temporary class phosphatidylinositol-3-kinase inhibitors
Relapsed follicular lymphoma in patients who have received ≥2 prior systemic therapies.
Inhibits phosphatidylinositol-3-kinase (PI3K) in malignant B cells which leads to apoptosis and inhibition of proliferation of primary malignant B cell lines.
Decreased progression of follicular lymphoma.
Absorption: IV administration results in complete bioavailability.
Distribution: Extensively distributed to tissues.
Metabolism and Excretion: Hepatically metabolized primarily by CYP3A (90%) and CYP1A1 (10%); the M-1 metabolite has pharmacologic activity comparable to that of the parent compound. Primarily excreted in feces (64%; 30% as unchanged drug) and urine (22%; 15% as unchanged drug).
Half-life: 39.1 hr.
TIME/ACTION PROFILE (plasma concentrations)
- Concurrent use with strong CYP3A inducers;
- OB: May cause fetal harm in pregnancy;
- Lactation: Avoid breast feeding.
Use Cautiously in:
- Diabetes mellitus;
- Rep: Women of reproductive potential and men with female partners of reproductive potential;
- Pedi: Safety and effectiveness in children not established.
Adverse Reactions/Side Effects
Derm: pruritus, rash
GU: ↓ fertility
Hemat: neutropenia, thrombocytopenia
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong CYP3A inducers, including carbamazepine, enzalutamide, mitotane, phenytoin, and rifampin may ↓ levels; avoid concurrent use.
- Strong CYP3A inhibitors, including clarithromycin, cobicistat, conivaptan, diltiazem, idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir, posaconazole, ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, and voriconazole may ↑ levels; if concurrent use necessary, ↓ copanlisib dose.
St. John's wort may ↓ levels; avoid concurrent use.
Grapefruit juice may ↑ levels; avoid concurrent use.
IV (Adults) 60 mg on Days 1, 8, and 15 of a 28–day treatment cycle. Continue until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A inhibitor– 45 mg on Days 1, 8, and 15 of a 28–day treatment cycle. Continue until disease progression or unacceptable toxicity.
Lyophilized powder for injection (requires reconstitution and further dilution): 60 mg/vial
- Assess for signs and symptoms of infection (fever, chills, dyspnea, cough) prior to and during therapy. Pneumocystis jiroveci pneumonia (PJP) has occurred; consider prophylaxis for populations at risk. For ≥Grade 3 infections, hold copanlisib until resolution. For suspected PJP infection of any grade, hold copanlisib until confirmed. If confirmed hold copanlisib until resolution, then restart at previous dose with PJP prophylaxis.
- Monitor blood pressure pre and post-infusion. Obtain optimal blood pressure prior to infusion. May cause hypertension lasting 6–8 hrs post-infusion. If pre-dose BP ≥150/90, hold copanlisib until BP <150/90 on two consecutive measures at least 15 min apart. If post-dose BP ≥150/90 (non-life-threatening), if antihypertensive not required, continue copanlisib at previous dose. If antihypertensive required, consider ↓ dose from 60 mg to 45 mg or from 45 mg to 30 mg. If BP remains uncontrolled (BP >150/90) despite antihypertensive treatment, discontinue copanlisib. If post-dose elevated BP with life-threatening consequences, discontinue copanlisib.
- Monitor for signs and symptoms of noninfectious pneumonitis [NIP] (cough, dyspnea, hypoxia, interstitial infiltrates on x-ray) during therapy. For Grade 2 pneumonitis, hold copanlisib and treat NIP. If NIP recovers to Grade 0 or 1, resume copanlisib at 45 mg. If Grade 2 NIP recurs, discontinue copanlisib. If ≥Grade 3 occurs, discontinue copanlisib.
- Assess skin for rash (dermatitis exfoliative, exfoliative rash, pruritus, maculopapular rash) periodically during therapy. If Grade 3 rash, hold copanlisib until toxicity is resolved and reduce dose from 60 mg to 45 mg or from 45 mg to 30 mg. If life-threatening rash, discontinue copanlisib.
Lab Test Considerations: Obtain negative pregnancy test prior to starting therapy.
- May cause hyperglycemia; usually peaks 5–8 hrs after infusion, then return to baseline. Monitor pre-infusion fasting blood glucose. If pre-dose fasting blood glucose ≥160 mg/dL or random/nonfasting blood glucose of ≥200 mg/dL, hold copanlisib until fasting blood glucose ≤160 mg/dL or nonfasting ≤200 mg/dL. If pre-dose or post-dose blood glucose ≥500 mg/dL, on first occurrence, hold copanlisib until fasting blood glucose is ≤160 mg/dL, or a random/nonfasting blood glucose of ≤200 mg/dL. Reduce dose from 60 mg to 45 mg and maintain. On subsequent occurrences, hold copanlisib until fasting blood glucose is ≤160 mg/dL, or a random/nonfasting blood glucose of ≤200 mg/dL. Reduce dose from 45 mg to 30 mg and maintain. If hyperglycemia persistent at 30 mg dose, discontinue copanlisib.
- Monitor CBC with platelet count weekly during therapy. May cause neutropenia, leukopenia, and thrombocytopenia. If ANC 0.5–1.0 x 103 cells/mm3 , maintain dose. Monitor ANC at least weekly. If ANC <0.5 x 103 cells/mm3 , hold copanlisib. Monitor ANC at least weekly until ANC ≥0.5 x 103 cells/mm3 , resume at previous dose. If ANC ≤0.5 x 103 cells/mm3 recurs, reduce dose to 45 mg. If platelets <25 x 109 /L, hold copanlisib; resume when platelet levels ≥75.0 x 109 /L. If recovery occurs within 21 days, reduce dose from 60 mg to 45 mg or from 45 mg to 30 mg. If recovery does not occur within 21 days, discontinue copanlisib.
- May cause hypertriglyceridemia, hypophosphatemia, hyperuricemia, and ↑ serum lipase.
- Risk for infection (Adverse Reaction)
- Intermittent Infusion: Reconstitute by adding 4.4 mL 0.9% NaCl to vial of copanlisib; dissolve by shaking gently for 30 seconds. Allow to stand for 1 min to allow bubbles to rise to surface; if undissolved substance remains repeat shaking and settling. Solution is colorless to slightly yellowish; do not administer solutions that are discolored or contain particulate matter. Diluent: For 60 mg dose, withdraw 4 mL; 45 mg dose withdraw 3 mL; 30 mg dose withdraw 2 mL. Dilute further with 100 mL 0.9% NaCl. Invert to mix well. Solution is stable for up to 24 hrs if refrigerated and protected from light. Allow to reach room temperature before infusing.
- Rate: Infuse over 1 hr.
- Y-Site Incompatibility: Do not mix or infuse with other diluents or medications.
- Explain purpose of medication to patient.
- Advise patient to avoid grapefruit, grapefruit juice or products with grapefruit extract during therapy; may cause toxicity.
- Advise patient to notify health care professional if signs and symptoms of infections, hyperglycemia (unusual hunger, excessive thirst, headaches, frequent urination), breathing problems (cough, shortness of breath, difficulty breathing), hypertension (dizziness, passing out, headache, and/or pounding heart), or skin reactions (skin peeling, itching, rash) occur.
- 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, especially St. John's wort, during therapy.
- Rep: Advise female and males with female partner with reproductive potential to use effective contraception and to avoid breast feeding during and for at least 1 month after last dose.
Decreased progression of follicular lymphoma.
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