Latin name: Capecitabinum

ATX code: L01BC06

Active ingredient: capecitabine (capecitabinum)

Producer: Novalek Pharmaceiticals (India), Shijiazhuang Yiling Pharmaceutical (China), ArSiAi Sintez (Russia)

Description and photo update: 2018-21-11

Prices in pharmacies: from 7200 rubles.

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Capecitabine is an antineoplastic drug, an antimetabolite.

Release form and composition

Dosage form of Kepecitabine - film-coated tablets: oval, biconvex, light peach color on the outside, white on the cut, engraved "150" (for 150 mg tablets) or "500" (for 500 mg tablets) on one side [by 10 pieces. in a blister strip packaging, in a cardboard box 6 (for tablets 150 mg) or 12 (for tablets 500 mg) blisters].

Composition of 1 tablet:

• active substance: capecitabine - 500 mg or 150 mg;
• auxiliary components: microcrystalline cellulose, lactose, croscarmellose sodium, hypromellose, magnesium stearate;
• shell: hypromellose, talc, titanium dioxide, dyes.

Pharmacological properties

Pharmacodynamics

Capecitabine is a fluoropyrimidine carbamate derivative, an oral cytostatic agent that is activated in tumor tissue and has a selective cytotoxic effect on it.

In vitro, capecitabine has no cytotoxic effect; in vivo it is converted to fluorouracil (FU), which undergoes further metabolism.

The formation of FU occurs in tumor tissues under the influence of thymidine phosphorylase (an angiogenic tumor factor), due to which it is possible to minimize the systemic effect of FU on healthy tissues.

Due to the sequential enzymatic biotransformation of capecitabine into FU, the concentration of the drug in tumor tissues is approximately 3.2 times higher than in healthy ones.

FU is metabolized to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluoruridine triphosphate (FUTP) by both tumor and healthy cells. These metabolites damage cells in two different ways. First, FdUMP and folate cofactor N5-10 - methylenetetrahydrofolate bind to thymidylate synthase (TS) to form a covalently bound tertiary complex, which has a suppressive effect on the formation of thymidylate, a precursor of thymidine triphosphate, which is extremely important for DNA, from uracil. This leads to inhibition of cell division. Second, during RNA synthesis, nuclear transcriptional enzymes can include FUTP instead of uridine triphosphate, which disrupts post-transcriptional RNA modifications and protein synthesis.

Pharmacokinetics

Capecitabine is rapidly and completely absorbed. Food intake slows it down, but the area under the concentration-time curve of 5'-deoxy-5-fluorocytidine (5'-DFUR) and the next FU metabolite has little effect.

The substance is biotransformed in tumor tissues. The maximum concentration is reached in 1.5–3.34 hours.

Capecitabine metabolites have varying degrees of protein binding. Their half-life is 1–3.3 hours, and capecitabine is 1.25 hours. It is excreted mainly in the urine and in small quantities in the feces.

Indications for use

• locally advanced or metastatic breast cancer - monotherapy or as part of combination therapy with docetaxel, in cases where chemotherapy, including an anthracycline drug, was ineffective, or with contraindications to it;
• colorectal cancer - therapy for metastatic cancer or adjuvant therapy for stage III colon cancer after surgery;
• stomach cancer - first-line therapy for advanced stomach cancer.

Contraindications

Absolute contraindications:

• severe renal or hepatic impairment;
• established deficiency of dihydropyrimidine dehydrogenase (DPD);
• severe leukopenia;
• the initial content of neutrophils <1.5 × 10 ⁹ / l or platelets <100 × 10 ⁹ / l;
• pregnancy and lactation;
• age up to 18 years (due to the lack of data on safety and effectiveness);
• hypersensitivity to any component of Capecitabine, fluorouracil and fluoropyrimidine derivatives in history.

Relative contraindications:

• ischemic heart disease (CHD);
• angina pectoris, including history;
• anemia;
• renal or hepatic impairment of moderate severity;
• hypocalcemia;
• hypercalcemia;
• diseases of the central and peripheral nervous system;
• diabetes;
• violations of water and electrolyte balance;
• age over 60;
• hereditary lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Instructions for the use of Capecitabine: method and dosage

Capecitabine tablets are taken orally within 30 minutes after a meal with water.

