ATORVASTATIN CALCIUM TABLETS

Transcription

1 EMERGENCY OVERVIEW Each Atorvastatin Calcium Tablets intended for oral administration contains Atorvastatin Calcium 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: Chemical Name: Atorvastatin Calcium Tablets C 33 H 34 FN 2 O 5 )2Ca 3H 2 O [R-(R*, R*)]-2-(4-fluorophenyl)-ß, δ-dihydroxy-5-(1- methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h- pyrrole-1- heptanoic acid, calcium salt (2:1) tri hydrate. 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 Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is recommended as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other non-pharmacologic measures alone has been inadequate. In patients with CHD or multiple risk factors for CHD, atorvastatin calcium tablets can be started simultaneously with diet.

2 Restriction on Use / Contraindications: Atorvastatin calcium tablets have not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types I and V). Active Liver Disease, Which May Include Unexplained Persistent Elevations in Hepatic Transaminase Levels Hypersensitivity to Any Component of This Medication Pregnancy Lactation Section 2. Hazard(s) Identification Dose and Administration Hyperlipidemia and Mixed Dyslipidemia The recommended starting dose of atorvastatin calcium is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of atorvastatin calcium is 10 to 80 mg once daily. Atorvastatin calcium can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of atorvastatin calcium should be individualized according to patient characteristics such as goal of therapy and response. After initiation and/or upon titration of atorvastatin calcium, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly. Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 Years to 17 Years of Age) The recommended starting dose of atorvastatin calcium is 10 mg/day; the usual dose range is 10 to 20mg orally once daily Doses should be individualized according to the recommended goal of therapy Adjustments should be made at intervals of 4 weeks or more. Homozygous Familial Hypercholesterolemia The dosage of atorvastatin calcium in patients with HoFH is 10 to 80 mg daily. Atorvastatin calcium should be used as an adjunct to other lipid- lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable. Concomitant Lipid-Lowering Therapy

3 Atorvastatin calcium may be used with bile acid resins. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution 2.5 Dosage in Patients with Renal Impairment Renal disease does not affect the plasma concentrations nor LDL- C reduction of atorvastatin calcium; thus, dosage adjustment in patients with renal dysfunction is not necessary Adverse Effects Over Dose Effect Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or Certain Protease Inhibitors In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor (telaprevir), therapy with atorvastatin calcium should be avoided. In patients with HIV taking lopinavir plus ritonavir, caution should be used when prescribing atorvastatin calcium and the lowest dose necessary employed. In patients taking clarithromycin, itraconazole, or in patients with HIV taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, therapy with atorvastatin calcium should be limited to 20 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium is employed. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, therapy with atorvastatin calcium should be limited to 40 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium is employed The following serious adverse reactions are discussed in greater detail in other sections of the label: Rhabdomyolysis and myopathy Liver enzyme abnormalities There is no specific treatment for atorvastatin calcium overdosage. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin calcium clearance.

4 Contraindications Pregnancy Comments Active Liver Disease, Which May Include Unexplained Persistent Elevations in Hepatic Transaminase Levels Hypersensitivity to Any Component of This Medication Pregnancy Lactation Atorvastatin calcium is contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit of lipid lowering drugs during pregnancy. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, atorvastatin calcium may cause fetal harm when administered to a pregnant woman. Atorvastatin calcium should be discontinued as soon as pregnancy is recognized.limited published data on the use of atorvastatin are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies in rats and rabbits there was no evidence of embryo-fetal toxicity or congenital malformations at doses up to 30 and 20 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 80 mg, based on body surface area (mg/m2). In rats administered atorvastatin during gestation and lactation, decreased postnatal growth and development was observed at doses 6 times the MRHD (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Human Data Limited published data on atorvastatin calcium from observational studies, meta-analyses and case reports have not shown an increased risk of major congenital malformations or miscarriage. Rare reports of congenital anomalies have been received following intrauterine exposure to other HMG-CoA reductase inhibitors. In a review of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate to exclude a

5 3to 4-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Pregnancy Category NA Section 3. Composition / information on ingredients Component Exposure Limit CAS No. Principle Component: Atorvastatin Calcium Not Found Inactive ingredients: Calcium Carbonate Not Found Lactose Monohydrate Not Found Microcrystalline Cellulose Not Found Croscarmellose Sodium Not Found Hydroxy propyl Cellulose Not Found Polysorbate 80 Not Found NA Magnesium Stearate Not Found OPADRY white YS Not Found NA 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.

6 Overdose Treatment Section 5. Fire -fighting measures Specific hazards arising from the chemical There is no specific treatment for atorvastatin calcium overdosage. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin calcium clearance. 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: 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.

7 Section 7. Handling and Storage Storage: Store at 20 to 25 C (68 to 77 F) 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. Section 8. Exposure controls / personal protection Respiratory Quarter mask (DIN EN 140) Protection 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 Atorvastatin Calcium Tablets, 10 mg is White to off white, oval shaped beveled, biconvex film coated tablets debossed with "249" on one side and plain on other side. Description of Atorvastatin Calcium Tablets, 20 mg is White to off white, oval shaped beveled, biconvex film coated tablets debossed with "250" on one side and plain on other side. Description of Atorvastatin Calcium Tablets, 40 mg is White to off white, oval shaped beveled, biconvex film coated tablets debossed with "251" on one side and plain on other side Description of Atorvastatin Calcium Tablets, 80 mg is White to off white, oval shaped beveled, biconvex film coated tablets debossed with "252" 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 Contact with incompatible materials. Stable Chemical stability Hazardous reactions Decomposition products Incompatible materials Reactivity The product is stable and non-reactive under normal conditions of use, storage and transport. Material is stable under normal conditions. No dangerous reaction known under conditions of normal use. When heated to decomposition, emits dangerous fumes. Strong Oxidizing agent

9 Section 11. Toxicological information General Ingestion Other Symptoms related to the physical, chemical and Toxicological characteristics 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. Expected to be a low ingestion hazard. However, ingestion is not likely to be a primary route of occupational exposure. Not Available Not available Information on toxicological effects Acute toxicity Not available 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: 11/07/18 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.