Description

Simple

A chemotherapy drug used to treat a type of skin cancer, lung cancer,and thyroid cancer.

Clinical

A kinase inhibitor used to treat patients with specific types of melanoma, non-small cell lung cancer, and thyroid cancer.

Overview

Dabrafenib mesylate (Tafinlar) is a reversible ATP-competitive kinase inhibitor and targets the MAPK pathway. It was approved on May 29, 2013 for the treatment of melanoma [7].

In May 2018, Tafinlar (dabrafenib) and Mekinist ([DB08911]) in combination have been approved to treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene [5].

Pharmacology

Indication

Tafinlar is a kinase inhibitor that was initially indicated as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test [FDA label].

Tafinlar in combination with [DB08911] is indicated for the treatment of p... Read more

Pharmacodynamic

Dabrafenib causes an inhibition of phosphorylated extracellular signal-regulated kinase (ERK). This indicates a decrease in cell proliferation. Furthermore, within 24 hours of administration, downstream mediators of the MAPK pathway were inhibited [FDA label].

The melanoma approval for use with M... Read more

Mechanism of action


Dabrafenib is an orally bioavailable inhibitor of B-raf (BRAF) protein with antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of seri... Read more

Absorption

After oral administration, median time to achieve peak plasma concentration (Tmax) is 2 hours. Mean absolute bioavailability of oral dabrafenib is 95% [2].

Protein binding

99.7% bound to human plasma protein [FDA label].

Volume of distribution

Apparent volume of distribution (Vd/F) = 70.3 L [FDA label].Distribution to the brain is restricted because dabrafenib is a substrate and undergoes efflux by P-glycoprotein and breast cancer resistance protein [FDA label].

Clearance

The clearance of dabrafenib is 17.0 L/h after single dosing and 34.4 L/h after 2 weeks of twice daily dosing [FDA label]

Half life

The average terminal half-life of dabrafenib is 8 hours after oral dosing [FDA label].

Route of elimination

Fecal excretion is the major route of elimination accounting for 71% of radioactive dose while urinary excretion accounted for 23% of total radioactivity as metabolites only [FDA label].

Toxicity

LD50 in rats is > 2000 mg/kg [MSDS].


The most common side effects of Daretinib (Tafinlar) as a single agent include: hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, and palmar-plantar erythrodysesthesia syndrome [FDA label].

The most common adverse reactions (≥20%) for Ta... Read more

Adverse Effects

Contraindications

Information currently not available.

Food Interactions

  • Take separate from meals. Take at least one hour before or two hours after a meal.

Interactions

Type in a drug name to check for interaction with Dabrafenib
Type a drug name in the box above to get started
  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The serum concentration of (R)-warfarin can be decreased when it is combined with Dabrafenib.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be decreased when it is combined with Dabrafenib.
2,4-thiazolidinedione
The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Dabrafenib.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be increased when combined with Dabrafenib.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be increased when combined with Dabrafenib.
Abatacept
The metabolism of Dabrafenib can be increased when combined with Abatacept.
Abemaciclib
Dabrafenib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Abexinostat
The risk or severity of QTc prolongation can be increased when Dabrafenib is combined with Abexinostat.
Abiraterone
The metabolism of Dabrafenib can be decreased when combined with Abiraterone.
Acarbose
The therapeutic efficacy of Acarbose can be decreased when used in combination with Dabrafenib.
Acebutolol
The risk or severity of QTc prolongation can be increased when Dabrafenib is combined with Acebutolol.
Acenocoumarol
The serum concentration of Acenocoumarol can be decreased when it is combined with Dabrafenib.
Aceprometazine
The risk or severity of QTc prolongation can be increased when Dabrafenib is combined with Aceprometazine.
Acetohexamide
The metabolism of Acetohexamide can be increased when combined with Dabrafenib.
Acetyldigoxin
The risk or severity of QTc prolongation can be increased when Dabrafenib is combined with Acetyldigoxin.
Acetylsalicylic acid
The metabolism of Acetylsalicylic acid can be increased when combined with Dabrafenib.
Acrivastine
The risk or severity of QTc prolongation can be increased when Dabrafenib is combined with Acrivastine.
Acyclovir
The excretion of Acyclovir can be decreased when combined with Dabrafenib.
Adalimumab
The metabolism of Dabrafenib can be increased when combined with Adalimumab.
Adefovir dipivoxil
The excretion of Adefovir dipivoxil can be decreased when combined with Dabrafenib.
10 References
  1. 1 . Gibney GT, Zager JS: Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies. Expert Opin Drug Metab Toxicol. 2013 Jul;9(7):893-9. doi: 10.1517/17425255.2013.794220. Epub 2013 Apr 29.PubMed: 23621583
  2. 2 . Dabrafenib Link
  3. 3 . Drug Duo, Tafinlar and Mekinist, Approved for Aggressive Thyroid Cancer Link
  4. 4 . FDA grants regular approval to dabrafenib and trametinib combination for metastatic NSCLC with BRAF V600E mutation Link
  5. 5 . Novartis receives FDA approval of Tafinlar® + Mekinist® for adjuvant treatment of BRAF V600-mutant melanoma Link
  6. 6 . Dabrafenib Link
  7. 7 . Cancer. gov Dabrafenib Link
  8. 8 . Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600–Mutant Anaplastic Thyroid Cancer Link
  9. 9 . NZ DrugSafe Tafinlar File
  10. 10 . Monograph, Tafinlar File