Tofacitinib: Difference between revisions

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==Overview==
* Content
Tofacitinib is a [[pharmaceutical drug|drug]] [[drug discovery|discovered]] and [[drug development|developed]] by [[Pfizer]].  It is currently approved for the treatment of [[rheumatoid arthritis]] (RA) in the United States and is being studied for treatment of [[psoriasis]], [[inflammatory bowel disease]], and other immunological diseases, as well as for the prevention of [[organ transplant]] rejection.


==Mechanism==
<!--Adult Indications and Dosage-->
It is an [[Janus kinase inhibitor|inhibitor]] of the enzyme [[janus kinase 3]] (JAK3), which means that it interferes with the [[JAK-STAT signaling pathway]], which transmits extracellular information into the cell nucleus, influencing [[DNA transcription]].<ref name="pmid21171673">{{cite journal| author=| title=Tofacitinib. | journal=Drugs R D | year= 2010 | volume= 10 | issue= 4 | pages= 271-84 | pmid=21171673 | doi=10.2165/11588080-000000000-00000 | pmc=PMC3585773 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21171673  }} </ref>


Recently it has been shown in a murine model of established arthritis that tofacitinib rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing [[STAT1]]-dependent genes in joint tissue. This efficacy in this disease model correlated with the inhibition of both [[JAK1]] and 3 signaling pathways, suggesting that tofacitinib may exert therapeutic benefit via pathways that are not exclusive to inhibition of JAK3.<ref name="pmid21383241">{{cite journal| author=Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW et al.| title=Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). | journal=J Immunol | year= 2011 | volume= 186 | issue= 7 | pages= 4234-43 | pmid=21383241 | doi=10.4049/jimmunol.1003668 | pmc=PMC3108067 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21383241  }} </ref>
<!--FDA-Labeled Indications and Dosage (Adult)-->
|fdaLIADAdult======Condition1=====


==Research History==
* Dosing Information
The potential significance of JAK3 inhibition was first discovered in the laboratory of [[John O'Shea (biologist)|John O'Shea]], an [[immunologist]] at the [[National Institute of Arthritis and Musculoskeletal and Skin Diseases]] of the [[National Institutes of Health]] (NIH). In 1994, Pfizer was approached by the NIH to form a public-private partnership in order to evaluate and bring to market experimental compounds based on this research. Pfizer initially declined the partnership but agreed in 1996, after the elimination of an NIH policy dictating that the market price of a product resulting from such a partnership would need to be commensurate with the investment of public taxpayer revenue and the "health and safety needs of the public." The [[drug discovery]], [[preclinical development]], and [[clinical development]] of tofacitinib took place exclusively at Pfizer.<ref name="pmid23302910">{{cite journal| author=Garber K| title=Pfizer's first-in-class JAK inhibitor pricey for rheumatoid arthritis market. | journal=Nat Biotechnol | year= 2013 | volume= 31 | issue= 1 | pages= 3-4 | pmid=23302910 | doi=10.1038/nbt0113-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23302910  }} </ref>


In November 2012, the U.S. [[Food and Drug Administration]] (FDA) approved tofacitinib for treatment of rheumatoid arthritis.  Once on the market, rheumatologists complained that the $2,055 a month wholesale price was too expensive, though the price is 7% less than related treatments.<ref name="pmid23302910">{{cite journal| author=Garber K| title=Pfizer's first-in-class JAK inhibitor pricey for rheumatoid arthritis market. | journal=Nat Biotechnol | year= 2013 | volume= 31 | issue= 1 | pages= 3-4 | pmid=23302910 | doi=10.1038/nbt0113-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23302910  }} </ref>
:* Dosage


===Clinical Trials===
=====Condition2=====
====Rheumatoid Arthritis====
[[Phase II clinical trial]]s tested the drug in RA patients that had not responded to [[DMARD]] therapy. In a tofacitinib monotherapy study, the [[ACR score for rheumatoid arthritis|ACR score]] improved by at least 20% (ACR-20) in 67% of patients versus 25% who received [[placebo]]; and a study that combined the drug with [[methotrexate]] achieved ACR-20 in 59% of patients versus 35% who received methotrexate alone. In a psoriasis study, the [[Psoriasis Area and Severity Index|PASI]] score improved by at at least 75% in between 25 and 67% of patients, depending on the dose, versus 2% in the placebo group. The most important side effects in Phase II studies were increased [[blood cholesterol]] levels (12 to 25&nbsp;mg/dl [[Low density lipoprotein|LDL]] and 8 to 10&nbsp;mg/dl [[High density lipoprotein|HDL]] at medium dosage levels) and [[neutropenia]]. Phase III trials testing the drug in rheumatoid arthritis started in 2007 and are scheduled to run until January 2015. In April 2011, four patients died after beginning clinical trials with tofacitinib. According to Pfizer, only one of the four deaths was related to tofacitinib. By April 2011, three phase III trials for RA had reported positive results. In November 2012, the U.S. FDA approved tofacitinib "to treat adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, methotrexate." A [[boxed warning]] that goes along with this approval warns patients that they are at higher risk of opportunistic infections, tuberculosis, cancers and lymphoma.


* Dosing Information


==References==
:* Dosage
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[[Category:Drug]]

Revision as of 20:00, 21 January 2015

Tofacitinib
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

Disclaimer

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Black Box Warning

ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content

Overview

Tofacitinib is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition1
  • Dosing Information
  • Dosage
Condition2
  • Dosing Information
  • Dosage
Condition3
  • Dosing Information
  • Dosage
Condition4
  • Dosing Information
  • Dosage

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Tofacitinib in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Tofacitinib in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Tofacitinib in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Tofacitinib in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Tofacitinib in pediatric patients.

Contraindications

  • Condition1

Warnings

ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content
  • Description

Precautions

  • Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Tofacitinib in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Tofacitinib in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tofacitinib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Tofacitinib during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Tofacitinib with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Tofacitinib with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Tofacitinib with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Tofacitinib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Tofacitinib with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Tofacitinib in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Tofacitinib in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Tofacitinib in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Tofacitinib in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Tofacitinib in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Tofacitinib in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Tofacitinib in the drug label.

Pharmacology

There is limited information regarding Tofacitinib Pharmacology in the drug label.

Mechanism of Action

Structure

File:Tofacitinib01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Tofacitinib in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Tofacitinib in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Tofacitinib in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Tofacitinib in the drug label.

How Supplied

Storage

There is limited information regarding Tofacitinib Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Tofacitinib |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Tofacitinib |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Tofacitinib in the drug label.

Precautions with Alcohol

  • Alcohol-Tofacitinib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Empty citation (help)
  2. ↑ "http://www.ismp.org". External link in |title= (help)

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