Severe and sometimes fatal hepatotoxicity has occurred in clinical trials. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue regorafenib for hepatotoxicity as manifested by elevated liver function tests (LFTs) or hepatocellular necrosis, depending upon severity and persistence.
Colorectal cancer, metastatic: Oral: 160 mg once daily for the first 21 days of each 28-day cycle; continue until disease progression or unacceptable toxicity (Grothey 2013).
Reduced initial dosing strategy in metastatic colorectal cancer (off-label): Oral: Initial: 80 mg once daily, escalated weekly (if tolerated) to a goal of 160 mg once daily; administer on days 1 to 21 of a 28-day treatment cycle (Bekaii-Saab 2019).
Gastrointestinal stromal tumor, locally advanced, unresectable, or metastatic: Oral: 160 mg once daily for the first 21 days of each 28-day cycle; continue until disease progression or unacceptable toxicity (Demetri 2013).
Hepatocellular carcinoma: Oral: 160 mg once daily for the first 21 days of a 28-day cycle; continue until disease progression or unacceptable toxicity (Bruix 2017).
Osteosarcoma, metastatic, progressive (recurrent, relapsed, or refractory) (off-label use): Oral: 160 mg once daily on days 1 to 21 of a 28-day cycle; continue until disease progression or unacceptable toxicity (Davis 2019; Duffaud 2019).
Missed doses: Do not administer 2 doses on the same day to make up for a missed dose from the previous day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥15 mL/minute: No dosage adjustment necessary.
ESRD on dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Preexisting mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin > ULN to ≤1.5 times ULN) or moderate (total bilirubin >1.5 times to ≤3 times ULN and any AST) impairment: No dosage adjustment necessary; closely monitor for adverse effects.
Preexisting severe impairment (total bilirubin >3 times ULN): Use is not recommended (has not been studied).
Hepatotoxicity during treatment:
Grade 3 AST and/or ALT elevation: Withhold dose until recovery. If benefit of treatment outweighs toxicity risk, resume therapy at a reduced dose of 120 mg once daily.
AST or ALT >20 times ULN: Discontinue permanently.
AST or ALT >3 times ULN and bilirubin >2 times ULN: Discontinue permanently.
Recurrence of AST or ALT >5 times ULN despite dose reduction to 120 mg: Discontinue permanently.
Refer to adult dosing.
If dose reduction is necessary, reduce in 40 mg increments; the lowest recommended dose is 80 mg/day.
Dermatologic:
Grade 2 hand-foot skin reaction (HFSR; palmar-plantar erythrodysesthesia syndrome [PPES]) of any duration: Reduce dose to 120 mg once daily for first occurrence. If grade 2 HFSR recurs at this dose, further reduce the dose to 80 mg once daily. Interrupt therapy for grade 2 HFSR that is recurrent or fails to improve within 7 days in spite of dosage reduction.
Grade 3 HFSR: Interrupt therapy for a minimum of 7 days. Upon recovery, reduce dose to 120 mg once daily. If grade 2 to 3 toxicity recurs at this dose, further reduce dose to 80 mg once daily upon recovery. Interrupt therapy for grade 2 to 3 HFSR that is recurrent or fails to improve within 7 days in spite of dosage reduction.
Recurrent or persistent HFSR at 80 mg once daily: Discontinue treatment.
Other dermatologic toxicity: Withhold treatment, reduce dose or permanently discontinue treatment depending on the severity and persistence of the dermatologic toxicity. Symptomatic relief may be managed with supportive measures.
Hypertension: Grade 2 (symptomatic): Interrupt therapy.
Infection: Grade 3 or 4 (or worsening infection of any grade): Interrupt therapy; resume regorafenib at the same dose following infection resolution.
Other toxicity: Any grade 3 or 4 adverse reaction (other than hepatotoxicity or infection): Interrupt therapy; upon recovery, reduce dose to 120 mg once daily (except infection). If any grade 3 or 4 adverse reaction occurs (other than hepatotoxicity or infection) while on this reduced dose, may further reduce dose to 80 mg once daily upon recovery. For any grade 4 adverse reaction, only resume therapy if the benefit outweighs the risk. Permanently discontinue therapy if unable to tolerate 80 mg once daily.
Gastrointestinal perforation/fistula: Discontinue permanently.
Hemorrhage (severe or life-threatening): Discontinue permanently.
Reversible posterior leukoencephalopathy syndrome (RPLS): Discontinue.
Dosage adjustment for surgery: Temporarily withhold regorafenib at least 2 weeks prior to elective surgery; do not administer regorafenib for at least 2 weeks following major surgery and until adequate wound healing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Stivarga: 40 mg [contains soybean lecithin]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Stivarga: 40 mg [contains soybean lecithin]
Oral: Administer at the same time each day. Swallow tablets whole with water after a low-fat meal (containing <600 calories and <30% fat).
