DILTIAZEM HYDROCHLORIDE EXTENDED-RELEASE CAPSULES, USP

Transcription

1 EMERGENCY OVERVIEW Each Diltiazem Hydrochloride Extended-Release Capsules, USP intended for oral administration contains Diltiazem Hydrochloride and excipients generally considered to be non- toxic and nonhazardous in small quantities and under conditions of normal occupational exposure. Section 1. Identification Identification of the product Product Name: Formula: Chemical Name: Diltiazem Hydrochloride Extended-Release Capsules, USP 1,5-Benzothiazepin-4(5H)-one, 3-(acetyloxy)-5-[2- dimethylamino)ethyl]-2, 3-dihydro-2-(4-methoxyphenyl)-, monohydrochloride, (+)-cis- 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 Diltiazem hydrochloride extended-release capsules, USP are indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medications. Diltiazem hydrochloride extended-release capsules, USP are indicated for the management of chronic stable angina and angina due to coronary artery spasm.

2 Restriction on Use / Contraindications: Section 2. Hazard(s) Identification Dose and Administration Diltiazem hydrochloride is contraindicated in patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker, patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker, patients with hypotension (less than 90 mm Hg systolic), patients who have demonstrated hypersensitivity to the drug, and patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission. Patients controlled on diltiazem alone or in combination with other medications may be switched to diltiazem hydrochloride extended-release capsules, USP at the nearest equivalent total daily dose. Higher doses of diltiazem hydrochloride extendedrelease capsules, USP may be needed in some patients. Monitor patients closely. Subsequent titration to higher or lower doses may be necessary. There is limited general clinical experience with doses above 360 mg, but doses to 540 mg have been studied in clinical trials. The incidence of side effects increases as the dose increases with first-degree AV block, dizziness, and sinus bradycardia bearing the strongest relationship to dose. Adverse Effects Over Dose Effect Serious adverse reactions have been rare in studies carried out to date, but it should be recognized that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from these studies. The oral LD50s in mice and rats range from 415 to 740 mg/kg and from 560 to 810 mg/kg, respectively. The intravenous LD50s in these species were 60 and 38 mg/kg, respectively. The oral LD50 in dogs is considered to be in excess of 50 mg/kg, while lethality was seen in monkeys at 360 mg/kg. The toxic dose in man is not known. Because of its extensive metabolism, blood levels after a standard dose of diltiazem can vary over tenfold, limiting the usefulness of blood levels in overdose cases. There have been reports of diltiazem overdose in amounts ranging from <1 g to 18 g. Of cases with known outcome, most patients recovered and in cases with a fatal outcome, the majority involved multiple drug ingestion.

3 Contraindications Pregnancy Comments Diltiazem hydrochloride is contraindicated in patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker, patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker, patients with hypotension (less than 90 mm Hg systolic), patients who have demonstrated hypersensitivity to the drug, and patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission. Reproduction studies have been conducted in mice, rats, and rabbits. Administration of doses ranging from five to ten times greater (on a mg/kg basis) than the daily recommended therapeutic dose has resulted in embryo and fetal lethality. These doses, in some studies, have been reported to cause skeletal abnormalities. In the perinatal/postnatal studies, there was an increased incidence of stillbirths at doses of 20 times the human dose or greater. There are no well-controlled studies in pregnant women; therefore, use diltiazem hydrochloride in pregnant women only if the potential benefit justifies the potential risk to the fetus. Pregnancy Category Not available Section 3. Composition / information on ingredients Component Exposure Limit CAS No. Principle Component: Diltiazem hydrochloride Not Found Inactive Ingredients: Sugar Sphere Not Found Hypermellose Not Found Colloidal Silicon Dioxide Not Found Ammonio Methacrylate Copolymer Type B Not Found Ammonio Methacrylate Copolymer Type A Not Found Talc Not Found Dichloro Methane Not Found Isopropyl Alcohol Not Found

4 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 Section 5. Fire -fighting measures Specific hazards arising from the chemical Limited data are available related to overdosage in humans. If symptomatic hypotension occurs, initiate supportive treatment. 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

5 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. Section 7. Handling and Storage Storage: Section 8. Exposure controls / personal protection Store at 20 to 25 C (68 to 77 F). Avoid excessive humidity. Dispense in a tight container as defined in the USP. 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. Respiratory Protection Quarter mask (DIN EN 140) Skin protection Eye/face protection Protective Clothing Biological limit values Exposure guidelines Thermal hazards 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.

6 General hygiene considerations 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 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. Section 9. Physical and chemical properties Appearance Capsules USP, 120 mg are white to off white pellets filled in size 2 empty hard gelatin capsules with light green colored cap & white colored body imprinted with 595 in black ink Capsules USP, 180 mg are white to off white pellets filled in size 0 empty hard gelatin capsules with light blue colored cap & grey colored body imprinted with 596 in black ink Capsules USP, 240 mg are white to off white pellets filled in size 00 empty hard gelatin capsules with light blue colored cap & white colored body imprinted with 597 in black ink Capsules USP, 300 mg are white to off white pellets filled in size 00 empty hard gelatin capsules with light green colored cap & grey colored body imprinted with 598 in black ink Capsules USP, 360 mg are white to off white pellets filled in size 00 empty hard gelatin capsules with grey colored cap & white colored body imprinted with 599 in black ink.

7 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 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

8 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: 19/08/17 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.