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Drug overview for FAKZYNJA (defactinib hydrochloride):
Generic name: DEFACTINIB HYDROCHLORIDE
Drug class: Antineoplastic - Protein-Tyrosine Kinase Inhibitors
Therapeutic class: Antineoplastics
No enhanced Introduction information available for this drug.
No enhanced Uses information available for this drug.
Generic name: DEFACTINIB HYDROCHLORIDE
Drug class: Antineoplastic - Protein-Tyrosine Kinase Inhibitors
Therapeutic class: Antineoplastics
No enhanced Introduction information available for this drug.
No enhanced Uses information available for this drug.
DRUG IMAGES
FAKZYNJA 200 MG TABLET
The following indications for FAKZYNJA (defactinib hydrochloride) have been approved by the FDA:
Indications:
Low-grade serous ovarian cancer with KRAS mutation
Professional Synonyms:
Low grade serous adenocarcinoma of ovary with KRAS mutation
Indications:
Low-grade serous ovarian cancer with KRAS mutation
Professional Synonyms:
Low grade serous adenocarcinoma of ovary with KRAS mutation
The following dosing information is available for FAKZYNJA (defactinib hydrochloride):
No enhanced Dosing information available for this drug.
No enhanced Administration information available for this drug.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| FAKZYNJA 200 MG TABLET | Maintenance | Adults take 1 tablet (200 mg) by oral route 2 times per day during weeks 1 through 3 of each 4-week cycle; per protocol with avutometinib |
No generic dosing information available.
The following drug interaction information is available for FAKZYNJA (defactinib hydrochloride):
There are 0 contraindications.
There are 4 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Defactinib/Strong CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong CYP3A4 inducers may accelerate the metabolism of defactinib by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of defactinib and strong CYP3A4 inducers may result in decreased levels and effectiveness of defactinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of defactinib states that the concurrent use of strong CYP3A4 inducers should be avoided.(1) DISCUSSION: In a study, defactinib maximum concentration (Cmax) decreased by 83% and area-under-curve (AUC) by 87% following coadministration with phenytoin (strong CYP3A4 inducer) three times daily for 23 days and a single dose of defactinib 200 mg (1.0 times the approved recommended dose) on Day 14. The AUC and Cmax of N-desmethyl amide (M4), a major active metabolite of defactinib, decreased by 79% and 70%, respectively.(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's Wort.(2) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EPITOL, EQUETRO, ERLEADA, FIORICET, FIORICET WITH CODEINE, FOSPHENYTOIN SODIUM, LYSODREN, MITOTANE, MYSOLINE, ORKAMBI, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFADIN, RIFAMPIN, SEZABY, TEGRETOL, TEGRETOL XR, TENCON, TIBSOVO, XTANDI |
| Defactinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate CYP3A4 inducers may accelerate the metabolism of defactinib by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of defactinib and a moderate CYP3A4 inducer may result in decreased levels and effectiveness of defactinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of defactinib states that the concurrent use of moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: The impact of moderate CYP3A4 inhibitors on the pharmacokinetics of defactinib has not been investigated in clinical studies. In a study, defactinib maximum concentration (Cmax) decreased by 83% and area-under-curve (AUC) by 87% following coadministration with phenytoin (strong CYP3A4 inducer) three times daily for 23 days and a single dose of defactinib 200 mg (1.0 times the approved recommended dose) on Day 14. The AUC and Cmax of N-desmethyl amide (M4), a major active metabolite of defactinib, decreased by 79% and 70%, respectively.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(2) |
AUGTYRO, BOSENTAN, CAMZYOS, DUZALLO, EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, ETRAVIRINE, INTELENCE, LORBRENA, LUMAKRAS, MODAFINIL, NAFCILLIN, NAFCILLIN SODIUM, OJEMDA, ORIAHNN, ORILISSA, PROVIGIL, PYRUKYND, RIFABUTIN, SYMFI, TAFINLAR, TALICIA, THIORIDAZINE HCL, THIORIDAZINE HYDROCHLORIDE, TRACLEER, TURALIO, VONJO, WELIREG, XCOPRI, XERMELO |
| Warfarin/Defactinib SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. Defactinib may inhibit the metabolism of warfarin by CYP2C9 or CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of defactinib may result in increased INR and risk of bleeding.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The manufacturer of defactinib states that concurrent administration with warfarin should be avoided. If concurrent use cannot be avoided, monitor INR frequently during treatment with defactinib.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. Discontinue anticoagulation in patients with active pathologic bleeding. DISCUSSION: In clinical trials, cases of bleeding and increased INR occurred in patients taking defactinib concomitantly with warfarin.(1) |
