Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C13H13N3.C2H2O4 |
| Molecular Weight | 301.2973 |
| Optical Activity | NONE |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)C(O)=O.C1[C@H]2CNC[C@@H]1C3=CC4=C(C=C23)N=CC=N4
InChI
InChIKey=KVMSYFKKTPXOQW-UFIFRZAQSA-N
InChI=1S/C13H13N3.C2H2O4/c1-2-16-13-5-11-9-3-8(6-14-7-9)10(11)4-12(13)15-1;3-1(4)2(5)6/h1-2,4-5,8-9,14H,3,6-7H2;(H,3,4)(H,5,6)/t8-,9+;
DescriptionCurator's Comment: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021928s039s041lbl.pdf
Curator's Comment: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021928s039s041lbl.pdf
Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain. Varenicline is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor partial agonist. The drug shows high selectiviyty for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms. Varenicline is sold under the trade name Chantix and Champix, it is indicated for use as an aid to smoking cessation treatment.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 0.4 nM [Ki] | |||
Target ID: CHEMBL2492 |
130.0 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | CHANTIX Approved UseCHANTIX is a nicotinic receptor partial agonist indicated for use as an aid to
smoking cessation treatment. Launch Date2006 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
6.38 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21053991/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
VARENICLINE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN |
|
5.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920893/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
VARENICLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
9.22 ng/mL |
1 mg 2 times / day multiple, oral dose: 1 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
VARENICLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
106 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21053991/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
VARENICLINE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN |
|
97.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920893/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
VARENICLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
186 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19916991/ |
1 mg 2 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
VARENICLINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
194 ng × h/mL |
1 mg 2 times / day multiple, oral dose: 1 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
VARENICLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
10.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21053991/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
VARENICLINE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN |
|
11.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920893/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
VARENICLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
24 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19916991/ |
1 mg 2 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
VARENICLINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
33 h |
1 mg 2 times / day multiple, oral dose: 1 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
VARENICLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.15 |
unhealthy, 46 n = 36 Health Status: unhealthy Condition: Smoking addiction Age Group: 46 Sex: M+F Population Size: 36 Sources: Page: p.15 |
Disc. AE: Nausea, Anger... AEs leading to discontinuation/dose reduction: Nausea (4%) Sources: Page: p.15Anger (1%) Insomnia (1%) |
15 mg single, oral Overdose |
healthy |
Disc. AE: Vomiting, Tachycardia... AEs leading to discontinuation/dose reduction: Vomiting Sources: Tachycardia |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
Disc. AE: Psychiatric disorder NOS, Suicidal ideation... AEs leading to discontinuation/dose reduction: Psychiatric disorder NOS (serious) Sources: Page: p.1Suicidal ideation (serious) Suicidal behavior (serious) Agitation Hostility Depressed mood Angioedema Hypersensitivity reaction Reaction skin (grade 3-4, rare) Accidental injury |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1,3 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1,3 |
Disc. AE: Nausea... AEs leading to discontinuation/dose reduction: Nausea (3%) Sources: Page: p.1,3 |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Anger | 1% Disc. AE |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.15 |
unhealthy, 46 n = 36 Health Status: unhealthy Condition: Smoking addiction Age Group: 46 Sex: M+F Population Size: 36 Sources: Page: p.15 |
| Insomnia | 1% Disc. AE |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.15 |
unhealthy, 46 n = 36 Health Status: unhealthy Condition: Smoking addiction Age Group: 46 Sex: M+F Population Size: 36 Sources: Page: p.15 |
| Nausea | 4% Disc. AE |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.15 |
unhealthy, 46 n = 36 Health Status: unhealthy Condition: Smoking addiction Age Group: 46 Sex: M+F Population Size: 36 Sources: Page: p.15 |
| Tachycardia | Disc. AE | 15 mg single, oral Overdose |
healthy |
| Vomiting | Disc. AE | 15 mg single, oral Overdose |
healthy |
