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Identification
Name Diltiazem
Accession Number DB00343 (APRD00473)
Type small molecule
Groups approved
Description

A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [PubChem]

Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
d-cis-Diltiazem
Salts Not Available
Brand names
Name Company
Acalix
Adizem
Altiazem
Anginyl
Angizem
Anoheal
Apo-Diltiaz
Britiazim
Bruzem
Calcicard
Cardizem
Cardizem CD
Cardizem SR
Cardizen LA
Cartia XT
Citizem
Cormax
Deltazen
Dilacor
Dilacor-XR
Diladel
Dilcontin
Dilpral
Dilrene
Dilt-cd
Dilta-Hexal
Diltia
Dilticard
Dilzem
Dilzen
Endrydil
Herbesser
Incoril AP
Masdil
Novo-Diltazem
Nu-Diltiaz
Syn-Diltiazem
Tiamate
Tiazac
Tiazac Tildiem
Tiazac XC
Viazem
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Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Vasodilator Agents
  • Calcium Channel Blockers
  • Cardiovascular Agents
CAS number 42399-41-7
Weight Average: 414.518
Monoisotopic: 414.16132802
Chemical Formula C22H26N2O4S
InChI Key InChIKey=HSUGRBWQSSZJOP-RTWAWAEBSA-N
InChI
InChI=1S/C22H26N2O4S/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3/h5-12,20-21H,13-14H2,1-4H3/t20-,21+/m1/s1
Plain Text
IUPAC Name
(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate
SMILES
COC1=CC=C(C=C1)[C@@H]1SC2=CC=CC=C2N(CCN(C)C)C(=O)[C@@H]1OC(C)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropylamines
  • Lactams
  • Benzothiazepines
Substructures
  • Carboxylic Acids and Derivatives
  • Ethers
  • Acetates
  • Phenols and Derivatives
  • Amino Ketones
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Lactams
  • Phenyl Esters
  • Anilines
  • Benzothiazepines
Pharmacology
Indication For the treatment of Hypertension
Pharmacodynamics Diltiazem, a benzothiazepine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Diltiazem is a non-dihydropyridine (DHP)member of the calcium channel blocker class, along with Verapamil. Diltiazem is similar to other peripheral vasodilators. Diltiazem inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Mechanism of action Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, diltiazem, like verapamil, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.
Absorption Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect.
Volume of distribution Not Available
Protein binding 70%-80%
Metabolism Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.
Route of elimination Not Available
Half life 3.0 - 4.5 hours
Clearance Not Available
Toxicity LD50=740mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00359 Diltiazem Pathway SMP00359
Pharmacoeconomics
Manufacturers
  • Biovail laboratories inc
  • Watson laboratories inc florida
  • Watson laboratories inc
  • Apotex inc
  • Actavis elizabeth llc
  • Kv pharmaceutical co
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Apotex inc etobicoke site
  • Biovail corp international
  • Biovail laboratories international srl
  • Apotex inc richmond hill
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • International medication systems ltd
  • Taylor pharmacal co
  • Teva parenteral medicines inc
  • Apothecon inc div bristol myers squibb
  • Dava pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Teva pharmaceuticals usa
  • Merck and co inc
Packagers
Dosage forms
Form Route Strength
Capsule, extended release Oral
Liquid Intravenous
Solution Intravenous
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Cormax 0.05% Solution 50ml Bottle 81.6 USD bottle
Cormax 0.05% Solution 25ml Bottle 45.99 USD bottle
Cormax 0.05% Cream 15 gm Tube 43.98 USD tube
Diltiazem hcl 100 mg vial 9.54 USD vial
Diltiazem hcl powder 8.42 USD g
Cardizem CD 360 mg 24 Hour Capsule 7.94 USD capsule
Cardizem cd 360 mg capsule 7.63 USD capsule
Cardizem CD 300 mg 24 Hour Capsule 7.3 USD capsule
