copanlisib (Rx)

Brand and Other Names:Aliqopa
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 60 mg (single dose)

Follicular Lymphoma

Indicated for relapsed follicular lymphoma (FL) in patients who have received at least 2 prior systemic therapies

60 mg IV on Days 1, 8, and 15 of a 28-day treatment cycle on an intermittent schedule (21 days on and 7 days off)

Continue treatment until disease progression or unacceptable toxicity

Dosage Modifications

Coadministration of CYP3A4 inducers or inhibitors

Avoid concomitant use with strong CYP3A inducers

Concomitant use with strong CYP3A4 inhibitors: Reduce copanlisib dose to 45 mg

Infections

  • Grade ≥3: Withhold until resolution
  • Suspected pneumocystis jiroveci pneumonia (PJP) infection (all grades): Withhold treatment; if confirmed, treat infection until resolution, and then resume treatment at previous dose with concomitant PJP prophylaxis

Hyperglycemia

  • Predose fasting blood glucose (FBG) ≥160 mg/dL or random/non-FBG ≥200 mg/dL: Withhold treatment until predose FBG ≤160 mg/dL or random/non-FBG ≤200 mg/dL
  • Predose or postdose blood glucose ≥500 mg/dL
    • First occurrence: Withhold treatment until FBG is ≤160 mg/dL, or a random/non-FBG ≤200 mg/dL; then reduce dose from 60 mg to 45 mg and maintain at 45 mg
    • Subsequent occurrences: Withhold treatment until FBG is ≤160 mg/dL, or a random/non-FBG ≤200 mg/dL; then reduce dose from 45 mg to 30 mg and maintain at 30 mg
    • Discontinue treatment if it persists at 30 mg

Hypertension

  • Predose blood pressure (BP) ≥150/90 mm Hg: Withhold treatment until BP <150/90 mm Hg based on 2 consecutive BP measurements at least 15 minutes apart
  • Postdose elevated BP with life-threatening consequences: Discontinue treatment
  • Non-life threatening postdose blood pressure (BP) ≥150/90 mm Hg
    • Antihypertensive treatment is not required: Continue treatment at previous dose
    • Antihypertensive treatment is required: Consider dose reduction from 60 mg to 45 mg or from 45 mg to 30 mg
    • Discontinue treatment if BP remains uncontrolled (BP >150/90 mm Hg) despite antihypertensive treatment

Noninfectious pneumonitis (NIP)

  • Grade 2: Withhold copanlisib and treat NIP; resume treatment at 45 mg once NIP recovers to grade 1 or less
  • Grade 2 recurs: Discontinue treatment
  • Grade ≥3: Discontinue treatment

Neutropenia

  • Absolute neutrophil count (ANC) 0.5-1.0 x 103 cells/mm3: Maintain dose; monitor ANC at least weekly
  • ANC <0.5 x 103 cells/mm3: Withhold treatment; monitor ANC at least weekly until ANC ≥0.5 x 103 cells/mm3, then resume treatment at previous dose
  • If ANC ≤0.5 x 103 cells/mm3 recurs, then reduce dose to 45 mg

Severe cutaneous reactions

  • Grade 3: Withhold treatment until toxicity is resolved and reduce dose from 60 mg to 45 mg, or from 45 mg to 30 mg
  • Life-threatening: Discontinue treatment

Thrombocytopenia

  • <25 X 109/L: Withhold treatment; resume when platelet levels return to ≥75 x 109/L; reduce dose from 60 mg to 45 mg, or from 45 mg to 30 mg if recovery occurs within 21 days
  • If recovery does not occur within 21 days, discontinue treatment

Other severe and non-life-threatening toxicities

  • Grade 3: Withhold until toxicity is resolved and reduce dose from 60 mg to 45 mg, or from 45 mg to 30 mg

Hepatic impairment

  • Mild (total bilirubin ≤1x ULN and AST >ULN, or total bilirubin >1-1.5x ULN and any AST): No dosage adjustment necessary
  • Moderate (Child-Pugh B): Reduce dose to 45 mg
  • Severe (Child-Pugh C): Not studied

Marginal Zone Lymphoma (Orphan)

Orphan designation for splenic, nodal, and extranodal subtypes of marginal zone lymphoma

Sponsor

  • Bayer HealthCare Pharmaceuticals, Inc; 100 Bayer Boulevard, PO Box 915; Hanover, New Jersey 07981

Safety and efficacy has not been established

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Interactions

Interaction Checker

and copanlisib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Any grade

            • Hyperglycemia (54-95%)
            • Decreased hemoglobin and lymphocytes (78%)
            • Decreased white blood cells (WBCs) (71%)
            • Decreased platelets (65%)
            • Decreased neutrophils (63%)
            • Hypertriglyceridemia (58%)
            • Hypophosphatemia (44%)
            • Leukopenia (36%)
            • Decreased general strength and energy (36%)
            • Diarrhea (36%)
            • Hypertension (35%)
            • Neutropenia (32%)
            • Nausea (26%)
            • Hyperuricemia (25%)
            • Thrombocytopenia (22%)

            Grade 3

            • Hyperglycemia (43%)
            • Decreased lymphocytes (27%)
            • Hypertension (27%)
            • Hyperuricemia (24%)
            • Decreased WBCs (18%)
            • Hyperphosphatemia (15%)
            • Leukopenia (12%)
            • Lower respiratory tract infections (12%)
            • Decreased neutrophils (12%)

            Grade 4

            • Leukopenia (15%)
            • Neutropenia (15%)

