Alpha-6-deoxy-5-oxytetracycline.

Transcription

1 EMERGENCY OVERVIEW Each intended for oral administration contains Tamoxifen Citrate and excipients generally considered to be non- toxic and non-hazardous in small quantities and under conditions of normal occupational exposure. Section 1. Identification Identification of the product Product Name: Formula: C 32 H 37 NO 8 Chemical Name: Alpha-6-deoxy-5-oxytetracycline. Manufacturer / supplier identification Company: Cadila Healthcare Ltd., Matoda, India Address: Cadila Healthcare Limited, Plot No- 1A/1 & 2, Pharmez Special Economic Zone, Sarkhej- Bavla N.H. No. 8A, Near Village Matoda, Tal. Sanand, Dist. Ahmedabad , India Contact for information: Tel: Fax: Emergency Telephone No. Tel: Recommended use / Therapeutic Category Restriction on Use / Contraindications: Tamoxifen citrate tablets USP, a nonsteroidal antiestrogen, Tamoxifen citrate tablets are contraindicated in patients with known hypersensitivity to the drug or any of its ingredients.

2 Section 2. Hazard(s) Identification Dose and Administration For patients with breast cancer, the recommended daily dose is 20 to 40 mg. Dosages greater than 20 mg per day should be given in divided doses (morning and evening). In three single agent adjuvant studies in women, one 10 mg tamoxifen citrate tablet was administered two (ECOG and NATO) or three (Toronto) times a day for two years. In the NSABP B-14 adjuvant study in women with node-negative breast cancer, one 10 mg tamoxifen citrate tablet was given twice a day for at least 5 years. Results of the B-14 study suggest that continuation of therapy beyond five years does not provide additional benefit. In the EBCTCG 1995 overview, the reduction in recurrence and mortality was greater in those studies that used tamoxifen for about 5 years than in those that used tamoxifen for a shorter period of therapy. There was no indication that doses greater than 20 mg per day were more effective. Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer. Ductal Carcinoma in Situ (DCIS) The recommended dose is tamoxifen 20 mg daily for 5 years. Adverse Effects Over Dose Effect Reduction in Breast Cancer Incidence in High Risk Women The recommended dose is tamoxifen 20 mg daily for 5 years. There are no data to support the use of tamoxifen other than for 5 years Adverse reactions to tamoxifen are relatively mild and rarely severe enough to require discontinuation of treatment in breast cancer patients. Continued clinical studies have resulted in further information which better indicates the incidence of adverse reactions with tamoxifen as compared to placebo. Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions. Acute overdosage in humans has not been reported. In a study of advanced metastatic cancer patients which specifically determined the maximum tolerated dose of tamoxifen in evaluating the use of very high doses to reverse multidrug resistance, acute neurotoxicity manifested by tremor, hyperreflexia, unsteady gait

3 Contraindications and dizziness were noted. These symptoms occurred within 3 to 5 days of beginning tamoxifen and cleared within 2 to 5 days after stopping therapy. No permanent neurologic toxicity was noted. One patient experienced a seizure several days after tamoxifen was discontinued and neurotoxic symptoms had resolved. The causal relationship of the seizure to tamoxifen therapy is unknown. Doses given in these patients were all greater than 400 mg/m2 loading dose, followed by maintenance doses of 150 mg/m2 of tamoxifen given twice a day. In the same study, prolongation of the QT interval on the electrocardiogram was noted when patients were given doses higher than 250 mg/m2 loading dose, followed by maintenance doses of 80 mg/m2 of tamoxifen given twice a day. For a woman with a body surface area of 1.5 m2 the minimal loading dose and maintenance doses given at which neurological symptoms and QT changes occurred were at least 6 fold higher in respect to the maximum recommended dose. No specific treatment for overdosage is known; treatment must be symptomatic. Tamoxifen citrate tablets are contraindicated in patients with known hypersensitivity to the drug or any of its ingredients. Reduction in Breast Cancer Incidence in High Risk Women and Women with DCIS Tamoxifen citrate tablets are contraindicated in women who require concomitant coumarin-type anticoagulant therapy or in women with a history of deep-vein thrombosis or pulmonary embolus. WARNINGS Effects in Metastatic Breast Cancer Patients As with other additive hormonal therapy (estrogens and androgens), hypercalcemia has been reported in some breast cancer patients with bone metastases within a few weeks of starting treatment with tamoxifen. If hypercalcemia does occur, appropriate measures should be taken and, if severe, tamoxifen should be discontinued

