Read Mosby's 2014 Nursing Drug Reference Online

Authors: Linda Skidmore-Roth

Mosby's 2014 Nursing Drug Reference (437 page)

Canada only Side effects:
italics
= common;
bold
= life-threatening
Nurse Alert

regorafenib

(re′goe-raf′e-nib)

Stivarga

Func. class.:
Antineoplastic biologic-response modifier; multikinase inhibitor

Chem. class.:
Signal transduction inhibitor (STI)

ACTION:

Inhibits tyrosine kinase in patients with colorectal cancer

USES:

Metastatic colorectal cancer in those who have received fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, an anti-VEGF therapy; and an anti-EGFR therapy if
KRAS
wild type

CONTRAINDICATIONS:

Pregnancy (D)

Precautions:
Breastfeeding, children, geriatric patients, cardiac/renal/hepatic/dental disease, fistula, GI bleeding or perforation, bone marrow suppression, infection, wound dehiscence, thrombocytopenia, neutropenia, immunosuppression

Black Box Warning:

Hepatic disease

DOSAGE AND ROUTES
Calculator

• Adult:
PO
160 mg/day with a low-fat breakfast × 21 days of a 28-day cycle, cycles may be repeated

Available forms:
Tabs 40 mg

Administer:

•
Store at 77°F (25°C)

•
Give at the same time each day with a low-fat breakfast that contains less than 30% fat such as 2 slices of white toast with 1 TBSP of low-fat margarine and 1 TBSP of jelly, and 8 oz of skim milk; or 1 cup of cereal, 8 oz of skim milk, 1 slice of toast with jam, apple juice, and 1 cup of coffee or tea

•
Swallow tablets whole

•
If a dose is missed, take as soon as possible that day; do not take 2 doses on the same day

Hand–foot skin reaction

Reduce to 120 mg (grade 2 palmar–plantar erythrodysesthesia); hold if grade 2 toxicity does not improve in ≤7 days or recurs; hold for ≥7 days in grade 3 toxicity; reduce to 80 mg for recurrent grade 2 toxicity; discontinue if 80 mg is not tolerated

Hypertension

Hold in grade 2 hypertension

Other severe toxicity (except hepatotoxicity)

Hold until toxicity resolves in grade 3 or 4 toxicity; consider the risk/benefits of continuing therapy in grade 4 toxicity, reduce dosage to 120 mg; if grade 3 or 4 toxicity recurs, hold until toxicity resolves, then reduce to 80 mg; discontinue in those who do not tolerate 80-mg dose

Hepatic dose

Baseline mild (Child-Pugh class A) or moderate (Child-Pugh class B): no change; baseline severe hepatic impairment (Child-Pugh class C): use not recommended; AST/ALT elevations during therapy: For grade 3 AST/AST level elevations, hold dose; if therapy is continued, reduce to 120 mg after levels recover; discontinue in those with AST/ALT > 20× ULN; AST/ ALT > 3× ULN and bilirubin >2× ULN; recurrence of AST/ALT >5× ULN despite a reduction to 120 mg

SIDE EFFECTS

CNS:
Headache, tremor

CV:
Hypertensive crisis, MI

EENT:
Blurred vision, conjunctivitis

GI:
Hepatotoxicity, GI hemorrhage,
diarrhea,
GI perforation, xerostomia

HEMA:
Neutropenia, thrombocytopenia, bleeding

INTEG:
Rash, alopecia

META:
Hypokalemia

MISC:
Fatigue, decreased weight, hand–foot syndrome, hypothyroidism

PHARMACOKINETICS

Protein binding 99%, metabolized by CYP3A4, UGT1A0, half-life 14-58 hr

INTERACTIONS

Increase:
regorafenib concentrations—CYP3A4 inhibitors (ketoconazole, itraconazole, erythromycin, clarithromycin)

Increase:
plasma concentrations of simvastatin, calcium-channel blockers, ergots

Increase:
plasma concentration of warfarin; avoid use with warfarin; use low-molecular-weight anticoagulants instead

Decrease:
regorafenib concentrations—CYP3A4 inducers (dexamethasone, phenytoin, carBAMazepine, rifampin, PHENobarbital)

Drug/Food

Increase:
regorafenib effect—grapefruit juice; avoid use while taking product

Drug/Herb

Decrease:
imatinib concentration—St. John’s wort

NURSING CONSIDERATIONS

Assess:

Black Box Warning:

Hepatic disease: fatal hepatotoxicity can occur; obtain LFTs baseline and at least every 2 wk × 2 mo, then monthly

Fatal bleeding:

From GI, respiratory, GU tracts; permanently discontinue in those with severe bleeding

Palmar–plantar erythrodysesthesia (hand–foot syndrome):

More common in those previously treated; reddening swelling, numbness, desquamation on palms, soles

GI perforation/fistula:

Discontinue if this occurs, assess for pain in epigastric area, dyspepsia, flatulence, fever, chills

Hypertension/hypertensive crisis:

Hypertension usually occurs in the first cycle in those with preexisting hypertension, do not start treatment until B/P is controlled; monitor B/P every wk × 6 wk, then at start of each cycle or more often if needed, temporarily or permanently discontinue for severe uncontrolled hypertension

Evaluate:

•
Therapeutic response: decrease in spread or size of tumor

Teach patient/family:

•
To report adverse reactions immediately: bleeding, rash

•
About reason for treatment, expected results

•
That effect on male fertility is unknown