The recommended dosage for monotherapy for colorectal cancer, colon cancer and breast cancer: 1250 mg / m ² twice a day (morning and evening), for 14 days, followed by a 7-day break.

The regimen should be prescribed by an experienced oncologist experienced with Capecitabine.

Recommended standard dosage for combination therapy:

• breast cancer: 1250 mg / m ² twice a day for 14 days, followed by a 7-day break, in combination with docetaxel 75 mg / m ² once every 21 days (intravenous infusion for 60 minutes). Before the introduction of docetaxel, medication is carried out according to its instructions for use;
• stomach cancer and colorectal cancer: 800–1000 mg / m ² twice a day for 14 days, followed by a 7-day break, or 625 mg / m ² without a break. The addition of bevacizumab to therapy does not affect the initial dose of Capecitabine. Before the administration of cisplatin and oxaliplatin, antiemetics and premedication are prescribed to ensure adequate hydration according to their instructions for use. For the adjuvant treatment of colon cancer, Capecitabine usually requires 8 courses, i.e. 6 months.

Dosing of Capecitabine, depending on the drugs used in combination therapy with it:

• combination with cisplatin: 100 mg / m ² twice a day for 14 days, followed by a 7-day break in combination with cisplatin (80 mg / m ² once every 21 days) administered as an intravenous (IV) infusion for 2 hours (the first infusion is prescribed on the 1st day of the cycle). The first dose of Capecitabine is taken in the evening of the 1st day of the cycle, the last in the morning on the 15th day;
• combination with oxaliplatin or oxaliplatin with bevacizumab: 100 mg / m ² twice a day for 14 days, followed by a 7-day break in combination with oxaliplatin or oxaliplatin with bevacizumab. The first dose of Capecitabine is taken in the evening of the 1st day of the cycle, the last in the morning on the 15th day. Bevacizumab: 7.5 mg / kg body weight once every 21 days (intravenous infusion over 30-90 minutes). First infusion on day 1 of the cycle. Immediately after bevacizumab, oxaliplatin (130 mg / m ²) is administered intravenously for 2 hours;
• combination with epirubicin and platinum-based agents: 625 mg / m ² twice a day without interruptions in combination with platinum and epirubicin (50 mg m ² once every 21 days, IV bolus). The introduction of 1 dose of epirubicin, and the drug platinum (cisplatin 60 mg / m ² or oxaliplatin about 130 mg / m ² as an intravenous infusion for 2 hours once every 21 days) is prescribed on the 1st day of the cycle;
• combination with irinotecan or irinotecan and bevacizumab: 800 mg / m ² twice a day, for 14 days, followed by a 7-day break. Irinotecan: 200 mg / m ² once every 21 days (intravenous infusion for 30 minutes), the first infusion is prescribed on the first day of the cycle. Bevacizumab: 7.5 mg / kg of body weight once every 21 days (intravenous infusion for 30–90 minutes), the first infusion is also prescribed on day 1 of the cycle.

To reduce the toxic effects of Capecitabine, symptomatic therapy is recommended, in some cases (with a serious and life-threatening nature of the toxic effect), a decrease in the dose of the drug may be required; it cannot be increased later. Only the attending physician can make an assessment of toxicity, as well as make a decision on adjusting the dose of Capecitabine. In case of grade I toxicity, the dose remains unchanged; grade II or III toxicity may cause drug withdrawal.

In the event of the disappearance of signs of toxicity or its reduction to grade I, Capecitabine therapy can be resumed at the full dose or adjusted.

Grade IV toxicity requires complete or temporary discontinuation of treatment with a decrease in symptoms to grade I. Then the therapy is continued at a dose reduced by 50%.

Due to the possible hematological toxicity with a baseline neutrophil count of less than 1.5 × 10 ⁹ / L or a baseline platelet level <100 × 10 ⁹ / L, Capecitabine therapy is contraindicated. You should also interrupt treatment if the number of neutrophils is less than 1.0 × 10 ⁹ / l, and the number of platelets is less than 75 × 10 ⁹ / l (hematological toxicity III or IV degree).

General recommendations for combination therapy:

1. If toxicity occurs during combination therapy, the doses of the drugs should be adjusted according to the instructions for their use.
2. If it is impossible to start taking all the drugs that are part of the combination therapy at once, you should postpone the intake, and then start taking them at the same time.
3. If toxicity not associated with Capecitabine occurs, its administration should be continued at the recommended dose, and the dose of the drug causing toxicity should be adjusted in accordance with the recommendations in the instructions for use.
4. In the event that it is necessary to cancel other drugs, Capecitabine may be continued if the requirements for resuming Capecitabine therapy are met.