4 Pregnancy Comments Tamoxifen may cause fetal harm when administered to a pregnant woman. Women should be advised not to become pregnant while taking tamoxifen or within 2 months of discontinuing tamoxifen and should use barrier or nonhormonal contraceptive measures if sexually active. Tamoxifen does not cause infertility, even in the presence of menstrual irregularity. Effects on reproductive functions are expected from the antiestrogenic properties of the drug. In reproductive studies in rats at dose levels equal to or below the human dose, nonteratogenic developmental skeletal changes were seen and were found reversible. In addition, in fertility studies in rats and in teratology studies in rabbits using doses at or below those used in humans, a lower incidence of embryo implantation and a higher incidence of fetal death or retarded in utero growth were observed, with slower learning behavior in some rat pups when compared to historical controls. Several pregnant marmosets were dosed with 10 mg/kg/day (about 2 fold the daily maximum recommended human dose on a mg/m2 basis) during organogenesis or in the last half of pregnancy. No deformations were seen and, although the dose was high enough to terminate pregnancy in some animals, those that did maintain pregnancy showed no evidence of teratogenic malformations. In rodent models of fetal reproductive tract development, tamoxifen (at doses to 2.4 fold the daily maximum recommended human dose on a mg/m2 basis) caused changes in both sexes that are similar to those caused by estradiol, ethynylestradiol and diethylstilbestrol. Although the clinical relevance of these changes is unknown, some of these changes, especially vaginal adenosis, are similar to those seen in young women who were exposed to diethylstilbestrol in utero and who have a 1 in 1,000 risk of developing clear-cell adenocarcinoma of the vagina or cervix. To date, in utero exposure to tamoxifen has not been shown to cause vaginal adenosis, or clear-cell adenocarcinoma of the vagina or cervix, in young women. However, only a small number of young women have been exposed to tamoxifen in utero, and a smaller number have been followed long enough (to age 15 to 20) to determine whether vaginal or cervical neoplasia could occur as a result of this exposure. There are no adequate and well-controlled trials of tamoxifen in pregnant women. There have been a small number of reports of vaginal bleeding, spontaneous abortions, birth defects, and fetal

5 deaths in pregnant women. If this drug is used during pregnancy, or the patient becomes pregnant while taking this drug, or within approximately two months after discontinuing therapy, the patient should be apprised of the potential risks to the fetus including the potential long-term risk of a DES-like syndrome. Pregnancy Category D Section 3. Composition / information on ingredients Component Exposure Limit CAS No. Principle Component: Tamoxifen Citrate USP Not Found Inactive ingredients: Carboxymethyl cellulose Not Found Mannitol Not Found Corn Starch Not Found Magnesium Stearate Not Found OPADRY white 02B Not Found Not Available Section 4. First -aid measures General After inhalation: Move to fresh air in case of accidental inhalation. assure fresh air breathing. After skin contact: Rinse skin with water/shower After eye contact: Rinse with water while holding the eyes wide open. Contact lenses should be removed. After swallowing: Rinse mouth out with water Information for doctor: Most important symptoms and effects, both acute and delayed- No further relevant information available. Indication of any immediate medical attention and special treatment needed- No further relevant information available. Overdose Treatment No specific treatment for overdosage is known; treatment must be symptomatic.

