DOO-ve-LIS-ib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: phosphatidylinositol-3-kinase inhibitors

• Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in patients who have received 2 prior therapies.
• Relapsed or refractory follicular lymphoma (FL) in patients who have received 2 prior systemic therapies.

• 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.

• Decreased progression of CLL, SLL, and FL.

Absorption: 42% absorbed after oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: 98%.

Metabolism/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.

(plasma concentrations)

Contraindicated in:

• Concurrent use with strong CYP3A inducers
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children.

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.

Metab: ↓appetite, ↓weight.

MS: arthralgia, pain.

Neuro: fatigue, headache.

Resp: PNEUMONITIS, cough, dyspnea.

Misc: INFECTION, fever.

Drug-Drug:

• Strong CYP3A inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
• Strong CYP3A inhibitors, including ketoconazole, may ↑ levels and risk of toxicity; ↓ duvelisib dose.
• May ↑ levels and risk of toxicity of CYP3A substrates.

• 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.

• Verify negative pregnancy test before starting therapy.
  • Monitor hepatic functions during therapy. If AST/ALT ↑ to 3–5× upper limit of normal (ULN) (Grade 2), continue duvelisib dose. Monitor AST and ALT at least weekly until return to <3× ULN. If AST/ALT ↑ to 5–20× ULN (Grade 3), hold duvelisib and monitor AST and ALT at least weekly until return to <3× ULN. Resume duvelisib at same dose for 1st occurrence or reduced dose for subsequent occurrences. If AST/ALT ↑ to >20× ULN (Grade 4), discontinue duvelisib.
  • Monitor neutrophil counts at least every 2 wks for first 2 months of therapy and at least weekly in patients with Grade 3 or 4 neutrophil counts. If absolute neutrophil count (ANC) 0.5–1 mm³/L, continue duvelisib dose. Monitor ANC at least weekly. If ANC <0.5 mm³/L, hold duvelisib. Monitor ANC until >0.5 mm³/L. Resume duvelisib at same dose for 1st occurrence or reduced dose for subsequent recurrence.
  • Monitor platelet count during therapy. If platelet count 25 to <50 mm³/L (Grade 3) with Grade 1 bleeding, continue duvelisib dose. Monitor platelet counts at least weekly. If platelet count 25 to <50 mm³/L (Grade 3) with Grade 2 bleeding or platelet count <25 mm³/L (Grade 4), hold duvelisib. Monitor platelet counts until 25 mm³/L and bleeding resolves. Resume duvelisib at same dose for 1st occurrence or reduced dose for subsequent recurrence.

• Provide prophylaxis for Pneumocystis jirovecii (PJP) during therapy with duvelisib. Once therapy is completed, continue PJP prophylaxis until absolute CD4+ T-cell count >200 cells/mm³.
• PO: Administer twice daily without regard to food. DNC: Swallow capsules whole; do not open, crush, or chew.

• Instruct patient to take duvelisib as directed. Take missed doses as soon as remembered if within 6 hrs of missed dose and take next dose as usual. If >6 hrs, skip dose and take next dose as scheduled. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• 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.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any new medications.
• Rep: May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 1 mo after last dose of duvelisib. Advise patient to notify health care professional immediately if pregnancy is suspected. May impair male fertility.

• Decreased progression of CLL, SLL, and FL.

Copiktra

• Risk for infection (Adverse Reactions).
• Diarrhea (Adverse Reactions).

NDC Code^*

• 71779- Verastem, Inc.
  • 71779-115- Copiktra
    • 71779-115-01- 56 CAPSULE in 1 BOTTLE (71779-115-01)

• 71779- Verastem, Inc.
  • 71779-115- Copiktra
    • 71779-115-02- 2 PACKAGE in 1 CARTON (71779-115-02) > 28 BLISTER PACK in 1 PACKAGE (71779-115-03) > 1 CAPSULE in 1 BLISTER PACK

• 71779- Verastem, Inc.
  • 71779-125- Copiktra
    • 71779-125-01- 56 CAPSULE in 1 BOTTLE (71779-125-01)

• 71779- Verastem, Inc.
  • 71779-125- Copiktra
    • 71779-125-02- 1 PACKAGE in 1 CARTON (71779-125-02) > 28 BLISTER PACK in 1 PACKAGE (71779-125-04) > 1 CAPSULE in 1 BLISTER PACK