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Colorectal cancer, metastatic: Treatment of metastatic colorectal cancer in patients previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy (if RAS wild type).
Gastrointestinal stromal tumors: Treatment of locally advanced, unresectable, or metastatic gastrointestinal stromal tumor in patients previously treated with imatinib and sunitinib.
Hepatocellular carcinoma: Treatment of hepatocellular carcinoma (HCC) in patients previously treated with sorafenib.
According to guidelines from the American Society of Clinical Oncology for systemic therapy for advanced HCC, regorafenib is a potential second-line therapy option in patients who received atezolizumab and bevacizumab as first-line therapy, although sorafenib or lenvatinib are preferred in this setting. Regorafenib is also a second-line therapy option in patients who received first-line therapy with sorafenib or lenvatinib (ASCO [Gordan 2020]).
Osteosarcoma, metastatic, progressive (recurrent, relapsed, or refractory)
Regorafenib may be confused with axitinib, cabozantinib, crizotinib, dasatinib, enasidenib, erlotinib, imatinib, lapatinib, neratinib, nilotinib, PAZOPanib, PONATinib, ramucirumab, ripretinib, rucaparib, ruxolitinib, sorafenib, sunitinib, tivozanib, vemurafenib.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (30% to 59%; hypertensive crisis: <1%)
Dermatologic: Alopecia (7% to 24%), palmar-plantar erythrodysesthesia (45% to 67%), skin rash (26% to 30%)
Endocrine & metabolic: Hypocalcemia (17% to 59%), hypokalemia (21% to 31%), hyponatremia (30%), hypophosphatemia (55% to 70%), hypothyroidism (6% to 18%), increased amylase (23% to 26%), weight loss (13% to 32%)
Gastrointestinal: Decreased appetite (31% to 47%), diarrhea (41% to 47%), gastrointestinal pain (60%), increased serum lipase (14% to 46%), nausea (17% to 20%), stomatitis (13% to 40%; grades ≥3: 1% to 4%), vomiting (13% to 17%)
Genitourinary: Proteinuria (51% to 84%)
Hematologic & oncologic: Anemia (79%; grade 3: 5%; grade 4: 1%), hemorrhage (11% to 21%; grades ≥3: 2% to 5%), increased INR (24% to 44%; grade 3: ≤4%), lymphocytopenia (30% to 68%; grade 3: 8% to 16%; grade 4: 2%), neutropenia (3% to 16%; grade 3: 1% to 3%; grade 4: 1%), thrombocytopenia (13% to 63%; grade 3: 1% to 5%; grade 4: <1%)
Hepatic: Hyperbilirubinemia (33% to 78%), increased serum alanine aminotransferase (45% to 70%), increased serum aspartate aminotransferase (58% to 93%)
Infection: Infection (31% to 32%)
Nervous system: Fatigue (≤64%), headache (10% to 16%), pain (55% to 59%), voice disorder (18% to 39%)
Neuromuscular & skeletal: Asthenia (≤64%), muscle spasm (10% to 14%)
Miscellaneous: Fever (20% to 28%)
1% to 10%:
Dermatologic: Exfoliative dermatitis (1%)
Gastrointestinal: Mucocutaneous candidiasis (≤3%), pancreatitis (2%)
Genitourinary: Urinary tract infection (6%)
Infection: Fungal infection (≤3%)
Neuromuscular & skeletal: Tremor (1%)
Respiratory: Nasopharyngitis (4%), pneumonia (3%)
<1%:
Cardiovascular: Acute myocardial infarction, ischemic heart disease
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Gastrointestinal: Gastrointestinal fistula, gastrointestinal perforation
Nervous system: Reversible posterior leukoencephalopathy syndrome
Frequency not defined: Hepatic: Hepatic failure, hepatotoxicity
Postmarketing:
Cardiovascular: Aneurysm (arterial), aortic aneurysm, aortic dissection, cardiac failure, coronary artery dissection, myocardial rupture (arterial rupture and aortic rupture)
Genitourinary: Nephrotic syndrome
Hypersensitivity: Hypersensitivity reaction
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to regorafenib, any component of the formulation, or sorafenib.
Concerns related to adverse effects:
• Cardiovascular events: Myocardial ischemia and infarction were observed at a higher incidence than placebo in a clinical trial. Interrupt therapy in patients who develop new or acute onset ischemia or infarction; resume only if the benefit of therapy outweighs the cardiovascular risk.
