Capscare

Capscare is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. Capscare is a prodrug, that is enzymatically converted to fluorouracil (antimetabolite) in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.

Colorectal Cancer

Breast Cancer

Capscare is a cancer medicine that interferes with the growth of cancer cells and slows their spread in the body.

Capscare is used to treat colon cancer, and breast or colorectal cancer that has spread to other parts of the body.

Capscare is often used in combination with other cancer medications and/or radiation treatments.

Capscare may also be used for purposes not listed in this medication guide.

Standard

Dosage: Monotherapy: Colon, Colorectal and Breast Cancer:The recommended monotherapy starting dose of Capscare is 1250 mg/m² administered twice daily (morning and evening; equivalent to 2500 mg/m² total daily dose) for 2 weeks followed by a 7-day rest period.

Combination Therapy: Breast Cancer:In combination with docetaxel, the recommended starting dose of Capscare is 1250 mg/m² twice daily for 2 weeks followed by a 7-day rest period, combined with docetaxel at 75 mg/m² as a 1 hour intravenous infusion every 3 weeks. Premedication, according to the docetaxel labeling, should be started prior to docetaxel administration for patients receiving the Capscare plus docetaxel combination.

Colon, Colorectal, Gastric and Oesophagogastric Cancer:In combination treatment (except with irinotecan), the recommended starting dose of Capscare is 800 to 1000 mg/m² administered twice daily for 2 weeks followed by a 7-day rest period, or 625 mg/m² twice daily when administered continuously. For combination with irinotecan (XELIRI), the recommended starting dose of Capscare is 800 mg/m² administered twice daily for 2 weeks followed by a 7-day rest period in combination with irinotecan 200 mg/m² on day 1 of each three week cycle.

The inclusion of bevacizumab in a combination regimen has no effect on the starting dose of Capscare. Adjuvant treatment in patients with stage III colon cancer is recommended for a total of 6 months.

Premedication to maintain adequate hydration and anti-emesis according to the cisplatin and oxaliplatin product information should be started prior to cisplatin administration for patients receiving the Capscare plus cisplatin or oxaliplatin combination.

Capscare dose is calculated according to body surface area. The following tables show examples of the standard and reduced dose calculations for a starting dose of Capscare of either 1250 mg/m² or 1000 mg/m².

Dosage Adjustments During Treatment: General: Toxicity due to Capscare administration may be managed by symptomatic treatment and/or modification of the Capscare dose (treatment interruption or dose reduction). Once the dose has been reduced it should not be increased at a later time.

For those toxicities considered by the treating physician to be unlikely to become serious or life-threatening treatment can be continued at the same dose without reduction or interruption.

Dosage modifications are not recommended for Grade 1 events. Therapy with Capscare should be interrupted if a Grade 2 or 3 adverse experience occurs. Once the adverse event has resolved or decreased in intensity to Grade 1, Capscare therapy may be restarted at full dose or as adjusted according to Table 7. If a Grade 4 experience occurs, therapy should be discontinued or interrupted until the experience has resolved or decreased to Grade 1, and therapy can then be restarted at 50% of the original dose. Patients taking Capscare should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs. Doses of Capscare omitted for toxicity are not replaced.

Haematology: Patients with baseline neutrophil counts of <1.5 x 10⁹/L and/or thrombocyte counts of <100 x 10⁹/L should not be treated with Capscare. If unscheduled laboratory assessments during a treatment cycle show grade 3 or 4 haematologic toxicity, treatment with Capscare should be interrupted.

Table 7 shows the recommended dose modifications following toxicity related to Capscare:

General Combination Therapy: Dose modifications for toxicity when Capscare is used in combination with other therapies should be made according to Table 7 above for Capscare and according to the appropriate Prescribing Information for the other agent(s).

At the beginning of a treatment cycle, if a treatment delay is indicated for either Capscare 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 Capscare, Capscare should be continued and the dose of the other agent adjusted according to the appropriate Prescribing Information.

