Version May 2024
Bayer has announced that they will work with the FDA on a voluntary withdrawal of the US New Drug Application for Aliqopa (copanlisib) for adult patients with relapsed follicular lymphoma who have received at least 2 prior systemic therapies. The addition of copanlisib to standard immunochemotherapy regimens did not meet the primary end point of progression-free survival benefit versus the standard immunochemotherapy control arm in patients with relapsed follicular lymphoma.
Bayer is exploring access options for patients currently receiving copanlisib; however, no new patients should be prescribed copanlisib.
Further information may be found at https://www.bayer.com/en/us/news-stories/update-on-aliqopar.
Dosage guidance:
Safety: Achieve optimal serum glucose control and optimize BP control prior to each copanlisib infusion.
Clinical considerations: Consider Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients at risk for PCP.
Follicular lymphoma, relapsed:
Note: Copanlisib received approval under the FDA's Accelerated Approval Program in September 2017 for the treatment of relapsed follicular lymphoma in adults who have received at least 2 prior systemic therapies based on data from the open-label, single-arm, phase 2 CHRONOS-1 study. In the FDA-required confirmatory, phase 3 CHRONOS-4 study, in patients with relapsed follicular lymphoma, the addition of copanlisib to standard chemoimmunotherapy did not meet the primary efficacy end point of progression-free survival. Given the results of the CHRONOS-4 study, the manufacturer has elected to voluntarily withdraw copanlisib for the treatment of relapsed follicular lymphoma from the market. Access options for patients currently receiving copanlisib are being explored; however, no new patients should be prescribed copanlisib.
IV: 60 mg on days 1, 8, and 15 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Marginal zone lymphoma, relapsed or refractory (off-label use): IV: 60 mg on days 1, 8, and 15 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Kidney function estimated using the Cockcroft-Gault formula.
CrCl ≥15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, CrCl ≥15 mL/minute did not significantly affect the pharmacokinetics of copanlisib.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease with or without dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment at treatment initiation :
Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST): No dosage adjustment necessary.
Moderate impairment (Child-Turcotte-Pugh class B): Reduce dose to 45 mg.
Severe hepatic impairment (Child-Turcotte-Pugh class C): Reduce dose to 30 mg.
Note: A minimum of 7 days should elapse between any 2 consecutive infusions.
|
Adverse reaction |
Adverse reaction severity |
Recommended management |
|---|---|---|
|
a Both systolic <150 mm Hg and diastolic <90 mm Hg are required. | ||
|
b PCP = Pneumocystis jirovecii pneumonia; CMV = cytomegalovirus. | ||
|
Hematologic toxicity | ||
|
Neutropenia |
ANC 500 to 1,000/mm3 |
Continue current copanlisib dose; monitor ANC at least weekly. |
|
ANC <500/mm3 |
First occurrence: Interrupt copanlisib therapy. Monitor ANC at least weekly until ANC ≥500/mm3; resume at the previous dose. Recurrent: Interrupt copanlisib therapy. Monitor ANC at least weekly until ANC ≥500/mm3; reduce copanlisib dose to 45 mg. | |
|
Thrombocytopenia |
Platelets <25,000/mm3 |
Interrupt copanlisib therapy. May resume copanlisib when platelets recover to ≥75,000/mm3; if recovery occurs within 21 days, reduce dose from 60 to 45 mg (or from 45 to 30 mg). If recovery does not occur within 21 days, discontinue copanlisib. |
|
Nonhematologic toxicity | ||
|
Dermatologic toxicity |
Grade 3 cutaneous reaction |
Withhold copanlisib until toxicity is resolved; reduce dose from 60 to 45 mg (or from 45 to 30 mg). |
|
Life-threatening |
Discontinue copanlisib. | |
|
Hyperglycemia |
Predose fasting blood glucose ≥160 mg/dL or random/nonfasting blood glucose ≥200 mg/dL |
Withhold copanlisib until fasting glucose is ≤160 mg/dL, or a random (nonfasting) blood glucose is ≤200 mg/dL. |
|
Predose or postdose blood glucose ≥500 mg/dL |
First occurrence: Withhold copanlisib until fasting blood glucose is ≤160 mg/dL, or a random (nonfasting) blood glucose is ≤200 mg/dL; reduce dose from 60 to 45 mg. Subsequent occurrences: Withhold copanlisib until fasting blood glucose is ≤160 mg/dL, or a random (nonfasting) blood glucose is ≤200 mg/dL; reduce dose from 45 to 30 mg. If hyperglycemia persists at the 30 mg dose, discontinue copanlisib. | |
|
Hypertension |
Predose BP ≥150/90 |
