Cacit 500mg (Capecitabine )

DESCRIPTION

Cacit  500mg tablets are containing an active constituent Capecitabine which is comes under the derivative of deoxycytidine and fluorouracil prodrug that consisting of anti-neoplastic activity anti-metabolite activity involved in the therapy of colon cancer; breast cancer & gastric cancer.
Capecitabine is classified as an inhibitor of nucleoside metabolite, in which the mechanism involved in this medicine is inhibiting nucleic acid synthesis.
Capecitabine is chemically classified as fluoropyrimidine carbamate associating to class of anti-neoplastic agents known as anti-metabolite.
For breast cancer Capecitabine is used in combination with docetaxel.

INDICATION

The primary indication of Cacit  500mg :

Colon rectal cancer

Breast cancer

Gastric cancer

In colon rectal:

Cacit  500mg is also indicated for the treatment of colon or rectal cancerwhich has become worse condition or spread to other body parts. The drug willinhibits colon cancer from spreading in people after the surgery to remove tumor.

For breast cancer therapies, Cacit  500mg should be used in combination with docetaxel with an advanced stage patient who are resistant to anthracycline containing chemotherapy.

Cacit  500mg is prescribed in the patients who are producing resistance against paclitaxel & for anthracycline chemotherapies.

MECHANISM OF ACTION

Enzymes are involved in mechanism of Capecitabine a prodrug, get converted into 5 fluorouracil in-vivo.

After conversion, 5-FU get turned into 5-fluoro-2’deoxyuridine monophosphate & 5 fluoro uridine triphosphate in both normal & cancer cells.

This converting metabolites causes cancer cell injuries by two distinct ways :

At first, FdUMP & the folate co factor, N5-10 methylenetetrahydrofolate, are binding to an enzyme thymidylate synthase which leads to produce a covalently bound ternary complex.

This binding concludes as inhibition of production of thymidylate from 2’ deoxy uridylate.

This thymidylate is essential messenger for thymidine triphosphate required for DNA synthesis.

Finally the insufficiency of thymidine triphosphate leads to cause obstruction in cell division.

In second way, the nuclear transcriptional enzymes are falsely inserted FUTP instead of uridine triphosphate which is occurred during RNA synthesis, this concluded as metabolic error and leads to intercede with RNA processing and protein synthesis.

ADME

Absorption:
Readily absorbed. Food decrease rate and extent of absorption. peak plasma concentration is 1.5hr.
Distribution:
Plasma protein binding: <60%, mainly to albumin.
Metabolism:
capecitabine hydrolyzed in the liver into 5'-deoxy-5-fluorocytidine (5'-DFCR) then to 5'-deoxy-5-fluorouridine (5'-DFUR), and subsequently in body tissues into 5-fluorouracil by thymidine phosphorylase enzyme.
Excretion:
Via urine (96%, (<3% as unchanged drug) and faces (<3%). Elimination half-life is 0.75 hr.

DOSAGE MANAGEMENT

Cacit  tablets should be administered on an empty stomach, taken within 30 minutes after the meals.
Dosage regimens of Cacit  :
The prescribed dose of Cacit  tablets are 1250mg/m2 should be administered orally as two times a day for the period of 2 weeks pursued by a one-week rest time given as 3 weeks cycle.
In combination of Cacit  with docetaxel, the prescribed dose is 1250mg/m2 of Cacit  as two times day and the dose of docetaxel are 75mg/m2 given as intravenous infusion over the period of 1 hour for every 3 weeks.
Premedication should be provided, based on the docetaxel labeling it should be initiated before starting the docetaxel therapy for the patients getting both Cacit  plus docetaxel.
The supporting therapy for the Duke’s C colon cancer patients, the prescribed treatment duration period is 6 months. The usual dose of Cacit  1250mg/m2 should be taken orally for 2 weeks which is follows as one-week rest period and the duration of therapy should be continue for 3 weeks cycle as total cycle is 8 (24 weeks).
In case of toxicity occurs due to Cacit  therapy, treatment should be interrupt or discontinue.
On the other way, dose adjustment should be suggested to reduce the adverse effect related to toxicity.
In any drugs that should be combined with Capnat, must require dose alteration such as :
Phenytoin, coumarin derivatives are combined with Cacit  tablets, must undergo dosage adjustment.
Depending on the toxicity grade of patients therapy should be followed :
At first, patients suspected with grade II toxicity at the time of 14 days of Cacit  therapy; the treatment should be postponed.
Therapy should be interrupted until grade changed to I; then therapy with Cacit  should be continuing as same dose.
Supporting therapy should be provided if possible, in case of toxicity.
Grade II toxicity sustains in case of combinational therapy of Cacit  with docetaxel; interrupts the therapy and toxicity decreases as grade 1 then continue the treatment at 100% original dose of Capnat.
In grade I toxicity: continue the dose of Capnat
In grade II;
1st appearance: Post pone the treatment until resolved to grade I and continue the therapy with 100% dose of Capnat
2nd appearance: Post pone the treatment until resolved to grade I and continue the therapy with 75% dose of Capnat
3rd appearance: Post pone the treatment until resolved to grade I and continue the therapy with 50% dose of Capnat.
4th appearance: stop the treatment of Capnat
In grade III:
1st appearance: Post pone the treatment until resolved to grade I and continue the therapy with 75% dose of Capnat.
2nd appearance: Post pone the treatment until resolved to grade I and continue the therapy with 50% dose of Capnat.
3rd appearance: stop the treatment.
In grade IV:
1st appearance: stop the treatment or if toxicity resolved to grade I, then resume the therapy with 50% dose of Capnat.
For hepatic damage patients:
No dosage adjustment should be recommended.
For renal damage patients:
In moderate renal damage, the dose of Cacit  reduced to 75% in both monotherapy & combinational therapy with docetaxel
By using Cockcroft & Gault equation; 140-age of patients x body weight in Kg used to analysis the kidney function to obtain creatinine clearance value.

