Diltiazem Hydrochloride Extended Release

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Overview

What is Diltiazem Hydrochloride Extended Release?

Diltiazem hydrochloride is a calcium ion cellular influx inhibitor (slow channel blocker or calcium antagonist). Chemically, diltiazem hydrochloride is 1,5-benzothiazepin-4(5H)one,3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2, 3-dihydro-2-(4-methoxyphenyl)-, monohydrochloride, (+)-cis-.

The structural formula is:

Diltiazem hydrochloride is a white to off-white crystalline powder with a bitter taste. It is soluble in water, methanol and chloroform. It has a molecular weight of 450.99. Diltiazem Hydrochloride Extended Release Tablets, for oral administration, are formulated as a once-a-day extended release tablet containing either120 mg, 180 mg, 240 mg, 300 mg, 360 mg or 420 mg of diltiazem hydrochloride.

Also contains: Monosodium Citrate Anhydrous Powder; Polyethylene Glycol, NF (PEG-6000); Povidone, USP; Magnesium Stearate, NF; Dehydrated Alcohol, USP; Lactose Monohydrate, NF; Acetyltributyl Citrate, NF; Sodium Bicarbonate, USP; Multipor Coating Polymer; Titanium Dioxide, USP; Acetone, NF; Ethylcellulose, NF; Hypromellose, USP; Purified Water, USP; Talc, USP; Isopropyl Alcohol, USP; n-Butyl Alcohol, NF; Propylene Glycol, USP; Opacode Black Ink.

What does Diltiazem Hydrochloride Extended Release look like?

What are the available doses of Diltiazem Hydrochloride Extended Release?

Sorry No records found.

What should I talk to my health care provider before I take Diltiazem Hydrochloride Extended Release?

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How should I use Diltiazem Hydrochloride Extended Release?

Diltiazem Hydrochloride Extended Release Tablets are indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medications. Diltiazem Hydrochloride Extended Release Tablets are indicated for the management of chronic stable angina.

Diltiazem Hydrochloride Extended Release Tablets are an extended release formulation intended for once-a-day administration.

Patients controlled on diltiazem alone or in combination with other medications may be switched to Diltiazem Hydrochloride Extended Release Tablets once-a-day at the nearest equivalent total daily dose. Higher doses of Diltiazem Hydrochloride Extended Release Tablets once-a-day dosage may be needed in some patients. Patients should be closely monitored. Subsequent titration to higher or lower doses may be necessary and should be initiated as clinically warranted. There is limited general clinical experience with doses above 360 mg, but the safety and efficacy of doses as high as 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.

The tablet should be swallowed whole and not chewed or crushed.

What interacts with Diltiazem Hydrochloride Extended Release?

Diltiazem is contraindicated in (1) patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker, (2) patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker, (3) patients with hypotension (less than 90 mm Hg systolic), (4) patients who have demonstrated hypersensitivity to the drug, and (5) patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission.

What are the warnings of Diltiazem Hydrochloride Extended Release?

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 ().

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 in combination with betablockers 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 ().

What are the precautions of Diltiazem Hydrochloride Extended Release?

General

Diltiazem hydrochloride is extensively metabolized by the liver and excreted by the kidneys and in bile. As with any drug given over prolonged periods, laboratory parameters of renal and hepatic function should be monitored at regular intervals. The drug should be used with caution in patients with impaired renal or hepatic function.

In subacute and chronic dog and rat studies designed to produce toxicity, high doses of diltiazem were associated with hepatic damage. In special subacute hepatic studies, oral doses of 125 mg/kg and higher in rats were associated with histological changes in the liver, which were reversible when the drug was discontinued. In dogs, doses of 20 mg/kg were also associated with hepatic changes; however, these changes were reversible with continued dosing.

Dermatological events () may be transient and may disappear despite continued use of diltiazem. However, skin eruptions progressing to erythema multiforme and/or exfoliative dermatitis have also been infrequently reported. Should a dermatologic reaction persist, the drug should be discontinued.

Drug interactions

Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction (). Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with diltiazem ().

As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem is both a substrate and an inhibitor of the cytochrome P-450 3A4 enzyme system. Other drugs that are specific substrates, inhibitors, or inducers of this enzyme system may have a significant impact on the efficacy and side effect profile of diltiazem. Patients taking other drugs that are substrates of CYP450, especially patients with renal and/or hepatic impairment, may require dosage adjustment when starting or stopping concomitantly administered diltiazem in order to maintain optimum therapeutic blood levels.