Cardizem LA 420 mg 24 Hour tablet 5.56 USD tablet
Cardizem CD 240 mg 24 Hour Capsule 5.48 USD capsule
Cardizem la 420 mg tablet 5.35 USD tablet
Diltiazem HCl Coated Beads 420 mg 24 Hour tablet 5.01 USD tablet
Cardizem la 360 mg tablet 4.94 USD tablet
Cardizem LA 360 mg 24 Hour tablet 4.81 USD tablet
Cardizem LA 300 mg 24 Hour tablet 4.71 USD tablet
Diltiazem HCl Coated Beads 360 mg 24 Hour tablet 4.62 USD tablet
Cardizem la 300 mg tablet 4.59 USD tablet
Diltiazem HCl Coated Beads 300 mg 24 Hour tablet 4.3 USD tablet
Cardizem CD 180 mg 24 Hour Capsule 3.98 USD capsule
Tiazac 420 mg 24 Hour Capsule 3.88 USD capsule
Tiazac 360 mg 24 Hour Capsule 3.7 USD capsule
Cardizem LA 240 mg 24 Hour tablet 3.67 USD tablet
Tiazac 300 mg 24 Hour Capsule 3.64 USD capsule
Cardizem la 240 mg tablet 3.53 USD tablet
Cardizem 120 mg tablet 3.49 USD tablet
Cardizem CD 120 mg 24 Hour Capsule 3.4 USD capsule
Dilacor XR 180 mg 24 Hour Capsule 3.3 USD capsule
Dilacor XR 240 mg 24 Hour Capsule 3.3 USD capsule
Diltiazem HCl Coated Beads 240 mg 24 Hour tablet 3.3 USD tablet
Dilacor xr 240 mg capsule 3.29 USD capsule
Cardizem Cd 300 mg Controlled-Delivery Capsule 3.25 USD capsule
Cardizem la 180 mg tablet 3.15 USD tablet
Cardizem LA 180 mg 24 Hour tablet 3.07 USD tablet
Dilacor xr 180 mg capsule 3.07 USD capsule
Tiazac er 420 mg capsule 3.03 USD capsule
Cardizem la 120 mg tablet 2.98 USD tablet
Diltiazem HCl Coated Beads 180 mg 24 Hour tablet 2.95 USD tablet
Diltiazem HCl ER Beads 420 mg 24 Hour Capsule 2.87 USD capsule
Dilacor XR 120 mg 24 Hour Capsule 2.86 USD capsule
Tiazac er 360 mg capsule 2.86 USD capsule
Tiazac er 300 mg capsule 2.83 USD capsule
Tiazac 240 mg 24 Hour Capsule 2.8 USD capsule
Cartia XT 300 mg 24 Hour Capsule 2.76 USD capsule
Dilt-CD 300 mg 24 Hour Capsule 2.76 USD capsule
Diltiazem HCl Coated Beads 300 mg 24 Hour Capsule 2.76 USD capsule
Cormax 0.05% cream 2.71 USD g
Cartia xt 300 mg capsule 2.66 USD capsule
Dilt-cd er 300 mg capsule 2.66 USD capsule
Dilacor xr 120 mg capsule 2.61 USD capsule
Cardizem Cd 240 mg Controlled-Delivery Capsule 2.6 USD capsule
Diltiazem HCl ER Beads 360 mg 24 Hour Capsule 2.44 USD capsule
Tiazac 360 mg Extended-Release Capsule 2.42 USD capsule
Diltiazem HCl ER Beads 300 mg 24 Hour Capsule 2.39 USD capsule
Cardizem LA 120 mg 24 Hour tablet 2.35 USD tablet
Tiazac 240 mg capsule sa 2.31 USD capsule
Tiazac er 240 mg capsule 2.18 USD capsule
Cardizem cd 300 mg capsule 2.15 USD capsule
Cartia XT 240 mg 24 Hour Capsule 2.13 USD capsule
Diltiazem HCl Coated Beads 240 mg 24 Hour Capsule 2.13 USD capsule
Dilt-cd 240 mg capsule 2.05 USD capsule
Cardizem 90 mg tablet 2.02 USD tablet
Tiazac 180 mg 24 Hour Capsule 1.98 USD capsule
Tiazac 300 mg Extended-Release Capsule 1.98 USD capsule
Cardizem Cd 180 mg Controlled-Delivery Capsule 1.96 USD capsule
Diltiazem HCl ER Beads 240 mg 24 Hour Capsule 1.85 USD capsule
Cardizem sr 120 mg capsule 1.83 USD capsule
Apo-Diltiaz Cd 300 mg Controlled-Delivery Capsule 1.82 USD capsule
Novo-Diltazem Cd 300 mg Controlled-Delivery Capsule 1.82 USD capsule
Ratio-Diltiazem Cd 300 mg Controlled-Delivery Capsule 1.82 USD capsule
Sandoz Diltiazem Cd 300 mg Controlled-Delivery Capsule 1.82 USD capsule
Cardizem cd 240 mg capsule 1.69 USD capsule
Tiazac 120 mg 24 Hour Capsule 1.69 USD capsule
Tiazac 240 mg Extended-Release Capsule 1.61 USD capsule
Tiazac er 180 mg capsule 1.52 USD capsule
Cartia XT 180 mg 24 Hour Capsule 1.5 USD capsule
Dilt-CD 180 mg 24 Hour Capsule 1.5 USD capsule
Diltiazem HCl Coated Beads 180 mg 24 Hour Capsule 1.5 USD capsule
Cardizem Cd 120 mg Controlled-Delivery Capsule 1.48 USD capsule
Apo-Diltiaz Cd 240 mg Controlled-Delivery Capsule 1.46 USD capsule
Novo-Diltazem Cd 240 mg Controlled-Delivery Capsule 1.46 USD capsule
Nu-Diltiaz-Cd 240 mg Controlled-Delivery Capsule 1.46 USD capsule
