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irinotecan liposomal

General

Genetic Implications: Genetic Implications

Pronunciation:
eye-rye-no-tee-kan lye-po-so-mal

Trade Name(s)

  • Onivyde

Ther. Class.
antineoplastics

Pharm. Class.
enzyme inhibitors

Indications

Metastatic adenocarcinoma of the pancreas that has progressed following gemcitabine-based therapy (with 5-fluorouracil and leucovorin).

Action

Interferes with DNA synthesis by inhibiting the enzyme topoisomerase 1.

Therapeutic Effect(s):

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: 95% of irinotecan remains liposome-encapsulated.

Metabolism and Excretion: Genetic implicationConverted by the liver to SN–38, its active metabolite, which is metabolized by the liver by UDP-glucuronosyl 111 transferase 1A1 (UGT1A1) to an inactive metabolite; irinotecan also metabolized by CYP3A4 to inactive metabolites. Asian patients have higher concentration of SN–38 compared to White patients. 11–20% excreted by kidneys.

Half-life: Irinotecan– 25.8 hr; SN–38– 67.8 hr.

TIME/ACTION PROFILE

ROUTEONSETPEAKDURATION
IVunknown unknownunknown

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Bowel obstruction;
  • OB: Pregnancy (may cause fetal harm);
  • Lactation:Avoid breastfeeding.

Use Cautiously in:

  • Genetic implicationAsian patients (↑ risk of severe neutropenia);
  • Genetic implicationPatients homozygous for the UGT1A1*28 allele (i.e. with genetically reduced UGT1A1 activity) (↑ risk of neutropenia);
  • Rep: Women of reproductive potential and men with female partners of reproductive potential;
  • Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CV: bradycardia

CNS: fatigue

Derm: alopecia, diaphoresis, flushing

EENT: lacrimation, miosis, rhinitis

F and E: hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia

GI: DIARRHEA, anorexia, hypoalbuminemia, ↑ liver enzymes, nausea, stomatitis, vomiting, abdominal cramping, ↑ salivation

GU: ↓ serum creatinine

Hemat: NEUTROPENIA, THROMBOCYTOPENIA, anemia, lymphopenia

Metabolic: ↓ weight

Resp: INTERSTITIAL LUNG DISEASE

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFUSION REACTIONS, fever

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

Interactions

Drug-Drug

Drug-Natural Products:

St. John's wort ↓ levels of irinotecan and SN-38; avoid concurrent use; discontinue use ≥2 wk before initiating irinotecan.

Route/Dosage

Do not substitute for other medications containing irinotecan.

IV: (Adults) 70 mg/m2 every 2 wk. Administer prior to leucovorin and 5–fluorouracil.

IV: (Adults Homozygous for homozygous for the UGT1A1*28 allele): 50 mg/m2 every 2 wk; may ↑ dose to 70 mg/m2 as tolerated in subsequent cycles. Administer prior to leucovorin and 5–fluorouracil.

Availability

Suspension for injection: 43 mg/10 mL

Assessment

  • Observe patient for signs and symptoms of hypersensitivity reactions (rash, pruritus, laryngeal edema, wheezing). Discontinue therapy permanently if symptoms are severe.
  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Monitor closely for the development of diarrhea. Do not administer to patients with bowel obstruction. If Grade 3 or 4 diarrhea occurs, withhold therapy. Two types may occur. The early type occurs within 24 hr of administration and may be preceded by cramps and sweating. Administer atropine 0.25–1 mg IV to decrease symptoms of early-onset diarrhea. Potentially life-threatening diarrhea may occur more than 24 hr after a dose and may be accompanied by severe dehydration and electrolyte imbalance. Use loperamide 4 mg to treat late-occurring diarrhea. Monitor fluid and electrolyte replacement to prevent complications. Once recovered to ≤Grade 1, decrease dose of irinotecan liposomal to 50 mg/m2 for patients receiving 70 mg/m2, or 43 mg/m2 in patients with homozygous for UGT1A1*28 without previous increase to 70 mg/m2 . Following second occurrence of recovery from Grade 3 or 4 diarrhea, decrease irinotecan liposomal dose to 43 mg/m2 for patients receiving 70 mg/m2, or 35 mg/m2 in patients with homozygous for UGT1A1*28 without previous increase to 70 mg/m2 . If diarrhea occurs a third time, discontinue therapy.
  • Nausea and vomiting are common. Pretreat with dexamethasone 10 mg along with agents such as ondansetron or granisetron at least 30 min before administration.
  • If signs of pulmonary toxicity (progressive dyspnea, cough, fever) occur, interrupt therapy. If interstitial lung disease is determined, discontinue therapy.
  • Assess for cholinergic symptoms (rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, abdominal cramping, diarrhea) during therapy. Atropine IV may be used to prevent or treat symptoms.
  • Monitor for signs and symptoms of infusion reactions (rash, urticaria, periorbital edema, pruritus). May occur day of infusion.

