Diltiazem Hydrochloride

Sun Pharma Global FZE

Diltiazem Hydrochloride Extended-Release Capsules, USP [Once-a-Day Dosage]

FULL PRESCRIBING INFORMATION: CONTENTS*

• DILTIAZEM HYDROCHLORIDE DESCRIPTION
• CLINICAL PHARMACOLOGY
  • Mechanisms of Action
  • Hemodynamic and Electrophysiologic Effects
  • Pharmacokinetics and Metabolism
• DILTIAZEM HYDROCHLORIDE INDICATIONS AND USAGE
• DILTIAZEM HYDROCHLORIDE CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
  • General
  • Drug Interactions
  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Pregnancy
  • Nursing Mothers
  • Pediatric Use
  • Geriatric Use
• DILTIAZEM HYDROCHLORIDE ADVERSE REACTIONS
• OVERDOSAGE
• DILTIAZEM HYDROCHLORIDE DOSAGE AND ADMINISTRATION
• HOW SUPPLIED
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 120 MG
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 180 MG
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 240 MG
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 300 MG
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 360 MG

FULL PRESCRIBING INFORMATION

DILTIAZEM HYDROCHLORIDE DESCRIPTION

CLINICAL PHARMACOLOGY

Mechanisms of Action

Hemodynamic and Electrophysiologic Effects

Pharmacokinetics and Metabolism

DILTIAZEM HYDROCHLORIDE INDICATIONS AND USAGE

DILTIAZEM HYDROCHLORIDE CONTRAINDICATIONS

WARNINGS

• Cardiac Conduction. Diltiazem prolongs AV node refractory periods without significantly prolonging sinus node recovery time, except in patients with sick sinus syndrome. This effect may rarely result in abnormally slow heart rates (particularly in patients with sick sinus syndrome) or second- or third-degree AV block (13 of 3290 patients or 0.40%). Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. A patient with Prinzmetal's angina developed periods of asystole (2 to 5 seconds) after a single dose of 60 mg of diltiazem (see ADVERSE REACTIONS ). 
• Congestive Heart Failure. Although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function have not shown a reduction in cardiac index nor consistent negative effects on contractility (dp/dt). An acute study of oral diltiazem in patients with impaired ventricular function (ejection fraction 24% ± 6%) showed improvement in indices of ventricular function without significant decrease in contractile function (dp/dt). Worsening of congestive heart failure has been reported in patients with preexisting impairment of ventricular function. Experience with the use of diltiazem hydrochloride in combination with beta-blockers in patients with impaired ventricular function is limited. Caution should be exercised when using this combination. 
• Hypotension. Decreases in blood pressure associated with diltiazem therapy may occasionally result in symptomatic hypotension. 
• Acute Hepatic Injury. Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed in clinical studies. Such elevations were usually transient and frequently resolved even with continued diltiazem treatment. In rare instances, significant elevations in enzymes such as alkaline phosphatase, LDH, SGOT, SGPT, and other phenomena consistent with acute hepatic injury have been noted. These reactions tended to occur early after therapy initiation (1 to 8 weeks) and have been reversible upon discontinuation of drug therapy. The relationship to diltiazem is uncertain in some cases, but probable in some (see PRECAUTIONS ).

PRECAUTIONS

General

Drug Interactions

_max

Carbamazepine.

Cimetidine.

Clonidine.
 
Cyclosporine.



Digitalis. WARNINGS

Quinidine. _{(0 → ∞)1/2oral}

Rifampin.

Statins.



_maxmax

Carcinogenesis, Mutagenesis, Impairment of Fertility

in vitroin vivoin vitro

Pregnancy

Nursing Mothers

Pediatric Use

Geriatric Use

DILTIAZEM HYDROCHLORIDE ADVERSE REACTIONS

Diltiazem Hydrochloride Extended-Release Capsule Placebo-Controlled Angina and Hypertension Trials Combined

Adverse Reactions	Diltiazem Hydrochloride Extended-Release Capsule (n=607)	Placebo (n=301)
Headache	5.4%	5%
Dizziness	3%	3%
Bradycardia	3.3%	1.3%
AV Block First Degree	3.3%	0%
Edema	2.6%	1.3%
ECG Abnormality	1.6%	2.3%
Asthenia	1.8%	1.7%

Cardiovascular:

Nervous System:

Gastrointestinal: WARNINGS, Acute Hepatic Injury

Dermatological:

Other:

OVERDOSAGE

₅₀₅₀₅₀










 
Bradycardia:
 
High-degree AV Block:
 
Cardiac Failure:
 
Hypotension:

DILTIAZEM HYDROCHLORIDE DOSAGE AND ADMINISTRATION

Hypertension.

