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Identification
NameDiltiazem
Accession NumberDB00343  (APRD00473)
Typesmall molecule
Groupsapproved
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
SynonymsNot Available
Salts
Name/CAS Structure Properties
Diltiazem hydrochloride
Thumb Not applicable DBSALT000865
Brand names
NameCompany
AcalixNot Available
AdizemNot Available
AltiazemNot Available
AnohealNot Available
CalcicardNot Available
CardizemNot Available
Cartia XTNot Available
Dilacor-XRNot Available
DilcontinNot Available
DilreneNot Available
Diltia XTNot Available
DilticardNot Available
DilzemNot Available
HerbesserNot Available
Incoril APNot Available
MasdilNot Available
SurazemNot Available
TiazacNot Available
ViazemNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number42399-41-7
WeightAverage: 414.518
Monoisotopic: 414.16132802
Chemical FormulaC22H26N2O4S
InChI KeyInChIKey=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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzothiazepines
SubclassNot Available
Direct parentBenzothiazepines
Alternative parentsAnisoles; Alkyl Aryl Ethers; Tertiary Carboxylic Acid Amides; Tertiary Amines; Carboxylic Acid Esters; Enolates; Carboxylic Acids; Polyamines; Thioethers
Substituentsphenol ether; anisole; alkyl aryl ether; benzene; tertiary carboxylic acid amide; tertiary amine; carboxamide group; carboxylic acid ester; thioether; polyamine; ether; carboxylic acid; enolate; carboxylic acid derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzothiazepines. These are organic compounds containing a benzene fused to a thiazepine ring (a seven-member ring with a nitrogen atom and a sulfur atom replacing two carbon atoms).
Pharmacology
IndicationFor the treatment of Hypertension
PharmacodynamicsDiltiazem, 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 actionPossibly 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.
AbsorptionDiltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect.
Volume of distributionNot Available
Protein binding70%-80%
Metabolism

Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.

SubstrateEnzymesProduct
Diltiazem
N-DesmethyldiltiazemDetails
Route of eliminationNot Available
Half life3.0 - 4.5 hours
ClearanceNot Available
ToxicityLD50=740mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Diltiazem Action PathwayDrug actionSMP00359
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Beta-1 adrenergic receptor
Gene symbol: ADRB1
UniProt: P08588
rs1801253 Not AvailableG > CBetter response to drug therapy22192668
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9788
Blood Brain Barrier + 0.506
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.8645
P-glycoprotein inhibitor I Inhibitor 0.8675
P-glycoprotein inhibitor II Inhibitor 0.8997
Renal organic cation transporter Non-inhibitor 0.7634
CYP450 2C9 substrate Non-substrate 0.699
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Substrate 0.7407
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Inhibitor 0.796
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8681
Ames test Non AMES toxic 0.6985
Carcinogenicity Non-carcinogens 0.8772
Biodegradation Not ready biodegradable 0.9951
