Diltiazem (Diltiazem Hydrochloride) - Summary

DILTIAZEM SUMMARY

Diltiazem Hydrochloride for Injection
For Continuous Intravenous Infusion
Not For Bolus
ADD-Vantage^® Vials
R_x only

Diltiazem Hydrochloride for Injection is a calcium ion influx inhibitor (slow channel blocker or calcium channel antagonist).

NOTE: This drug product is not for direct bolus injection. Text referring to direct bolus injection is provided for information purposes only. Diltiazem Hydrochloride for Injection is indicated for the following:

1. Atrial Fibrillation or Atrial Flutter. Temporary control of rapid ventricular rate in atrial fibrillation or atrial flutter. It should not be used in patients with atrial fibrillation or atrial flutter associated with an accessory bypass tract such as in Wolff-Parkinson-White (WPW) syndrome or short PR syndrome.

2. Paroxysmal Supraventricular Tachycardia. Rapid conversion of paroxysmal supraventricular tachycardias (PSVT) to sinus rhythm. This includes AV nodal reentrant tachycardias and reciprocating tachycardias associated with an extranodal accessory pathway such as the WPW syndrome or short PR syndrome. Unless otherwise contraindicated, appropriate vagal maneuvers should be attempted prior to administration of diltiazem hydrochloride injection.

   The use of diltiazem hydrochloride should be undertaken with caution when the patient is compromised hemodynamically or is taking other drugs that decrease any or all of the following: peripheral resistance, myocardial filling, myocardial contractility, or electrical impulse propagation in the myocardium.

For either indication and particularly when employing continuous intravenous infusion, the setting should include continuous monitoring of the ECG and frequent measurement of blood pressure. A defibrillator and emergency equipment should be readily available.

In domestic controlled trials in patients with atrial fibrillation or atrial flutter, bolus administration of diltiazem hydrochloride injection was effective in reducing heart rate by at least 20% in 95% of patients. Diltiazem hydrochloride injection rarely converts atrial fibrillation or atrial flutter to normal sinus rhythm. Following administration of one or two intravenous bolus doses of diltiazem hydrochloride injection, response usually occurs within 3 minutes and maximal heart rate reduction generally occurs in 2 to 7 minutes. Heart rate reduction may last from 1 to 3 hours. If hypotension occurs, it is generally short-lived, but may last from 1 to 3 hours.

A 24-hour continuous infusion of diltiazem injection in the treatment of atrial fibrillation or atrial flutter maintained at least a 20% heart rate reduction during the infusion in 83% of patients. Upon discontinuation of infusion, heart rate reduction may last from 0.5 hours to more than 10 hours (median duration 7 hours). Hypotension, if it occurs, may be similarly persistent.

In the controlled clinical trials, 3.2% of patients required some form of intervention (typically, use of intravenous fluids or the Trendelenburg position) for blood pressure support following diltiazem hydrochloride injection.

In domestic controlled trials, bolus administration of diltiazem hydrochloride injection was effective in converting PSVT to normal sinus rhythm in 88% of patients within 3 minutes of the first or second bolus dose.

Symptoms associated with the arrhythmia were improved in conjunction with decreased heart rate or conversion to normal sinus rhythm following administration of diltiazem hydrochloride injection.

See all Diltiazem indications & dosage >>

NEWS HIGHLIGHTS

Published Studies Related to Diltiazem

Topical diltiazem cream versus botulinum toxin a for the treatment of chronic anal fissure: a double-blind randomized clinical trial. [2012]
the purpose of this study... CONCLUSIONS: BTA yields higher healing rates in the short term, though after 3

Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients: from retrospective to prospective. [2011.08]
The impact of CYP3A5*3, a CYP3A5 nonexpresser genotype, on inhibitory effects of diltiazem on tacrolimus metabolism has not been assessed. In retrospective study, when coadministered with diltiazem, mean increments in dose-adjusted C(0D7), C(max) and AUC(0-12 h) for tacrolimus were larger in CYP3A5 expressers than in CYP3A5 nonexpressers (48.7 vs 3.7%, 31.7 vs 17.2% and 38.2 vs 18.5%, respectively).