If the other agent(s) have to be discontinued permanently, Capscare treatment can be resumed when the requirements for restarting Capscare are met.

This advice is applicable to all indications and to all special populations.

Special Dosage Instructions: Patients with Hepatic Impairment Due to Liver Metastases: In patients with mild to moderate hepatic impairment due to liver metastases, no starting dose adjustment is necessary. However, such patients should be carefully monitored. Patients with severe hepatic impairment have not been studied.

Patients with Renal Impairment:In patients with moderate renal impairment [creatinine clearance 30-50 mL/min (Cockroft and Gault)] at baseline, a dose reduction to 75% for a starting dose of 1250 mg/m² is recommended. In patients with mild renal impairment (creatinine clearance 51-80 mL/min), no adjustment in starting dose is recommended.

Careful monitoring and prompt treatment interruption is recommended if the patient develops a Grade 2, 3, or 4 adverse event with subsequent dose adjustment as outlined in Table 7 previously. If the calculated creatinine clearance decreases during treatment to a value below 30 mL/min, Capscare should be discontinued. The dose adjustment recommendations for patients with moderate renal impairment apply both to monotherapy and combination use. For dosage calculations, see Tables 5 and 6.

Children:The safety and efficacy of Capscare in children have not been established.

Elderly: For Capscare monotherapy, no adjustment of the starting dose is needed. However, severe Grade 3 or 4 treatment-related adverse events were more frequent in patients over 80 years of age compared to younger patients.

When Capscare was used in combination with other agents, elderly patients (≥65 years) experienced more Grade 3 and Grade 4 adverse drug reactions (ADRs) and ADRs that led to discontinuation, than younger patients. Careful monitoring of elderly patients is advisable.

In Combination with Docetaxel: An increased incidence of Grade 3 or 4 treatment-related adverse events and treatment-related serious adverse events was observed in patients 60 years of age or more. For patients 60 years of age or more treated with the combination of Capscare plus docetaxel, a starting dose reduction of Capscare to 75% (950 mg/m² twice daily) is recommended. For dosage calculations, see Table 5.

See also:
What is the most important information I should know about Capscare?

You should not take this medication if you are allergic to Capscare or fluorouracil (Adrucil), or if you have severe kidney disease or a metabolic disorder called DPD (dihydropyrimidine dehydrogenase) deficiency.

Before you take Capscare, tell your doctor if you have liver or kidney disease, a history of coronary artery disease, or if you are also taking folic acid (contained in many vitamin and mineral supplements), leucovorin (Wellcovorin), phenytoin (Dilantin), or a blood thinner (warfarin, Coumadin).

Do not use this medication without telling your doctor if you are pregnant or breast-feeding a baby. Use effective birth control while you are taking Capscare, whether you are a man or a woman. Tell your doctor if a pregnancy occurs during treatment.

Capscare can have long lasting effects on your body. You may need frequent medical tests while you are using this medication and for a short time after your treatment ends.

Call your doctor at once if you have a serious side effect such as severe vomiting or diarrhea, fever or flu symptoms, pain or redness of your hands or feet, jaundice (yellowing of the skin or eyes), chest pain, sudden numbness or weakness, or fainting.

Use Capscare as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Capscare. Talk to your pharmacist if you have questions about this information.
• Take Capscare with food or within 30 minutes after a meal.
• Swallow Capscare whole with water. Do not break, crush, or chew before swallowing.
• It is recommended to use gloves and safety glasses to avoid exposure in case a tablet breaks. If powder from a broken tablet comes into contact with skin, wash the skin immediately with soap and water. If powder comes into contact with your mouth, nose, or eyes, rinse thoroughly with water.
• If you miss a dose of Capscare, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once. Check with your doctor if you miss a dose.

Ask your health care provider any questions you may have about how to use Capscare.

Capscare is used to treat breast, colon, or rectal cancer. It works by slowing or stopping the growth of cancer cells.