            1-10%

            Pneumonitis (9%)

            Mucosal inflammation (8%)

            Paresthesia and dysesthesia (7%)

            Grade 3

            • Neutropenia (10%)
            • Thrombocytopenia (7%)
            • Serum lipase increased (7%)
            • Decreased platelets (7%)
            • Hypertriglyceridemia (5%)
            • Diarrhea (5%)
            • Decreased general strength and energy (4%)
            • Decreased hemoglobin (4%)
            • Stomatitis (2%)
            • Rash (1%)

            Grade 4

            • Hyperglycemia (5%)
            • Lower respiratory tract infections (2%)
            • Decreased lymphocytes (2%)
            • Decreased WBCs (2%)
            • Decreased platelets (2%)
            • Thrombocytopenia (1%)
            • Hyperuricemia (1%)
            • Serum lipase increased (1%)

            <1%

            Nausea, grade 3

            Rash, grade 4

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            Warnings

            Contraindications

            None

            Cautions

            Serious, including fatal, infections may occur; the most common serious infection was pneumonia; monitor patients for signs/symptoms of infection and withhold treatment for grade 3 and higher infection

            Grade 3 or 4 hyperglycemia (blood glucose ≥250 mg/dL) reported; achieve optimal blood glucose control before starting each infusion; withhold, reduce dose, or discontinue treatment depending on the severity and persistence of hyperglycemia

            Grade 3 hypertension (systolic 160 mm Hg or greater or diastolic 100 mm Hg or greater) may occur; optimal BP control should be achieved before starting each infusion; monitor BP preinfusion and postinfusion; withhold, reduce dose, or discontinue copanlisib depending on severity and persistence of hypertension

            Noninfectious pneumonitis reported; withhold treatment and conduct a diagnostic examination of a patient who is experiencing pulmonary symptoms (eg, cough, dyspnea, hypoxia, interstitial infiltrates) on radiologic examination; withhold, reduce dose, or discontinue treatment depending on the severity and persistence of noninfectious pneumonitis

            Grade 3 or 4 neutropenia may occur; withhold, reduce dose, or discontinue copanlisib depending on the severity and persistence of neutropenia

            Serious cutaneous reaction events (eg, exfoliative dermatitis, exfoliative rash, pruritus, rash [including maculopapular rash]) may occur; withhold, reduce dose, or discontinue treatment depending on the severity and persistence of severe cutaneous reactions

            Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose

            Drug interaction overview

            • Concomitant use of copanlisib with strong CYP3A4 inducers may decrease copanlisib’s AUC and peak plasma concentrations
            • Coadministration with strong CYP3A5 inhibitors may increase the AUC of copanlisib
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            Pregnancy

            Pregnancy

            Based on animal studies and the mechanism of action, copanlisib can cause fetal harm when administered to a pregnant woman

            Advise pregnant women of the potential risk to a fetus

            Conduct pregnancy testing prior to initiation of treatment

            Contraception

            • Advise female patients of reproductive potential to use highly effective contraception during treatment and for at least 1 month after the last dose
            • Advise male patients with female partners of reproductive potential to use highly effective contraception during and for at least 1 month after the last dose

            Lactation

            There are no data on the presence of copanlisib and/or metabolites in human milk, the effects on the breastfed child, or on milk production

            Because of the potential for serious adverse reactions in a breastfed child from copanlisib, advise a lactating woman not to breastfeed during treatment with copanlisib and for at least 1 month after the last dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Nutrition

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            Pharmacology

            Mechanism of Action

            Pan class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells; by inhibiting several key cell-signaling pathways may induce apoptosis and inhibition of proliferation of premalignant B cells and in turn cause tumor cell death

            Absorption

            Peak plasma concentration: 463 ng/mL

            AUC (0-25): 1570 ng·hr/mL

            Distribution

            Protein binding: 84.2% (mainly albumin)

            Vd: 871 L

            Metabolism

            Metabolism is mediated by CYP3A (~90%) and CYP1A1 (<10%)

            Elimination

            Half-life: 39.1 hr Clearance: 17.9 L/hr

            Excreted ~50% as unchanged compound and 50% as metabolites

            Excretion, unchanged compound: Feces (30%), urine (15%)

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            Administration

            IV Compatibilities

            0.9% NaCl

            IV Preparation

            IV infusion only

            Do not mix or inject copanlisib with other drugs or other diluents

            Reconstitute copanlisib with 4.4 mL of sterile 0.9% NaCl solution for a concentration of 15 mg/mL

            Inspect visually for discoloration and particulate matter; the solution should be colorless to slightly yellowish after reconstitution

            Further dilute the reconstituted solution in 100 mL sterile 0.9% NaCl solution for injection

            Withdraw required amount of the reconstituted solution for the desired dosage (see prescribing information for further information)

            Inject the contents of the syringe into the patient infusion bag of 100 mL sterile 0.9% NaCl solution

            Mix the dose well by inverting

            Use reconstituted and diluted copanlisib immediately or store the reconstituted solution in the vial or diluted solution in the infusion bag at 2-8°C (36-46°F) for up to 24 hours before use

            Avoid exposure of the diluted solution to direct sunlight

            IV Administration

            Allow the product to come to room temperature before use following refrigeration

            Infuse over 1 hr

            Storage

            Unused vials: Refrigerate at 2-8°C (36-46°F)

            Diluted solutions: Refrigerate at 2-8°C (36-46°F) for up to 24 hours before use

            Protect from direct sunlight

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            Images

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            Formulary

            FormularyPatient Discounts

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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.