**REMS Drug**
Pronunciation:
doo-ve-lis-ib
Trade Name(s)
Ther. Class.
Pharm. Class.
phosphatidylinositol-3-kinase inhibitors
Inhibits phosphatidylinositol-3-kinase (PI3K) in malignant B cells which leads to apoptosis and inhibition of proliferation of primary malignant B cell lines and primary CLL tumor cells.
Therapeutic Effect(s):
Decreased progression of CLL, SLL, and FL.
Absorption: 42% absorbed after oral administration.
Distribution: Extensively distributed to tissues.
Protein Binding: 98%.
Metabolism and Excretion: Primarily metabolized by the liver by the CYP3A4 isoenzyme. 79% of drug excreted in feces (11% as unchanged drug), 14% in urine (<1% as unchanged drug).
Half-life: 4.7 hr.
TIME/ACTION PROFILE (plasma concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | unknown | 1–2 hr | 12 hr |
Contraindicated in:
Use Cautiously in:
CV: edema
Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, rash
F and E: hyperkalemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia
GI: COLITIS, DIARRHEA, HEPATOTOXICITY, abdominal pain, constipation, hypoalbuminemia, ↑ amylase, ↑ lipase, ↑ liver enzymes, mucositis, nausea, vomiting, hyperbilirubinemia
GU: ↓ fertility (men), ↑ serum creatinine
Hemat: NEUTROPENIA, anemia, leukopenia, lymphocytosis, lymphopenia, thrombocytopenia
Metabolic: ↓ appetite, ↓ weight
MS: arthralgia, pain
Neuro: fatigue, headache
Resp: PNEUMONITIS, cough, dyspnea
Misc: INFECTION, fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
PO (Adults): 25 mg twice daily. Concurrent use of strong CYP3A inhibitor– 15 mg twice daily.
Capsules: 15 mg, 25 mg
Monitor for signs and symptoms of infection (fever, chills) during therapy. If ≥Grade 3 infections occur, hold duvelisib until infection resolved. Resume as same or reduced dose. If clinical cytomegalovirus (CMV) infection or viremia (positive PCR or antigen test) occurs, hold duvelisib until resolved. Resume at same or reduced dose. If resumed, monitor patient for CMV reactions (by PCR or antigen test) at least monthly. If Pneumocystis jirovecii pneumonia (PJP) occurs, hold duvelisib until infections evaluated. If PJP confirmed, discontinue duvelisib.
Monitor for new or worsening non-infectious diarrhea or colitis. For mild/moderate diarrhea (Grade 1-2, up to 6 stools per day over baseline) and responsive to antidiarrheal agents, OR asymptomatic (Grade 1) colitis, continue duvelisib at same dose. Initiate antidiarrheal agents and monitor weekly until resolved. For mild/moderate diarrhea (Grade 1-2, up to 6 stools per day over baseline) and unresponsive to antidiarrheal agents, hold duvelisib until resolved. Start enteric-acting steroids (budesonide). Monitor weekly until resolved. Resume duvelisib at reduced dose. If abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, OR severe diarrhea (Grade 3, >6 stools per day over baseline) occurs, hold duvelisib until resolved. Start enteric-acting steroids or systemic steroids. Monitor weekly until resolved. For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue duvelisib. If life-threatening diarrhea occurs, discontinue duvelisib.
Monitor for signs and symptoms of skin reactions (pruritic, erythematous, maculopapular) during therapy. For Grade 1–2 skin reactions, continue duvelisib dose. Begin therapy with emollients, antihistamines (for pruritus), or topical steroids. Monitor closely. For Grade 3 skin reactions, hold duvelisib until resolved. Begin therapy with emollients, antihistamines (for pruritus), or topical steroids. Monitor at least weekly until resolved. Resume duvelisib at reduced dose. If skin reaction does not improve, worsens, or recurs, discontinue duvelisib. If life-threatening skin reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS occur, discontinue duvelisib.
Monitor for signs and symptoms of non-infectious pneumonitis (new or progressive cough, dyspnea, hypoxia, interstitial infiltrates on a radiologic exam, decline by >5% in oxygen saturation) during therapy. For moderate (Grade 2) symptoms, hold duvelisib. Treat with systemic steroids. If recovery to Grade 0–1, resume duvelisib at reduced dose. If non-infectious pneumonitis recurs or no response to steroid therapy, discontinue duvelisib. For severe (Grade 3) or life-threatening pneumonitis, discontinue duvelisib and treat with systemic steroids.
Lab Test Considerations:
Verify negative pregnancy test before starting therapy.
Advise patient to notify health care professional immediately if signs and symptoms of infections, diarrhea (any new or worsening diarrhea, stool with mucus or blood, abdominal pain), new or worsening skin rash (painful sores or ulcers on skin, lips, or in mouth; severe rash with blisters or peeling skin; rash with itching; rash with fever), lung inflammation occur.
Decreased progression of CLL, SLL, and FL.