How to use Capscare

Read the Patient Information Leaflet if available from your pharmacist before you start taking Capscare and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually 2 times a day; once in the morning and once in the evening. Swallow the tablets whole with a full glass of water (8 ounces/240 milliliters) within 30 minutes after a meal. Do not crush or split the tablets. Capscare is usually taken every day for 2 weeks, then stopped for 1 week for each treatment cycle.

The dosage is based on your medical condition, body size, and response to treatment. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

See also:
What other drugs will affect Capscare?

Coumarin Anticoagulants: Altered coagulation parameters and/or bleeding have been reported in patients taking Capscare concomitantly with coumarin-derivative anticoagulants eg, warfarin and phenprocoumon. These events occurred within several days and up to several months after initiating Capscare therapy and in a few cases, within 1 month after stopping Capscare. In a clinical interaction study, after a single 20-mg dose of warfarin, Capscare treatment increased the AUC of S-warfarin by 57% with a 91% increase in INR value. Patients taking coumarin-derivative anticoagulants concomitantly with Capscare should be monitored regularly for alterations in their coagulation parameters (PT or INR) and the anticoagulant dose adjusted accordingly.

Cytochrome P450 (CYP450) 2C9 Substrates: No formal drug-drug interaction studies with Capscare and other drugs known to be metabolized by the CYP450 2C9 isoenzyme have been conducted. Care should be exercised when Capscare is co-administered with these drugs.

Phenytoin: Increased phenytoin plasma concentrations have been reported during concomitant use of Capscare with phenytoin. Formal drug-drug interaction studies with phenytoin have not been conducted, but the mechanism of interaction is presumed to be inhibition of the CYP2C9 isoenzyme system by Capscare. Patients taking phenytoin concomitantly with Capscare should be regularly monitored for increased phenytoin plasma concentrations.

Drug-Food Interaction: In all clinical trials, patients were instructed to take Capscare within 30 min after a meal. Since current safety and efficacy data are based upon administration with food, it is recommended that Capscare be administered with food.

Antacid: The effect of an aluminium hydroxide and magnesium hydroxide-containing antacid on the pharmacokinetics of Capscare was investigated in cancer patients. There was a small increase in plasma concentrations of Capscare and 1 metabolite (5'DFCR); there was no effect on the 3 major metabolites (5'DFUR, 5-FU and FBAL).

Leucovorin Folinic Acid: The effect of leucovorin on the pharmacokinetics of Capscare was investigated in cancer patients. Leucovorin has no effect on the pharmacokinetics of Capscare and its metabolites. However, leucovorin has an effect on the pharmacodynamics of Capscare and its toxicity may be enhanced by leucovorin.

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 in the literature. This interaction, which leads to increased fluoropyrimidine toxicity, is potentially fatal. Therefore, Capscare should not be administered with sorivudine or its chemically related analogues eg, brivudine. There must be at least a 4-week waiting period between the end of treatment with sorivudine or its chemically related analogues eg, brivudine and start of Capscare therapy.

Oxaliplatin: No clinically significant differences in exposure to Capscare or its metabolites, free platinum or total platinum occured when Capscare or oxaliplatin were administered in combination with or without bevacizumab.

Bevacizumab: There was no clinically significant effect of bevacizumab on the pharmacokinetic parameters of Capscare or its metabolites.

See also:
What are the possible side effects of Capscare?

Clinical Trials: Adverse drug reactions (ADRs) considered by the investigator to be possibly, probably, or remotely related to the administration of Capscare have been obtained from clinical studies conducted with Capscare monotherapy (in adjuvant therapy of colon cancer, in metastatic colorectal cancer and metastatic breast cancer), and clinical studies conducted with Capscare in combination with different chemotherapy regimens for multiple indications. ADRs are added to the appropriate category in the tables below according to the highest incidence from the pooled analysis of seven clinical trials. Within each frequency grouping ADRs are listed in descending order of seriousness. Frequencies are defined as very common ≥1/10, common ≥5/100 to <1/10 and uncommon ≥1/1000 to <1/100.

