Tìm theo
Venlafaxine
Các tên gọi khác (4 ) :
  • Elafax
  • Venlafaxina
  • Venlafaxine
  • Venlafaxinum
Thuốc điều trị về tâm thần
Thuốc Gốc
Small Molecule
CAS: 93413-69-5
ATC: N06AX16, N06AX23
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C17H27NO2
PTK: 277.4018
Venlafaxine (Effexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. It is prescribed for the treatment of clinical depression and anxiety disorders. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs. Venlafaxine was the sixth most widely-used antidepressant based on the amount of retail prescriptions in the US (17.1 million) in 2006. [Wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C17H27NO2
Phân tử khối
277.4018
Monoisotopic mass
277.204179113
InChI
InChI=1S/C17H27NO2/c1-18(2)13-16(17(19)11-5-4-6-12-17)14-7-9-15(20-3)10-8-14/h7-10,16,19H,4-6,11-13H2,1-3H3
InChI Key
InChIKey=PNVNVHUZROJLTJ-UHFFFAOYSA-N
IUPAC Name
1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol
Traditional IUPAC Name
venlafaxine
SMILES
COC1=CC=C(C=C1)C(CN(C)C)C1(O)CCCCC1
Độ tan chảy
215-217 °C (Hydrochloride salt)
Độ hòa tan
572 mg/ml (Hydrochloride salt)
logP
2.74
logS
-3.1
pKa (strongest acidic)
14.42
pKa (Strongest Basic)
8.91
PSA
32.7 Å2
Refractivity
83.02 m3·mol-1
Polarizability
32.33 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Venlafaxine potentiates the neurotransmitter activity in the central nervous system. Furthermore, venlafaxine and its metabolite, O-desmethylvenlafaxine (ODV) potently inhibit the reuptake of serotonin and norepinephrine and weakly inhibit dopamine reuptake. Both molecules do not bind to muscarinic, histaminergic, or alpha-1 adrenergic receptors. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Both also do not have any monoamine oxidase (MAO) inhibitory activity.
Cơ Chế Tác Dụng : Venlafaxine (Effexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. It is prescribed for the treatment of clinical depression and anxiety disorders. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs. Venlafaxine was the sixth most widely-used antidepressant based on the amount of retail prescriptions in the US (17.1 million) in 2006. [Wikipedia] The exact mechanism of action of venlafaxine is unknown, but appears to be associated with the its potentiation of neurotrasmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
Dược Động Học :
▧ Absorption :
Venlafaxine is well absorbed. Food does not effect the absorption of venlafaxine or its subsequent metabolism into ODV. Bioavailability is 45% following oral administration. Time to steady state = 3 days.
▧ Volume of Distribution :
* 7.5 ± 3.7 L/kg [venlafaxine] * 5.7 ± 1.8 L/kg [O-desmethylvenlafaxine(active metabolite)]
▧ Protein binding :
The degree of binding of venlafaxine to human plasma is 27% ± 2% at concentrations ranging from 2.5 to 2215 ng/mL. The degree of ODV binding to human plasma is 30% ± 12% at concentrations ranging from 100 to 500 ng/mL. Protein-binding-induced drug interactions with venlafaxine are not expected.
▧ Metabolism :
Undergoes extensive first pass metabolism in the liver to its major, active metabolite, ODV, and two minor, less active metabolites, N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine. Formation of ODV is catalyzed by cytochrome P450 (CYP) 2D6, whereas N-demethylation is catalyzed by CYP3A4, 2C19 and 2C9. ODV possesses antidepressant activity that is comparable to that of venlfaxine.
▧ Route of Elimination :
Renal elimination of venlafaxine and its metabolites is the primary route of excretion. Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as either unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%).
▧ Half Life :
5 hours
▧ Clearance :
Steady state plasma clearance, venlafaxine = 1.3 ± 0.6 L/h/kg; Steady state plasma clearance, ODV = 0.4 ± 0.2 L/h/kg.
Độc Tính : Most patients overdosing with venlafaxine develop only mild symptoms. However, severe toxicity is reported with the most common symptoms being CNS depression, serotonin toxicity, seizure, or cardiac conduction abnormalities. Venlafaxine's toxicity appears to be higher than other SSRIs, with a fatal toxic dose closer to that of the tricyclic antidepressants than the SSRIs. Doses of 900 mg or more are likely to cause moderate toxicity. Deaths have been reported following large doses.
Chỉ Định : For the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (social phobia), panic disorder with or without agoraphobia, vasomotor symptoms in women with breast cancer and in postmenopausal women, and neuropathic pain.
Tương Tác Thuốc :
  • Almotriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Amitriptyline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Amoxapine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Amprenavir Amprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Amprenavir is initiated, discontinued, or dose changed.
  • Atazanavir Atazanavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Atazanavir is initiated, discontinued, or dose changed.
  • Bromocriptine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Buspirone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Cabergoline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Chlorpromazine Chlorpromazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Chlorpromazine is initiated, discontinued, or dose changed.
  • Cinacalcet Cinacalcet, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Cinacalcet is initiated, discontinued, or dose changed.
