Capecitabine (Page 2 of 14)

2.3 Dose Management Guidelines

General

Capecitabine tablets dosage may need to be individualized to optimize patient management. Patients should be carefully monitored for toxicity and doses of capecitabine tablets should be modified as necessary to accommodate individual patient tolerance to treatment [see Clinical Studies (14)]. Toxicity due to capecitabine tablet administration may be managed by symptomatic treatment, dose interruptions and adjustment of capecitabine tablets dose. Once the dose has been reduced, it should not be increased at a later time. Doses of capecitabine tablets omitted for toxicity are not replaced or restored; instead the patient should resume the planned treatment cycles.

The dose of phenytoin and the dose of coumarin-derivative anticoagulants may need to be reduced when either drug is administered concomitantly with capecitabine tablets [see Drug Interactions (7.1)].

Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer)

Capecitabine tablets dose modification scheme as described below (see Table 2) is recommended for the management of adverse reactions.

Table 2 Recommended Dose Modifications of Capecitabine Tablets

* National Cancer Institute of Canada Common Toxicity Criteria were used except for the hand-and-foot syndrome [see Warnings and Precautions (5)].
Toxicity NCIC Grades *	During a Course of Therapy	Dose Adjustment for Next Treatment (% of starting dose)
Grade 1	Maintain dose level	Maintain dose level
Grade 2
-1st appearance	Interrupt until resolved to grade 0 to 1	100%
-2nd appearance		75%
-3rd appearance		50%
-4th appearance	Discontinue treatment permanently	–
Grade 3
-1st appearance	Interrupt until resolved to grade 0 to 1	75%
-2nd appearance		50%
-3rd appearance	Discontinue treatment permanently	–
Grade 4
-1st appearance	Discontinue permanentlyORIf physician deems it to be in the patient’s best interest to continue, interrupt until resolved to grade 0 to 1	50%

In Combination With Docetaxel (Metastatic Breast Cancer)

Dose modifications of capecitabine tablets for toxicity should be made according to Table 2 above for capecitabine tablets. At the beginning of a treatment cycle, if a treatment delay is indicated for either capecitabine tablets or docetaxel, then administration of both agents should be delayed until the requirements for restarting both drugs are met.

The dose reduction schedule for docetaxel when used in combination with capecitabine tablets for the treatment of metastatic breast cancer is shown in Table 3.

Table 3 Docetaxel Dose Reduction Schedule in Combination with Capecitabine Tablets

* National Cancer Institute of Canada Common Toxicity Criteria were used except for hand-and-foot syndrome [see Warnings and Precautions (5)].
Toxicity NCIC Grades *	Grade 2	Grade 3	Grade 4
1st appearance	Delay treatment until resolved to grade 0 to 1; Resume treatment with original dose of 75 mg/m2 docetaxel	Delay treatment until resolved to grade 0 to 1; Resume treatment at 55 mg/m2 of docetaxel.	Discontinue treatment with docetaxel
2nd appearance	Delay treatment until resolved to grade 0 to 1; Resume treatment at 55 mg/m2 of docetaxel.	Discontinue treatment with docetaxel	–
3rd appearance	Discontinue treatment with docetaxel	–	–

2.4 Adjustment of Starting Dose in Special Populations

Renal Impairment

No adjustment to the starting dose of capecitabine tablets is recommended in patients with mild renal impairment (creatinine clearance = 51 to 80 mL/min [Cockroft and Gault, as shown below]). In patients with moderate renal impairment (baseline creatinine clearance = 30 to 50 mL/min), a dose reduction to 75% of the capecitabine tablets starting dose when used as monotherapy or in combination with docetaxel (from 1250 mg/m² to 950 mg/m² twice daily) is recommended [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Subsequent dose adjustment is recommended as outlined in Table 2 and Table 3 (depending on the regimen) if a patient develops a grade 2 to 4 adverse event [see Warnings and Precautions (5.5)]. The starting dose adjustment recommendations for patients with moderate renal impairment apply to both capecitabine tablets monotherapy and capecitabine tablets in combination use with docetaxel.

Cockroft and Gault Equation:
	(140 — age [yrs]) (body wt [kg])
Creatinine clearance for males =	—————————————
	(72) (serum creatinine [mg/dL])
Creatinine clearance for females = 0.85 × male value

Geriatrics

Physicians should exercise caution in monitoring the effects of capecitabine tablets in the elderly. Insufficient data are available to provide a dosage recommendation.