JANTOVEN, WARFARIN SODIUM |
| Defactinib/H2 Antagonists; Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The aqueous solubility of defactinib is pH dependent. Higher gastric pH leads to lower solubility which may reduce defactinib absorption.(1) CLINICAL EFFECTS: Coadministration of H2 antagonists or proton pump inhibitors (PPIs) may reduce the bioavailability of defactinib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of defactinib states that concurrent use with H2 antagonists or proton pump inhibitors should be avoided.(1) If concurrent use with an acid-reducing agent cannot be avoided, administer defactinib 2 hours before or 2 hours after the administration of a locally acting antacid.(1) DISCUSSION: In an interaction study, defactinib area-under-the-curve (AUC) decreased by 79% and maximum concentration (Cmax) decreased by 85% following concomitant use of multiple doses of omeprazole 40 mg daily. The AUC and Cmax of N-desmethyl amide (M4), a major metabolite of defactinib, decreased by 83% and 88%, respectively.(1) |
ACIPHEX, ACIPHEX SPRINKLE, CIMETIDINE, DEXILANT, DEXLANSOPRAZOLE DR, ESOMEPRAZOLE MAGNESIUM, ESOMEPRAZOLE SODIUM, FAMOTIDINE, IBUPROFEN-FAMOTIDINE, KONVOMEP, LANSOPRAZOL-AMOXICIL-CLARITHRO, LANSOPRAZOLE, NAPROXEN-ESOMEPRAZOLE MAG, NEXIUM, NIZATIDINE, OMECLAMOX-PAK, OMEPRAZOLE, OMEPRAZOLE-SODIUM BICARBONATE, PANTOPRAZOLE SODIUM, PANTOPRAZOLE SODIUM-0.9% NACL, PEPCID, PREVACID, PRILOSEC, PROTONIX, PROTONIX IV, RABEPRAZOLE SODIUM, TALICIA, VIMOVO, YOSPRALA |
There are 1 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Defactinib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of defactinib is pH dependent. Higher gastric pH leads to lower solubility which may reduce defactinib absorption.(1) CLINICAL EFFECTS: Coadministration with antacids may reduce the bioavailability of defactinib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of defactinib states that patients requiring acid-lowering therapy should separate defactinib from antacid administration by 2 hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: The impact of antacids on the pharmacokinetics of defactinib has not been investigated in clinical studies. In an interaction study, defactinib area-under-the-curve (AUC) decreased by 79% and maximum concentration (Cmax) decreased by 85% following concomitant use of multiple doses of omeprazole 40 mg daily. The AUC and Cmax of N-desmethyl amide (M4), a major active metabolite of defactinib, decreased by 83% and 88%, respectively.(1) |
CALCIUM ACETATE, CALCIUM GLUCONATE MONOHYDRATE, GAVILYTE-C, GAVILYTE-G, GAVILYTE-N, GOLYTELY, KONVOMEP, OMEPRAZOLE-SODIUM BICARBONATE, PEG 3350-ELECTROLYTE, PEG-3350 AND ELECTROLYTES, Q-CARE RX, SODIUM BICARBONATE, VAXCHORA BUFFER COMPONENT |
The following contraindication information is available for FAKZYNJA (defactinib hydrochloride):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
There are 1 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Pregnancy |
There are 0 moderate contraindications.
The following adverse reaction information is available for FAKZYNJA (defactinib hydrochloride):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 4 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Hydronephrosis Intestinal obstruction Pyelonephritis Sepsis |
| Rare/Very Rare |
|---|
| None. |
There are 46 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Abnormal hepatic function tests Acute abdominal pain Anemia Constipation Cough Diarrhea Dry skin Dyspepsia Dyspnea Edema Fatigue Hyperbilirubinemia Hypertriglyceridemia Increased creatine kinase level Lymphopenia Musculoskeletal pain Nausea Neutropenic disorder Pruritus of skin Skin rash Stomatitis Thrombocytopenic disorder Urinary tract infection Visual changes Vomiting |
Alopecia Anorexia Dizziness Dry eye Dysgeusia Headache disorder Hemorrhage Hypertension Hypoalbuminemia Hypokalemia Paronychia Periorbital edema Peripheral neuropathy Proteinuria Retinal detachment Skin photosensitivity Upper respiratory infection Venous thrombosis Vitreous floater Weight loss Xerostomia |
| Rare/Very Rare |
|---|
| None. |
The following precautions are available for FAKZYNJA (defactinib hydrochloride):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
No enhanced Pregnancy information available for this drug.
No enhanced Lactation information available for this drug.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for FAKZYNJA (defactinib hydrochloride):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for FAKZYNJA (defactinib hydrochloride)'s list of indications:
| Low-grade serous ovarian cancer with KRAS mutation | |
| C56 | Malignant neoplasm of ovary |
| C56.1 | Malignant neoplasm of right ovary |
| C56.2 | Malignant neoplasm of left ovary |
| C56.3 | Malignant neoplasm of bilateral ovaries |
| C56.9 | Malignant neoplasm of unspecified ovary |
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