6 Section 5. Fire -fighting measures Specific hazards arising from the chemical Extinguishing media Suitable extinguishing agents: Use extinguishing media appropriate for surrounding fire. Extinguishing blanket. Carbon dioxide. Dry powder Special hazards arising from the substance or mixture Stable under normal conditions. Advice for firefighters Small amounts: Use normal individual fire protective equipment. Large amounts: Not Protective equipment: Hand protection : Gloves Skin and body protection : Lab coat Respiratory protection : Quarter mask (DIN EN 140) No additional information available Special protective equipment and precautions for firefighters General fire hazards Use normal individual fire protective equipment No unusual fire or explosion hazards noted Section 6. Accidental Release Measures Personal precautions, protective Avoid raising dust. Wear suitable protective clothing, gloves equipment and emergency and eye or face protection. procedures Environmental precautions: No additional information available Methods and material for containment and cleaning up: Section 7. Handling and Storage Storage: Sweep spilled substance into containers; if appropriate, moisten first to prevent dusting. Ensure waste is collected and contained. Clean thoroughly. Poorly soluble in water. Clean with the help of detergents. Store at 20 to 25 C (68 to 77 F) [See USP Controlled Room Temperature]. Dispense in a well-closed, light-resistant container as defined in the USP, with a child-resistant closure (as required). Precautions for safe handling: Keep it dry & in a cool, well ventilated place away from heat. Store in original container Information about fire - and explosion protection: No special measures required.

7 Section 8. Exposure controls / personal protection Respiratory Protection Quarter mask (DIN EN 140) Skin protection Eye/face protection Protective Clothing Biological limit values Exposure guidelines Thermal hazards General hygiene considerations Engineering controls For prolonged or repeated skin contact use suitable protective gloves. If contact is likely, safety glasses with side shields are recommended. Protective clothing is not normally necessary, however it is good practice to use apron. No biological exposure limits noted for the ingredient(s). General ventilation normally adequate. Wear appropriate thermal protective clothing, when necessary. Keep away from foodstuffs, beverages and feed. Wash hands before breaks and at the end of work. Routinely wash work clothing and protective equipment to remove contaminants. For advice on suitable monitoring methods, seek guidance from a qualified environment, health and safety professional. Engineering controls should be used as the primary means to control exposures. General room ventilation is adequate unless the process generates dust, mist or fumes. Keep airborne contamination levels below the exposure limits listed above in this section.

8 Section 9. Physical and chemical properties Appearance Description of Tamoxifen Citrate Tablets USP 10 mg is White to off white, round film coated tablets with bevel edged debossed with "826" on one side and plain on other side. Description of Tamoxifen Citrate Tablets USP 20 mg is White to off white, round film coated tablets with bevel edged debossed with "827" on one side and plain on other side Solubility Not available Odour Not available. Boiling point Not available. Melting Point Not available. Evaporation rate Not available. Vapour density Not available. Reactivity in water Not available. Vapour pressure Not available. % Volatile by volume Not available. Specific gravity Not available. Section 10. Stability and Reactivity Conditions to avoid Stable Contact with incompatible materials. Reactivity The product is stable and non-reactive under normal conditions of use, storage and transport. Chemical stability Hazardous reactions Decomposition products Material is stable under normal conditions. No dangerous reaction known under conditions of normal use. When heated to decomposition, emits dangerous fumes. Incompatible materials Strong Oxidizing agent Section 11. Toxicological information General Ingestion Handling of formulated product is not expected to cause any toxicological affects. The data pertains to the ingredient in formulations, rather than this specie formulation. Health injuries are not known or expected under normal use.

9 Other Not Available Symptoms related to the Not available physical, chemical and Toxicological characteristics Information on toxicological effects Acute toxicity Not available Expected to be a low ingestion hazard. However, ingestion is not likely to be a primary route of occupational exposure. Further information Not available Section 12. Ecological information Poorly soluble in water. No data available on ecotoxicity. Section 13. Disposal Consideration Dispose the waste in accordance with all applicable Federal, State and local laws. Section 14. Transport Information The product is not hazardous when shipping via air (IATA), ground (DOT), or sea (IMDG). In accordance with ADR / RID / IMDG / IATA / ADN Section 15. Regulatory Information Generic Medicine. Under Approval by USFDA & the ANDA Number is Section 16. Other information None Date of issue: 02/01/18 Supersedes edition: New Edition The information contained herein is based on the state of our knowledge. It characterizes the product with regard to the appropriate safety precautions. It does not represent a guarantee of the properties of the product.