Angina

Concomitant Use With Other Cardiovascular Agents

• Sublingual NTG. May be taken as required to abort acute anginal attacks during diltiazem hydrochloride therapy.
• Prophylactic Nitrate Therapy. Diltiazem hydrochloride extended-release capsules may be safely coadministered with short- and long-acting nitrates.
• Beta-blockers (see WARNINGS and PRECAUTIONS ).
• Antihypertensives. Diltiazem hydrochloride extended-release capsules have an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochloride extended-release capsules or the concomitant antihypertensives may need to be adjusted when adding one to the other.

HOW SUPPLIED

Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-Day Dosage)

Strength	Quantity	NDC Number	Description
120 mg	Bottle of 30 CRC Bottle of 90 CRC Bottle of 90 NCRC Bottle of 500 NCRC Bottle of 1000 NCRC	47335-675-83 47335-675-81 47335-675-19 47335-675-13 47335-675-18	Hard gelatin capsules, size ‘2’Light turquoise blue colored cap and body, with “675” imprinted in black ink on cap and body, containing white to off white pellets.
180 mg	Bottle of 30 CRC Bottle of 90 CRC Bottle of 90 NCRC Bottle of 500 NCRC Bottle of 1000 NCRC	47335-676-83 47335-676-81 47335-676-19 47335-676-13 47335-676-18	Hard gelatin capsules, size ‘0’ blue colored cap and light turquoise blue body, with “676” imprinted in black ink on cap and body, containing white to off white pellets.
240 mg	Bottle of 30 CRC Bottle of 90 CRC Bottle of 90 NCRC Bottle of 500 NCRC Bottle of 1000 NCRC	47335-677-83 47335-677-81 47335-677-19 47335-677-13 47335-677-18	Hard gelatin capsules, size ‘0’ blue colored cap and blue colored body, with “677” imprinted in black ink on cap and body, containing white to off white pellets.
300 mg	Bottle of 30 CRC Bottle of 90 CRC Bottle of 90 NCRC Bottle of 500 NCRC Bottle of 1000 NCRC	47335-678-83 47335-678-81 47335-678-19 47335-678-13 47335-678-18	Hard gelatin capsules, size ‘00’ blue colored cap and gray colored body, with “678” imprinted in black ink on cap and body, containing white to off white pellets.
360 mg	Bottle of 30 CRC Bottle of 90 CRC Bottle of 90 NCRC Bottle of 500 NCRC Bottle of 1000 NCRC	47335-679-83 47335-679-81 47335-679-19 47335-679-13 47335-679-18	Hard gelatin capsules, size ‘00’ blue colored cap and white colored body with “679” imprinted in black ink on cap and body, containing white to off white pellets.

Caraco Pharmaceutical Laboratories, Ltd.



Sun Pharmaceutical Ind. Ltd.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 120 MG

NDC 47335-675-83
Diltiazem Hydrochloride Extended-Release Capsules, USP
(Once-a-Day Dosage)
120 mg
Rx only
30 CAPSULES
SUN PHARMACEUTICAL INDUSTRIES LTD.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 180 MG

NDC 47335-676-83
Diltiazem Hydrochloride Extended-Release Capsules, USP
(Once-a-Day Dosage)
180 mg
Rx only
30 CAPSULES
SUN PHARMACEUTICAL INDUSTRIES LTD.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 240 MG

NDC 47335-677-83
Diltiazem Hydrochloride Extended-Release Capsules, USP
(Once-a-Day Dosage)
240 mg
Rx only
30 CAPSULES
SUN PHARMACEUTICAL INDUSTRIES LTD.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 300 MG

NDC 47335-678-83
Diltiazem Hydrochloride Extended-Release Capsules, USP
(Once-a-Day Dosage)
300 mg
Rx only
30 CAPSULES
SUN PHARMACEUTICAL INDUSTRIES LTD.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL - 360 MG

NDC 47335-679-83
Diltiazem Hydrochloride Extended-Release Capsules, USP
(Once-a-Day Dosage)
360 mg
Rx only
30 CAPSULES
SUN PHARMACEUTICAL INDUSTRIES LTD.

Diltiazem Hydrochloride Diltiazem Hydrochloride CAPSULE, EXTENDED RELEASE Product Information Product Type Human prescription drug label Item Code (Source) NDC:47335-675 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DILTIAZEM HYDROCHLORIDE DILTIAZEM 120 mg Inactive Ingredients Ingredient Name Strength Hypromellose 2910 (5 Mpa.s) talc ETHYLCELLULOSE (20 MPA.S) TRIETHYL CITRATE AMMONIO METHACRYLATE COPOLYMER TYPE B ACETYLTRIBUTYL CITRATE polysorbate 80 MAGNESIUM STEARATE GELATIN SODIUM LAURYL SULFATE titanium dioxide FD&C BLUE NO. 1 Product Characteristics Color Size Imprint Code Shape TURQUOISE (light turquoise blue) 18 mm 675;675 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:47335-675-83 30 in 1 BOTTLE 2 NDC:47335-675-81 90 in 1 BOTTLE 3 NDC:47335-675-19 90 in 1 BOTTLE 4 NDC:47335-675-13 500 in 1 BOTTLE 5 NDC:47335-675-18 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090492 2011-10-31

