idelalisib

EYE-dela-li-sib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

REMS

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

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

Therapeutic effects:

Decreased progression of CLL.

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

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

Half-Life: 8.2 hr.

(↑ in progression-free survival‡)

ROUTE	ONSET	PEAK	DURATION
PO	2 mo	6 mo	10–12 mo

‡Noted for CLL.

Contraindicated in:

History of serious allergic reactions including anaphylaxis or toxic epidermal necrolysis;
Concurrent use of strong CYP3A inducers or substrates;
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 x upper limit of normal [ULN] or bilirubin >1.5 x ULN not established);
Strong CYP3A inhibitors;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be more sensitive to drug effects.

CV: peripheral edema

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

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

Metab: hypertriglyceridemia

MS: arthralgia, pain

Neuro: fatigue, headache, insomnia, weakness

Resp: cough, dyspnea, PNEUMONITIS

Misc: chills, fever, infection(pneumonia, sepsis, febrile neutropenia, Pneumocystis jiroveci pneumonia, and Cytomegalovirus infection), night sweats, ANAPHYLAXIS

Drug-drug:

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

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

Tablets: 100 mg; 150 mg

Monitor for diarrhea (stools increased by >6 or more/day); may occur at any time. Responds poorly to antidiarrheal agents; may respond to corticosteroids. If moderate diarrhea (increase of 4–6 stools/day over baseline) occurs, maintain dose and monitor at least weekly until resolved. If severe diarrhea (increase 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. 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 (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 x upper limit of normal (ULN) or bilirubin >1.5–3 x ULN, maintain dose and monitor weekly until ≤ 1 times ULN. If AST/ALT >5–20 x ULN or bilirubin >3–10 x ULN, withhold dose. Monitor at least weekly until AST/ALT and/or bilirubin <1 x ULN, then resume dose at 100 mg twice daily. If AST/ALT >20 x ULN and/or if bilirubin >10 x 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 to <75 Gi/L, maintain idelalisib dose. If platelets 25 to <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.

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.

Instruct patient to take idelalisib as directed. If a dose is missed by less than 6 hr take as soon as remembered; if missed by more than 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 increase by six 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), 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 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 and for 3 mo after last dose.

Decreased progression of CLL.

Zydelig

NDC Code

61958- Gilead Sciences, Inc.
- 61958-1701- Zydelig
  - 61958-1701-1- 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (61958-1701-1)

61958- Gilead Sciences, Inc.
- 61958-1702- Zydelig
  - 61958-1702-1- 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (61958-1702-1)

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