PRECAUTIONS

Cardio toxicity: monitor cardiac toxicity like myocardial infarction, ischemic conditions, or any other cardiac problems during the therapy with Cacit  500mg.
Hand foot syndrome: the dose of Cacit  500mg should be reduced to reduce the toxicity.
Dihydropyrimidine dehydrogenase insufficiency: adverse reactions related to 5-FU is contributed to this deficiency.
Liver insufficiency: mild or moderate liver damage patients administered Cacit  500mg carefully and monitor the adverse effects. Hematological problems: check the blood cell counts regularly before or after the treatment
Embryo fetal toxicity :
Cacit  500mg causes fetal harm, which may causes death.
Pregnancy: Cacit  500mg is contraindicated; produce carcinogenesis, mutagenesis, and fertility impairments.
Diarrhea: anti-diarrheal therapy should be provided.
Coagulopathy:
During the co administration of Cacit  500mg with warfarin, the anti-coagulant response rate should be monitored frequently. This combination may cause severe bleeding effect which leads to death also. By increasing the prothrombin time & INR values, bleeding may occur.
This event may appear within several days & also several months after initiation of therapy.
In some cases after stopping the therapy of Cacit  500mg, may occurs

SIDE EFFECTS

Stomatitis, diarrhea, vomiting, abdominal pain, nausea, dyspepsia, hand and foot syndrome, alopecia, rashes, Erythema, fatigue, pyrexia, asthenia, dizziness, headache, eye disorders, conjunctivitis, neutropenia, Epistaxis, elevated ALAT, increased in calcium levels, anemia, decreased platelets, weakness, edema, chest pain.

DRUG INTERACTION

Interaction of Cacit  500mg with anti-coagulant: altered coagulation problem and bleeding occurs to control this adverse effect; monitored the prothrombin time frequently Interaction of Cacit  500mg with phenytoin: level of phenytoin should be monitored for reducing the toxicity of phenytoin Interaction of Leucovorin with Cacit  500mg: 5-FU concentration should be increased, and toxicity elevated by Leucovorin. Hence leads to death due to diarrhea, enterocolitis, and dehydration in elder patients Whileconcomitant with Cacit  500mg tablets with CYP2C9 substrates: care should be taken Interaction of Food drug occurs in Cacit  500mg tablets, food may interfere with absorption of Cacit  500mg. Reduce the rate and duration of absorption of Cacit  500mg occurs. Cacit  500mg should be taken within 30minutes after meal

CONTRAINDICATIONS

Hypersensitivity reaction produce due to patients may contraindicate to component present in Cacit  500mg. Cacit  500mg is contraindicate to the patient who are having hypersensitive to 5-FU Patient who are having insufficient known enzyme like Dihydropyrimidine dehydrogenase are contraindicated to Cacit  500mg. Cacit  500mg is also contraindicating to severe renal damage patients with creatinine clearance less than 30ml/min.

PREGNANCY & LACTATION

Pregnancy category: D
Cacit  500mg should not be used in pregnancy and lactating period
The safety and potency of Capecitabine should not been evaluated for pediatric patients.
The adverse events should be monitored periodically in elderly patients.

STORAGE 

Cacit  500mg tablet container should be stored at 25°C (77°F).
Protect the cartoon free from moisture, heat & light.

MISSED DOSE

If you missed the dose, then have it soon you remember before next dose timing or Missed dose can beswapped and follow the regular dosing schedule.
Do not have double the dose at the same time.