Controlled and uncontrolled domestic studies suggest that concomitant use of diltiazem and beta-blockers is usually well tolerated, but available data are not sufficient to predict the effects of concomitant treatment in patients with left ventricular dysfunction or cardiac conduction abnormalities.

Administration of diltiazem concomitantly with propranolol in five normal volunteers resulted in increased propranolol levels in all subjects and bioavailability of propranolol was increased approximately 50%. , propranolol appears to be displaced from its binding sites by diltiazem. If combination therapy is initiated or withdrawn in conjunction with propranolol, an adjustment in the propranolol dose may be warranted ().

A study in six healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and area-under-the-curve (53%) after a 1-week course of cimetidine at 1200 mg per day and a single dose of diltiazem 60 mg. Ranitidine produced smaller, nonsignificant increases. The effect may be mediated by cimetidine's known inhibition of hepatic cytochrome P-450, the enzyme system responsible for the first-pass metabolism of diltiazem. Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with cimetidine. An adjustment in the diltiazem dose may be warranted.

Digitalis

Administration of diltiazem with digoxin in 24 healthy male subjects increased plasma digoxin concentrations approximately 20%. Another investigator found no increase in digoxin levels in 12 patients with coronary artery disease. Since there have been conflicting results regarding the effect of digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing diltiazem therapy to avoid possible over or under-digitalization ().

The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with anesthetics may be potentiated by calcium channel blockers. When used concomitantly, anesthetics and calcium blockers should be titrated carefully.

Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3- to 4-fold and the C by 2-fold, compared to placebo. The elimination half-life of midazolam and triazolam also increase (1.5 to 2.5 fold) during coadministration with diltiazem. These pharmacokinetic effects seen during diltiazem coadministration can result in increased clinical effects (e.g., prolonged sedation) of both midazolam and triazolam.

A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporine dose ranging from 15% to 48% was necessary to maintain cyclosporine trough concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted, or discontinued.

The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated.

Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of carbamazepine (40% to 72% increase), resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction.

In a ten-subject study, coadministration of diltiazem (120 mg bid diltiazem SR) with lovastatin resulted in a 3 to 4 times increase in mean lovastatin AUC and C versus lovastatin alone; no change in pravastatin AUC and C was observed during diltiazem coadministration. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin.

Coadministration of rifampin with diltiazem lowered the diltiazem plasma concentrations to undetectable levels. Coadministration of diltiazem with rifampin or any known CYP 3A4 inducer should be avoided when possible, and alternative therapy considered.

Carcinogenesis, mutagenesis, impairment of fertility

A 24-month study in rats at oral dosage levels of up to 100 mg/kg/day, and a 21-month study in mice at oral dosage levels of up to 30 mg/kg/day showed no evidence of carcinogenicity. There was also no mutagenic response or in mammalian cell assays or in bacteria. No evidence of impaired fertility was observed in a study performed in male and female rats at oral dosages of up to 100 mg/kg/day.

Pregnancy

Category C. Reproduction studies have been conducted in mice, rats, and rabbits. Administration of doses ranging from 4 to 6 times (depending on species) the upper limit of the optimum dosage range in clinical trials (480 mg q.d. or 8 mg/kg q.d. for a 60 kg patient) resulted in embryo and fetal lethality. These studies revealed, in one species or another, a propensity to cause fetal abnormalities of the skeleton, heart, retina, and tongue. Also observed were reductions in early individual pup weights, pup survival, as well as prolonged delivery times and an increased incidence of stillbirths. There are no well-controlled studies in pregnant women; therefore, use diltiazem in pregnant women only if the potential benefit justifies the potential risk to the fetus.

Nursing mothers

Diltiazem is excreted in human milk. One report suggests that concentrations in breast milk may approximate serum levels. If use of diltiazem is deemed essential, an alternative method of infant feeding should be instituted.

Pediatric use

Safety and effectiveness in pediatric patients have not been established.

Geriatric use

Clinical studies of diltiazem did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

What are the side effects of Diltiazem Hydrochloride Extended Release?

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. In the hypertension study, the following table presents adverse reactions more common on diltiazem than on placebo (but excluding events with no plausible relationship to treatment), as reported in placebo-controlled hypertension trials in patients receiving a diltiazem hydrochloride extended-release formulation (once-a-day dosing) up to 540 mg.

