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药品详细

Verapamil(维拉帕米)

化学结构式图
中文名
维拉帕米
英文名
Verapamil
分子式
C27H38N2O4
化学名
2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
分子量
Average: 454.6016
Monoisotopic: 454.283157714
CAS号
52-53-9
ATC分类
C08D 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

A calcium channel blocker that is a class IV anti-arrhythmia agent. [PubChem]

生产厂家
  • Abraxis pharmaceutical products
  • Actavis elizabeth llc
  • Bedford laboratories div ben venue laboratories inc
  • Elan drug delivery inc
  • Fsc laboratories inc
  • Gd searle llc
  • Glenmark generics ltd
  • Heritage pharmaceuticals inc
  • Hospira inc
  • International medication system
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Luitpold pharmaceuticals inc
  • Marsam pharmaceuticals llc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Pliva inc
  • Ranbaxy laboratories inc
  • Sandoz inc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Warner chilcott div warner lambert co
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Catecholamines and Derivatives
Substructures
  • Phenols and Derivatives
  • Nitriles and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Cumenes and Derivatives
  • Cyanides
  • Aliphatic and Aryl Amines
  • Catechols
  • Phenethylamines
  • Aromatic compounds
  • Anisoles
  • Phenyl Esters
  • Catecholamines and Derivatives
适应症
药理
Indication For the treatment of hypertension, angina, and cluster headache prophylaxis.
Pharmacodynamics Verapamil is an L-type calcium channel blocker that also has antiarrythmic activity. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias.
Mechanism of action Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known.
Absorption 90%
Volume of distribution Not Available
Protein binding 90%
Metabolism
Not Available

