pharmacopeia
GET
/api/v1/drug/defactinib

Mechanism of action

Sourced from openFDA

Avutometinib Avutometinib is a MEK1 inhibitor. Avutometinib induces the formation of inactive RAF/MEK complexes and prevents phosphorylation of MEK1/2 by RAF.

Focal Adhesion KinaseProline-rich Tyrosine Kinase 2Tyrosine KinaseUGT1A1

Indications

Sourced from openFDA
  • AVMAPKI FAKZYNJA CO-PACK is indicated for the treatment of adult patients with KRAS -mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14) ].ICD-10: C56.9

Contraindications

Sourced from openFDA
  • None. None.contraindicated

Dosage & administration

Sourced from openFDA

AVMAPKI 3.2 mg administered orally twice weekly (Day 1 and Day 4) for the first 3 weeks of each 4-week cycle. ( 2.3 ) FAKZYNJA 200 mg administered orally twice daily for the first 3 weeks of each 4-week cycle. ( 2.3 ) 2.1 Patient Selection Select patients for the treatment of recurrent LGSOC with AVMAPKI FAKZYNJA CO-PACK based on the presence of a KRAS mutation in tumor specimens [see Clinical Studies (14) ] . An FDA-approved test for the detection of a KRAS mutation in LGSOC for selecting patients for treatment with AVMAPKI FAKZYNJA CO-PACK is not available. 2.2 Eye Exams and Prophylactic Skin Medications Ophthalmic Exams Conduct a comprehensive ophthalmic exam at baseline, prior to cycle 2, and every three cycles thereafter regardless of baseline exam findings, and as clinically indicated [see Warnings and Precautions (5.1) ]. Prophylactic Medications for Skin Reactions With initiation of and during at least the first 2 cycles of AVMAPKI FAKZYNJA CO-PACK administer [see Warnings and Precautions (5.2) ] : Topical corticosteroid (applied to the face, scalp, neck, upper chest and upper back) Systemic oral antibiotics 2.3 Recommended Dosage and Administration AVMAPKI Capsules The recommended dosage of AVMAPKI capsules is 3.2 mg (four 0.8 mg capsules) taken orally twice weekly (Day 1 and Day 4) for the first 3 weeks of each 4-week cycle until disease progression or unacceptable toxicity. Take AVMAPKI at the same time with each dose. AVMAPKI should be taken with food [see Clinical Pharmacology (12.3) ] . Swallow capsules whole. Do not chew, break, or open the capsules.

Warnings & precautions

Sourced from openFDA

Ocular Toxicities: Ocular toxicities, including visual impairment and vitreoretinal disorders, occurred. Perform comprehensive ophthalmic evaluation at baseline, prior to cycle 2, every three cycles thereafter, and as clinically indicated. Withhold AVMAPKI FAKZYNJA CO-PACK for ocular toxicities until improvement at the same or reduced dose. Permanently discontinue AVMAPKI FAKZYNJA CO-PACK for any grade 4 toxicity. ( 2.4 , 5.1 ) Serious Skin Toxicities : Skin toxicities, including photosensitivity and severe cutaneous adverse reactions (SCARs), occurred. Adhere to concomitant medications. Monitor for skin toxicities and interrupt, reduce or permanently discontinue AVMAPKI FAKZYNJA CO-PACK based on severity, tolerability and duration. ( 2.4 , 5.2 ) Hepatotoxicity : Monitor liver function tests prior to each cycle, on day 15 of the first 4 cycles, and as clinically indicated. Withhold, reduce or discontinue AVMAPKI FAKZYNJA CO-PACK based on severity and persistence of abnormality. ( 2.4 , 5.3 ) Rhabdomyolysis: Monitor creatine phosphokinase prior to the start of each cycle, on day 15 of the first four cycles, and as clinically indicated. If increased CPK occurs, evaluate patients for rhabdomyolysis or other causes. Withhold, reduce or permanently discontinue AVMAPKI FAKZYNJA CO-PACK based on severity and duration of the adverse reaction. ( 2.4 , 5.4 ) Embryo-Fetal Toxicity : AVMAPKI FAKZYNJA CO-PACK can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Adverse reactions