In the angina study, the adverse event profile of Diltiazem Hydrochloride Extended Release Tablets was consistent with what has been previously described for Diltiazem Hydrochloride Extended Release Tablets and other formulations of diltiazem HCl. The most frequent adverse effects experienced by Diltiazem Hydrochloride Extended Release Tablet -treated patients were edema lower-limb (6.8%), dizziness (6.4%), fatigue (4.8%), bradycardia (3.6%), first-degree atrioventricular block (3.2%), and cough (2%).

In clinical trials of other diltiazem formulations involving over 3200 patients, the most common events (i.e. greater than 1%) were edema (4.6%), headache (4.6%), dizziness (3.5%), asthenia (2.6%), first-degree AV block (2.4%), bradycardia (1.7%), flushing (1.4%), nausea (1.4%) and rash (1.2%). In addition, the following events have been reported infrequently (less than 2%) in hypertension trials with other diltiazem products:

Cardiovascular:

Nervous System:

Gastrointestinal:

Dermatological:

Other:

The following postmarketing events have been reported infrequently in patients receiving diltiazem: allergic reactions, alopecia, angioedema (including facial or periorbital edema), asystole, erythema multiforme (including Stevens-Johnson syndrome, toxic epidermal necrolysis), exfoliative dermatitis, extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, increased bleeding time, leukopenia, purpura, retinopathy, and thrombocytopenia. In addition, events such as myocardial infarction have been observed which are not readily distinguishable from the natural history of the disease in these patients. A number of well-documented cases of generalized rash, some characterized as leukocytoclastic vasculitis, have been reported. However, a definitive cause and effect relationship between these events and diltiazem therapy is yet to be established.

	Adverse Reactions (MedDRA Term)	Placebo	Diltiazem hydrochloride extended-release
n = 120# pts (%)	120–360 mgn = 501# pts (%)	540 mgn = 123# pts (%)
Edema lower limb	4 (3)	24 (5)	10 (8)
Sinus congestion	0 (0)	2 (1)	2 (2)
Rash NOS	0 (0)	3 (1)	2 (2)

What should I look out for while using Diltiazem Hydrochloride Extended Release?

Diltiazem is contraindicated in (1) patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker, (2) patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker, (3) patients with hypotension (less than 90 mm Hg systolic), (4) patients who have demonstrated hypersensitivity to the drug, and (5) patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission.

What might happen if I take too much Diltiazem Hydrochloride Extended Release?

The oral LD's in mice and rats range from 415 to 740 mg/kg and from 560 to 810 mg/kg, respectively. The intravenous LD's in these species were 60 and 38 mg/kg, respectively. The oral LD 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. Due to 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 29 reports of diltiazem overdose in doses ranging from less than 1 g to 10.8 g. Sixteen of these reports involved multiple drug ingestions.

Twenty-two reports indicated patients had recovered from diltiazem overdose ranging from less than 1 g to 10.8 g. There were seven reports with a fatal outcome; although the amount of diltiazem ingested was unknown, multiple drug ingestions were confirmed in six of the seven reports.

Events observed following diltiazem overdose included bradycardia, hypotension, heart block, and cardiac failure. Most reports of overdose described some supportive medical measure and/or drug treatment. Bradycardia frequently responded favorably to atropine as did heart block, although cardiac pacing was also frequently utilized to treat heart block. Fluids and vasopressors were used to maintain blood pressure, and in cases of cardiac failure, inotropic agents were administered. In addition, some patients received treatment with ventilatory support, gastric lavage, activated charcoal, and/or intravenous calcium. Evidence of the effectiveness of intravenous calcium administration to reverse the pharmacological effects of diltiazem overdose was conflicting.

In the event of overdose or exaggerated response, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. Diltiazem does not appear to be removed by peritoneal or hemodialysis. Limited data suggest that plasmapheresis or charcoal hemoperfusion may hasten diltiazem elimination following overdose. Based on the known pharmacological effects of diltiazem and/or reported clinical experiences, the following measures may be considered:

Bradycardia:

High-Degree AV Block:

Cardiac Failure:

Hypotension:

How should I store and handle Diltiazem Hydrochloride Extended Release?