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Verapamil
O-Desmethylverapamil (D-702) Details
Verapamil
D-617 Details
Verapamil
Norverapamil Details
Verapamil
O-Desmethylverapamil (D-703) Details
Verapamil
    		O-Desmethylverapamil Details
    Route of elimination Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days. About 3% to 4% is excreted in the urine as unchanged drug.
    Half life 2.8-7.4 hours
    Clearance Not Available
    Toxicity LD50=8 mg/kg (i.v. in mice)
    Affected organisms
    • Humans and other mammals
    Pathways
    Pathway Name SMPDB ID
    Smp00375 Verapamil Pathway SMP00375
    理化性质
    Properties
    State liquid
    Experimental Properties
    Property Value Source
    melting point < 25 °C PhysProp
    boiling point 243-246 °C at 1.00E-02 mm Hg PhysProp
    water solubility 4.47 mg/L Not Available
    logP 3.79 HANSCH,C ET AL. (1995)
    Caco2 permeability -4.58 ADME Research, USCD
    pKa 8.92 SANGSTER (1994)
    Predicted Properties
    Property Value Source
    water solubility 3.94e-03 g/l ALOGPS
    logP 5.23 ALOGPS
    logP 5.04 ChemAxon
    logS -5.1 ALOGPS
    pKa (strongest basic) 9.68 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 6 ChemAxon
    hydrogen donor count 0 ChemAxon
    polar surface area 63.95 ChemAxon
    rotatable bond count 13 ChemAxon
    refractivity 132.65 ChemAxon
    polarizability 51.7 ChemAxon
    药物相互作用
    Drug Interaction
    Acebutolol Increased effect of both drugs
    Amifostine Verapamil may enhance the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Verapamil should be withheld for 24 hours prior to Amifostine administration. Caution should be used at lower Amifostine doses used during radiotherapy, but routine interruption of Verapamil therapy is not recommended.
    Aminophylline Verapamil increases the effect of theophylline
    Amiodarone Additive bradycardic effects may occur. One case report of sinus arrest has been reported. Monitor for changes in the therapeutic effect and signs of Verapamil toxicity if Amiodarone is initiated, discontinued or dose changed.
    Amobarbital Amobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Amobarbital is initiated, discontinued or dose changed.
    Amprenavir Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Amprenavir is initiated, discontinued or dose changed.
    Atazanavir Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Atazanavir is initiated, discontinued or dose changed.
    Atenolol Increased effect of both drugs
    Atorvastatin Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Atorvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce lovastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Atorvastatin if Verapamil is initiated, discontinued or dose changed.
    Bisoprolol Increased effect of both drugs
    Bromazepam Verapamil 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 verapamil is initiated, discontinued or dose changed.
    Buspirone Verapamil may increase the serum concentration of Buspirone. The likely occurs via Verapamil-mediated CYP3A4 inhibition resulting in decreased Buspirone metabolism. Monitor for changes in the therapeutic/adverse effects of Buspirone if Verpamil is initiated, discontinued or dose changed.
    Butabarbital Butabarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Butabarbital is initiated, discontinued or dose changed.
    Butalbital Butalbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Butalbital is initiated, discontinued or dose changed.
    Carbamazepine Verapamil may increase the serum concentration of Carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Carbamazepine if Verapamil is initiated, discontinued or dose changed.
    Carvedilol Increased effect of both drugs
    Clarithromycin Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Clarithromycin is initiated, discontinued or dose changed.
    Colchicine Verapamil may increase the serum concentration of Colchicine. This likely occurs via Verapamil-mediated inhibition of CYP3A4 and p-glycoprotein-mediated transport. Monitor for changes in the therapeutic/adverse effects of Colchicine if Verapamil is initiated, discontinued or dose changed.
    Conivaptan Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Conivaptan is initiated, discontinued or dose changed.
    Cyclosporine Verapamil may increase the serum concentration of cyclosporine by inhibiting CYP3A4-mediated metabolism of cyclosporine. Monitor for changes in the therapeutic/adverse effects of cyclosporine if verapamil is initiated, discontinued or dose changed.
    Dabigatran etexilate Verapamil may increase serum concentrations of the active metabolite(s) of dabigatran etexilate, resulting in an increased risk of bleeding. It is also a strong p-glycoprotein inhibitor. Therapy modification should be considered.
    Darunavir Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Darunavir is initiated, discontinued or dose changed.
    Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Delavirdine is initiated, discontinued or dose changed.
    Digitoxin Verapamil may increase the serum concentration of Digitoxin by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of Digitoxin if Verpamail is initiated, discontinued or dose changed.
    Digoxin Verapamil may increase the serum concentration of Digoxin by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of Digoxin if Verpamail is initiated, discontinued or dose changed.
    Dofetilide Verapamil may increase the plamsa levels of Dofetilide. Increased risk of torsade de pointes. Concomitant therapy is contraindicated.
    Dronedarone Verapamil is a moderate CYP3A4 inhibitor and will increase dronedarone levels 1.4-1.7 fold. Decrease doses of non-dihyropyridinic calcium-channel blocker.
    Eplerenone This CYP3A4 inhibitor increases the effect and toxicity of eplerenone
    Erythromycin Erythromycin, a moderate CYP3A4 inhibitor, may increase the serum concentration of veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of verapamil if erythromycin is initiated, discontinued or dose changed.
    Esmolol Increased effect of both drugs
    Everolimus Concomitant administration may increase the serum concentrations of both agents. Concurrent use should be avoided.
    Fluconazole Fluconazole may increase the serum concentration of Verapamil by decreasing Verapamil metabolism. This likely occurs via Fluconazole-mediated CYP3A4 inhibition. Monitor for changes in the therapeutic/adverse effects of Verapamil if Fluconazole is initiated, discontinued, or dose changed.
    Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Fosamprenavir is initiated, discontinued or dose changed.
    Halofantrine Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Halofantrine by decreasing its metabolism. Extreme caution with increased cardiac status monitoring should be used during concomitant therapy.
    Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Imatinib is initiated, discontinued or dose changed.
    Indacaterol Strong inhibitors of CYP3A4 may increase levels of indacaterol. Monitor closely for adverse events.
    Indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Indinavir is initiated, discontinued or dose changed.
    Isoniazid Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Isoniazid is initiated, discontinued or dose changed.
    Itraconazole Itraconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Itraconazole is initiated, discontinued or dose changed.
    Ketoconazole Ketoconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Ketoconazole is initiated, discontinued or dose changed.
    Labetalol Increased effect of both drugs
    Lithium Signs of lithium toxicity
    Lopinavir Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Lopinavir is initiated, discontinued or dose changed.
    Lovastatin Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Lovastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce lovastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Lovastatin if Verapamil is initiated, discontinued or dose changed.
    Methohexital Methohexital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Methohexital is initiated, discontinued or dose changed.
    Methylphenobarbital Methylphenobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Methylphenobarbital is initiated, discontinued or dose changed.
    Metoprolol Increased effect of both drugs
    Miconazole Miconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Miconazole is initiated, discontinued or dose changed.
    Midazolam Verapamil may increase the serum concentration of Midazolam by decreasing its metabolism. Avoid concomitant therapy if possible or consider a dose reduction in the initial dose of Midazolam.
    Nadolol Increased effect of both drugs
    Nafcillin Nafcillin may decrease the serum concentration of Verapamil by increasing its metabolism via CYP3A4. Monitor for changes in the therapeutic/adverse effects of Verapamil if Nafcillin is initiated, discontinued or dose changed.
    Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Nefazodone is initiated, discontinued or dose changed.
    Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Nelfinavir is initiated, discontinued or dose changed.
    Nicardipine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Nicardipine is initiated, discontinued or dose changed.
    Oxprenolol Increased effect of both drugs
    Oxtriphylline Verapamil increases the effect of theophylline
    Pentobarbital Pentobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Pentobarbital is initiated, discontinued or dose changed.
    Phenobarbital Phenobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Phenobarbital is initiated, discontinued or dose changed.
    Phenytoin Verapamil may increase the serum concentration of Phenytoin by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Phenytoin if Verapamil is initiated, discontinued or dose changed.
    Pindolol Increased effect of both drugs
    Posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Posaconazole is initiated, discontinued or dose changed.
    Prazosin Risk of hypotension at the beginning of therapy
    Primidone The barbiturate, primidone, decreases the effect of the calcium channel blocker, verapamil.
    Propranolol Increased effect of both drugs
    Quinidine Concurrent therapy may result in increased serum levels of both agents. Both agents are CYP3A4 inhibitors and substrates. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of the agent if the other is initiated, discontinued or dose changed.
    Quinupristin This combination presents an increased risk of toxicity
    Ranolazine Verapamil, a CYP3A4 inhibitor, may increase the serum concentration of Ranolazine. Concomitant therapy is contraindicated.
    Rifabutin Rifabutin, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifabutin is initiated, discontinued or dose changed.
    Rifampin Rifampin, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifampin is initiated, discontinued or dose changed.
    Rifapentine Rifapentine, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifapentine is initiated, discontinued or dose changed.
    Ritonavir Ritonavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Ritonavir is initiated, discontinued or dose changed.
    Rituximab Verapamil may increase the hypotensive effects of Rituximab. Consider withholding Verapamil therapy for 12 hours prior to Rituximab infusion.
    Saquinavir Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Saquinavir is initiated, discontinued or dose changed.
    Secobarbital Secobarbital, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Secobarbital is initiated, discontinued or dose changed.
    Silodosin Verapamil is a moderate inhibitor of CYP3A4 and inhibits P-glycoprotein thus increasing the potential for adverse effects
    Simvastatin Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Simvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce Simvastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Simvastatin if Verapamil is initiated, discontinued or dose changed.
    Tacrolimus The calcium channel blocker, Verapamil, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Verapamil therapy is initiated, discontinued or altered.
    Tamsulosin Verapamil, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Verapamil is initiated, discontinued, or dose changed.
    Telithromycin Telithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Telithromycin is initiated, discontinued or dose changed.
    Terfenadine Increased risk of cardiotoxicity and arrhythmias
    Theophylline Verapamil increases the effect of theophylline
    Thiopental Thiopental, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Thiopental is initiated, discontinued or dose changed.
    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 Verapamil. Monitor for efficacy and adverse/toxic effects of Verapamil.
    Tolterodine Verapamil may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
    Tolvaptan Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Tolvaptan. Concomitant therapy is contraindicated.
    Topotecan The p-glycoprotein inhibitor, Verapamil, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
    Tramadol Verapamil may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
    Trazodone The CYP3A4 inhibitor, Verapamil, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Verapamil is initiated, discontinued or dose changed.
    Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
    Triazolam Verapamil may increase the serum concentration of Triazolam by decreasing its metabolism. Avoid concomitant therapy if possible or consider a dose reduction in the initial dose of Triazolam.
    Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of verapamil by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of verapamil if voriconazole is initiated, discontinued or dose changed.
    食物相互作用
    • Avoid alcohol.
    • Avoid excessive quantities of coffee or tea (Caffeine).
    • Avoid natural licorice.
    • Avoid taking with grapefruit juice.
    • Take with food.

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