Ratio-Diltiazem Cd 240 mg Controlled-Delivery Capsule 1.46 USD capsule
Sandoz Diltiazem Cd 240 mg Controlled-Delivery Capsule 1.46 USD capsule
Tiazac Xc 240 mg Extended-Release Tablet 1.46 USD tablet
Tiazac Xc 300 mg Extended-Release Tablet 1.46 USD tablet
Tiazac Xc 360 mg Extended-Release Tablet 1.46 USD tablet
Dilt-cd 180 mg capsule 1.45 USD capsule
Diltiazem HCl 120 mg tablet 1.42 USD tablet
Diltiazem 120 mg tablet 1.36 USD tablet
Apo-Diltiaz Tz 360 mg Extended-Release Capsule 1.36 USD capsule
Novo-Diltiazem Hcl Er 360 mg Extended-Release Capsule 1.36 USD capsule
Sandoz Diltiazem T 360 mg Extended-Release Capsule 1.36 USD capsule
Cardizem 30 mg tablet 1.34 USD tablet
Diltiazem HCl ER Beads 180 mg 24 Hour Capsule 1.3 USD capsule
Diltiazem HCl CR 120 mg 12 Hour Capsule 1.29 USD capsule
Tiazac er 120 mg capsule 1.26 USD capsule
Cartia XT 120 mg 24 Hour Capsule 1.25 USD capsule
Dilt-CD 120 mg 24 Hour Capsule 1.25 USD capsule
Diltiazem HCl Coated Beads 120 mg 24 Hour Capsule 1.25 USD capsule
Cardizem cd 180 mg capsule 1.24 USD capsule
Tiazac 180 mg Extended-Release Capsule 1.21 USD capsule
Cartia xt 120 mg capsule 1.2 USD capsule
Dilt-cd 120 mg capsule 1.2 USD capsule
Diltiazem HCl CR 240 mg 24 Hour Capsule 1.19 USD capsule
Diltia XT 240 mg 24 Hour Capsule 1.17 USD capsule
Diltiazem HCl CR 180 mg 24 Hour Capsule 1.11 USD capsule
Apo-Diltiaz Tz 300 mg Extended-Release Capsule 1.11 USD capsule
Novo-Diltiazem Hcl Er 300 mg Extended-Release Capsule 1.11 USD capsule
Sandoz Diltiazem T 300 mg Extended-Release Capsule 1.11 USD capsule
Tiazac Xc 180 mg Extended-Release Tablet 1.1 USD tablet
Diltia XT 180 mg 24 Hour Capsule 1.1 USD capsule
Apo-Diltiaz Cd 180 mg Controlled-Delivery Capsule 1.1 USD capsule
Novo-Diltazem Cd 180 mg Controlled-Delivery Capsule 1.1 USD capsule
Nu-Diltiaz-Cd 180 mg Controlled-Delivery Capsule 1.1 USD capsule
Ratio-Diltiazem Cd 180 mg Controlled-Delivery Capsule 1.1 USD capsule
Sandoz Diltiazem Cd 180 mg Controlled-Delivery Capsule 1.1 USD capsule
Diltiazem HCl ER Beads 120 mg 24 Hour Capsule 1.08 USD capsule
Diltiazem HCl 90 mg tablet 1.05 USD tablet
Diltiazem 90 mg tablet 1.01 USD tablet
Diltiazem HCl CR 90 mg 12 Hour Capsule 0.99 USD capsule
Cardizem cd 120 mg capsule 0.97 USD capsule
Cardizem 60 mg tablet 0.95 USD tablet
Diltiazem HCl CR 120 mg 24 Hour Capsule 0.95 USD capsule
Apo-Diltiaz Tz 240 mg Extended-Release Capsule 0.9 USD capsule
Novo-Diltiazem Hcl Er 240 mg Extended-Release Capsule 0.9 USD capsule
Sandoz Diltiazem T 240 mg Extended-Release Capsule 0.9 USD capsule
Tiazac 120 mg Extended-Release Capsule 0.89 USD capsule
Diltiazem HCl CR 60 mg 12 Hour Capsule 0.86 USD capsule
Apo-Diltiaz Cd 120 mg Controlled-Delivery Capsule 0.83 USD capsule
Novo-Diltazem Cd 120 mg Controlled-Delivery Capsule 0.83 USD capsule
Nu-Diltiaz-Cd 120 mg Controlled-Delivery Capsule 0.83 USD capsule
Ratio-Diltiazem Cd 120 mg Controlled-Delivery Capsule 0.83 USD capsule
Sandoz Diltiazem Cd 120 mg Controlled-Delivery Capsule 0.83 USD capsule
Tiazac Xc 120 mg Extended-Release Tablet 0.83 USD tablet
Cartia xt 240 mg capsule 0.81 USD capsule
Diltiazem HCl 60 mg tablet 0.77 USD tablet
Diltiazem 60 mg tablet 0.74 USD tablet
Apo-Diltiaz Tz 180 mg Extended-Release Capsule 0.68 USD capsule
Novo-Diltiazem Hcl Er 180 mg Extended-Release Capsule 0.68 USD capsule
Sandoz Diltiazem T 180 mg Extended-Release Capsule 0.68 USD capsule
Cartia xt 180 mg capsule 0.6 USD capsule
Apo-Diltiaz Tz 120 mg Extended-Release Capsule 0.5 USD capsule
Novo-Diltiazem Hcl Er 120 mg Extended-Release Capsule 0.5 USD capsule
Sandoz Diltiazem T 120 mg Extended-Release Capsule 0.5 USD capsule
Diltiazem HCl 30 mg tablet 0.49 USD tablet
Diltiazem 30 mg tablet 0.47 USD tablet
Diltia xt 240 mg capsule 0.43 USD capsule
Diltia xt 180 mg capsule 0.42 USD capsule
Diltiazem-d5w 250 mg/250 ml 0.42 USD ml
