Duvelisib – Uses, Dosage, Side Effects, Interaction

Contraindications

• a bad infection
• low levels of a type of white blood cell called neutrophils
• a type of inflammation of the lung called interstitial pneumonitis
• inflammation of the large intestine
• abnormal liver function tests
• pregnancy
• a patient who is producing milk and breastfeeding

Dosage

Strengths: 15 mg; 25 mg

Chronic Lymphocytic Leukemia

• 25 mg orally 2 times a day in 28-day cycles until unacceptable toxicity or progressive disease
• If a dose is missed by fewer than 6 hours, take the missed dose right away and take the next dose as usual. If a dose is missed by more than 6 hours, wait and take the next dose at the usual time.
• Provide prophylaxis for Pneumocystis jirovecii (PJP) during therapy with this drug.
• Withhold therapy in patients with suspected PJP of any Grade and discontinue if PJP is confirmed.
• Consider prophylactic antivirals during therapy to prevent cytomegalovirus (CMV) infection/reactivation.

Dose Adjustments

DOSE MODIFICATION LEVELS:

• Initial dose: 25 mg orally 2 times a day
• Dose reduction: 15 mg orally 2 times a day
• Subsequent dose modification: Discontinue therapy if the patient is unable to tolerate 15 mg orally 2 times a day.

Nonhematologic Adverse Reactions:
INFECTION:

• Grade 3 or greater infection: Withhold therapy until resolved; resume at the same or reduced dose.
• CMV infection or viremia (positive PCR or antigen test): Withhold therapy until resolved; resume at the same or reduced dose; if therapy is resumed, monitor for CMV reactivation (by PCR or antigen test) monthly.
• Pneumocystis jiroveci pneumonia (PJP): For suspected PJP, withhold therapy until evaluated; for confirmed PJP, discontinue therapy.

NON-INFECTIOUS DIARRHEA OR COLITIS:

• Mild/moderate diarrhea (Grade 1 or 2, up to 6 stools per day over baseline) and responsive to antidiarrheal agents, OR asymptomatic (Grade 1) colitis: Maintain current dose; initiate antidiarrheals if needed; monitor weekly until resolved.
• Mild/moderate diarrhea (Grade 1 or 2, up to 6 stools per day over baseline) and unresponsive to antidiarrheals: Withhold therapy until resolved; initiate enteric-acting steroids (e.g., budesonide); monitor weekly until resolved; resume at a reduced dose.
• Abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, OR severe diarrhea (Grade 3, greater than 6 stools per day over baseline): Withhold therapy until resolved; initiate enteric acting steroids (e.g., budesonide) or systemic steroids; monitor weekly until resolved; resume at a reduced dose. For life-threatening recurrent Grade 3 diarrhea or recurrent colitis of any Grade, discontinue therapy.

CUTANEOUS REACTIONS:

• Grade 1 to 2: Maintain dose; initiate emollients, antihistamines, or topical steroids; monitor closely.
• Grade 3: Withhold therapy until resolved; initiate emollients, antihistamines, or topical steroids; monitor weekly until resolved; resume at a reduced dose. If the severe cutaneous reaction does not improve, worsens, recurs, or becomes life-threatening, discontinue therapy.
• SJS, TEN, DRESS (any Grade): Discontinue therapy.

PNEUMONITIS WITHOUT SUSPECTED INFECTIOUS CAUSE:

• Moderate (Grade 2) symptomatic pneumonitis: Withhold therapy; initiate systemic steroids; if pneumonitis recovers to Grade 0 or 1, resume therapy at a reduced dose; if non-infectious pneumonitis recurs or the patient does not respond to steroid therapy, discontinue this drug.
• Severe (Grade 3) or life-threatening pneumonitis: Discontinue therapy; initiate systemic steroids.

ALT/AST ELEVATION:

• Grade 2 (3 to 5 x upper limit of normal [ULN]): Maintain dose; monitor weekly until recovery to less than 3 x ULN.
• Grade 3 (greater than 5 to 20 x ULN: Withhold therapy and monitor weekly until recovery to less than 3 x ULN; resume at the same dose (first occurrence) or reduce dose for subsequent occurrences.
• Grade 4 (greater than 20 x ULN: Discontinue therapy.

Hematologic Adverse Reactions:
NEUTROPENIA:

• Absolute neutrophil count (ANC) 0.5 to 1 Gi/L: Maintain dose; monitor ANC weekly.
• ANC less than 0.5 Gi/L: Withhold therapy; monitor ANC until greater than 0.5 Gi/L; resume at the same dose (first occurrence) or reduce dose for subsequent occurrences.

THROMBOCYTOPENIA:

• Grade 3 (platelet count 25 to less than 50 Gi/L with Grade 1 bleeding: Maintain dose; monitor platelet counts weekly.
• Grade 3 (platelet count 25 to less than 50 Gi/L with Grade 2 bleeding or Grade 4 (platelet count less than 25 Gi/L): Withhold therapy; monitor platelet count until 25 Gi/L or greater and resolution of bleeding; resume at the same dose (first occurrence) or reduce dose for subsequent occurrences.

Dose Modification for Concomitant Use with CYP450 3A4 Inhibitors:

• When given with strong CYP450 3A4 inhibitors (e.g., ketoconazole), reduce the dose of this drug to 15 mg orally 2 times a day.

Administration advice:

• This drug may be taken with or without food.
• Capsules should be swallowed whole, not opened, broken, or chewed.

Side Effects

The Most Common

• nausea
• vomiting
• constipation
• tiredness
• headache
• muscle or joint pain
• yellow eyes or skin; abdominal pain; unexplained bruising or bleeding;
• loss of appetite; yellow or brown-colored urine; pale stools;
• pain in the upper right part of the stomach
• Bone pain
• constipation
• decreased appetite
• difficulty in moving
• muscle stiffness

More common

• Black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of the skin
• blood in the urine or stools
• body aches or pain
• chest pain or tightness
• chills
• cough
• cracked lips
• decreased urine
• difficulty in swallowing
• dry mouth
• ear congestion
• fever
• headache
• increased thirst
• irregular heartbeat
• itching
• joint or muscle pain
• loss of appetite
• loss of voice
• lower back or side pain
• mood changes
• muscle pain or cramps
• nausea
• numbness or tingling in the hands, feet, or lips
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• red skin lesions, often with a purple center
• red, irritated eyes
• runny or stuffy nose
• seizures
• sneezing
• sore throat
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth
• stomach cramps or pain
• swelling
• swollen glands
• tenderness
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• watery or bloody diarrhea

Rare

• chest pain
• fainting
• fever
• high blood pressure
• mouth sores
• numbness, tingling, muscle weakness, and pain
• rash
• ringing, buzzing, hissing, or clicking sounds in the ears
• shortness of breath
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of clotting problems (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
• signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• swollen hands, feet, or joints
• symptoms of fluid around the lungs (e.g., chest pain, difficult or painful breathing, cough)
• symptoms of irregular heartbeat (e.g., chest pain, dizziness, rapid, pounding heartbeat, shortness of breath)
• symptoms of a lung infection (LRTI) (e.g., shortness of breath, cough, chest pain)
• symptoms of skin cancer (e.g., skin sore, wart, or bump that does not heal)
• symptoms of a urinary tract infection (e.g., pain when urinating, urinating more often than usual, low back or flank pain)
• symptoms of fluid around the lungs (e.g., chest pain, painful breathing, cough)
• waking up in the night to urinate
• signs of bleeding in the stomach (e.g., bloody, black, or tarry stools; spitting up of blood; vomiting blood or material that looks like coffee grounds)
• signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)

Drug Interaction

References