Duvelisib

Duvelisib is a prescription medication indicated for adults with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least 2 prior therapies

• Duvelisib is available under the following different brand names: Copiktra

Common side effects of Duvelisib include:

• diarrhea or colitis
• low white blood cell count (neutropenia)
• rash
• fatigue
• fever
• cough
• nausea
• upper respiratory infection
• pneumonia
• musculoskeletal pain
• anemia

Serious side effects of Duvelisib include:

• neutropenia
• thrombocytopenia
• sepsis 
• hypokalemia 
• increased lipase
• pneumonia and pneumonitis 

Rare side effects of Duvelisib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 15 mg
• 25 mg

CLL or SLL

Adult dosage

• 25 mg orally two times a day with or without food
• Cycle consists of 28 days

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Duvelisib has severe interactions with no other drugs.
• Duvelisib has serious interactions with at least 33 drugs.
• Duvelisib has moderate interactions with at least 223 drugs.
• Duvelisib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Duvelisib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Duvelisib?"

Cautions

• Serious, including fatal (4%), infections occurred in 31%; most common serious infections were pneumonia, sepsis, and lower respiratory tract infections; median time to onset of any grade infection was 3 months, with 75% of cases occurring within 6 months
• Cytomegalovirus (CMV) reactivation/infection and serious/fatal Pneumocystis jiroveci pneumonia (PJP) occurred in 1% of treated patients; consider prophylactic antivirals during treatment
• For clinical CMV infection or viremia, withhold therapy until infection or viremia resolves; if therapy is resumed, administer the same or reduced dose and monitor patients for CMV reactivation by PCR or antigen test at least monthly
• Treat infections prior to initiation of therapy; advise patients to report any new or worsening signs and symptoms of infection
• Serious, including fatal (1% and less), cutaneous reactions occurred in 5%; fatal cases included drug rash with eosinophilia and systemic signs (DRESS) and toxic epidermal necrolysis (TEN); median time to onset of any grade cutaneous reaction was 3 months, with median event duration of 1 month; presenting features for serious events include pruritic, erythematous, or maculopapular rash; less common features include exanthem, desquamation, erythroderma, skin exfoliation, keratinocyte necrosis, and papular rash
• Grade 3 and 4 alanine transaminase and/or aspartate aminotransferase elevation developed in 8% and 2%, respectively; median time to onset of any grade transaminase elevation was 2 months, with a median event duration of 1 month; monitor hepatic function during treatment
• Based on findings in animals and their mechanism of action, fetal harm may occur when administered to a pregnant woman
• Neutropenia
  • Grade 3 or 4 neutropenia occurred in 42%; the median time to onset of grade 3 and more neutropenia was 2 months, with 75% of cases occurring within 4 months
  • Monitor neutrophil counts at least every 2 weeks for the first 2 months of therapy, and at least weekly in patients with neutrophil counts less than 1.0 Gi/L (grades 3-4); withhold therapy in patients presenting with neutrophil counts less than 0.5 Gi/L (grade 4); monitor until absolute neutrophil count is more than 0.5 Gi/L, resume treatment at the same dose for first occurrence or a reduced dose for subsequent occurrence
• Cutaneous reactions
  • Serious, including fatal (1% and less), cutaneous reactions occurred in 5%; fatal cases included DRESS and TEN; median time to onset of any grade cutaneous reaction was 3 months, with median event duration of 1 month
  • Presenting features for serious events include pruritic, erythematous, or maculopapular rash; less common features include exanthem, desquamation, erythroderma, skin exfoliation, keratinocyte necrosis, and papular rash
  • Advise patients to report any new or worsening cutaneous reactions; review all concomitant medications and discontinue any medications potentially contributing to the event
  • For patients presenting with mild or moderate (grades 1-2) cutaneous reactions, continue therapy at the current dose, initiate supportive care with emollients, antihistamines (for pruritus), or topical steroids, and monitor the patient closely
  • Withhold treatment for severe (grade 3) cutaneous reaction until resolution; initiate supportive care with steroids (topical or systemic) or antihistamines (for pruritus); monitor at least weekly until resolved; upon resolution of the event, restart drug at a reduced dose; discontinue drug if a severe cutaneous reaction does not improve, worsens, or recurs; for life-threatening cutaneous reactions, discontinue the drug. In patients with Stevens-Johnson syndrome, TEN, or DRESS of any grade, discontinue treatment