| Accidental injury | Disc. AE | 1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Agitation | Disc. AE | 1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Angioedema | Disc. AE | 1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Depressed mood | Disc. AE | 1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Hostility | Disc. AE | 1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Hypersensitivity reaction | Disc. AE | 1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Reaction skin | grade 3-4, rare Disc. AE |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Psychiatric disorder NOS | serious Disc. AE |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Suicidal behavior | serious Disc. AE |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Suicidal ideation | serious Disc. AE |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1 |
| Nausea | 3% Disc. AE |
1 mg 2 times / day multiple, oral Recommended Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: Page: p.1,3 |
unhealthy Health Status: unhealthy Condition: Smoking addiction Sources: Page: p.1,3 |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no [IC50 >30 uM] | ||||
| no | ||||
| no | ||||
| no | no (co-administration study) Comment: digoxin remained unchanged in the presence of varenicline Page: 36.0 |
|||
| weak |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | no (co-administration study) Comment: digoxin remained unchanged in the presence of varenicline Page: 36.0 |
|||
Page: 37, 272, 276 |
yes | |||
| yes | yes (co-administration study) Comment: cimetidine increased the systemic exposure of varenicline by 29% Page: 46, 72 |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| [Medication for ending tobacco dependency. Current state]. | 2005 Jun 30 |
|
| Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. | 2005 May 19 |
|
| Varenicline: new drug. Smoking cessation: no better than nicotine. | 2006 Dec |
|
| Effectiveness of smoking cessation therapies: a systematic review and meta-analysis. | 2006 Dec 11 |
|
| Efficacy of varenicline for smoking cessation. | 2006 Dec 6 |
|
| Varenicline (CHANTIX): a stop-smoking pill. | 2006 Fall |
|
| FDA speeds smoking cessation drug review. | 2006 Feb 8 |
|
| Developments in pharmacotherapy for tobacco dependence: past, present and future. | 2006 Jan |
|
| Varenicline. | 2006 Jul |
|
| The FDA approves new drug for smoking cessation. | 2006 Jul-Aug |
|
| [Smoking cessation intervention: 2006 update]. | 2006 Jun 28 |
|
| Current and emerging pharmacotherapies for treating tobacco dependence. | 2006 Sep |
|
| Smoking: tackling the silent epidemic. | 2007 |
|
| Rimonabant for treating tobacco dependence. | 2007 |
|
| A double-blind study evaluating the long-term safety of varenicline for smoking cessation. | 2007 Apr |
|
| Comment: Oral varenicline for smoking cessation. | 2007 Apr |
|
| Optimizing on smoke free legislation making the most of the opportunity. | 2007 Aug |
|
| Varenicline-induced manic episode in a patient with bipolar disorder. | 2007 Aug |
|
| Varenicline: new treatment with efficacy in smoking cessation. | 2007 Feb |
|
| Smoking cessation in patients with respiratory diseases: a high priority, integral component of therapy. | 2007 Feb |
|
| [Giving up smoking is crucial for COPD patients]. | 2007 Feb 22 |
|
| [The best of epidemiology and cardiovascular prevention in 2006]. | 2007 Jan |
|
| Dopamine D3 receptor ligands for the treatment of tobacco dependence. | 2007 Jan |
|
| Antidepressants for smoking cessation. | 2007 Jan 24 |
|
| Alcohol history and smoking cessation in nicotine replacement therapy, bupropion sustained release and varenicline trials: a review. | 2007 May-Jun |
|
| Smoking cessation interventions in clinical practice. | 2007 Oct |
|
| Neuronal nicotinic receptors: a perspective on two decades of drug discovery research. | 2007 Oct 15 |
|
| Maximizing smoking cessation in clinical practice: pharmacologic and behavioral interventions. | 2007 Spring |
|
| Cytisine for smoking cessation: a research agenda. | 2008 Jan 1 |
Patents
Sample Use Guides
Begin CHANTIX (Varenicline) dosing one week before the date set by the patient to
stop smoking. Alternatively, the patient can begin CHANTIX dosing and
then quit smoking between days 8 and 35 of treatment. (2.1)
• Starting week: 0.5 mg once daily on days 1-3 and 0.5 mg twice daily on
days 4-7. (2.1)
• Continuing Weeks: 1 mg twice daily for a total of 12 weeks. (2.1)
• An additional 12 weeks of treatment is recommended for successful
quitters to increase likelihood of long-term abstinence. (2.1)
• Consider a gradual approach to quitting smoking with CHANTIX for
patients who are sure that they are not able or willing to quit abruptly.
Patients should begin CHANTIX dosing and reduce smoking by 50% from
baseline within the first four weeks, by an additional 50% in the next four
weeks, and continue reducing with the goal of reaching complete
abstinence by 12 weeks. Continue treatment for an additional 12 weeks,
for a total of 24 weeks. (2.1)
CHANTIX should be taken orally after eating and with a full glass of water.
Route of Administration:
Oral
| Name | Type | Language | ||
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Preferred Name | English | ||
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Common Name | English | ||
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Preferred Name | English |
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H9NLT16A4C
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ACTIVE MOIETY
SUBSTANCE RECORD