Withhold copanlisib until BP is <150/90 (both systolic and diastolic) based on 2 consecutive measurements at least 15 minutes apart.a |
|
Postdose BP ≥150/90 (non–life-threatening) |
If antihypertensive treatment is not required, continue copanlisib at previous dose. If antihypertensive treatment is necessary, consider dose reduction from 60 to 45 mg (or from 45 to 30 mg). Discontinue copanlisib if BP remains uncontrolled (>150/90) despite appropriate antihypertensive treatment.a | |
|
Postdose elevated BP with life-threatening consequences |
Discontinue copanlisib. | |
|
Infection |
≥ Grade 3 |
Withhold copanlisib until resolution. |
|
Suspected PCPb infection of any grade |
Withhold copanlisib. If confirmed, treat infection until resolution; resume copanlisib at previous dose with concomitant PCP prophylaxis. | |
|
CMVb infection or viremia of any grade |
Withhold copanlisib until infection or viremia resolves; resume copanlisib at the previous dose. | |
|
Pulmonary toxicity |
Pulmonary symptoms (eg, cough, dyspnea, hypoxia, interstitial infiltrates on exam) |
Withhold copanlisib and conduct a diagnostic exam to determine cause. |
|
Noninfectious pneumonitis: grade 2 |
Withhold copanlisib and treat pneumonitis appropriately. If noninfectious pneumonitis recovers to grade 0 or 1, resume copanlisib at 45 mg. If grade 2 toxicity recurs, discontinue copanlisib. | |
|
Noninfectious pneumonitis: ≥ grade 3 |
Discontinue copanlisib. May require management with systemic corticosteroids. | |
|
Other severe and non–life-threatening toxicities |
Grade 3 |
Withhold copanlisib until toxicity is resolved; reduce dose from 60 to 45 mg (or from 45 to 30 mg). |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (35%)
Central nervous system: Fatigue (36%)
Dermatologic: Skin rash (15%)
Endocrine & metabolic: Hyperglycemia (54% to 95%), hypertriglyceridemia (58%), hypophosphatemia (44%), hyperuricemia (25%)
Gastrointestinal: Diarrhea (36%), nausea (26%), increased serum lipase (21%), stomatitis (14%), vomiting (13%)
Hematologic & oncologic: Decreased hemoglobin (78%; grade 3: 4%), leukopenia (36%; grade 3: 12%; grade 4: 15%), decreased absolute lymphocyte count (78%; grade 3: 27%; grade 4: 2%), neutropenia (32%; grade 3: 10% to ≤24%; grade 4: 15% to ≤24%), thrombocytopenia (22%; grade 3: 7%; grade 4: 1%)
Infection: Serious infection (19%)
Respiratory: Lower respiratory tract infection (21%)
1% to 10%:
Central nervous system: Dysesthesia (≤7%), paresthesia (≤7%)
Endocrine & metabolic: Severe hyperglycemia (3% to 5%)
Gastrointestinal: Mucosal inflammation (8%)
Hematologic & oncologic: Severe neutropenia (1%)
Respiratory: Pneumonitis (5% to 9%), pneumonia (8%)
<1%, postmarketing and/or case reports: Exfoliative dermatitis, pneumonia due to pneumocystis, pruritus
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Bone marrow suppression: Leukopenia, neutropenia, thrombocytopenia, lymphopenia, and anemia (including grade 3 or 4 events), have been reported with copanlisib therapy. Grade 3 or 4 neutropenia has occurred in close to one quarter of patients receiving copanlisib; serious neutropenic events also were reported.
• Dermatologic toxicity: Dermatologic toxicities, including grade 3 and 4 cutaneous events, have been observed with copanlisib monotherapy. Toxicities included exfoliative dermatitis, exfoliative rash, pruritus, and rash (including maculopapular rash).
• Hyperglycemia: Grade 3 or 4 hyperglycemia was reported commonly in patients treated with copanlisib monotherapy, including serious hyperglycemic events; infusion-related hyperglycemia may occur. Serum glucose levels typically peaked at 5 to 8 hours post infusion, and then declined to baseline levels in the majority of patients; some patients had elevated serum glucose levels one day after the infusion. In patients with baseline HbA1c <5.7%, 10% had HbA1c >6.5% at the conclusion of copanlisib therapy. Patients with diabetes mellitus should only be treated with copanlisib if adequate glucose control is achieved; monitor closely.
• Hypertension: Hypertension (including grade 3 and serious events) has occurred during copanlisib therapy; infusion-related hypertension may occur. Grade 3 hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg) was reported in over one quarter of patients treated with copanlisib monotherapy. Systolic and diastolic blood pressures increased 16.8 mm Hg and 7.8 mm Hg, respectively, from baseline to 2 hours post infusion (in cycle 1 day 1); the mean blood pressure began decreasing ~2 hours post infusion, however, blood pressure remained elevated for 6 to 8 hours after the start of infusion.