Diltia xt 120 mg capsule 0.38 USD capsule
Apo-Diltiaz 60 mg Tablet 0.38 USD tablet
Novo-Diltazem 60 mg Tablet 0.38 USD tablet
Nu-Diltiaz 60 mg Tablet 0.38 USD tablet
Apo-Diltiaz 30 mg Tablet 0.22 USD tablet
Novo-Diltazem 30 mg Tablet 0.22 USD tablet
Nu-Diltiaz 30 mg Tablet 0.22 USD tablet
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6923984 2001-02-25 2021-02-25
United States 5286497 1994-05-20 2011-05-20
Canada 2307547 2007-08-14 2020-05-04
Canada 2111085 1999-04-27 2012-06-25
Properties
State solid
Experimental Properties
Property Value Source
melting point 231 °C Not Available
water solubility 465 mg/L (at 25 °C) MCFARLAND,JW ET AL. (2001)
logP 2.8 Not Available
Caco2 permeability -4.38 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 1.68e-02 g/l ALOGPS
logP 3.09 ALOGPS
logP 2.73 ChemAxon
logS -4.4 ALOGPS
pKa (strongest acidic) 12.86 ChemAxon
pKa (strongest basic) 8.18 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 59.08 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 114.37 ChemAxon
polarizability 43.65 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06958 Link_out
PubChem Compound 39186 Link_out
PubChem Substance 46505667 Link_out
ChemSpider 35850 Link_out
BindingDB 50004704 Link_out
ChEBI 101278 Link_out
ChEMBL 101278 Link_out
Therapeutic Targets Database DAP001262 Link_out
PharmGKB PA449334 Link_out
Drug Product Database 2244728 Link_out
RxList http://www.rxlist.com/cgi/generic/diltiaz.htm Link_out
Drugs.com http://www.drugs.com/diltiazem.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/car1068.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Diltiazem Link_out
ATC Codes
  • C08DB01
AHFS Codes
  • 24:28.92
PDB Entries Not Available
FDA label Not Available
MSDS show (73.2 KB)
Interactions
Drug Interactions
Drug Interaction
Amiodarone Increased risk of cardiotoxicity and arrhythmias
Amlodipine Diltiazem may increase the serum concentration of amlodipine. Concomitant therapy will result in additive hypotensive effects. Monitor for changes in the hypotensive effect of amlodipine if diltiazem is initiated, discontinued or dose changed.
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Atazanavir Atazanavir may increase the therapeutic and adverse effects of diltiazem resulting in increased risk of AV block. Consider alternate therapy, a 50% dose reduction of diltiazem and monitor for changes in the therapeutic and adverse effects of diltiazem if atazanavir is initiated, discontinued or dose changed.
Atenolol Increased risk of bradycardia
Atorvastatin Diltiazem may increase the serum concentration of atorvastatin. Atorvastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Bromazepam Diltiazem may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or a reductin in the bromazepam dose. Monitor for changes in the therapeutic and adverse effects of bromazepam if diltiazem is initiated, discontinued or dose changed.
Buspirone The calcium channel blocker, diltiazem, increases the effect and toxicity of buspirone.
Carbamazepine Carbamazepine may decrease the serum concentration of diltiazem by increasing its metabolism. Diltiazem may increase the serum concentration of carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if dosages are changed.
Cerivastatin Diltiazem may increase the serum concentration of cerivastatin. Cerivastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Cilostazol Diltiazem, a moderate CYP3A4 inhibitor, may increase the serum concentration of cilostazol by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cilostazol if diltiazem is initiated, discontinued or dose changed.
Cisapride Diltiazem, a moderate CYP3A4 inhibitor, may increase the serum concentration of cisapride by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cisapride if diltiazem is initiated, discontinued or dose changed.