Rat acute toxicity 2.4130 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9971
hERG inhibition (predictor II) Inhibitor 0.7723
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
FormRouteStrength
Capsule, extended releaseOral
LiquidIntravenous
SolutionIntravenous
TabletOral
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Cormax 0.05% Solution 50ml Bottle81.6USDbottle
Cormax 0.05% Solution 25ml Bottle45.99USDbottle
Cormax 0.05% Cream 15 gm Tube43.98USDtube
Diltiazem hcl 100 mg vial9.54USDvial
Diltiazem hcl powder8.42USDg
Cardizem CD 360 mg 24 Hour Capsule7.94USDcapsule
Cardizem cd 360 mg capsule7.63USDcapsule
Cardizem CD 300 mg 24 Hour Capsule7.3USDcapsule
Cardizem LA 420 mg 24 Hour tablet5.56USDtablet
Cardizem CD 240 mg 24 Hour Capsule5.48USDcapsule
Cardizem la 420 mg tablet5.35USDtablet
Diltiazem HCl Coated Beads 420 mg 24 Hour tablet5.01USDtablet
Cardizem la 360 mg tablet4.94USDtablet
Cardizem LA 360 mg 24 Hour tablet4.81USDtablet
Cardizem LA 300 mg 24 Hour tablet4.71USDtablet
Diltiazem HCl Coated Beads 360 mg 24 Hour tablet4.62USDtablet
Cardizem la 300 mg tablet4.59USDtablet
Diltiazem HCl Coated Beads 300 mg 24 Hour tablet4.3USDtablet
Cardizem CD 180 mg 24 Hour Capsule3.98USDcapsule
Tiazac 420 mg 24 Hour Capsule3.88USDcapsule
Tiazac 360 mg 24 Hour Capsule3.7USDcapsule
Cardizem LA 240 mg 24 Hour tablet3.67USDtablet
Tiazac 300 mg 24 Hour Capsule3.64USDcapsule
Cardizem la 240 mg tablet3.53USDtablet
Cardizem 120 mg tablet3.49USDtablet
Cardizem CD 120 mg 24 Hour Capsule3.4USDcapsule
Dilacor XR 180 mg 24 Hour Capsule3.3USDcapsule
Dilacor XR 240 mg 24 Hour Capsule3.3USDcapsule
Diltiazem HCl Coated Beads 240 mg 24 Hour tablet3.3USDtablet
Dilacor xr 240 mg capsule3.29USDcapsule
Cardizem Cd 300 mg Controlled-Delivery Capsule3.25USDcapsule
Cardizem la 180 mg tablet3.15USDtablet
Cardizem LA 180 mg 24 Hour tablet3.07USDtablet
Dilacor xr 180 mg capsule3.07USDcapsule
Tiazac er 420 mg capsule3.03USDcapsule
Cardizem la 120 mg tablet2.98USDtablet
Diltiazem HCl Coated Beads 180 mg 24 Hour tablet2.95USDtablet
Diltiazem HCl ER Beads 420 mg 24 Hour Capsule2.87USDcapsule
Dilacor XR 120 mg 24 Hour Capsule2.86USDcapsule
Tiazac er 360 mg capsule2.86USDcapsule
Tiazac er 300 mg capsule2.83USDcapsule
Tiazac 240 mg 24 Hour Capsule2.8USDcapsule
Cartia XT 300 mg 24 Hour Capsule2.76USDcapsule
Dilt-CD 300 mg 24 Hour Capsule2.76USDcapsule
Diltiazem HCl Coated Beads 300 mg 24 Hour Capsule2.76USDcapsule
Cormax 0.05% cream2.71USDg
Cartia xt 300 mg capsule2.66USDcapsule
Dilt-cd er 300 mg capsule2.66USDcapsule
Dilacor xr 120 mg capsule2.61USDcapsule
Cardizem Cd 240 mg Controlled-Delivery Capsule2.6USDcapsule
Diltiazem HCl ER Beads 360 mg 24 Hour Capsule2.44USDcapsule
Tiazac 360 mg Extended-Release Capsule2.42USDcapsule
Diltiazem HCl ER Beads 300 mg 24 Hour Capsule2.39USDcapsule
Cardizem LA 120 mg 24 Hour tablet2.35USDtablet
Tiazac 240 mg capsule sa2.31USDcapsule
Tiazac er 240 mg capsule2.18USDcapsule
Cardizem cd 300 mg capsule2.15USDcapsule
Cartia XT 240 mg 24 Hour Capsule2.13USDcapsule
Diltiazem HCl Coated Beads 240 mg 24 Hour Capsule2.13USDcapsule
Dilt-cd 240 mg capsule2.05USDcapsule
Cardizem 90 mg tablet2.02USDtablet
Tiazac 180 mg 24 Hour Capsule1.98USDcapsule