Capscare Monotherapy: Safety data of Capscare monotherapy were reported for patients who received adjuvant treatment for colon cancer and for patients who received treatment for metastatic breast cancer or metastatic colorectal cancer. The safety information includes data from a phase III trial in adjuvant colon cancer (995 patients treated with Capscare and 974 treated with i.v. 5-FU/LV) and from 4 phase II trials in female patients with breast cancer (N=319) and 3 trials (1 phase II and 2 phase III trials) in male and female patients with colorectal cancer (N=630). The safety profile of Capscare monotherapy is comparable in patients who received adjuvant treatment for colon cancer and in those who received treatment for metastatic breast cancer or metastatic colorectal cancer. The intensity of ADRs was graded according to the toxicity categories of the NCIC CTC Grading System.

Skin fissures were reported to be at least remotely related to Capscare in less than 2% of the patients in seven completed clinical trials (N=949).

The following ADRs represent known toxicities with fluoropyrimidine therapy and were reported to be at least remotely related to Capscare in less than 5% of patients in seven completed clinical trials (N=949): Gastrointestinal Disorders: Dry mouth, flatulence, ADRs related to inflammation/ulceration of mucous membranes such as esophagitis, gastritis, duodenitis, colitis, gastrointestinal hemorrhage.

Cardiac Disorders: Edema lower limb, cardiac chest pain including angina, cardiomyopathy, myocardial ischemia/infarction, cardiac failure, sudden death, tachycardia, atrial arrhythmias including atrial fibrillation, and ventricular extrasystoles.

Nervous System Disorders: Taste disturbance, insomnia, confusion, encephalopathy, and cerebellar signs such as ataxia, dysarthria, impaired balance, abnormal coordination.

Infections and Infestations: ADRs related to bone marrow depression, immune system compromise, and/or disruption of mucous membranes, such as local and fatal systemic infections (including bacterial, viral, fungal etiologies) and sepsis.

Blood and Lymphatic System Disorders: Anemia, bone marrow depression/pancytopenia.

Skin and Subcutaneous Tissue Disorders: Pruritus, localized exfoliation, skin hyperpigmentation, nail disorders, photosensitivity reactions, radiation recall syndrome.

General Disorders and Administration Site Conditions: Pain in limb, chest pain (non-cardiac).

Eye: Eye Irritation.

Respiratory: Dyspnoea, cough.

Musculoskeletal: Back pain, myalgia, arthralgia.

Psychiatric Disorders: Depression.

Hepatic failure and cholestatic hepatitis have been reported during clinical trials and post-marketing exposure. A causal relationship with Capscare treatment has not been established.

Capscare in Combination Therapy: Table 9 lists ADRs associated with the use of Capscare in combination therapy with different chemotherapy regimens in multiple indications and occurred in addition to those seen with monotherapy and/or at a higher frequency grouping. The safety profile was similar across all indications and combination regimens. These reactions occurred in ≥5% of patients treated with Capscare in combination with other chemotherapies. Adverse drug reactions are added to the appropriate category in Table 9 according to the highest incidence seen in any of the major clinical trials. Some of the adverse reactions are reactions commonly seen with chemotherapy (e.g. peripheral sensory neuropathy with docetaxel or oxaliplatin) or with bevacizumab (e.g. hypertension); however, an exacerbation by Capscare therapy cannot be excluded.

Hypersensitivity reactions (2%) and cardiac ischaemia/infarction (3%) have been reported commonly for Capscare in combination with other chemotherapy but in less than 5% of patients.

Rare or uncommon ADRs reported for Capscare in combination with other chemotherapy are consistent with the ADRs reported for Capscare monotherapy or the combination product monotherapy.

Laboratory Abnormalities: Table 10 displays laboratory abnormalities observed in 995 patients (adjuvant colon cancer) and 949 patients (metastatic breast and colorectal cancer), regardless of relationship to treatment with Capscare.

Post-Marketing: The following ADRs have been identified during post-marketing exposure:

Laboratory Abnormalities: No text.