idelalisib

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
eye-dela-li-sib

Trade Name(s)

• Zydelig

Ther. Class.

antineoplastics

Pharm. Class.

kinase inhibitors

Indications

Relapsed chronic lymphocytic leukemia (CLL) (in combination with rituximab).

Action

Acts as an inhibitor of phosphatidylinositol 3-kinase; induces apoptosis and inhibits cell proliferation in malignant B-cell and tumor cells; also inhibits some cell-signaling pathways, chemotaxis, adhesion, and cell viability.

Therapeutic Effect(s):

Decreased progression of CLL.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A isoenzymes. Metabolites are excreted in feces (78%) and urine (14%).

Half-life: 8.2 hr.

TIME/ACTION PROFILE (↑ in progression-free survival†)

Contraindication/Precautions

Contraindicated in:

• History of serious allergic reactions including anaphylaxis or toxic epidermal necrolysis;
• Concurrent use of other hepatotoxic drugs;
• Concurrent use of drugs that cause diarrhea;
• OB:  Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Renal impairment (CCr ≤15 mL/min);
• Underlying hepatic impairment (monitor for toxicity; safety and effectiveness in patients with baseline ALT or AST values >2.5 times upper limit of normal [ULN] or bilirubin >1.5 times ULN not established);
• Rep:  Women of reproductive potential;
• Pedi:  Safety and effectiveness not established in children;
• Geri:  Older adults may be more sensitive to drug effects.

Adverse Reactions/Side Effects

CV: peripheral edema

Derm: rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: nasal congestion

Endo: hyperglycemia, hypoglycemia

F and E: hyponatremia

GI: ↑ liver enzymes, abdominal pain, COLITIS/DIARRHEA, HEPATOTOXICITY, nausea, vomiting, INTESTINAL PERFORATION, stomatitis

Hemat: anemia, NEUTROPENIA, thrombocytopenia

Metabolic: hypertriglyceridemia

MS: arthralgia, pain

Neuro: fatigue, headache, insomnia, weakness

Resp: cough, dyspnea, PNEUMONITIS

Misc: chills, fever, INFECTION, night sweats, ANAPHYLAXIS

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Strong CYP3A inducers, including  carbamazepine,,  phenytoin  or  rifampin, may ↓ levels and effectiveness; avoid concurrent use.
•  Strong CYP3A inhibitors, including  ketoconazole, may ↑ levels and risk of toxicity; careful monitoring recommended.
• May ↑ levels and risk of toxicity of  CYP3A substrates, including  midazolam ; avoid concurrent use.

Route/Dosage

PO (Adults): 150 mg twice daily; continue until disease progression or unacceptable toxicity.

Availability

Tablets: 100 mg, 150 mg

Assessment

• Monitor for diarrhea (stools ↑ by >6 or more/day); may occur at any time. Responds poorly to antidiarrheal agents; may respond to corticosteroids.  If moderate diarrhea (↑ of 4–6 stools/day over baseline) occurs,  maintain dose and monitor at least weekly until resolved.  If severe diarrhea (↑ of ≥7 stools/day over baseline) or diarrhea requiring hospitalization occurs,  withhold dose and monitor at least weekly until resolved; then resume idelalisib at 100 mg twice daily.  If life-threatening diarrhea occurs,  discontinue idelalisib permanently.
• Monitor for signs and symptoms of pneumonitis (cough, dyspnea, hypoxia, interstitial infiltrates, decline >5% in oxygen saturation). Discontinue therapy with any symptoms of pneumonitis and treat with corticosteroids.
• Monitor for signs and symptoms of intestinal perforation (moderate to severe diarrhea, new or worsening abdominal pain, chills, fever, nausea, vomiting). Discontinue idelalisib permanently if intestinal perforation occurs.
• Assess for signs and symptoms of infection (fever), including pneumonia, sepsis, febrile neutropenia, cytomegalovirus (CMV) or viremia,  Pneumocystis jiroveci (PJP), periodically during therapy. If symptoms of infection, CMV infection or viremia, or PJP occur, hold therapy until infection resolved. If therapy resumed, monitor for CMV reactivation (positive PCR or antigen test) at least monthly. If PJP infection confirmed, discontinue therapy permanently.
• Assess for cutaneous reactions (SJS, TEN, exfoliative dermatitis, rash, erythema, macular or maculopapular rash, pruritus). Discontinue idelalisib if skin reactions occur.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling, eosinophilia) periodically during therapy. If symptoms occur, discontinue idelalisib.
• Monitor for signs and symptoms of anaphylaxis (dyspnea, wheezing, facial swelling). Discontinue idelalisib if symptoms occur.

Lab Test Considerations:

Verify negative pregnancy test prior to starting therapy. Monitor AST, ALT, and serum bilirubin every 2 wk for 3 mo, then every 4 wk for next 3 mo, then every 1–3 mo thereafter.  If AST/ALT >3–5 times ULN or bilirubin >1.5–3 times ULN,  maintain dose and monitor weekly until ≤ 1 times ULN.  If AST/ALT >5–20 times ULN or bilirubin >3–10 times ULN,  withhold dose. Monitor at least weekly until AST/ALT and/or bilirubin <1 times ULN; then resume dose at 100 mg twice daily.  If AST/ALT >20 times ULN and/or if bilirubin >10 times ULN,  discontinue idelalisib permanently. Usually occurs within first 12 wk of therapy and reversible with dose interruption.

• Monitor CBC and platelet counts at least every 2 wk for first 3 mo.  If neutropenia occurs and ANC is 1.0–<1.5 Gi/L,  maintain idelalisib dose.  If ANC 0.5–1.0 Gi/L,  maintain dose and monitor ANC at least weekly.  If ANC <0.5 Gi/L, hold idelalisib; monitor ANC at least weekly until ANC ≥0.5 Gi/L; then may resume idelalisib at 100 mg twice daily.
• If thrombocytopenia occurs and platelets 50–<75 Gi/L, maintain idelalisib dose. If platelets 25–<50 Gi/L, maintain dose and monitor platelet count at least weekly. If platelets <25 Gi/L, hold idelalisib; monitor platelet counts at least weekly until platelet count ≥25 Gi/L; then may resume idelalisib at 100 mg twice daily.
• May cause ↓ hemoglobin.

Implementation

• Avoid concurrent use of medications causing hepatotoxicity or diarrhea.

  • Administer PJP prophylaxis during therapy.
• PO Administer twice daily without regard to food.  DNC: Swallow tablets whole; do not crush, break, or chew. 

Patient/Family Teaching

• Instruct patient to take idelalisib as directed. If a dose is missed by <6 hr, take as soon as remembered; if missed by >6 hr, wait and take next scheduled dose at usual time. 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 diarrhea (bowel movements ↑ by 6 or more/day), severe abdominal pain, severe skin reactions (painful sores or ulcers on skin, lips, or mouth; severe rash with blisters or peeling skin), signs and symptoms of anaphylaxis, DRESS, fever, or signs of infection occur or if signs and symptoms of liver toxicity (yellowing of skin or whites of eyes, dark or brown urine, bruising, abdominal pain in upper right side, bleeding) or pneumonitis (cough, dyspnea), occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Rep:  May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during therapy and for at least 1 mo after last dose of idelalisib. Advise patient to notify health care professional promptly if pregnancy is suspected. Advise males with female partners of reproductive potential to use effective contraception during therapy and for 3 mo after last dose.

Evaluation/Desired Outcomes

Decreased progression of CLL.