Recommended dose adjustment of capecitabine depending on the degree of toxicity:

• I degree of toxicity: dose adjustment of Capecitabine is not required;
• II degree of toxicity: the first manifestation is to interrupt therapy until the first degree is reached, then continue at the usual dose; the second manifestation is to interrupt therapy until the first degree is reached, then reduce the dose to 75%; the third manifestation is to interrupt therapy until the first degree is reached, then reduce the dose to 50%; the fourth manifestation is to completely stop using the drug;
• III degree of toxicity: the first manifestation is to interrupt therapy until the first degree is reached, then reduce the dose to 75%; the second manifestation is to interrupt therapy until the first degree is reached, then reduce the dose to 50%; the third manifestation is to completely stop using Capecitabine;
• IV degree of toxicity: the first manifestation is to interrupt the therapy completely, or, by the decision of the attending physician, before reaching the I degree, further reduce the dose to 50%; the second manifestation is to completely stop using the drug.

Side effects

Most of the side effects of the drug are temporary and do not require discontinuation of therapy, however, a dose adjustment or a temporary interruption in admission may be required.

The most common use of Capecitabine is diarrhea, nausea, vomiting, stomatitis, abdominal pain, fatigue, palmar-plantar syndrome (edema, paresthesia, hyperemia, skin peeling, blistering), asthenia, anorexia, cardiotoxicity, thrombosis / embolism, growth renal failure (with a history of impaired renal function).

Side effects of monotherapy:

• infectious and parasitic diseases: herpes, nasopharyngitis, lower respiratory tract infections, sepsis, urinary tract infections, pharyngitis, tonsillitis, candidiasis of the oral mucosa, gastroenteritis, influenza, fungal infections, tooth abscess, other infections;
• malignant and benign tumors, unspecified neoplasms: lipoma;
• blood and lymphatic system: neutropenia, febrile neutropenia, granulocytopenia, leukopenia, thrombocytopenia, hemolytic anemia, increased international normalized ratio, prolonged prothrombin time;
• immune system: hypersensitivity reactions;
• metabolism and nutrition: anorexia, dehydration, weight loss, diabetes mellitus, hypokalemia, digestive disorders, hypertriglyceridemia;
• psyche: panic attacks, depressed mood, decreased libido;
• nervous system: headache, dizziness, lethargy, paresthesia, dysgeusia, aphasia, memory disorder, imbalance, fainting, loss of sensitivity, peripheral neuropathy;
• organ of vision: conjunctivitis, increased lacrimation, diplopia, decreased visual acuity;
• hearing organ and labyrinth disorders: vertigo, ear pain;
• cardiovascular system: thrombophlebitis, angina pectoris (including unstable), arrhythmia, sinus tachycardia, palpitations, deep vein thrombosis, increase or decrease in blood pressure (BP), petechiae, hot flashes, cooling of the distal extremities;
• respiratory system, chest and mediastinal organs: rhinorrhea, epistaxis, pneumothorax, hemoptysis, bronchial asthma, shortness of breath during exertion;
• gastrointestinal tract (GIT): diarrhea, vomiting, nausea, stomatitis (including ulcerative), abdominal pain, constipation, epigastric pain, dyspepsia, intestinal obstruction, ascites, enteritis, lower abdominal pain, abdominal discomfort, gastroesophageal reflux disease, dysphagia, melena;
• liver and biliary tract: changes in liver function tests, jaundice;
• skin and subcutaneous tissues: palmar-plantar syndrome, dermatitis, skin hyperpigmentation, macular rash, alopecia, erythema, rash, dry skin, blisters, ulcers, urticaria, palmar erythema, purpura, facial edema, skin cracks (less than 2% of patients);
• musculoskeletal and connective tissue: back and limb pain, joint swelling, bone pain, facial pain, stiffness, muscle weakness;
• kidney and urinary tract: hydronephrosis, hematuria, urinary incontinence, nocturia, increased plasma creatinine;
• genitals and mammary gland: vaginal bleeding;
• general disorders and disorders at the injection site: drowsiness, fatigue, peripheral edema, chest pain, malaise, weakness, fever, asthenia, chills, edema, flu-like syndrome, tremors, fever;
• laboratory parameters: hyperbilirubinemia.

