carfilzomib

Contraindicated in:

Severe hepatic impairment;
Concurrent use with melphalan and prednisone in newly diagnosed patients ineligible for transplant (↑ risk of serious/fatal adverse reactions);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

History of cardiovascular disease (may ↑ risk of adverse cardiovascular reactions, safe and effective use in patients with New York Heart Association Class III and IV HF, recent MI, or conduction abnormalities has not been established);
Large tumor load (↑ risk of tumor lysis syndrome);
Dehydration, diarrhea or electrolyte abnormalities (correct prior to treatment);
Mild or moderate hepatic impairment (↓ dose);
Renal impairment (↑ risk of acute renal failure);
Prior or current use of immunosuppressants (↑ risk of progressive multifocal leukoencephalopathy);
Rep: Women of reproductive potential and men with female sexual partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: ↑risk of cardiovascular events in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, peripheral edema, DEEP VEIN THROMBOSIS, HF, MYOCARDIAL ISCHEMIA/INFARCTION, SUDDEN CARDIAC DEATH

Endo: hypoglycemia, atrial fibrillation

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

GI: anorexia, constipation, diarrhea, HEPATIC FAILURE, hepatotoxicity, nausea

GU: acute renal failure

Hemat: anemia, leukopenia, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (hus), lymphopenia

MS: back pain, chest wall pain, muscle spasms

Neuro: dizziness, fatigue, headache, hypoesthesia, insomnia, posterior reversible encephalopathy syndrome (pres), weakness, peripheral neuropathy, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Resp: cough, dyspnea, ACUTE RESPIRATORY DISTRESS SYNDROME, INTERSTITIAL LUNG DISEASE, PNEUMONITIS, pulmonary edema, PULMONARY EMBOLISM, pulmonary hypertension

Misc: fever/chills, INFUSION REACTIONS (INCLUDING FACIAL AND LARYNGEAL EDEMA), TUMOR LYSIS SYNDROME

Interactions ⬆ ⬇

Drug-drug:

None reported.

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 10 mg/vial; 30 mg/vial; 60 mg/vial

Route/Dosage ⬆ ⬇

Combination Therapy with Lenalidomide + Dexamethasone

IV (Adults ): Cycle 1: 20 mg/m² daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 27 mg/m²on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 2–12: 27 mg/m² on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; Cycles 13–18: 27 mg/m² on Days 1, 2, 15, and 16 of a 28-day treatment cycle. Cycles 19 and subsequent cycles: Continue lenalidomide and dexamethasone (without carfilzomib) until unacceptable toxicity or disease progression.

Combination Therapy with Daratumumab + Dexamethasone or Daratumumab/Hyaluronidase + Dexamethasone

Twice Weekly Regimen
IV (Adults ): Cycle 1: 20 mg/m² daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 56 mg/m²on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 56 mg/m² on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle. Continue carfilzomib, daratumumab (or daratumumab/hyaluronidase), and dexamethasone until unacceptable toxicity or disease progression.
Once Weekly Regimen
IV (Adults ): Cycle 1: 20 mg/m² on Day 1; if tolerated, ↑ dose to 70 mg/m²on Days 8 and 15 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 70 mg/m² on Days 1, 8, and 15 of a 28-day treatment cycle. Continue carfilzomib, daratumumab (or daratumumab/hyaluronidase), and dexamethasone until unacceptable toxicity or disease progression.

Combination Therapy with Isatuximab + Dexamethasone

Twice Weekly Regimen
IV (Adults ): Cycle 1: 20 mg/m² daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 56 mg/m²on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 56 mg/m² on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle. Continue carfilzomib, isatuximab, and dexamethasone until unacceptable toxicity or disease progression.

Combination Therapy with Dexamethasone

Twice Weekly Regimen
IV (Adults ): Cycle 1: 20 mg/m² daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 56 mg/m²on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 56 mg/m² on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle. Continue both carfilzomib and dexamethasone until unacceptable toxicity or disease progression.
Once Weekly Regimen
IV (Adults ): Cycle 1: 20 mg/m² on Day 1; if tolerated, ↑ dose to 70 mg/m²on Days 8 and 15 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 70 mg/m² on Days 1, 8, and 15 of a 28-day treatment cycle. Continue both carfilzomib and dexamethasone until unacceptable toxicity or disease progression.

Monotherapy

20/27 mg/m² Regimen
IV (Adults ): Cycle 1: 20 mg/m² daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 27 mg/m²on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 2–12: 27 mg/m² on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; Cycle 13 and subsequent cycles: 27 mg/m² on Days 1, 2, 15, and 16 of a 28-day treatment cycle. Continue carfilzomib until unacceptable toxicity or disease progression.
20/56 mg/m² Regimen
IV (Adults ): Cycle 1: 20 mg/m² daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 56 mg/m²on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 2–12: 56 mg/m² on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; Cycle 13 and subsequent cycles: 56 mg/m² on Days 1, 2, 15, and 16 of a 28-day treatment cycle. Continue carfilzomib until unacceptable toxicity or disease progression.

Renal Impairment

IV (Adults ): Hemodialysis: Administer dose after hemodialysis.

Hepatic Impairment

IV (Adults ): Mild or moderate hepatic impairment: ↓dose by 25%.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as a proteasome inhibitor by binding to sites on the 20s proteasome. Has antiproliferative and proapoptotic activity.

Therapeutic effects:

Delayed progression of multiple myeloma.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: proteasome inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Rapidly and extensively metabolized by extrahepatic enzymes. Metabolites have no antineoplastic activity.

Half-Life: Unknown.

Time/Action Profile ⬆ ⬇

(proteasome inhibition)

ROUTE	ONSET	PEAK	DURATION
IV	within 1 hr	unknown	>48 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose of medication to patient.
Advise patient to notify health care professional immediately if signs and symptoms of infusion reactions (fever, chills, rigors, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, chest pain, cough, swelling of feet or legs), venous thrombosis, bleeding, hepatitis (worsening fatigue, yellow discoloration of skin or eyes), or dyspnea occur.
May cause fatigue, dizziness, fainting, and drop in BP. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to maintain hydration status during therapy; may cause vomiting and/or diarrhea.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy and for 6 mo following last dose of therapy and to avoid breastfeeding during and for 2 wk after last dose. Avoid hormonal contraceptives during combination therapy to prevent increased risk of thrombosis. Advise male patients with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose. May impair fertility in male and female patients.

section name header

Indications ⬇

Contraind./Precautions ⬆ ⬇