Tiazac 300 mg Extended-Release Capsule1.98USDcapsule
Cardizem Cd 180 mg Controlled-Delivery Capsule1.96USDcapsule
Diltiazem HCl ER Beads 240 mg 24 Hour Capsule1.85USDcapsule
Cardizem sr 120 mg capsule1.83USDcapsule
Apo-Diltiaz Cd 300 mg Controlled-Delivery Capsule1.82USDcapsule
Novo-Diltazem Cd 300 mg Controlled-Delivery Capsule1.82USDcapsule
Ratio-Diltiazem Cd 300 mg Controlled-Delivery Capsule1.82USDcapsule
Sandoz Diltiazem Cd 300 mg Controlled-Delivery Capsule1.82USDcapsule
Cardizem cd 240 mg capsule1.69USDcapsule
Tiazac 120 mg 24 Hour Capsule1.69USDcapsule
Tiazac 240 mg Extended-Release Capsule1.61USDcapsule
Tiazac er 180 mg capsule1.52USDcapsule
Cartia XT 180 mg 24 Hour Capsule1.5USDcapsule
Dilt-CD 180 mg 24 Hour Capsule1.5USDcapsule
Diltiazem HCl Coated Beads 180 mg 24 Hour Capsule1.5USDcapsule
Cardizem Cd 120 mg Controlled-Delivery Capsule1.48USDcapsule
Apo-Diltiaz Cd 240 mg Controlled-Delivery Capsule1.46USDcapsule
Novo-Diltazem Cd 240 mg Controlled-Delivery Capsule1.46USDcapsule
Nu-Diltiaz-Cd 240 mg Controlled-Delivery Capsule1.46USDcapsule
Ratio-Diltiazem Cd 240 mg Controlled-Delivery Capsule1.46USDcapsule
Sandoz Diltiazem Cd 240 mg Controlled-Delivery Capsule1.46USDcapsule
Tiazac Xc 240 mg Extended-Release Tablet1.46USDtablet
Tiazac Xc 300 mg Extended-Release Tablet1.46USDtablet
Tiazac Xc 360 mg Extended-Release Tablet1.46USDtablet
Dilt-cd 180 mg capsule1.45USDcapsule
Diltiazem HCl 120 mg tablet1.42USDtablet
Diltiazem 120 mg tablet1.36USDtablet
Apo-Diltiaz Tz 360 mg Extended-Release Capsule1.36USDcapsule
Novo-Diltiazem Hcl Er 360 mg Extended-Release Capsule1.36USDcapsule
Sandoz Diltiazem T 360 mg Extended-Release Capsule1.36USDcapsule
Cardizem 30 mg tablet1.34USDtablet
Diltiazem HCl ER Beads 180 mg 24 Hour Capsule1.3USDcapsule
Diltiazem HCl CR 120 mg 12 Hour Capsule1.29USDcapsule
Tiazac er 120 mg capsule1.26USDcapsule
Cartia XT 120 mg 24 Hour Capsule1.25USDcapsule
Dilt-CD 120 mg 24 Hour Capsule1.25USDcapsule
Diltiazem HCl Coated Beads 120 mg 24 Hour Capsule1.25USDcapsule
Cardizem cd 180 mg capsule1.24USDcapsule
Tiazac 180 mg Extended-Release Capsule1.21USDcapsule
Cartia xt 120 mg capsule1.2USDcapsule
Dilt-cd 120 mg capsule1.2USDcapsule
Diltiazem HCl CR 240 mg 24 Hour Capsule1.19USDcapsule
Diltia XT 240 mg 24 Hour Capsule1.17USDcapsule
Diltiazem HCl CR 180 mg 24 Hour Capsule1.11USDcapsule
Apo-Diltiaz Tz 300 mg Extended-Release Capsule1.11USDcapsule
Novo-Diltiazem Hcl Er 300 mg Extended-Release Capsule1.11USDcapsule
Sandoz Diltiazem T 300 mg Extended-Release Capsule1.11USDcapsule
Tiazac Xc 180 mg Extended-Release Tablet1.1USDtablet
Diltia XT 180 mg 24 Hour Capsule1.1USDcapsule
Apo-Diltiaz Cd 180 mg Controlled-Delivery Capsule1.1USDcapsule
Novo-Diltazem Cd 180 mg Controlled-Delivery Capsule1.1USDcapsule
Nu-Diltiaz-Cd 180 mg Controlled-Delivery Capsule1.1USDcapsule
Ratio-Diltiazem Cd 180 mg Controlled-Delivery Capsule1.1USDcapsule
Sandoz Diltiazem Cd 180 mg Controlled-Delivery Capsule1.1USDcapsule
Diltiazem HCl ER Beads 120 mg 24 Hour Capsule1.08USDcapsule
Diltiazem HCl 90 mg tablet1.05USDtablet
Diltiazem 90 mg tablet1.01USDtablet
Diltiazem HCl CR 90 mg 12 Hour Capsule0.99USDcapsule
Cardizem cd 120 mg capsule0.97USDcapsule
Cardizem 60 mg tablet0.95USDtablet
