Description

Simple

A medication used to lower blood pressure and to treat chronic chest pain or pressure caused by heart disease.

Clinical

A calcium channel blocker used to treat hypertension and to manage chronic stable angina.

Overview

Diltiazem is a benzothiazepine derivative with antihypertensive and vasodilating properties. Approved in 1982 by the FDA, it is a member of the non-dihydropyridine calcium channel blockers drug class. It works through various mechanisms of action, but it primarily works by inhibiting the calcium influx into cardiac and vascular smooth muscle during depolarization.[11] Compared to dihydropyridine drugs, such as [nifedipine], that preferentially act on vascular smooth muscle and [verapamil] that directly acts on the heart muscle, diltiazem displays an intermediate specificity to target both the cardiac and vascular smooth muscle.[7] Being a potent vasodilator, diltiazem is used clinically as an antihypertensive, anti-arrhythmic, and as an anti-anginal agent [8] for the management of cardiovascular conditions such as hypertension, chronic stable angina, atrial fibrillation, atrial flutter. Apart from its main FDA-approved indications, diltiazem has also been used for numerous off-label indications, such as anal fissures (in topical formulations), migraine prophylaxis, pulmo... Read more

Pharmacology

Indication

**Oral**

Indicated for the management of hypertension, to lower blood pressure, alone or in combination with other antihypertensive agents.[11]

Indicated fo... Read more

Pharmacodynamic

Diltiazem is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and my... Read more

Mechanism of action

Excitation of cardiac muscle involves the activation of a slow calcium inward current that is induced by L-type slow calcium channels, which are voltage-sensitive, ion-selective channels[ Read more

Absorption

Diltiazem is readily absorbed from the gastrointestinal tract. Minimum therapeutic plasma diltiazem concentrations appear to be in the range of 50 to 200 ng/mL. Following oral administration of extended formulations of 360 mg diltiazem, the drug in plasma was detectable within 3 to 4 hours and the p... Read more

Protein binding

Diltiazem is about 70-80% bound to plasma proteins, according to _in vitro_ binding studies.[11] About 40% of the drug is thought to bind to alpha-1-glycoprotein... Read more

Volume of distribution

The apparent volume of distribution of diltiazem was approximately 305 L following a single intravenous injection in healthy male volunteers.[9]

Clearance

Following a single intravenous injection in healthy male volunteers, the systemic clearance of diltiazem was approximately 65 L/h. After constant rate intravenous infusion, the systemic clearance decreased to 48 L/h.[ Read more

Half life

The plasma elimination half-life is approximately 3.0 - 4.5 hours following single and multiple oral doses. The half-life may slightly increase with dose and the extent of hepatic impairment.[ Read more

Route of elimination

Due to its extensive metabolism, only 2% to 4% of the unchanged drug can be detected in the urine.[11]

Toxicity

**Clinical Toxicity and Overdose**

The oral LD50 ranges from 415 to 740mg/kg in mice and 560 to 810 mg/kg in rats. The oral LD50 in dogs is considered to be in excess of 50 mg/kg. A dose of 360 mg/kg resulted in lethality in monkeys. The intravenous LD50 is 60 mg/... Read more

Adverse Effects

Contraindications

  • Route:
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Ventricular Tachycardia
      • Drugbank Id: DBCOND0031960
  • Route:
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Cardiogenic Shock
      • Drugbank Id: DBCOND0030788
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Pulmonary Congestion
      • Drugbank Id: DBCOND0069956
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Myocardial Infarction
      • Drugbank Id: DBCOND0027900
  • Route:
    • Oral
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Second-degree AV block
      • Drugbank Id: DBCOND0096365
  • Patient Conditions Associated With:
      • Name: Absence of a functioning ventricular pacemaker
      • Drugbank Id: DBCOND0107650
  • Route:
    • Oral
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Sinus shock syndrome
      • Drugbank Id: DBCOND0107651
  • Patient Conditions Associated With:
      • Name: Absence of a functioning ventricular pacemaker
      • Drugbank Id: DBCOND0107650
  • Route:
    • Oral
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Third-degree AV block
      • Drugbank Id: DBCOND0096366
  • Patient Conditions Associated With:
      • Name: Absence of a functioning ventricular pacemaker
      • Drugbank Id: DBCOND0107650
  • Route:
    • Oral
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Severe hypotension
      • Drugbank Id: DBCOND0095479
      • Modification Of:
        • Base:
          • Name: Hypotension
          • Drugbank Id: DBCOND0020133
        • Severity:
          • Includes:
            • severe
  • Route:
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Atrial Fibrillation
      • Drugbank Id: DBCOND0000503
  • Patient Conditions Associated With:
      • Name: Accessory bypass tract
      • Drugbank Id: DBCOND0107652
  • Route:
    • Intravenous
  • Regions: US
  • Patient Conditions:
      • Name: Atrial Flutter
      • Drugbank Id: DBCOND0000496
  • Patient Conditions Associated With:
      • Name: Accessory bypass tract
      • Drugbank Id: DBCOND0107652