Cyclosporine Diltiazem may increase the effect and toxicity of cyclosporine.
Dihydroquinidine barbiturate Increases the effect and toxicity of quinidine
Dronedarone Diltiazem is a moderate CYP3A4 inhibitor and will increase dronedarone levels 1.4-1.7 fold. Decrease doses of non-dihyropyridinic calcium-channel blocker.
Eltrombopag Affects hepatic CYP1A2 metabolism, increases Eltrombopag level or affect.
Lovastatin Diltiazem may increase the serum concentration of lovastatin. Lovastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Metoprolol Increased risk of bradycardia
Midazolam The calcium channel blocker, diltiazem, may increase the effect and toxicity of the benzodiazepine, midazolam.
Moricizine Increased effect/toxicity of moricizine
Pindolol Increased risk of bradycardia
Propranolol Increased risk of bradycardia
Quinidine Diltiazem may increase the serum concentration of quinidine. Monitor for changes in the therapeutic and adverse effects of quinidine if diltiazem is initiated, discontinued or dose changed.
Quinidine barbiturate Increases the effect and toxicity of quinidine
Quinupristin This combination presents an increased risk of toxicity
Ranolazine Diltiazem may increase the serum concentration of ranolazine. Consider alternate therapy or limit ranolazine dose to 500 mg twice daily and monitor for changes in the therapeutic and adverse effects if diltiazem is initiated, discontinued or dose changed.
Rifampin Rifampin decreases levels of diltiazem
Ritonavir Ritonavir increases diltiazem levels
Saxagliptin Diltiazem is a moderate inhibitor of CYP3A4 and increases AUC of saxagliptin by 109%. Exposure of the active metabolite decreased by 34%. However, these changes in pharmacokinetics are not clinical significant.
Simvastatin Diltiazem may increase the serum concentration of simvastatin. Simvastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Sirolimus Increases the effect and toxicity of sirolimus
Tacrolimus Diltiazem may increase the serum concentration of tacrolimus by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of tacrolimus if diltiazem therapy is initiated, discontinued or dose changed.
Tamsulosin Diltiazem, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Diltiazem is initiated, discontinued, or dose changed.
Telithromycin Telithromycin may reduce clearance of Diltiazem. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Diltiazem if Telithromycin is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Diltiazem, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Diltiazem if Thiopental is initiated, discontinued or dose changed.
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Timolol Additive effects of decreased heart rate and contractility may occur. Increased risk of heart block.
Tipranavir Tipranavir, co-administered with Ritonavir, may alter the concentration of Diltiazem. Monitor for efficacy and adverse/toxic effects of Diltiazem.
Tolterodine Diltiazem may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tolvaptan Diltiazem is a moderate inhibitor of CYP3A4 and will considerably increase tolvaptan serum concentrations
Tramadol Diltiazem may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inhibitor, Diltizem, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Diltiazem is initiated, discontinued or dose changed.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Triazolam The calcium channel blocker, diltiazem, may increase the effect and toxicity of the benzodiazepine, triazolam.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of diltiazem by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of diltiazem if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Avoid natural licorice.
  • Take this medication 30 minutes before meals.
Targets