Sourced from openFDA

The following adverse reactions are discussed in more detail in other sections of the labeling: Ocular Toxicities [see Warnings and Precautions (5.1) ] Serious Skin Toxicities [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.3) ] Rhabdomyolysis [see Warnings and Precautions (5.4) ] The most common (≥ 25%) adverse reactions, including laboratory abnormalities, were increased creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased alanine aminotransferase, vomiting, increased blood bilirubin, increased triglycerides, decreased lymphocyte count, abdominal pain, dyspepsia, dermatitis acneiform, vitreoretinal disorders, increased alkaline phosphatase, stomatitis, pruritus, visual impairment, decreased platelet count, constipation, dry skin, dyspnea, cough, urinary tract infection, and decreased neutrophil count. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Verastem at 1-833-633-8786 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Use in specific populations

Sourced from openFDA

Lactation : Advise not to breastfeed. ( 8.2 ) Infertility : May impair fertility in males and females. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on the mechanisms of action, AVMAPKI FAKZYNJA CO-PACK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of AVMAPKI FAKZYNJA CO-PACK in pregnant women to inform a drug-associated risk. Animal reproductive and developmental toxicity studies have not been conducted with avutometinib or defactinib; however, inhibition of either molecular pathway has been associated with embryo-fetal anomalies and lethality in animals. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 8.2 Lactation Risk Summary There are no data on the presence of avutometinib, defactinib, or their metabolites in human milk, the effects on the breastfed child, or the effects on milk production.

Pharmacokinetics

Sourced from openFDA
Metabolism
The pharmacokinetics of avutometinib and defactinib were studied in healthy subjects and in patients with advanced solid tumors and are presented as mean (%CV) unless otherwise specified. Avutometinib Avutometinib exhibits dose proportional increases peak plasma concentrations (C max ) and area under the concentration time curve (AUC) with a single dose ranging from 0.1 mg to 5 mg (0.03 to 1.6 times the approved recommended dose).

Approval history

Sourced from openFDA
  • May 8, 2025NDANDA219616Verastem Inc

FAERS reports

View JSON
Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
525 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Fatigue8316%
  2. 2Off Label Use8316%
  3. 3Nausea7915%
  4. 4Product Dose Omission Issue5410%
  5. 5Diarrhoea5310%
  6. 6Rash499.3%
  7. 7Vomiting428.0%
  8. 8Vision Blurred397.4%
  9. 9Peripheral Swelling326.1%
  10. 10Acne295.5%
  11. 11Pruritus244.6%
  12. 12Dizziness234.4%
  13. 13Dry Skin224.2%
  14. 14Blood Creatine Phosphokinase Increased214.0%
  15. 15Visual Impairment203.8%

Clinical trials

View JSON

The 10 most recently updated of 40 ClinicalTrials.gov registrations naming Defactinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Defactinib work?
Avutometinib Avutometinib is a MEK1 inhibitor. Avutometinib induces the formation of inactive RAF/MEK complexes and prevents phosphorylation of MEK1/2 by RAF.
What is Defactinib used for?
According to FDA labeling, Defactinib carries indications including: AVMAPKI FAKZYNJA CO-PACK is indicated for the treatment of adult patients with KRAS -mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14) ].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Defactinib?
Defactinib is classified as Kinase Inhibitor, Focal Adhesion Kinase Inhibitors, Proline-rich Tyrosine Kinase 2 Inhibitors, Tyrosine Kinase Inhibitors, UGT1A1 Inhibitors, Cellular Proliferation Alteration.
What are the brand names for Defactinib?
Defactinib is marketed under brand names including Fakzynja.
What are the contraindications for Defactinib?
Defactinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.
Note. Data for defactinib is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

Search pharmacopeia

Search drugs, classes, and ingredients