Toxic reactions when using fluoropyrimidines:

• Gastrointestinal tract: dry mouth, flatulence, inflammation, ulceration of the mucous membranes (esophagitis, gastritis, duodenitis, colitis, gastrointestinal bleeding);
• cardiovascular system: edema of the lower extremities, cardialgia (including angina pectoris), cardiomyopathy, myocardial infarction or ischemia, heart failure, tachycardia, supraventricular arrhythmias (including atrial fibrillation), ventricular extrasystoles, sudden death;
• nervous system: taste disturbances, insomnia, encephalopathy, confusion, symptoms of cerebellar disorders (ataxia, dysarthria, impaired coordination and balance);
• psyche: depression;
• infectious and parasitic diseases: infectious complications of myelosuppression, weakening of the immune system, mucositis, sepsis, local and fatal fungal, viral or bacterial systemic infections;
• blood and lymphatic system: pancytopenia, myelosuppression, anemia;
• skin and subcutaneous tissues: itching, focal peeling, hyperpigmentation, photosensitization reactions, nail changes, radiation dermatitis;
• organ of vision: eye irritation;
• respiratory system, chest and mediastinal organs: cough, shortness of breath;
• musculoskeletal and connective tissue: back pain, myalgia, arthralgia;
• general disorders and disorders at the injection site: pain in the limbs and in the chest.

When Capecitabine is used in combination therapy, the adverse reactions listed with monotherapy may occur with a greater frequency.

Side effects in combination therapy (in addition to those encountered in monotherapy):

• infectious and parasitic diseases: herpes zoster, oral herpes, rhinitis;
• blood and lymphatic system: anemia, myelosuppression;
• metabolism and nutrition: decreased appetite, hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, hyperglycemia;
• psyche: anxiety, sleep disorder;
• nervous system: peripheral sensory neuropathy, dysesthesia, neurotoxicity, tremor, neuralgia, hypesthesia;
• organ of vision: blurred vision, dry eyes, eye pain, visual impairment;
• organ of hearing and labyrinthine disorders: ringing in the ears, hearing loss;
• cardiovascular system: embolism, edema of the lower extremities, hyperemia, atrial fibrillation, phlebitis, hot flashes, hypertensive crisis;
• respiratory system, chest and mediastinal organs: pharyngeal dysesthesia, sore throat, dysphonia, epistaxis, hiccups, rhinorrhea, pain in the pharynx and larynx;
• Gastrointestinal tract: bleeding from the upper gastrointestinal tract and from the rectum, oral ulcers, gastritis, bloating, pain in the mouth, paresthesia and hypesthesia in the mouth;
• liver and biliary tract: liver dysfunction;
• skin and subcutaneous tissues: alopecia, nail changes, erythematous rash, urticaria, rash, hyperhidrosis, night sweats;
• musculoskeletal and connective tissue: pain in the limbs or jaw, trismus, muscle spasms, weakness;
• kidney and urinary tract: decreased creatinine clearance (CC), hematuria, proteinuria, dysuria;
• general disorders and disorders at the injection site: lethargy, hypersensitivity to high and low temperatures, pain, inflammation of the mucous membrane, contusion. Cases of liver failure and cholestatic hepatitis have been reported, but a causal relationship with Capecitabine has not been established. In 2% of cases, hypersensitivity reactions were observed, in 3% - ischemia or myocardial infarction;
• laboratory and instrumental studies: hyperbilirubinemia, neutropenia, anemia, granulocytopenia, lymphocytopenia, thrombocytopenia, increased activity of liver enzymes (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase), hypercreatininemia, hyperglycemia, hypocalcemia, hyponcalcemia

Overdose

Symptoms of an overdose of Capecitabine: nausea, vomiting, diarrhea, mucositis, irritation and bleeding from the gastrointestinal tract, depression of bone marrow function.

Treatment: symptomatic and supportive therapy to prevent possible complications.

special instructions

In the event of severe diarrhea and dehydration while taking the drug, it is recommended to rehydrate and replace the loss of electrolytes. Antidiarrheal drugs are prescribed as early as possible when indicated. In severe cases, the dose of Capecitabine can be reduced. Dehydration can lead to the development of acute renal failure, up to death, in this regard, it must be eliminated at the very beginning of the onset.