Lab Test Considerations:

Monitor CBC with differential and platelet count on Days 1 and 8 of every cycle and more frequently if indicated. Temporarily discontinue therapy if absolute neutrophil count is <1500 cells/mm3 or if neutropenic fever occurs. Resume therapy when ANC ≥1500/mm3 If Grade 3 or 4 neutropenia occurs, decrease subsequent dose of irinotecan liposomal to 50 mg/m2 for patients receiving 70 mg/m2, or 43 mg/m2 in patients with homozygous for UGT1A1*28 without previous increase to 70 mg/m2 . Following second occurrence of recovery from Grade 3 or 4 neutropenia, decrease irinotecan liposomal dose to 43 mg/m2 for patients receiving 70 mg/m2, or 35 mg/m2 in patients with homozygous for UGT1A1*28 without previous increase to 70 mg/m2 . Discontinue therapy if neutropenia occurs again.

  • May cause ↑ serum alkaline phosphatase and AST concentrations and ↓ serum levels of calcium, potassium, magnesium, sodium, phosphate, and albumin.

Potential Diagnoses

Implementation

  • Intermittent Infusion: Diluent: Dilute dose in 500 mL or D5W or 0.9% NaCl. Mix by gentle inversion. Solution is a white to slightly yellow, opaque, liposomal dispersion. Administer within 4 hrs of dilution if stored at room temperature or 24 hrs if refrigerated; do not freeze. Protect solution from light.
  • Rate: Administer over 90 min; do not use in-line filters. Discard unused portion.

Patient/Family Teaching

  • Instruct patient to report occurrence of diarrhea to health care professional immediately, especially if it occurs more than 24 hr after dose. Diarrhea may be accompanied by severe dehydration and electrolyte imbalance. It may be life-threatening and should be treated promptly. Patient should have loperamide for treatment.
  • Instruct patient to notify health care professional promptly if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or other NSAIDs.
  • Instruct patient to notify health care professional immediately if signs and symptoms of hypersensitivity reaction (chest tightness; shortness of breath; wheezing; dizziness or faintness; or swelling of face, eyelids, or lips) or if cough or shortness of breath occurs.
  • Advise parents to notify health care professional of all Rx or OTC medications, vitamins, or herbal products, especially St. John's Wort, being taken and to consult with health care professional before taking other medications.
  • Discuss with patient possibility of hair loss. Explore methods of coping.
  • Rep: Advise female patients of the need for effective contraception and to avoid breast feeding during and for 1 mo following final dose. Advise male patients with female partners of reproductive potential to use effective contraception during and for at least 1 mo after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

Decrease in size and spread of malignancy.

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Citation

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TY - ELEC T1 - irinotecan liposomal ID - 110546 A1 - Quiring,Courtney, AU - Sanoski,Cynthia A, AU - Vallerand,April Hazard, BT - Davis's Drug Guide UR - https://im.unboundmedicine.com/medicine/view/Davis-Drug-Guide/110546/all/irinotecan_liposomal PB - F.A. Davis Company ET - 16 DB - Medicine Central DP - Unbound Medicine ER -