DILTIAZEM HYDROCHLORIDE
Generic: DILTIAZEM HYDROCHLORIDE
Basic Information
Manufacturer
Apotex Corp.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
56573e9d-7bd2-694c-cd6d-26039590e548
Indications & Usage
INDICATIONS AND USAGE DILT-XR [Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage)] are indicated for the treatment of hypertension.
Diltiazem hydrochloride may be used alone or in combination with other antihypertensive medications, such as diuretics.
DILT-XR [Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage)] are indicated for the management of chronic stable angina.
Diltiazem hydrochloride may be used alone or in combination with other antihypertensive medications, such as diuretics.
DILT-XR [Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage)] are indicated for the management of chronic stable angina.
Warnings
WARNINGS Cardiac Conduction Diltiazem hydrochloride 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 (22 of 10,119 patients, or 0.2%); 41% of these 22 patients were receiving concomitant β-adrenoceptor antagonists versus 17% of the total group.
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 60 mg dose of diltiazem.
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 of 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 hydrochloride therapy may occasionally result in symptomatic hypotension.
Acute Hepatic Injury Mild elevations of serum 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 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 6 weeks) and have been reversible upon discontinuation of drug therapy.
The relationship to diltiazem is uncertain in some cases, but probable in some others (see PRECAUTIONS ).
This effect may rarely result in abnormally slow heart rates (particularly in patients with sick sinus syndrome) or second, or third degree AV block (22 of 10,119 patients, or 0.2%); 41% of these 22 patients were receiving concomitant β-adrenoceptor antagonists versus 17% of the total group.
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 60 mg dose of diltiazem.
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 of 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 hydrochloride therapy may occasionally result in symptomatic hypotension.
Acute Hepatic Injury Mild elevations of serum 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 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 6 weeks) and have been reversible upon discontinuation of drug therapy.
The relationship to diltiazem is uncertain in some cases, but probable in some others (see PRECAUTIONS ).
Adverse Reactions
ADVERSE REACTIONS Serious adverse reactions to diltiazem hydrochloride have been rare in studies with other formulations, as well as with Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage).
It should be recognized, however, that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from these studies.
Hypertension The most common adverse events (frequency ≥1%) in placebo-controlled, clinical hypertension studies with Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage) using daily doses up to 540 mg, are listed in the table below with placebo-treated patients included for comparison.
MOST COMMON ADVERSE EVENTS IN DOUBLE-BLIND, PLACEBO-CONTROLLED HYPERTENSION TRIALS Adverse Events (COSTART Term) Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage)* N = 303 # pts (%) Placebo N = 87 # pts (%) rhinitis 29 (9.6) 7 (8.0) headache 27 (8.9) 12 (13.8) pharyngitis 17 (5.6) 4 (4.6) constipation 11 (3.6) 2 (2.3) cough increase 9 (3.0) 2 (2.3) flu syndrome 7 (2.3) 1 (1.1) edema, peripheral 7 (2.3) 0 (0.0) myalgia 7 (2.3) 0 (0.0) diarrhea 6 (2.0) 0 (0.0) vomiting 6 (2.0) 0 (0.0) sinusitis 6 (2.0) 1 (1.1) asthenia 5 (1.7) 0 (0.0) pain, back 5 (1.7) 2 (2.3) nausea 5 (1.7) 1 (1.1) dyspepsia 4 (1.3) 0 (0.0) vasodilatation 4 (1.3) 0 (0.0) injury, accident 4 (1.3) 0 (0.0) pain, abdominal 3 (1.0) 0 (0.0) arthrosis 3 (1.0) 0 (0.0) insomnia 3 (1.0) 0 (0.0) dyspnea 3 (1.0) 0 (0.0) rash 3 (1.0) 1 (1.1) tinnitus 3 (1.0) 0 (0.0) *Adverse events occurring in 1% or more of patients receiving Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage).
Angina The most common adverse events (frequency ≥1%) in a placebo-controlled, short-term (2 week) clinical angina study with Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage) are listed in the table below with placebo-treated patients included for comparison.
In this trial, following a placebo phase, patients were randomly assigned to once daily doses of either 120, 240, or 480 mg of Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage).