1. Voltage-dependent calcium channel gamma-1 subunit

Pharmacological action: yes
Actions: inhibitor

This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex

Organism class: human
UniProt ID: Q06432 Link_out
Gene: CACNG1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Budriesi R, Ioan P, Carosati E, Cruciani G, Zhorov BS, Chiarini A: Ligands of diltiazem binding site: an overview of some chemotypes. Mini Rev Med Chem. 2009 Oct;9(12):1379-88. Pubmed
  4. Romero M, Sanchez I, Pujol MD: New advances in the field of calcium channel antagonists: cardiovascular effects and structure-activity relationships. Curr Med Chem Cardiovasc Hematol Agents. 2003 Jun;1(2):113-41. Pubmed

Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. Pubmed

2. Cytochrome P450 3A5

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kosuge K, Jun Y, Watanabe H, Kimura M, Nishimoto M, Ishizaki T, Ohashi K: Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Drug Metab Dispos. 2001 Oct;29(10):1284-9. Pubmed
  2. McGinnity DF, Parker AJ, Soars M, Riley RJ: Automated definition of the enzymology of drug oxidation by the major human drug metabolizing cytochrome P450s. Drug Metab Dispos. 2000 Nov;28(11):1327-34. Pubmed

5. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2C9

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
  2. Takara K, Sakaeda T, Tanigawara Y, Nishiguchi K, Ohmoto N, Horinouchi M, Komada F, Ohnishi N, Yokoyama T, Okumura K: Effects of 12 Ca2+ antagonists on multidrug resistance, MDR1-mediated transport and MDR1 mRNA expression. Eur J Pharm Sci. 2002 Aug;16(3):159-65. Pubmed
  3. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T: P-glycoprotein-mediated transcellular transport of MDR-reversing agents. FEBS Lett. 1993 Jun 7;324(1):99-102. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19