Diltiazem HCl CR 120 mg 24 Hour Capsule0.95USDcapsule
Apo-Diltiaz Tz 240 mg Extended-Release Capsule0.9USDcapsule
Novo-Diltiazem Hcl Er 240 mg Extended-Release Capsule0.9USDcapsule
Sandoz Diltiazem T 240 mg Extended-Release Capsule0.9USDcapsule
Tiazac 120 mg Extended-Release Capsule0.89USDcapsule
Diltiazem HCl CR 60 mg 12 Hour Capsule0.86USDcapsule
Apo-Diltiaz Cd 120 mg Controlled-Delivery Capsule0.83USDcapsule
Novo-Diltazem Cd 120 mg Controlled-Delivery Capsule0.83USDcapsule
Nu-Diltiaz-Cd 120 mg Controlled-Delivery Capsule0.83USDcapsule
Ratio-Diltiazem Cd 120 mg Controlled-Delivery Capsule0.83USDcapsule
Sandoz Diltiazem Cd 120 mg Controlled-Delivery Capsule0.83USDcapsule
Tiazac Xc 120 mg Extended-Release Tablet0.83USDtablet
Cartia xt 240 mg capsule0.81USDcapsule
Diltiazem HCl 60 mg tablet0.77USDtablet
Diltiazem 60 mg tablet0.74USDtablet
Apo-Diltiaz Tz 180 mg Extended-Release Capsule0.68USDcapsule
Novo-Diltiazem Hcl Er 180 mg Extended-Release Capsule0.68USDcapsule
Sandoz Diltiazem T 180 mg Extended-Release Capsule0.68USDcapsule
Cartia xt 180 mg capsule0.6USDcapsule
Apo-Diltiaz Tz 120 mg Extended-Release Capsule0.5USDcapsule
Novo-Diltiazem Hcl Er 120 mg Extended-Release Capsule0.5USDcapsule
Sandoz Diltiazem T 120 mg Extended-Release Capsule0.5USDcapsule
Diltiazem HCl 30 mg tablet0.49USDtablet
Diltiazem 30 mg tablet0.47USDtablet
Diltia xt 240 mg capsule0.43USDcapsule
Diltia xt 180 mg capsule0.42USDcapsule
Diltiazem-d5w 250 mg/250 ml0.42USDml
Diltia xt 120 mg capsule0.38USDcapsule
Apo-Diltiaz 60 mg Tablet0.38USDtablet
Novo-Diltazem 60 mg Tablet0.38USDtablet
Nu-Diltiaz 60 mg Tablet0.38USDtablet
Apo-Diltiaz 30 mg Tablet0.22USDtablet
Novo-Diltazem 30 mg Tablet0.22USDtablet
Nu-Diltiaz 30 mg Tablet0.22USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States69239842001-02-252021-02-25
United States52864971994-05-202011-05-20
Canada23075472007-08-142020-05-04
Canada21110851999-04-272012-06-25
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point231 °CNot Available
water solubility465 mg/L (at 25 °C)MCFARLAND,JW ET AL. (2001)
logP2.8Not Available
Caco2 permeability-4.38ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility1.68e-02 g/lALOGPS
logP3.09ALOGPS
logP2.73ChemAxon
logS-4.4ALOGPS
pKa (strongest acidic)12.86ChemAxon
pKa (strongest basic)8.18ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count0ChemAxon
polar surface area59.08ChemAxon
rotatable bond count7ChemAxon
refractivity114.37ChemAxon
polarizability43.65ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US3562257
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC06958
PubChem Compound39186
PubChem Substance46505667
ChemSpider35850
BindingDB50004704
ChEBI101278
ChEMBLCHEMBL23
Therapeutic Targets DatabaseDAP001262
PharmGKBPA449334
Drug Product Database2244728
RxListhttp://www.rxlist.com/cgi/generic/diltiaz.htm
Drugs.comhttp://www.drugs.com/diltiazem.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/car1068.shtml
WikipediaDiltiazem
ATC CodesC08DB01
AHFS Codes
  • 24:28.92
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.2 KB)
Interactions
Drug Interactions
Drug
AmiodaroneIncreased risk of cardiotoxicity and arrhythmias
AmlodipineDiltiazem 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.
