). There are data to suggest that, if possible, treatment should not be discontinued before a minimum of three to four weeks. In clinical studies, the median duration of treatment before the onset of a definite objective response has been two months.
However, approximately one-quarter of patients who eventually responded were treated for four or more months before a definite objective response was recorded. 2 Recommended Dose and Dosage Adjustment The recommended daily dose of APO-TAMOX is 20 to 40 mg in a single or two divided doses.
The lowest effective dose should be used. In early disease, the recommended duration of therapy is 5 years. The optimal duration of therapy remains to be determined. Splitting the 20 mg tablet is not recommended.
Pediatric Use:
Health Canada has not authorized an indication for pediatric use. 4 Administration APO-TAMOX is for oral use only. 5 Missed Dose If a patient misses a dose, they should take the next usual dose as soon as they remember. Do not take two doses at the same time.
5 OVERDOSAGE Acute overdosage in humans has not been reported. Possible overdosage effects might include hot flushes, nausea, vomiting, and vaginal bleeding. No specific treatment for overdosage is known and treatment must be symptomatic.
In the case of accidental ingestion by a child, gastric emptying is suggested. There have been reports in the literature that tamoxifen citrate given at several times the standard dose may be associated with prolongation of the QT interval of the ECG.
For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1- 844-764-7669). 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1 – Dosage Forms, Strengths, and Composition Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Use Tablet / 10 mg and 20 mg Colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate and microcrystalline cellulose.
APO-TAMOX (tamoxifen citrate) tablets 10 mg:
Each tablet contains 10 mg tamoxifen (as tamoxifen citrate). White to off-white, round, biconvex tablets, engraved “APO” on one side and “TAM” over “10” on the other side. Available in bottles of 100 and 500.
APO-TAMOX (tamoxifen citrate) tablets 20 mg:
Each tablet contains 20 mg tamoxifen (as tamoxifen citrate). White to off-white, octagonal, biconvex tablets, engraved “APO” on one side and “TAM” over score “20” on the other side. Available in bottles of 100 and 250 7 WARNINGS AND PRECAUTIONS Please see the 3 SERIOUS WARNINGS AND PRECAUTIONS BOX at the beginning of Part I: Health Professional Information.
General APO-TAMOX (tamoxifen tablets) should be used only for the conditions listed under the 1 APO-TAMOX (Tamoxifen Tablets) Page 7 of 35 INDICATIONS section. g. paroxetine, a known CYP2D6 inhibitor) (see 9 DRUG-INTERACTIONS). Carcinogenesis and Mutagenesis An increased incidence of uterine malignancies has been reported in association with tamoxifen citrate treatment.
The underlying mechanism is unknown, but may be related to the estrogen- like effect of tamoxifen tablets. Most uterine malignancies seen in association with tamoxifen citrate are classified as adenocarcinoma of the endometrium. However, rare uterine sarcomas, including malignant mixed Mullerian tumours, have also been reported.
Uterine sarcoma is generally associated with a higher FIGO stage (III/IV) at diagnosis, poorer prognosis, and shorter survival. Uterine sarcoma has been reported to occur more frequently among long-term users (≥ 2 years) of tamoxifen citrate than non-users.
An increased incidence of endometrial cancer and uterine sarcoma (mostly malignant mixed Mullerian tumours) has been reported in association with tamoxifen citrate treatment. The incidence and pattern of this increase suggest that the underlying mechanism may be related to estrogenic properties of tamoxifen citrate.
Any patients receiving APO-TAMOX or having previously received APO-TAMOX who report abnormal gynaecological symptoms, especially vaginal bleeding, should be promptly investigated. Incidence rates for the following events were estimated from a long-term clinical study called the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention (NSABP P-1) Trial.
In this trial, high-risk patients were randomized to either tamoxifen citrate therapy or placebo, for the prevention of breast cancer. Uterine malignancies were separated into cases of endometrial adenocarcinomas and uterine sarcomas.
6 for deep vein thrombosis. Hepatocellular carcinomas have been reported in a 2 year oncogenicity study in rats receiving tamoxifen citrate (see 16 NON-CLINICAL TOXICOLOGY). In addition, gonadal tumours have been reported in mice receiving tamoxifen citrate in long-term studies (see 16 NON-CLINICAL TOXICOLOGY).
The clinical relevance of these cancer findings has not been established. A number of second primary tumours, occurring at sites other than the endometrium and the opposite breast, have been reported in clinical trials, following the treatment of breast cancer patients with tamoxifen citrate.
No causal link has been established and the clinical significance of these observations remains unclear. Cardiovascular An increased risk of stroke has been found to be associated with tamoxifen citrate therapy in high-risk patients being treated for the prevention of breast cancer.
The use of tamoxifen APO-TAMOX (Tamoxifen Tablets) Page 8 of 35 tablets for the prevention of breast cancer is not an approved […]