MOST COMMON ADVERSE EVENTS IN A DOUBLE-BLIND, PLACEBO-CONTROLLED SHORT-TERM, ANGINA TRIAL Adverse Events (COSTART Term) Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage)* N = 139 # pts (%) Placebo N = 50 # pts (%) asthenia 5 (3.6) 2 (4.0) headache 4 (2.9) 3 (6.0) pain, back 4 (2.9) 1 (2.0) rhinitis 4 (2.9) 1 (2.0) constipation 3 (2.2) 1 (2.0) nausea 3 (2.2) 0 (0.0) edema, peripheral 3 (2.2) 1 (2.0) dizziness 3 (2.2) 0 (0.0) cough, increased 3 (2.2) 0 (0.0) bradycardia 2 (1.4) 0 (0.0) fibrillation, atrial 2 (1.4) 0 (0.0) arthralgia 2 (1.4) 0 (0.0) dream, abnormal 2 (1.4) 0 (0.0) dyspnea 2 (1.4) 0 (0.0) pharyngitis 2 (1.4) 1 (2.0) * Adverse events occurring in 1% or more of patients receiving Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage).
Infrequent Adverse Events The following additional events (COSTART Terms), listed by body system, were reported infrequently (less than 1%) in all subjects, hypertensive (n=425) or angina (n=318) patients who received Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage), or with other formulations of diltiazem.
Hypertension Cardiovascular: First-degree AV block, arrhythmia, postural hypotension, tachycardia, pallor, palpitations, phlebitis, ECG abnormality, ST elevation.
Nervous System Vertigo, hypertonia, paresthesia, dizziness, somnolence.
Digestive System Dry mouth, anorexia, tooth disorder, eructation.
Skin and Appendages Sweating, urticaria, skin hypertrophy (nevus).
Respiratory System Epistaxis, bronchitis, respiratory disorder.
Urogenital System Cystitis, kidney calculus, impotence, dysmenorrhea, vaginitis, prostate disease.
Metabolic and Nutritional Disorders Gout, edema.
Musculoskeletal System Arthralgia, bursitis, bone pain.
Hemic and Lymphatic System Lymphadenopathy.
Body as a Whole Pain, unevaluable reaction, neck pain, neck rigidity, fever, chest pain, malaise.
Special Senses Amblyopia (blurred vision), ear pain.
Angina Cardiovascular: Palpitations, AV block, sinus bradycardia, bigeminal extrasystole, angina pectoris, hypertension, hypotension, myocardial infarct, myocardial ischemia, syncope, vasodilatation, ventricular extrasystole.
Nervous System Abnormal thinking, neuropathy, paresthesia.
Digestive System Diarrhea, dyspepsia, vomiting, colitis, flatulence, GI hemorrhage, stomach ulcers.
Skin and Appendages Contact dermatitis, pruritus, sweating.
Respiratory System Respiratory distress.
Urogenital System Kidney failure, pyelonephritis, urinary tract infection.
Metabolic and Nutritional Disorders Weight increase.
Musculoskeletal System Myalgia.
Body as a Whole Chest pain, accidental injury, infection.
Special Senses Eye hemorrhage, ophthalmitis, otitis media, taste perversion, tinnitus.
There have been post-marketing reports of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of diltiazem hydrochloride.
It should be recognized, however, that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from these studies.
Hypertension The most common adverse events (frequency ≥1%) in placebo-controlled, clinical hypertension studies with Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage) using daily doses up to 540 mg, are listed in the table below with placebo-treated patients included for comparison.
MOST COMMON ADVERSE EVENTS IN DOUBLE-BLIND, PLACEBO-CONTROLLED HYPERTENSION TRIALS Adverse Events (COSTART Term) Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage)* N = 303 # pts (%) Placebo N = 87 # pts (%) rhinitis 29 (9.6) 7 (8.0) headache 27 (8.9) 12 (13.8) pharyngitis 17 (5.6) 4 (4.6) constipation 11 (3.6) 2 (2.3) cough increase 9 (3.0) 2 (2.3) flu syndrome 7 (2.3) 1 (1.1) edema, peripheral 7 (2.3) 0 (0.0) myalgia 7 (2.3) 0 (0.0) diarrhea 6 (2.0) 0 (0.0) vomiting 6 (2.0) 0 (0.0) sinusitis 6 (2.0) 1 (1.1) asthenia 5 (1.7) 0 (0.0) pain, back 5 (1.7) 2 (2.3) nausea 5 (1.7) 1 (1.1) dyspepsia 4 (1.3) 0 (0.0) vasodilatation 4 (1.3) 0 (0.0) injury, accident 4 (1.3) 0 (0.0) pain, abdominal 3 (1.0) 0 (0.0) arthrosis 3 (1.0) 0 (0.0) insomnia 3 (1.0) 0 (0.0) dyspnea 3 (1.0) 0 (0.0) rash 3 (1.0) 1 (1.1) tinnitus 3 (1.0) 0 (0.0) *Adverse events occurring in 1% or more of patients receiving Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage).
