Impaired wound healing can occur in patients who receive drugs that inhibit the VEGF signaling pathway. Therefore, NEXAVAR® (sorafenib) has the potential to adversely affect wound healing. Withhold NEXAVAR for at least 10 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of NEXAVAR after resolution of wound healing complications has not been established.
Dose Reduction | Hepatocellular Carcinoma and Renal Cell Carcinoma | Differentiated Thyroid Carcinoma |
---|---|---|
First dose reduction | 400 mg orally once daily | 400 mg orally in the morning and 200 mg orally in the evening about 12 hours apart OR 200 mg orally in the morning and 400 mg orally in the evening about 12 hours apart |
Second dose reduction | 200 mg orally once daily OR 400 mg every other day | 200 mg orally twice daily |
Third dose reduction | None | 200 mg orally once daily |
The following may require temporary interruption or permanent discontinuation of NEXAVAR (see table below):
Adverse Reaction | Severity* | NEXAVAR Dosage Modification |
---|---|---|
Cardiovascular events | ||
Cardiac ischemia and/or infarction | Grade 2 and above | Permanently discontinue |
Congestive heart failure | Grade 3 | Interrupt† until Grade 1 or less, resume at reduced dose by 1 dose level‡ |
Grade 4 | Permanently discontinue | |
Hemorrhage | Grade 2 and above requiring medical intervention | Permanently discontinue |
Hypertension | Grade 2 (symptomatic/persistent) OR Grade 2 symptomatic increase by greater than 20 mm Hg (diastolic) or greater than 140/90 mm Hg if previously within normal limits OR Grade 3 | Interrupt until symptoms resolve and diastolic blood pressure less than 90 mm Hg, then resume at reduced dose by 1 dose level‡ If needed, reduce another dose level‡ |
Grade 4 | Permanently discontinue | |
Gastrointestinal perforation | Any grade | Permanently discontinue |
QT interval prolongation | Greater than 500 milliseconds OR Increase from baseline of 60 milliseconds or greater | Interrupt and correct electrolyte abnormalities (magnesium, potassium, calcium) Use medical judgment before restarting |
Drug-induced liver injury | Grade 3 ALT or higher in the absence of another cause§ OR AST/ALT greater than 3 x upper limit normal (ULN) with bilirubin greater than 2 x ULN in the absence of another cause§ | Permanently discontinue |
Non-hematological toxicities | Grade 2 | Continue treatment at reduced dose by 1 dose level |
Grade 3 | ||
1st occurrence | Interrupt until Grade 2 or less, then resume at reduced dose by 1 dose level | |
No improvement within 7 days OR 2nd or 3rd occurrence | Interrupt until Grade 2 or less, then resume at reduced dose by 2 dose levels | |
4th occurrence | Interrupt until Grade 2 or less, then resume at reduced dose by 2 dose levels for HCC and RCC or 3 dose levels for DTC | |
Grade 4 | Permanently discontinue |
Adverse Reaction | |
---|---|
Cardiovascular events | |
Adverse Reaction | |
Cardiac ischemia and/or infarction | |
Severity* | NEXAVAR Dosage Modification |
Grade 2 and above | Permanently discontinue |
Adverse Reaction | |
Congestive heart failure | |
Severity* | NEXAVAR Dosage Modification |
Grade 3 | Interrupt† until Grade 1 or less, resume at reduced dose by 1 dose level‡ |
Severity* | NEXAVAR Dosage Modification |
Grade 4 | Permanently discontinue |
Adverse Reaction | |
Hemorrhage | |
Severity* | NEXAVAR Dosage Modification |
Grade 2 and above requiring medical intervention | Permanently discontinue |
Adverse Reaction | |
Hypertension | |
Severity* | NEXAVAR Dosage Modification |
Grade 2 (symptomatic/persistent) OR Grade 2 symptomatic increase by greater than 20 mm Hg (diastolic) or greater than 140/90 mm Hg if previously within normal limits OR Grade 3 | Interrupt until symptoms resolve and diastolic blood pressure less than 90 mm Hg, then resume at reduced dose by 1 dose level‡ If needed, reduce another dose level‡ |
Severity* | NEXAVAR Dosage Modification |
Grade 4 | Permanently discontinue |
Adverse Reaction | |
Gastrointestinal perforation | |
Severity* | NEXAVAR Dosage Modification |
Any grade | Permanently discontinue |
Adverse Reaction | |
QT interval prolongation | |
Severity* | NEXAVAR Dosage Modification |
Greater than 500 milliseconds OR Increase from baseline of 60 milliseconds or greater | Interrupt and correct electrolyte abnormalities (magnesium, potassium, calcium) Use medical judgment before restarting |
Adverse Reaction | |
Drug-induced liver injury | |
Severity* | NEXAVAR Dosage Modification |
Grade 3 ALT or higher in the absence of another cause§ OR AST/ALT greater than 3 x upper limit normal (ULN) with bilirubin greater than 2 x ULN in the absence of another cause§ | Permanently discontinue |
Adverse Reaction | |
Non-hematological toxicities | |
Severity* | NEXAVAR Dosage Modification |
Grade 2 | Continue treatment at reduced dose by 1 dose level |
Severity* | |
Grade 3 | |
Severity* | NEXAVAR Dosage Modification |