• Dermatologic toxicity: Skin reactions occurred commonly, including hand-foot skin reaction (HFSR), also known as palmar-plantar erythrodysesthesia syndrome, and severe rash requiring dose reduction. Grade 3 or 4 HFSR was observed more frequently in regorafenib-treated patients (compared to placebo), and although rare, erythema multiforme and Stevens Johnson syndrome were also observed more frequently in regorafenib-treated patients. Toxic epidermal necrolysis has also been reported (rare). Onset of HFSR typically occurs in the first cycle of treatment. Therapy interruptions, dosage reductions, and/or discontinuation may be necessary depending on the severity and persistence. Supportive treatment may be of benefit for symptomatic relief. Pooled data from several clinical trials showed a higher incidence of HFSR in Asian patients compared to Caucasians.
In addition to recommended dosage modifications, the following treatments may be used for management of HFSR (McLellan 2015): A manicure/pedicure to remove hyperkeratotic areas/calluses which may predispose to HFSR and mechanical support/correction for abnormal weight bearing prior to treatment are recommended. During treatment, patients should use alcohol-free moisturizers liberally, reduce exposure to hot water (may exacerbate hand-foot symptoms), avoid constrictive footwear and excessive skin friction, and avoid vigorous exercise/activities that may stress hands or feet. Patients should wear thick cotton gloves/socks and wear shoes with padded insoles. Grade 1 HFSR may be relieved with moisturizing creams, cotton gloves and socks (at night) and/or keratolytic creams such as urea (10% to 40%) or salicylic acid (6%) along with a topical analgesic (eg, lidocaine gel) to relieve pain. Apply topical steroid (eg, clobetasol ointment or foam) twice daily to erythematous areas of grade 2 HFSR (in addition to continuing grade 1 management); topical analgesics and then systemic analgesics (if appropriate) may be used for pain control; dose reduction may be necessary. Grade 3 HFSR should be managed by continuing grades 1 and 2 symptomatic management and interrupting treatment for at least 7 days until resolved to grade 1 or lower.
• Gastrointestinal perforation: Gastrointestinal perforation or fistula has occurred in a small number of patients treated with regorafenib; some cases were fatal. Monitor for signs/symptoms of perforation (fever, abdominal pain with constipation, and/or nausea/vomiting); permanently discontinue if perforation or fistula develop.
• Hemorrhage: The incidence of hemorrhage was increased with regorafenib. Hemorrhage of the respiratory, gastrointestinal, or genitourinary tracts was observed in trials; some cases were fatal. Permanently discontinue in patients who experience severe or life-threatening bleeding. In patients receiving concomitant warfarin, monitor INR frequently.
• Hepatotoxicity: [US Boxed Warning]: Severe and sometimes fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function at baseline and during treatment. Interrupt therapy for hepatotoxicity; dose reductions or discontinuation are necessary depending on the severity and persistence. Hepatic dysfunction, characterized by a hepatocellular injury pattern, typically occurred with the first 2 months of treatment in clinical trials. Closely monitor in patients with mild or moderate impairment for adverse events; use is not recommended in severe impairment. A higher incidence of hepatotoxicity has been observed in Asian patients (particularly Japanese), compared to Caucasians (Li 2015).
• Hypersensitivity: Hypersensitivity reactions have been observed with regorafenib.
• Hypertension: Elevated blood pressure was observed in clinical trials (onset typically in the first cycle of therapy); ensure blood pressure is adequately controlled prior to initiation. Monitor blood pressure weekly for the first 6 weeks and monthly thereafter or as clinically indicated; if hypertension develops, interrupt therapy or permanently discontinue for severe or uncontrolled hypertension. Hypertensive crisis has occurred in some patients. Patients 65 years and older had an increased incidence of grade 3 or higher hypertension (compared to younger patients).
• Infection: An increased rate of infection (including fatal events) was observed in regorafenib-treated patients in clinical trials. The most commonly reported infections were urinary tract infections, nasopharyngitis, mucocutaneous and systemic fungal infections, and pneumonia. Respiratory infections were the most commonly reported fatal infections. Interrupt therapy for grade 3 or 4 infections (or worsening infection of any grade).
• Reversible posterior leukoencephalopathy syndrome (RPLS): RPLS occurred very rarely in regorafenib-treated patients; evaluate promptly if symptoms (eg, seizures, severe headache, visual disturbances, confusion or altered mental function) occur. Discontinue if diagnosis is confirmed.
• Wound healing impairment: VEGF-receptor inhibitors are associated with impaired wound healing, therefore, regorafenib may affect wound healing. Withhold regorafenib treatment for ≥2 weeks prior to elective surgery; do not administer regorafenib for ≥2 weeks following major surgery and until adequate wound healing. The safety of resuming regorafenib treatment after resolution of wound healing complications has not been established.
Special populations:
• Asian patients: A higher incidence of hepatotoxicity and hand-foot skin reactions were observed in Asian patients, particularly in Japanese patients, compared to non-Asian patients (Li 2015).
