Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C13H13N3.C6H6O3S.H2O |
| Molecular Weight | 387.453 |
| Optical Activity | NONE |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
| Stereo Comments | Meso |
SHOW SMILES / InChI
SMILES
O.OS(=O)(=O)C1=CC=CC=C1.C2[C@H]3CNC[C@@H]2C4=CC5=NC=CN=C5C=C34
InChI
InChIKey=KWNVPXRPGMLJGH-DRJPZDRJSA-N
InChI=1S/C13H13N3.C6H6O3S.H2O/c1-2-16-13-5-11-9-3-8(6-14-7-9)10(11)4-12(13)15-1;7-10(8,9)6-4-2-1-3-5-6;/h1-2,4-5,8-9,14H,3,6-7H2;1-5H,(H,7,8,9);1H2/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 |
|---|---|---|
| Treating smoking dependence in depressed alcoholics. | 2006 |
|
| 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 |
|
| The FDA approves new drug for smoking cessation. | 2006 Jul-Aug |
|
| Smoking cessation efficacy and safety of varenicline, an alpha4beta2 nicotinic receptor partial agonist. | 2006 Nov-Dec |
|
| New prescription drug available to help smokers stop. | 2006 Oct |
|
| Smoking: tackling the silent epidemic. | 2007 |
|
| Rimonabant for treating tobacco dependence. | 2007 |
|
| [Varenicline (Champix)]. | 2007 |
|
| [Tobacco use prevention and cessation in the dental practice]. | 2007 |
|
| Non-nicotinic therapies for smoking cessation. | 2007 |
|
| An employer-based cost-benefit analysis of a novel pharmacotherapy agent for smoking cessation. | 2007 Apr |
|
| A double-blind study evaluating the long-term safety of varenicline for smoking cessation. | 2007 Apr |
|
| Optimizing on smoke free legislation making the most of the opportunity. | 2007 Aug |
|
| Varenicline: progress in smoking cessation treatment. | 2007 Aug |
|
| Exacerbation of schizophrenia by varenicline. | 2007 Aug |
|
| Varenicline-induced manic episode in a patient with bipolar disorder. | 2007 Aug |
|
| Emerging pharmacotherapies for smoking cessation. | 2007 Aug 15 |
|
| [Drug of the month. Varenicline (Champix)]. | 2007 Feb |
|
| Varenicline: new treatment with efficacy in smoking cessation. | 2007 Feb |
|
| Varenicline for smoking cessation. | 2007 Feb |
|
| Drug approvals. | 2007 Feb |
|
| Smoking cessation in patients with respiratory diseases: a high priority, integral component of therapy. | 2007 Feb |
|
| Impact of pharmacometric reviews on new drug approval and labeling decisions--a survey of 31 new drug applications submitted between 2005 and 2006. | 2007 Feb |
|
| [Giving up smoking is crucial for COPD patients]. | 2007 Feb 22 |
|
| [The best of epidemiology and cardiovascular prevention in 2006]. | 2007 Jan |
|
| Oral varenicline for smoking cessation. | 2007 Jan |
|
| Advances in the management of chronic obstructive pulmonary disease. | 2007 Jan |
|
| Nicotine receptor partial agonists for smoking cessation. | 2007 Jan 24 |
|
| Antidepressants for smoking cessation. | 2007 Jan 24 |
|
| [Champix has become a registered drug]. | 2007 Jan 28 |
|
| Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation. | 2007 Jul |
|
| Smoking cessation: lessons learned from clinical trial evidence. | 2007 Jul |
|
| The pharmacist's role in tobacco cessation: overview and introduction to the series. | 2007 Jul 1 |
|
| Varenicline: the newest agent for smoking cessation. | 2007 Jul 1 |
|
| Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. | 2007 Jun |
|
| A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers. | 2007 Jun |
|
| How well does the new drug varenicline work for people who want to stop smoking? | 2007 Jun |
|
| Smoking cessation update. | 2007 Jun |
|
| Why choose varenicline (chantix) for smoking cessation treatment? | 2007 Jun |
|
| New non-nicotine drug to help smoking cessation efforts. | 2007 Jun 12-18 |
|
| [New smoking cessation preparations unsuitable in mental disorders]. | 2007 Jun 4-11 |
|
| The most addictive drug, the most deadly substance: smoking cessation tactics for the busy clinician. | 2007 Mar |
|
| Kicking butts: smoking cessation update. | 2007 May-Jun |
|
| Alcohol history and smoking cessation in nicotine replacement therapy, bupropion sustained release and varenicline trials: a review. | 2007 May-Jun |
|
| Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. | 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 |
|
| A call to action: new treatment options provide even more reasons to intervene in tobacco dependence. | 2007 Sep |
|
| 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
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PARENT (SALT/SOLVATE)
SUBSTANCE RECORD