Store at 20°-25°C (68°-77°F) (See USP Controlled Room Temperature). Protect from light. Replace cap securely after each opening and retain blisters in carton until time of use.Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005Diltiazem Hydrochloride Extended Release Tablets are supplied as:120 mg: white to off-white round tablets imprinted with “WPI” over “3360” in black ink, supplied in bottles of 30, 90 and 1000.180 mg: white to off-white round tablets imprinted with “WPI” over “3361” in black ink, supplied in bottles of 30, 90 and 1000.240 mg: white to off-white round tablets imprinted with “WPI” over “3362” in black ink, supplied in bottles of 30, 90 and 1000.300 mg: white to off-white round tablets imprinted with “WPI” over “3368” in black ink, supplied in bottles of 30, 90 and 1000.360 mg: white to off-white round tablets imprinted with “WPI” over “3363” in black ink, supplied in bottles of 30, 90 and 1000.420 mg: white to off-white round tablets imprinted with “WPI” over “3364” in black ink, supplied in bottles of 30, 90 and 1000.StoreAvoid excessive humidity and temperatures above 30°C (86°F).Dispense in tight, light resistant container as defined in USP.Rx Only.Watson Laboratories Inc.Corona, CA 92880 USARev. October 2005

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Clinical Information

Chemical Structure

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Clinical Pharmacology

The therapeutic effects of diltiazem are believed to be related to its ability to inhibit the influx of calcium ions during membrane depolarization of cardiac and vascular smooth muscle.

Non-Clinical Toxicology

Diltiazem is contraindicated in (1) patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker, (2) patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker, (3) patients with hypotension (less than 90 mm Hg systolic), (4) patients who have demonstrated hypersensitivity to the drug, and (5) patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission.

Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction (). Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with diltiazem ().

As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem is both a substrate and an inhibitor of the cytochrome P-450 3A4 enzyme system. Other drugs that are specific substrates, inhibitors, or inducers of this enzyme system may have a significant impact on the efficacy and side effect profile of diltiazem. Patients taking other drugs that are substrates of CYP450, especially patients with renal and/or hepatic impairment, may require dosage adjustment when starting or stopping concomitantly administered diltiazem in order to maintain optimum therapeutic blood levels.

Diltiazem hydrochloride is extensively metabolized by the liver and excreted by the kidneys and in bile. As with any drug given over prolonged periods, laboratory parameters of renal and hepatic function should be monitored at regular intervals. The drug should be used with caution in patients with impaired renal or hepatic function.

In subacute and chronic dog and rat studies designed to produce toxicity, high doses of diltiazem were associated with hepatic damage. In special subacute hepatic studies, oral doses of 125 mg/kg and higher in rats were associated with histological changes in the liver, which were reversible when the drug was discontinued. In dogs, doses of 20 mg/kg were also associated with hepatic changes; however, these changes were reversible with continued dosing.

Dermatological events () may be transient and may disappear despite continued use of diltiazem. However, skin eruptions progressing to erythema multiforme and/or exfoliative dermatitis have also been infrequently reported. Should a dermatologic reaction persist, the drug should be discontinued.

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. In the hypertension study, the following table presents adverse reactions more common on diltiazem than on placebo (but excluding events with no plausible relationship to treatment), as reported in placebo-controlled hypertension trials in patients receiving a diltiazem hydrochloride extended-release formulation (once-a-day dosing) up to 540 mg.

In the angina study, the adverse event profile of Diltiazem Hydrochloride Extended Release Tablets was consistent with what has been previously described for Diltiazem Hydrochloride Extended Release Tablets and other formulations of diltiazem HCl. The most frequent adverse effects experienced by Diltiazem Hydrochloride Extended Release Tablet -treated patients were edema lower-limb (6.8%), dizziness (6.4%), fatigue (4.8%), bradycardia (3.6%), first-degree atrioventricular block (3.2%), and cough (2%).

In clinical trials of other diltiazem formulations involving over 3200 patients, the most common events (i.e. greater than 1%) were edema (4.6%), headache (4.6%), dizziness (3.5%), asthenia (2.6%), first-degree AV block (2.4%), bradycardia (1.7%), flushing (1.4%), nausea (1.4%) and rash (1.2%). In addition, the following events have been reported infrequently (less than 2%) in hypertension trials with other diltiazem products:

Cardiovascular:

Nervous System:

Gastrointestinal:

Dermatological:

Other:

The following postmarketing events have been reported infrequently in patients receiving diltiazem: allergic reactions, alopecia, angioedema (including facial or periorbital edema), asystole, erythema multiforme (including Stevens-Johnson syndrome, toxic epidermal necrolysis), exfoliative dermatitis, extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, increased bleeding time, leukopenia, purpura, retinopathy, and thrombocytopenia. In addition, events such as myocardial infarction have been observed which are not readily distinguishable from the natural history of the disease in these patients. A number of well-documented cases of generalized rash, some characterized as leukocytoclastic vasculitis, have been reported. However, a definitive cause and effect relationship between these events and diltiazem therapy is yet to be established.

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Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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Professional

Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72

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Interactions

A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).

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