  • Citalopram Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Clarithromycin Clarithromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Clarithromycin is initiated, discontinued, or dose changed.
  • Clomipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Cocaine Cocaine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Cocaine is initiated, discontinued, or dose changed.
  • Conivaptan Conivaptan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Conivaptan is initiated, discontinued, or dose changed.
  • Darunavir Darunavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Darunavir is initiated, discontinued, or dose changed.
  • Delavirdine Delaviridine, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Delavirdine is initiated, discontinued, or dose changed.
  • Desipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Dexfenfluramine Risk of serotoninergic syndrome
  • Dextromethorphan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Diethylpropion Risk of serotoninergic syndrome
  • Dihydroergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Dipivefrin Venlafaxine may increase the tachycardic and vasopressor effects of dipivefrin. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
  • Doxepin Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Duloxetine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Eletriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Ephedrine Venlafaxine may increase the tachycardic and vasopressor effects of ephedrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
  • Epinephrine Venlafaxine may increase the tachycardic and vasopressor effects of epinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
  • Ergoloid mesylate Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Ergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Ergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Escitalopram Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Fenfluramine Risk of serotoninergic syndrome
  • Fluoxetine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Fluvoxamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Fosamprenavir Fosamprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Fosamprenavir is initiated, discontinued, or dose changed.
  • Frovatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Furazolidone Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Imatinib Imatinib, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Imatinib is initiated, discontinued, or dose changed.
  • Imipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Indinavir Indinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Indinavir is initiated, discontinued, or dose changed.
  • Isocarboxazid Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Isoniazid Isoniazid, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Isoniazid is initiated, discontinued, or dose changed.
  • Itraconazole Itraconaole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Itraconazole is initiated, discontinued, or dose changed.
  • Ketoconazole Ketoconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Ketoconazole is initiated, discontinued, or dose changed.
  • Linezolid Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Lithium Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Lopinavir Lopinavir, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Lopinavir is initiated, discontinued, or dose changed.
  • Maprotiline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Mazindol Risk of serotoninergic syndrome
  • Methylergometrine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Metoclopramide Possible serotoninergic syndrome with this combination
  • Miconazole Miconazole, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Miconazole is initiated, discontinued, or dose changed.
  • Milnacipran Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Mirtazapine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Moclobemide Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Naratriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Nefazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Nelfinavir Nelfinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Nelfinavir is initiated, discontinued, or dose changed.
  • Nicardipine Nicardipine, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Nicardipine is initiated, discontinued, or dose changed.
  • Norepinephrine Venlafaxine may increase the tachycardic and vasopressor effects of Norepinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
  • Nortriptyline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Paroxetine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Pergolide Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Pethidine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Phenelzine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Phentermine Risk of serotoninergic syndrome
  • Phenylpropanolamine Risk of serotoninergic syndrome
  • Posaconazole Posaconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Posaconazole is initiated, discontinued, or dose changed.
  • Procarbazine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Promethazine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Propafenone Propafenone increases the effect and toxicity of venlafaxine
  • Protriptyline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Pseudoephedrine Venlafaxine may increase the tachycardic and vasopressor effects of Pseudoephedrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
  • Quinidine Quinidine, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Quinidine is initiated, discontinued, or dose changed.
  • Quinupristin This combination presents an increased risk of toxicity
  • Rasagiline Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Ritonavir Ritonavir, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Ritonavir is initiated, discontinued, or dose changed.
  • Rizatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • S-Adenosylmethionine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Saquinavir Saquinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Saquinavir is initiated, discontinued, or dose changed.
  • Selegiline Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Sertraline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Sibutramine Increased risk of serotonin syndrome. Concurrent therapy should be avoided.
  • St. John's Wort Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Sumatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Telithromycin Telithromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Telithromycin is initiated, discontinued, or dose changed.
  • Terbinafine Terbinafine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Terbinafine is initiated, discontinued, or dose changed.
  • Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
  • Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Triprolidine The CNS depressants, Triprolidine and Venlafaxine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of venlafaxine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of venlafaxine if voriconazole is initiated, discontinued or dose changed.
  • Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and venlafaxine, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Liều Lượng & Cách Dùng : Capsule, extended release - Oral - 150 mg
Capsule, extended release - Oral - 37.5 mg
Capsule, extended release - Oral - 75 mg
Tablet - Oral - 100 mg
Tablet - Oral - 25 mg
Tablet - Oral - 37.5 mg
Tablet - Oral - 50 mg
Tablet - Oral - 75 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Effexor
  • Công ty :
    Sản phẩm biệt dược : Effexor XR
  • Công ty :
    Sản phẩm biệt dược : Elafax
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00285
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5656
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504593
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07187
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08670
ChemSpider
http://www.chemspider.com/Chemical-Structure.5454.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-4881-01
PharmGKB
http://www.pharmgkb.org/drug/PA451866
Wikipedia
http://en.wikipedia.org/wiki/Venlafaxine
RxList
http://www.rxlist.com/cgi/generic/venlafax.htm
PDRhealth
http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=eff1794.html&contentName=Effexor%20XR&contentId=277
Drugs.com
http://www.drugs.com/venlafaxine.html
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