• Pneumonitis
  • Serious, including fatal (less than 1%), pneumonitis without an apparent infectious cause occurred in 5%; the median time to onset of any grade pneumonitis was 4 months, with 75% of cases occurring within 9 months; median event duration was 1 month, with 75% of cases resolving by 2 months
  • If the pneumonitis is infectious, patients may be restarted at the previous dose once infection, pulmonary signs and symptoms resolve; for moderate non-infectious pneumonitis (grade 2), treat with systemic corticosteroids, and resume drug at a reduced dose upon resolution
  • If noninfectious pneumonitis recurs or does not respond to steroid therapy, discontinue the drug; for severe or life-threatening non-infectious pneumonitis, discontinue the drug and treat with systemic steroids
• Diarrhea or colitis
  • For patients presenting with mild or moderate diarrhea (grades 1-2) (ie, up to 6 stools per day over baseline) or asymptomatic (grade 1) colitis, initiate supportive care with antidiarrheal agents as appropriate, continue drug at the current dose, and monitor the patient at least weekly until the event resolves
  • If the diarrhea is unresponsive to antidiarrheal therapy, withhold the drug and initiate supportive therapy with enteric-acting steroids (eg, budesonide); monitor the patient at least weekly; upon resolution of diarrhea, consider restarting the drug at a reduced dose
  • For patients presenting with abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, or with severe diarrhea (grade 3) (ie, more than 6 stools per day over baseline) withhold drug and initiate supportive therapy with enteric acting steroids (eg, budesonide) or systemic steroids; a diagnostic workup to determine etiology, including colonoscopy, should be performed; monitor at least weekly
  • Upon resolution of diarrhea or colitis, restart the drug at a reduced dose; for recurrent grade 3 diarrhea or recurrent colitis of any grade, discontinue; discontinue the drug for life-threatening diarrhea or colitis
• Increase risk for death and serious side effects
  • On June 30, 2022, the FDA released a warning based on results from the phase 3 DUO trial
  • Results showed a possible increased risk for death with duvelisib compared to ofatumumab
  • Duvelisib was also associated with a higher risk for serious side effects (eg, infections, diarrhea, inflammation of the intestines and lungs, skin reactions, increased liver enzyme levels)
  • Consider the risks and benefits of continuing duvelisib compared with other available treatments
  • Advise patients currently on duvelisib of the possible increased risk for death and serious adverse events
  • Report any adverse events or side effects related to the use of these products to the FDA MedWatch Safety Information and Adverse Event Reporting Program
• Drug interactions overview
  • Effects of other drugs on duvelisib
    • Strong CYP3A4 inducers: Coadministration with strong or moderate CYP3A inducers decreases duvelisib area under the curve (AUC), which may reduce the efficacy of duvelisib; avoid coadministration of strong or moderate CYP3A4 inducers; if coadministration with moderate CYP3A4 inducer cannot be avoided, increase dose
    • Strong CYP3A inhibitors: Coadministration with a strong CYP3A inhibitor increases duvelisib AUC, which may increase the risk for duvelisib toxicities; reduce the dose when co-administered with a strong CYP3A4 inhibitor
    • Mild or moderate CYP3A4 inhibitors: No effect based on physiologically based pharmacokinetic modeling and simulation
  • Effects of duvelisib on other drugs
  • Sensitive CYP3A substrates: Coadministration with duvelisib increases the AUC of a sensitive CYP3A4 substrate, which may increase the risk for toxicities of these drugs
  • Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate

Pregnancy and Lactation

• There are no available data on pregnant women to inform the drug-associated risk
• Based on findings from animal studies and its mechanism of action, duvelisib can cause fetal harm when administered to a pregnant woman
• Conduct pregnancy testing before initiation of treatment
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for at least 1 month after the last dose
  • Males: Male patients with female partners of reproductive potential should use effective contraception during treatment and for at least 1 month after the last dose
• Infertility
  • Based on testicular findings in animals, male fertility may be impaired by treatment; no data available on drug effects on human fertility
• Lactation
  • Unknown