• Infection: Serious and fatal infections have occurred during treatment with copanlisib. The most commonly reported infection was pneumonia. Serious Pneumocystis jirovecii pneumonia (PCP) has also been reported (rarely). Cytomegalovirus infection or reactivation (grade 1 or 2) has occurred with copanlisib.
• Pulmonary toxicity: Noninfectious pneumonitis has been reported with copanlisib monotherapy. Signs and symptoms of noninfectious pneumonitis may include cough, dyspnea, hypoxia, or interstitial infiltrates on radiologic exam.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Aliqopa: 60 mg (1 ea)
No
Solution (reconstituted) (Aliqopa Intravenous)
60 mg (per each): $6,304.32
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Infuse over 1 hour. Do not mix with or administer with any other medications. Do not infuse with any solutions other than NS.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Copanlisib may cause reproductive toxicity and teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Follicular lymphoma, relapsed: Treatment of relapsed follicular lymphoma in adults who have received at least 2 prior systemic therapies.
Note: Copanlisib received approval under the FDA's Accelerated Approval Program in September 2017 for the treatment of relapsed follicular lymphoma in adults who have received at least 2 prior systemic therapies based on data from the open-label, single-arm, phase 2 CHRONOS-1 study. In the FDA-required confirmatory, phase 3 CHRONOS-4 study, in patients with relapsed follicular lymphoma, the addition of copanlisib to standard chemoimmunotherapy did not meet the primary efficacy end point of progression-free survival. Given the results of the CHRONOS-4 study, the manufacturer has elected to voluntarily withdraw copanlisib for the treatment of relapsed follicular lymphoma from the market. Access options for patients currently receiving copanlisib are being explored; however, no new patients should be prescribed copanlisib.
Marginal zone lymphoma, relapsed or refractory
Copanlisib may be confused with alpelisib, crizotinib, duvelisib, idelalisib
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Copanlisib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Copanlisib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Copanlisib. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Grapefruit juice may increase serum copanlisib levels.
Pregnancy testing should be conducted prior to therapy in patients who could become pregnant. Highly effective contraception (contraception with a failure rate of <1% per year) is recommended during treatment and for at least 1 month after the last copanlisib dose for patients who could become pregnant. Patients with partners who could become pregnant should also use highly effective contraception during treatment and for at least 1 month after the last copanlisib dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to copanlisib may cause fetal harm.
It is not known if copanlisib is present in breast milk.
Due to the potential for serious adverse events in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for at least 1 month after treatment is discontinued.
Monitor blood counts at least weekly during treatment; blood glucose pre- and postdose and more frequently if clinically indicated (monitor patients with diabetes closely). BP pre- and postdose and more frequently if clinically indicated. Evaluate pregnancy status prior to treatment in patients who could become pregnant. Monitor for signs/symptoms of infection, including Pneumocystis jirovecii pneumonia (PCP), cytomegalovirus (CMV) infection, and viremia; if CMV occurs, monitor for CMV reactivation at least monthly via PCR or antigen testing. Monitor for signs/symptoms of noninfectious pneumonitis, hyperglycemia, and dermatologic toxicity.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Copanlisib inhibits phosphatidylinositol 3-kinase (PI3K), primarily the P13K-alpha and P13K-delta isoforms which are expressed in malignant B-cells. Copanlisib induces tumor cell death through apoptosis and inhibition of proliferation of primary malignant B cell lines. In addition, copanlisib inhibits several signaling pathways, including B-cell receptor signaling, CXCR12 mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines.
Distribution: 871 L (range: 423 to 2,150 L)
Protein binding: 84.2%, primarily to albumin
Metabolism: Primarily hepatic (>90%) though CYP3A and <10% through CYP1A1; the M-1 metabolite has pharmacologic activity comparable to the parent compound (against P13K-alpha and P13K-beta)
Half-life elimination: 39.1 hours (range: 14.6 to 82.4 hours)
Excretion: 12 mg IV dose: Feces (~64%; ~30% as unchanged drug); urine (~22%; ~15% as unchanged drug); metabolites account for 41% of the administered dose
Hepatic function impairment: In a pharmacokinetic study evaluating a single 12 mg IV copanlisib dose in subjects with hepatic impairment, the geometric mean of total copanlisib Cmax and AUC increased 1.38- and 1.71-fold, respectively, in subjects with moderate impairment (Child-Pugh class B) and 1.44- and 2.71-fold, respectively, in subjects with severe impairment (Child-Pugh class C) when compared to subjects with normal hepatic function. The geometric mean unbound AUC of copanlisib was increased by 1.23-fold and 3.77-fold in patients with moderate and severe impairment, respectively. The geometric mean unbound Cmax of copanlisib did not increase in patients with moderate impairment, but increased 1.92-fold in patients with severe impairment.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