• Colorectal cancer: Consider a reduced initial dose in patients with metastatic colorectal cancer. In a dose escalation study comparing an initial dose of 80 mg/day (escalated gradually to 160 mg/day on days 1 to 21 every 28 days) to the standard dose (160 mg/day on days 1 to 21 every 28 days), more patients receiving the lower initial dose were able to initiate a third treatment cycle. The lower initial dose demonstrated a decreased incidence of adverse events, with no significant difference in median overall survival, compared to the standard dose (Bekaii-Saab 2019).
Substrate of CYP3A4 (major), UGT1A9; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, UGT1A1
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Regorafenib may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Belinostat: UGT1A1 Inhibitors may increase the serum concentration of Belinostat. Risk X: Avoid combination
Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification
Bisphosphonate Derivatives: Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: Monitor therapy
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Regorafenib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Regorafenib. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Risk X: Avoid combination
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Grapefruit Juice: May decrease serum concentrations of the active metabolite(s) of Regorafenib. Grapefruit Juice may increase the serum concentration of Regorafenib. Risk X: Avoid combination
Irinotecan Products: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase the serum concentration of Irinotecan Products. Risk X: Avoid combination
Neomycin (Systemic): May decrease serum concentrations of the active metabolite(s) of Regorafenib. Risk C: Monitor therapy
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Rosuvastatin: Regorafenib may increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 10 mg daily when combined with regorafenib. Monitor closely for increased rosuvastatin effects/toxicities (eg, myalgias, rhabdomyolysis) when these agents are combined. Risk D: Consider therapy modification
Sacituzumab Govitecan: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be increased. Risk X: Avoid combination
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
St John's Wort: May increase serum concentrations of the active metabolite(s) of Regorafenib. St John's Wort may decrease the serum concentration of Regorafenib. Risk X: Avoid combination
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification
Warfarin: May enhance the adverse/toxic effect of Regorafenib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
A high-fat meal (945 calories and ~55 g fat) increased the mean AUC of the parent drug by 48% compared to the fasted state and decreased the mean AUC of the M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl) active metabolites by 20% and 51%, respectively (compared to a fasted state). A low-fat meal (319 calories and ~8 g fat) increased the mean AUC of regorafenib, M-2, and M-5 by 36%, 40%, and 23%, respectively (as compared to the fasted state). Management: Administer after a low-fat meal (containing <600 calories and <30% fat).
Regorafenib serum concentrations may be altered when taken with grapefruit or grapefruit juice. Management: Avoid concurrent use.
Women of reproductive potential and men with female partners of reproductive potential should use effective contraception during therapy and for at least 2 months following treatment.
Based on animal reproduction studies and on the mechanism of action, regorafenib may cause fetal harm if administered during pregnancy.
It is not known if regorafenib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 2 weeks after the last dose.
Avoid grapefruit juice.
Obtain liver function tests at baseline, every 2 weeks during the first 2 months of treatment, then monthly or more frequently if clinically necessary (weekly until improvement if liver function tests are elevated). CBC with differential and platelets and serum electrolytes (baseline and periodic). Monitor INR more frequently if receiving warfarin. Monitor blood pressure weekly for the first 6 weeks of therapy and with every subsequent cycle, or more frequently if indicated. Monitor for hand-foot skin reaction (HFSR)/palmar-plantar erythrodysesthesia syndrome (PPES); it is recommended to monitor for signs of HFSR during the first weeks of treatment, then every 1 to 2 weeks for 2 cycles, then every 4 to 6 weeks thereafter (McLellan 2015). Monitor for signs/symptoms of cardiac ischemia or infarction, bleeding, GI perforation or fistula, infection, and reversible posterior leukoencephalopathy syndrome (severe headaches, seizure, confusion, or change in vision). Monitor for impaired wound healing. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Regorafenib is a multikinase inhibitor; it targets kinases involved with tumor angiogenesis, oncogenesis, and maintenance of the tumor microenvironment which results in inhibition of tumor growth. Specifically, it inhibits VEGF receptors 1-3, KIT, PDGFR-alpha, PDGFR-beta, RET, FGFR1 and 2, TIE2, DDR2, TrkA, Eph2A, RAF-1. BRAF, BRAFV600E, SAPK2, PTK5, and Abl.
Protein binding: 99.5% to plasma proteins (active metabolites M-2 and M-5 are also highly protein bound).
Metabolism: Hepatic via CYP3A4 and UGT1A9, primarily to active metabolites M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl).
Bioavailability: Tablets: 69% to 83% (compared to an oral solution).
Half-life elimination: Regorafenib: 28 hours (range: 14 to 58 hours); M-2 metabolite: 25 hours (range: 14 to 32 hours); M-5 metabolite: 51 hours (range: 32 to 70 hours).
Time to peak: 4 hours.
Excretion: Feces (~71%; 47% as parent compound; 24% as metabolites); Urine (19%; 17% as glucuronides).
Tablets (Stivarga Oral)
40 mg (per each): $292.18
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