Food Interactions

  • Avoid natural licorice.
  • Take this medication 30 minutes before meals.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The serum concentration of (R)-warfarin can be increased when it is combined with Diltiazem.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be increased when it is combined with Diltiazem.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Diltiazem can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may decrease the antihypertensive activities of Diltiazem.
1-benzylimidazole
1-benzylimidazole may decrease the antihypertensive activities of Diltiazem.
2,4-thiazolidinedione
The risk or severity of hypoglycemia can be increased when Diltiazem is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine
2,5-Dimethoxy-4-ethylamphetamine may decrease the antihypertensive activities of Diltiazem.
2,5-Dimethoxy-4-ethylthioamphetamine
2,5-Dimethoxy-4-ethylthioamphetamine may decrease the antihypertensive activities of Diltiazem.
4-Bromo-2,5-dimethoxyamphetamine
4-Bromo-2,5-dimethoxyamphetamine may decrease the antihypertensive activities of Diltiazem.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Diltiazem.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Diltiazem.
5-methoxy-N,N-dimethyltryptamine
5-methoxy-N,N-dimethyltryptamine may decrease the antihypertensive activities of Diltiazem.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Diltiazem.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Diltiazem.
Abafungin
The therapeutic efficacy of Abafungin can be increased when used in combination with Diltiazem.
Abatacept
The metabolism of Diltiazem can be increased when combined with Abatacept.
Abediterol
Abediterol may decrease the antihypertensive activities of Diltiazem.
Abemaciclib
The serum concentration of Abemaciclib can be increased when it is combined with Diltiazem.
Abexinostat
The risk or severity of QTc prolongation can be increased when Diltiazem is combined with Abexinostat.
Abiraterone
The metabolism of Diltiazem can be decreased when combined with Abiraterone.
12 References
  1. 1 . Hermann P, Rodger SD, Remones G, Thenot JP, London DR, Morselli PL: Pharmacokinetics of diltiazem after intravenous and oral administration. Eur J Clin Pharmacol. 1983;24(3):349-52.PubMed: 6861848
  2. 2 . Rodriguez Padial L, Baron-Esquivias G, Hernandez Madrid A, Marzal Martin D, Pallares-Carratala V, de la Sierra A: Clinical Experience with Diltiazem in the Treatment of Cardiovascular Diseases. Cardiol Ther. 2016 Jun;5(1):75-82. doi: 10.1007/s40119-016-0059-1. Epub 2016 Mar 25.PubMed: 27016085
  3. 3 . Nayler WG, Dillon JS: Calcium antagonists and their mode of action: an historical overview. Br J Clin Pharmacol. 1986;21 Suppl 2:97S-107S. doi: 10.1111/j.1365-2125.1986.tb02859.x.PubMed: 3019374
  4. 4 . Sutton MS, Morad M: Mechanisms of action of diltiazem in isolated human atrial and ventricular myocardium. J Mol Cell Cardiol. 1987 May;19(5):497-508.PubMed: 3498047
  5. 5 . O'Connor SE, Grosset A, Janiak P: The pharmacological basis and pathophysiological significance of the heart rate-lowering property of diltiazem. Fundam Clin Pharmacol. 1999;13(2):145-53.PubMed: 10226758
  6. 6 . Yeung PK, Prescott C, Haddad C, Montague TJ, McGregor C, Quilliam MA, Xei M, Li R, Farmer P, Klassen GA: Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. Eur J Drug Metab Pharmacokinet. 1993 Apr-Jun;18(2):199-206. doi: 10.1007/BF03188796.PubMed: 8243504
  7. 7 . 4, 22. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 50, 272). Edinburgh: Elsevier/Churchill Livingstone.
  8. 8 . Diltiazem - StatPearls - NCBI Bookshelf Link
  9. 9 . Diltiazem Hydrochloride Injection Label - Bedford Laboratories Link
  10. 10 . Cardizem (diltiazem hydrochloride) Drug Summary - PDR.net Link
  11. 11 . CARDIZEM® LA (diltiazem hydrochloride) extended-release tablets - FDA Label Link
  12. 12 . CARDIZEM® CD (diltiazem HCl) Capsules - FDA Label Link