1st occurrence | Interrupt until Grade 2 or less, then resume at reduced dose by 1 dose level |
Severity* | NEXAVAR Dosage Modification |
No improvement within 7 days OR 2nd or 3rd occurrence | Interrupt until Grade 2 or less, then resume at reduced dose by 2 dose levels |
Severity* | NEXAVAR Dosage Modification |
4th occurrence | Interrupt until Grade 2 or less, then resume at reduced dose by 2 dose levels for HCC and RCC or 3 dose levels for DTC |
Severity* | NEXAVAR Dosage Modification |
Grade 4 | Permanently discontinue |
Dermatologic Toxicity Grade | Occurrence | NEXAVAR Dosage Modification | |
---|---|---|---|
Hepatocellular and Renal Cell Carcinoma | Differentiated Thyroid Carcinoma | ||
Grade 2: Painful erythema and swelling of the hands or feet and/or discomfort affecting the patient’s normal activities | 1st occurrence | Continue NEXAVAR and consider topical therapy for symptomatic relief If no improvement within 7 days, see below | Decrease NEXAVAR to 600 mg daily If no improvement within 7 days, see below |
No improvement within 7 days at reduced dose OR 2nd and 3rd occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1 | Interrupt NEXAVAR until completely resolved or improved to Grade 1 | |
When resuming treatment, decrease dose by 1 dose level | When resuming treatment, decrease dose by 1 dose level for 2nd occurrence and 2 dose levels for 3rd occurrence | ||
4th occurrence | Discontinue NEXAVAR treatment | ||
Grade 3: Moist desquamation, ulceration, blistering, or severe pain of the hands or feet, resulting in inability to work or perform activities of daily living | 1st occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1 | Interrupt NEXAVAR until completely resolved or improved to Grade 1 |
When resuming treatment, decrease dose by 1 dose level | When resuming treatment, decrease dose by 1 dose level | ||
2nd occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1 | Interrupt NEXAVAR until completely resolved or improved to Grade 1 | |
When resuming treatment, decrease dose by 1 dose level | When resuming treatment, decrease dose by 2 dose levels | ||
3rd occurrence | Discontinue NEXAVAR treatment |
Dermatologic Toxicity Grade | Occurrence | NEXAVAR Dosage Modification |
---|---|---|
Hepatocellular and Renal Cell Carcinoma | ||
Grade 2: Painful erythema and swelling of the hands or feet and/or discomfort affecting the patient’s normal activities | 1st occurrence | Continue NEXAVAR and consider topical therapy for symptomatic relief If no improvement within 7 days, see below |
No improvement within 7 days at reduced dose OR 2nd and 3rd occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1 | |
When resuming treatment, decrease dose by 1 dose level | ||
4th occurrence | Discontinue NEXAVAR treatment | |
Grade 3: Moist desquamation, ulceration, blistering, or severe pain of the hands or feet, resulting in inability to work or perform activities of daily living | 1st occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1 |
When resuming treatment, decrease dose by 1 dose level | ||
2nd occurrence | Interrupt NEXAVAR until resolved or improved to Grade 0 to 1 | |
When resuming treatment, decrease dose by 1 dose level | ||
3rd occurrence | Discontinue NEXAVAR treatment |
Dermatologic Toxicity Grade | Occurrence | NEXAVAR Dosage Modification |
---|---|---|
Differentiated Thyroid Carcinoma | ||
Grade 2: Painful erythema and swelling of the hands or feet and/or discomfort affecting the patient’s normal activities | 1st occurrence | Decrease NEXAVAR to 600 mg daily If no improvement within 7 days, see below |
No improvement within 7 days at reduced dose OR 2nd and 3rd occurrence | Interrupt NEXAVAR until completely resolved or improved to Grade 1 | |
When resuming treatment, decrease dose by 1 dose level for 2nd occurrence and 2 dose levels for 3rd occurrence | ||
4th occurrence | Discontinue NEXAVAR treatment | |
Grade 3: Moist desquamation, ulceration, blistering, or severe pain of the hands or feet, resulting in inability to work or perform activities of daily living | 1st occurrence | Interrupt NEXAVAR until completely resolved or improved to Grade 1 |
When resuming treatment, decrease dose by 1 dose level | ||
2nd occurrence | Interrupt NEXAVAR until completely resolved or improved to Grade 1 | |
When resuming treatment, decrease dose by 2 dose levels | ||
3rd occurrence | Discontinue NEXAVAR treatment |
Following improvement of Grade 2 or 3 dermatologic toxicity to Grade 0 or 1 for at least 28 days on a reduced dose of NEXAVAR, the dose of NEXAVAR may be increased 1 dose level from the reduced dose. Approximately 50% of patients requiring a dose reduction for dermatologic toxicity are expected to meet these criteria for resumption of the higher dose and roughly 50% of patients resuming the previous dose are expected to tolerate the higher dose (that is, maintain the higher dose level without recurrent Grade 2 or higher dermatologic toxicity).
Learn more about AE management