A randomized, prospective, double-blind, placebo-controlled trial of the effect of topical diltiazem on posthaemorrhoidectomy pain. [2011.03]
CONCLUSION: Perianal application of DTZ cream after haemorrhoidectomy significantly reduces postoperative pain and is perceived as beneficial, with no increase in associated morbidity. (c) 2011 The Authors. Colorectal Disease (c) 2011 The Association of Coloproctology of Great Britain and Ireland.

[A comparative study on the efficacy and safety of intravenous esmolol, amiodarone and diltiazem for controlling rapid ventricular rate of patients with atrial fibrillation during anesthesia period]. [2010.11]
OBJECTIVE: To evaluate the efficacy and safety of intravenous esmolol, amiodarone and diltiazem for controlling rapid ventricular rate in patients with atrial fibrillation (AF) during anesthesia period... CONCLUSIONS: Intravenous esmolol, amiodarone and diltiazem are all equally effective and safe on controlling rapid ventricular rate in patients with atrial fibrillation during the anesthesia period. Esmolol use is associated with the shortest mean reacting time and amiodarone use is associated with the lowest total side effect rate in this patient cohort.

Comparison of the effects of long-acting nifedipine CR and diltiazem R in patients with vasospastic angina: Aomori coronary spastic angina study. [2010.11]
CONCLUSION: Once-daily administration of nifedipine CR was as effective as twice-daily diltiazem R in the prevention of VSA attacks. Copyright (c) 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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Clinical Trials Related to Diltiazem

The Effect of Concomitant Administration of Erythromycin and Diltiazem on CYP3A Activity in Healthy Volunteers [Completed]
We, the researchers at the Indiana University School of Medicine, are doing this study to better understand how the effects of certain medications are altered when taken simultaneously, or in combination with each other. We will also look at how each volunteer's genes (DNA) may affect the way these medications are metabolized.

Hypothesis:

We will test the hypothesis that the extent of drug-drug interaction caused by the combination of erythromycin and diltiazem is not predictable from the extent of interaction produced by each inhibitor alone. Specifically we will test the hypothesis that the combination of erythromycin and diltiazem will cause a greater decrease in midazolam intravenous and oral clearance than the sum of the decreases caused by each inhibitor alone.

Study Investigating the Pharmacokinetic Interaction Between INX-08189 and Verapamil HCL ER in Healthy Volunteers [Recruiting]
The purpose of this study is to evaluate the potential for a pharmacokinetic (PK) drug-drug interaction between INX-08189 and extended release verapamil hydrochloride (verapamil HCL ER).

Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem [Recruiting]
This is a pilot clinical study to assess whether the administration of diltiazem may be able to decrease the development or progression of hypertrophic cardiomyopathy (HCM). Diltiazem is a commonly used medication for the treatment of high blood pressure and studies on animals with HCM suggest that diltiazem decreases disease development. This study specifically targets individuals in the "prehypertrophic" phase of HCM-- those with documented sarcomere gene mutations without echocardiographic or EKG evidence of LVH.

The hypothesis of this study is that starting diltiazem administration early in life (in the prehypertrophic phase) will decrease the progression of HCM in individuals with sarcomere gene mutations. This will be assessed by looking at an improvement in the heart's ability to relax using echocardiography.

Diltiazem Hydrochloride Cream for Anal Fissure [Recruiting]
A Phase III, multicentre, randomised, double blind, placebo-controlled study in subjects having anal fissure (AF) with AF-related pain. Subjects will undertake a 1-week screening period to provide baseline data and for assessment of eligibility. At the Baseline visit (Week 0), eligible subjects (having an average Numerical Rating Scale (NRS) score of >4 for worst pain associated with or following defaecation) will be randomised on a 1: 1:1 basis to one of the three treatment groups. Subjects will receive diltiazem hydrochloride 2% cream or diltiazem hydrochloride 4% cream or placebo cream. Study treatment will be applied in and around the anus, three times daily, for up to 8 weeks. Following the Week 0 Visit, subjects will be contacted by telephone during Week 1 to ensure adequate compliance with study treatment, to ensure that study drug is being tolerated and that any concomitant medications are used at a level consistent with that prior to randomisation. Subjects will return to the clinic for safety and efficacy assessments at Weeks 2, 4, and 8 and receive a follow-up telephone call at Week 12, following cessation of therapy.