With dehydration of the II degree, the drug is canceled and not resumed until rehydration and elimination of the causes that led to dehydration.

Against the background of drug therapy, an exacerbation of diabetes mellitus and disturbances in the water-electrolyte balance are possible.

If severe skin reactions develop, Capecitabine should be discontinued and not resumed, due to the risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis.

Influence on the ability to drive vehicles and complex mechanisms

In the event of such side effects of the drug as dizziness and drowsiness, one should refrain from driving vehicles and other complex mechanisms that require the speed of psychomotor reactions.

Application during pregnancy and lactation

According to the instructions, Capecitabine is contraindicated in pregnancy and lactation. In addition, you should use reliable methods of contraception during therapy and within 3 months after drug withdrawal.

Pediatric use

There is no data on the safety and efficacy of Capecitabine in children.

With impaired renal function

With mild renal failure (CC from 51 to 80 ml / min), dose adjustment is not required. With CC from 30 to 50 ml / min, the initial dose of Capecitabine should be reduced to 75% of 1250 mg / m ². If CC has decreased to уровня 30 ml / min during capecitabine therapy, it should be interrupted.

If liver function is impaired

In patients with mild or moderate liver dysfunction, with liver metastases, dose adjustment is not required. This group of patients needs careful monitoring. There is no data on the use of Capecitabine in patients with severe hepatic impairment.

Use in the elderly

Elderly people do not need to adjust the initial dose of Capecitabine, although over the age of 80 with monotherapy and over 65 with combination therapy, severe grade III and IV adverse reactions are more common than in younger patients.

Elderly patients need more careful monitoring of their health.

In combination therapy with docetaxel in patients older than 60 years it recommended to reduce the initial dose of the capecitabine to 75% (950 mg / m ² twice daily), due to the increased incidence of serious adverse reactions III and IV degree. In the absence of toxic reactions, it is possible to increase the dose to 1250 mg / m ² twice a day.

When combined therapy with irinotecan in patients over 65 years of age, it is recommended to reduce the initial dose of capecitabine to 800 mg / m ² twice a day.

Drug interactions

Co-administration of sorivudine or its structural analogs such as brivudine is contraindicated. An interval of at least 28 days must be observed between taking them and taking Capecitabine.

Other interaction reactions when combined with capecitabine:

• coumarin anticoagulants: the risk of bleeding disorders and the occurrence of bleeding during the admission period and within 1 month after increases, and therefore it is necessary to monitor the clotting indicators;
• CYP2C9 isoenzyme substrates: due to lack of research, caution should be exercised;
• phenytoin: the risk of an increase in its plasma concentration, its control is necessary;
• antacids: there was a slight increase in the concentration of capecitabine and one of the metabolites (5'-DFUR) in blood plasma;
• calcium folinate: risk of increased toxicity of capecitabine;
• allopurinol: should be avoided together due to the decrease in the effectiveness of FU;
• interferon alpha: the maximum dose of Capecitabine in this combination is reduced to 2000 mg / m ² / day, compared to 3000 mg / m ² / day with monotherapy;
• radiation therapy of colorectal cancer (at continuous therapy or 5-day course from Monday to Friday for 6 weeks): capecitabine dose of the combination is reduced to 2000 mg / m ² / day, compared to 3000 mg / m ² / day at monotherapy.

Analogs

Capecitabine analogs are Cabetsin, Xeloda, Capecitover, Tutabin, etc.

Terms and conditions of storage

Store in a dry place, away from light, at a temperature not exceeding 30 ° C. Keep out of the reach of children.

Shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews of Capecitabine

Reviews of Capecitabine on the network confirm the effectiveness of the drug in the fight against cancer, however, there are references to a lot of side effects such as nausea, vomiting, diarrhea and others. Some patients indicate a lack of therapeutic effect.

Price for Capecitabine in pharmacies

The approximate price for Capecitabine 500 mg is 8,860 rubles. per pack containing 120 tablets.

Capecitabine: prices at online pharmacies

Drug name Price Pharmacy

Capecitabine 500 mg film-coated tablets 120 pcs. RUB 7200 Buy

Capecitabine 500 mg film-coated tablets 120 pcs. RUB 11135 Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!