Description

Simple

A chemotherapy drug used to treat patients with colorectal cancer, digestive tract tumors, and liver cancer.

Clinical

A kinase inhibitor used to treat patients with metastatic colorectal cancer, unresectable, locally advanced, or metastatic gastrointestinal stromal tumors, and hepatocellular carcinoma.

Overview

Regorafenib is an orally-administered inhibitor of multiple kinases. It is used for the treatment of metastatic colorectal cancer and advanced gastrointestinal stromal tumours. FDA approved on September 27, 2012. Approved use of Regorafenib was expanded to treat Hepatocellular Carcinoma in April 2017.

Pharmacology

Indication

Regorafenib is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Regorafenib is also indicated fo... Read more

Pharmacodynamic

Information currently not available.

Mechanism of action

Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. In in vitro biochemical or cellular assays, regoraf... Read more

Absorption

Cmax = 2.5 μg/mL;
Tmax = 4 hours;
AUC = 70.4 μg*h/mL;
Cmax, steady-state = 3.9 μg/mL;
AUC, steady-state = 58.3 μg*h/mL;
The mean relative bioavailability of tablets compared to an oral solution is 69% to 83%.

Protein binding

Regorafenib is highly bound (99.5%) to human plasma proteins.

Volume of distribution

Regorafenib undergoes enterohepatic circulation with multiple plasma concentration peaks observed across the 24-hour dosing interval.

Clearance

Information currently not available.

Half life

Regorafenib, 160 mg oral dose = 28 hours (14 - 58 hours);
M2 metabolite, 160 mg oral dose = 25 hours (14-32 hours);
M5 metabolite, 160 mg oral dose = 51 hours (32-72 hours);

Route of elimination

Approximately 71% of a radiolabeled dose was excreted in feces (47% as parent compound, 24% as metabolites) and 19% of the dose was excreted in urine (17% as glucuronides) within 12 days after administration of a radiolabeled oral solution at a dose of 120 mg.

Toxicity

The most common adverse reactions (≥20%) are asthenia/fatigue, HFSR, diarrhea, decreased appetite/food intake, hypertension, mucositis, dysphonia, and infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever, and nausea

Adverse Effects

Contraindications

Information currently not available.

Food Interactions

  • Drink plenty of fluids.
  • Take after a meal. Should be taken following a low-fat meal containing less than 600 calories and less than 30% fat.
  • Take at the same time every day.

Interactions

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  • 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 increased when it is combined with Regorafenib.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be increased when it is combined with Regorafenib.
3,5-diiodothyropropionic acid
The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Regorafenib.
3,5-Diiodotyrosine
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Regorafenib.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Regorafenib.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Regorafenib.
Abacavir
The metabolism of Abacavir can be decreased when combined with Regorafenib.
Abaloparatide
The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Regorafenib.
Abemaciclib
Regorafenib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Acebutolol
Regorafenib may increase the bradycardic activities of Acebutolol.
Acenocoumarol
The serum concentration of Acenocoumarol can be increased when it is combined with Regorafenib.
Acetaminophen
The metabolism of Acetaminophen can be decreased when combined with Regorafenib.
Acetohexamide
The metabolism of Acetohexamide can be decreased when combined with Regorafenib.
Acetyldigoxin
Regorafenib may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Acetylsalicylic acid
The metabolism of Acetylsalicylic acid can be decreased when combined with Regorafenib.
Afatinib
The serum concentration of Afatinib can be increased when it is combined with Regorafenib.
Agmatine
Agmatine may increase the bradycardic activities of Regorafenib.
Albendazole
The metabolism of Albendazole can be decreased when combined with Regorafenib.
Alfentanil
The metabolism of Alfentanil can be decreased when combined with Regorafenib.
Alfuzosin
The metabolism of Alfuzosin can be decreased when combined with Regorafenib.
1 References
  1. 1 . Hotta K, Ueyama J, Tatsumi Y, Tsukiyama I, Sugiura Y, Saito H, Matsuura K, Hasegawa T: Lack of Contribution of Multidrug Resistance-associated Protein and Organic Anion-transporting Polypeptide to Pharmacokinetics of Regorafenib, a Novel Multi-Kinase Inhibitor, in Rats. Anticancer Res. 2015 Sep;35(9):4681-9.PubMed: 26254357