Concomitant laxatives and stool softeners will be permitted, as needed, during the entire study period (screening and treatment) to ensure that constipation or passage of hard stools does not confound evaluation or improvement of the condition. Fibre supplements will be allowed but should be continued at the baseline level.

Instructions on the use of the IVRS diary will be issued to subjects to record fissure-related pain (NRS) and bowel symptoms daily during the 1-week screening period, to confirm eligibility and post-randomisation to record worst anal pain associated with or following defaecation (NRS) and daily overall AF-related pain (NRS). A record of the number of times the subject has defaecated, laxative and analgesic usage will also be made as well as the number of applications of study treatment, any changes to concurrent medications and any Adverse Events (AEs).

In addition, at some or all study visits, subjects will record the Patient's Global Impression of Improvement (PGI-I) on a 7 point Likert scale, complete a Short Form 36 (SF-36) quality of life questionnaire and will undergo examination of their AF. Routine blood samples will be taken and the Skin Irritation Score (SIS) recorded for safety evaluations.

Subjects may receive permitted medications for pain per Entry Criteria, but these should remain stable, where possible, up to the Week 8 Visit. Introduction of any new medication for AF will not be permitted unless the Investigator deems "rescue" intervention necessary. A subject will be deemed a treatment failure if rescue intervention is required and will have to be withdrawn from the study.

Any subject leaving the study following randomisation for any reason will be asked to complete the Early Withdrawal Visit. This includes subjects who withdraw due to the development of AEs or intolerance, as well as subjects who require rescue intervention. These subjects will return for safety follow-up visits at their previously scheduled follow-up assessment appointments. If complete healing has occurred at the 2 or 4 Week visits, (i. e. prior to the end of the 8-week treatment period), subjects will be asked to continue applying the medication for the full 8 week course, up to the final assessment.

Following the Week 8 visit (or Early Withdrawal Visit), subjects will be followed up for a further 4 weeks (following cessation of study medication) to note any AEs.

All routine blood analyses (haematology and biochemistry) and plasma levels of diltiazem and of its principal metabolites will be analysed by central laboratories.

Verapamil as Therapy for Children and Young Adults With Dravet Syndrome [Recruiting]
This study will assess how well the drug verapamil can improve control of seizures and dysautonomia symptoms in children and young adults diagnosed with Dravet syndrome. The safety of verapamil when given with all concomitant medications will also be assessed.

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Reports of Suspected Diltiazem Side Effects

Toxicity TO Various Agents (47),  Completed Suicide (45),  Nausea (24),  Cardiac Arrest (23),  Drug Interaction (22),  Hypotension (20),  Dizziness (16),  Blood Pressure Increased (16),  Intentional Drug Misuse (15),  Visual Impairment (15), more >>

PATIENT REVIEWS / RATINGS / COMMENTS

Diltiazem review by care giver of 74 year old female patient
		Rating
Overall rating:
Effectiveness:		Marginally Effective
Side effects:		Severe Side Effects
		Treatment Info
Condition / reason:		atrial fib
Dosage & duration:		30 mg taken 1/day for the period of 5 days
Other conditions:		high blood pressure, sick sinus syndrome
Other drugs taken:		warfarin lipitor flecanide
		Reported Results
Benefits:		It seemed to reduced blood pressure. No other benefits were observed.
Side effects:		Itchy red urticartia over entire body. This rash covered every inch of skin, causing swelled face and eyes. Anti-histimines did not relieve. Condition self relieved 2 weeks after stopping drug.
Comments:		This was taken in case atrial fib resumed, in order to keep heart rate down. Atrial fib did not return during drug treatment, so it is unknown if it would have help to keep heart rate down in the event of atrial fib.