imetelstat

IM-e-TEL-stat

Therapeutic Classification: antineoplastics

Pharmacologic Classification: temporary class

High Alert

Low to intermediate-1 risk myelodysplastic syndromes in patients with transfusion-dependent anemia requiring ≥4 RBC units over 8 wk who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents.

Acts as a telomerase inhibitor, which reduces malignant stem and progenitor cell proliferation and apoptosis.

Therapeutic effects:

Reduction of RBC transfusions.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Protein Binding: >94%.

Metabolism/Excretion: Metabolized by nucleases to nucleotides.

Half-Life: 4.9 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

CV: atrial fibrillation/flutter

Derm: pruritus

EENT: epistaxis

GI: ↑liver enzymes

GU: ↓fertility (women), urinary tract infection

Hemat: ↑activated partial thromboplastin time, leukopenia, neutropenia, thrombocytopenia, hematoma

MS: arthralgia, myalgia, fracture

Neuro: fatigue, headache, syncope

Misc: INFUSION-RELATED REACTIONS

Drug-drug:

None reported.

IV (Adults ): 7.1 mg/kg every 4 wk. Discontinue if patient does not experience ↓ RBC transfusions after 24 wk of treatment (6 doses) or if unacceptable toxicity occurs at any time.

Lyophilized powder for injection: 47 mg/vial; 188 mg/vial

Monitor for adverse reactions for ≥1 hr after infusion completion.
Monitor for signs/symptoms of infection (fever, chills, sore throat, cough).
Assess for infusion-related reactions (fever, hypertension, hypotension, pruritus, fatigue) during and after infusion. For 1st and 2nd occurrence of Grade 2–3 infusion-related reaction, hold infusion until Grade ≤1. Restart infusion at 50% of the infusion rate administered prior to adverse reaction. For 3rd occurrence of Grade 2–3 infusion-related reaction, if Grade 2, stop infusion and restart at next cycle. If Grade 3, permanently discontinue imetelstat. For 1st occurrence of Grade 4 infusion-related reaction, stop infusion, manage symptoms with supportive care as clinically indicated, and permanently discontinue imetelstat.
Assess for other adverse reactions (GI effects, cardiac arrhythmias). For 1st and 2nd occurrence of Grade 3–4 reactions, hold infusion until Grade ≤1. Restart at one dose level lower. For 3rd occurrence of Grade 3–4 reactions, permanently discontinue imetelstat.

Lab Test Considerations:

Verify negative pregnancy status in women of reproductive potential before starting therapy.
Evaluate CBC before starting, weekly for the 1st 2 cycles, and before each cycle thereafter.
- Monitor for neutropenia. For 1st occurrence of Grade 3 neutropenia, delay dose until ANC ≥1000/mm³; restart at same dose. For 2nd and 3rd occurrences of Grade 3 neutropenia, hold dose until ANC ≥1000/mm³; restart at one dose level lower. For 4th occurrence of Grade 3 neutropenia, permanently discontinue imetelstat. For 1st and 2nd occurrences of Grade 4 neutropenia, hold dose until ANC ≥1000/mm³; restart at one dose level lower. For 3rd occurrence of Grade 4 neutropenia, permanently discontinue imetelstat. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate.
- Monitor for thrombocytopenia. For 1st occurrence of Grade 3 thrombocytopenia, hold dose until platelet count ≥50,000/mm³; restart at same dose. For 2nd and 3rd occurrences of Grade 3 thrombocytopenia, hold dose until platelet count ≥50,000/mm³; restart at one dose level lower.For 4th occurrence of Grade 3 thrombocytopenia, permanently discontinue imetelstat. For 1st and 2nd occurrences of Grade 4 thrombocytopenia,hold dose until platelet count ≥50,000/mm³; restart at one dose level lower. For 3rd occurrence of Grade 4 thrombocytopenia, permanently discontinue imetelstat. Administer platelet transfusions as appropriate.
Evaluate AST, ALT, and alkaline phosphatase before starting therapy, weekly for the 1st cycle, before each cycle thereafter, and as clinically indicated. For 1st and 2nd occurrences of Grade 3 or 4 ↑ liver enzymes, hold dose until Grade ≤1; restart at one dose lower. For 3rd occurrence of Grade 3 or 4 ↑ liver enzymes,permanently discontinue imetelstat.
Obtain hepatitis B virus screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen before starting therapy.

To prevent or reduce infusion-related reactions: Premedicate ≥30 min before each dose with antihistamine (diphenhydramine 25–50 mg IV/PO or equivalent) and corticosteroid (hydrocortisone 100–200 mg IV/PO or equivalent).
Recommended dose reduction for adverse reactions:1st dose ↓: 5.6 mg/kg. 2nd dose ↓: 4.4 mg/kg. Permanently discontinue imetelstat if unable to tolerate 4.4 mg/kg once every 4 wk.

IV Administration:

Intermittent Infusion: Reconstitution: Remove vials from refrigerator 10–15 min (not >30 min) before use. Withdraw volume equal to the required reconstituted solution from a 500-mL infusion bag of 0.9% NaCl and discard it. Reconstitute 47 mg/vial and 188 mg/vial with 1.8 mL and 6.3 mL of 0.9% NaCl. Swirl gently until powder is fully reconstituted (not >15 min). Do not shake to avoid foaming. Do not use solution if particles or discoloration present. Discard vials with any unused solution. Concentration: 31.4 mg/mL. Diluent: 500 mL 0.9% NaCl. Add reconstituted solution into the infusion bag for total final volume of approximately 500 mL. Gently invert bag 5 times to mix. Do not shake. If not used immediately, can be stored at room temperature for 18 hr or in refrigerator for 48 hr from the time of reconstitution and infusion. Rate: Infuse over 2 hr.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy. Emphasize the importance of routine laboratory testing.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Advise patient of signs/symptoms of liver dysfunction such as jaundice, abdominal pain, and dark-colored urine.
Advise patient about signs/symptoms of thrombocytopenia such as unusual bleeding or bruising and to notify health care provider immediately if symptoms occur.
Advise patient about infection prevention strategies such as hand hygiene, avoidance of crowds, wearing a mask in public, and avoiding raw foods and fresh flowers if neutropenic.
Advise patient of infusion-related reactions, to report signs/symptoms to health care provider immediately, and to seek immediate medical attention if needed.
Encourage a diet rich in iron and protein to support RBC production.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected. Advise women of reproductive potential to use effective contraception during therapy and for 1 wk after the last dose. Advise women not to breastfeed during therapy and for 1 wk after the last dose.

Reduction of RBC transfusions.

Rytelo

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US Brand Names ⬆