Angina The most common adverse events (frequency ≥1%) in a placebo-controlled, short-term (2 week) clinical angina study with Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage) are listed in the table below with placebo-treated patients included for comparison.
In this trial, following a placebo phase, patients were randomly assigned to once daily doses of either 120, 240, or 480 mg of Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage).
MOST COMMON ADVERSE EVENTS IN A DOUBLE-BLIND, PLACEBO-CONTROLLED SHORT-TERM, ANGINA TRIAL Adverse Events (COSTART Term) Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage)* N = 139 # pts (%) Placebo N = 50 # pts (%) asthenia 5 (3.6) 2 (4.0) headache 4 (2.9) 3 (6.0) pain, back 4 (2.9) 1 (2.0) rhinitis 4 (2.9) 1 (2.0) constipation 3 (2.2) 1 (2.0) nausea 3 (2.2) 0 (0.0) edema, peripheral 3 (2.2) 1 (2.0) dizziness 3 (2.2) 0 (0.0) cough, increased 3 (2.2) 0 (0.0) bradycardia 2 (1.4) 0 (0.0) fibrillation, atrial 2 (1.4) 0 (0.0) arthralgia 2 (1.4) 0 (0.0) dream, abnormal 2 (1.4) 0 (0.0) dyspnea 2 (1.4) 0 (0.0) pharyngitis 2 (1.4) 1 (2.0) * Adverse events occurring in 1% or more of patients receiving Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage).
Infrequent Adverse Events The following additional events (COSTART Terms), listed by body system, were reported infrequently (less than 1%) in all subjects, hypertensive (n=425) or angina (n=318) patients who received Diltiazem Hydrochloride Extended-Release Capsules, USP (Once-a-day dosage), or with other formulations of diltiazem.
Hypertension Cardiovascular: First-degree AV block, arrhythmia, postural hypotension, tachycardia, pallor, palpitations, phlebitis, ECG abnormality, ST elevation.
Nervous System Vertigo, hypertonia, paresthesia, dizziness, somnolence.
Digestive System Dry mouth, anorexia, tooth disorder, eructation.
Skin and Appendages Sweating, urticaria, skin hypertrophy (nevus).
Respiratory System Epistaxis, bronchitis, respiratory disorder.
Urogenital System Cystitis, kidney calculus, impotence, dysmenorrhea, vaginitis, prostate disease.
Metabolic and Nutritional Disorders Gout, edema.
Musculoskeletal System Arthralgia, bursitis, bone pain.
Hemic and Lymphatic System Lymphadenopathy.
Body as a Whole Pain, unevaluable reaction, neck pain, neck rigidity, fever, chest pain, malaise.
Special Senses Amblyopia (blurred vision), ear pain.
Angina Cardiovascular: Palpitations, AV block, sinus bradycardia, bigeminal extrasystole, angina pectoris, hypertension, hypotension, myocardial infarct, myocardial ischemia, syncope, vasodilatation, ventricular extrasystole.
Nervous System Abnormal thinking, neuropathy, paresthesia.
Digestive System Diarrhea, dyspepsia, vomiting, colitis, flatulence, GI hemorrhage, stomach ulcers.
Skin and Appendages Contact dermatitis, pruritus, sweating.
Respiratory System Respiratory distress.
Urogenital System Kidney failure, pyelonephritis, urinary tract infection.
Metabolic and Nutritional Disorders Weight increase.
Musculoskeletal System Myalgia.
Body as a Whole Chest pain, accidental injury, infection.
Special Senses Eye hemorrhage, ophthalmitis, otitis media, taste perversion, tinnitus.
There have been post-marketing reports of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of diltiazem hydrochloride.