AprepitantThis CYP3A4 inhibitor increases the effect and toxicity of aprepitant
AtazanavirAtazanavir 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.
AtenololIncreased risk of bradycardia
AtorvastatinDiltiazem 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.
BromazepamDiltiazem 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.
BuspironeThe calcium channel blocker, diltiazem, increases the effect and toxicity of buspirone.
CarbamazepineCarbamazepine 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.
CerivastatinDiltiazem 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.
CilostazolDiltiazem, 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.
CisaprideDiltiazem, 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.
CyclosporineDiltiazem may increase the effect and toxicity of cyclosporine.
Dihydroquinidine barbiturateIncreases the effect and toxicity of quinidine
DronedaroneDiltiazem is a moderate CYP3A4 inhibitor and will increase dronedarone levels 1.4-1.7 fold. Decrease doses of non-dihyropyridinic calcium-channel blocker.
EltrombopagAffects hepatic CYP1A2 metabolism, increases Eltrombopag level or affect.
LovastatinDiltiazem 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.
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
MetoprololIncreased risk of bradycardia
MidazolamThe calcium channel blocker, diltiazem, may increase the effect and toxicity of the benzodiazepine, midazolam.
MoricizineIncreased effect/toxicity of moricizine
PindololIncreased risk of bradycardia
PropranololIncreased risk of bradycardia
QuinidineDiltiazem 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 barbiturateIncreases the effect and toxicity of quinidine
QuinupristinThis combination presents an increased risk of toxicity
RanolazineDiltiazem 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.
RifampicinRifampin decreases levels of diltiazem
RitonavirRitonavir increases diltiazem levels
SaxagliptinDiltiazem 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.
SilodosinModerate inhibitors of CYP3A4 may increase levels of silodosin. Monitor concomitant therapy closely.
SimvastatinDiltiazem 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.
SirolimusIncreases the effect and toxicity of sirolimus
TacrolimusDiltiazem 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.
TamsulosinDiltiazem, 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.
TelithromycinTelithromycin 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.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
ThiopentalThe 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.
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
TimololAdditive effects of decreased heart rate and contractility may occur. Increased risk of heart block.
TipranavirTipranavir, co-administered with Ritonavir, may alter the concentration of Diltiazem. Monitor for efficacy and adverse/toxic effects of Diltiazem.
TolterodineDiltiazem may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
TolvaptanDiltiazem is a moderate inhibitor of CYP3A4 and will considerably increase tolvaptan serum concentrations
TramadolDiltiazem may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
TrazodoneThe 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.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TriazolamThe calcium channel blocker, diltiazem, may increase the effect and toxicity of the benzodiazepine, triazolam.
VoriconazoleVoriconazole, 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.

1. Voltage-dependent calcium channel gamma-1 subunit

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel gamma-1 subunit Q06432 Details

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

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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 October 08, 2013 14:23