Diltiazem Hydrochloride Diltiazem Hydrochloride CAPSULE, EXTENDED RELEASE Product Information Product Type Human prescription drug label Item Code (Source) NDC:47335-676 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DILTIAZEM HYDROCHLORIDE DILTIAZEM 180 mg Inactive Ingredients Ingredient Name Strength Hypromellose 2910 (5 Mpa.s) talc ETHYLCELLULOSE (20 MPA.S) TRIETHYL CITRATE AMMONIO METHACRYLATE COPOLYMER TYPE B ACETYLTRIBUTYL CITRATE polysorbate 80 MAGNESIUM STEARATE GELATIN SODIUM LAURYL SULFATE titanium dioxide FD&C BLUE NO. 1 FERROSOFERRIC OXIDE Product Characteristics Color Size Imprint Code Shape TURQUOISE (light turquoise blue) 21 mm 676;676 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:47335-676-83 30 in 1 BOTTLE 2 NDC:47335-676-81 90 in 1 BOTTLE 3 NDC:47335-676-19 90 in 1 BOTTLE 4 NDC:47335-676-13 500 in 1 BOTTLE 5 NDC:47335-676-18 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090492 2011-10-31

Diltiazem Hydrochloride Diltiazem Hydrochloride CAPSULE, EXTENDED RELEASE Product Information Product Type Human prescription drug label Item Code (Source) NDC:47335-677 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DILTIAZEM HYDROCHLORIDE DILTIAZEM 240 mg Inactive Ingredients Ingredient Name Strength Hypromellose 2910 (5 Mpa.s) talc ETHYLCELLULOSE (20 MPA.S) TRIETHYL CITRATE AMMONIO METHACRYLATE COPOLYMER TYPE B ACETYLTRIBUTYL CITRATE polysorbate 80 MAGNESIUM STEARATE GELATIN SODIUM LAURYL SULFATE titanium dioxide FD&C BLUE NO. 1 FERROSOFERRIC OXIDE Product Characteristics Color Size Imprint Code Shape BLUE 21 mm 677;677 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:47335-677-83 30 in 1 BOTTLE 2 NDC:47335-677-81 90 in 1 BOTTLE 3 NDC:47335-677-19 90 in 1 BOTTLE 4 NDC:47335-677-13 500 in 1 BOTTLE 5 NDC:47335-677-18 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090492 2011-10-31

Diltiazem Hydrochloride Diltiazem Hydrochloride CAPSULE, EXTENDED RELEASE Product Information Product Type Human prescription drug label Item Code (Source) NDC:47335-678 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DILTIAZEM HYDROCHLORIDE DILTIAZEM 300 mg Inactive Ingredients Ingredient Name Strength Hypromellose 2910 (5 Mpa.s) talc ETHYLCELLULOSE (20 MPA.S) TRIETHYL CITRATE AMMONIO METHACRYLATE COPOLYMER TYPE B ACETYLTRIBUTYL CITRATE polysorbate 80 MAGNESIUM STEARATE GELATIN SODIUM LAURYL SULFATE titanium dioxide FD&C BLUE NO. 1 FERROSOFERRIC OXIDE Product Characteristics Color Size Imprint Code Shape GRAY 24 mm 678;678 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:47335-678-83 30 in 1 BOTTLE 2 NDC:47335-678-81 90 in 1 BOTTLE 3 NDC:47335-678-19 90 in 1 BOTTLE 4 NDC:47335-678-13 500 in 1 BOTTLE 5 NDC:47335-678-18 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090492 2011-10-31

Diltiazem Hydrochloride Diltiazem Hydrochloride CAPSULE, EXTENDED RELEASE Product Information Product Type Human prescription drug label Item Code (Source) NDC:47335-679 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DILTIAZEM HYDROCHLORIDE DILTIAZEM 360 mg Inactive Ingredients Ingredient Name Strength Hypromellose 2910 (5 Mpa.s) talc ETHYLCELLULOSE (20 MPA.S) TRIETHYL CITRATE AMMONIO METHACRYLATE COPOLYMER TYPE B ACETYLTRIBUTYL CITRATE polysorbate 80 MAGNESIUM STEARATE GELATIN SODIUM LAURYL SULFATE titanium dioxide FD&C BLUE NO. 1 FERROSOFERRIC OXIDE Product Characteristics Color Size Imprint Code Shape WHITE 24 mm 679;679 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:47335-679-83 30 in 1 BOTTLE 2 NDC:47335-679-81 90 in 1 BOTTLE 3 NDC:47335-679-19 90 in 1 BOTTLE 4 NDC:47335-679-13 500 in 1 BOTTLE 5 NDC:47335-679-18 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090492 2011-10-31