AliqopaTM preparation and administration
Considerations for preparing Aliqopa1
Aliqopa is for intravenous (IV) infusion only
Administer Aliqopa as a single agent, following reconstitution and dilution. Mix only with 0.9% NaCl solution
Do not mix or inject Aliqopa with other drugs or other diluents
Reconstitute Aliqopa with 4.4 mL of sterile 0.9% NaCl solution leading to a concentration of 15 mg/mL.
WITHDRAW AND INJECT
- 1Withdraw 4.4 mL of sterile 0.9% NaCl solution by using a 5 mL sterile syringe with needle
- 2Inject the measured volume through the disinfected stopper surface into the vial of Aliqopa
- 3Dissolve the lyophilized solid by gently shaking the injection vial for 30 seconds
- 4Allow to stand for 1 minute to let bubbles rise to the surface
- 5Check if any undissolved substance is still seen. If yes, repeat the gentle shaking and settling procedure
- 6Inspect visually for discoloration and particulate matter. After reconstitution, the solution should be colorless to slightly yellowish
- 7Once the solution is free of visible particles, withdraw the reconstituted solution for further dilution
Dilution instructions for intravenous (IV) use1
Further dilute the reconstituted solution in 100 mL sterile 0.9% NaCl solution for injection.
- 1 With a sterile syringe, withdraw the required amount of the reconstituted solution for the desire dosage
45 mgWithdraw 3 mL of the reconstituted solution with a sterile syringe
30 mgWithdraw 2 mL of the reconstituted solution with a sterile syringe
- 2 Inject the contents of the syringe into the patient infusion bag of 100 mL sterile 0.9% NaCl solution
- 3 Mix the dose well by inverting
- 4 Discard any unused reconstituted or diluted solution appropriately
Use reconstituted and diluted Aliqopa immediately or store the reconstituted solution in the vial, or diluted solution in the infusion bag, at 2°C to 8°C (36°F to 46°F) for up to 24 hours before use. Allow the product to adapt to room temperature before use following refrigeration. Avoid exposure of the diluted solution to direct sunlight.
ALIQOPA (copanlisib) is indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Important Safety Information
Infections: Serious, including fatal, infections occurred in 19% of 317 patients treated with ALIQOPA monotherapy. The most common serious infection was pneumonia. Monitor patients for signs and symptoms of infection and withhold ALIQOPA for Grade 3 and higher infection.
Serious pneumocystis jiroveci pneumonia (PJP) infection occurred in 0.6% of 317 patients treated with ALIQOPA monotherapy. Before initiating treatment with ALIQOPA, consider PJP prophylaxis for populations at risk. Withhold ALIQOPA in patients with suspected PJP infection of any grade. If confirmed, treat infection until resolution, then resume ALIQOPA at previous dose with concomitant PJP prophylaxis.
Hyperglycemia: Grade 3 or 4 hyperglycemia (blood glucose 250 mg/dL or greater) occurred in 41% of 317 patients treated with ALIQOPA monotherapy. Serious hyperglycemic events occurred in 2.8% of patients. Treatment with ALIQOPA may result in infusion-related hyperglycemia. Blood glucose levels typically peaked 5 to 8 hours post-infusion and subsequently declined to baseline levels for a majority of patients; blood glucose levels remained elevated in 17.7% of patients one day after ALIQOPA infusion. Of 155 patients with baseline HbA1c <5.7%, 16 (10%) patients had HbA1c >6.5% at the end of treatment.
Of the twenty patients with diabetes mellitus treated in CHRONOS-1, seven developed Grade 4 hyperglycemia and two discontinued treatment. Patients with diabetes mellitus should only be treated with ALIQOPA following adequate glucose control and should be monitored closely.
Achieve optimal blood glucose control before starting each ALIQOPA infusion. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hyperglycemia.
Hypertension: Grade 3 hypertension (systolic 160 mmHg or greater or diastolic 100 mmHg or greater) occurred in 26% of 317 patients treated with ALIQOPA monotherapy. Serious hypertensive events occurred in 0.9% of 317 patients. Treatment with ALIQOPA may result in infusion-related hypertension. The mean change of systolic and diastolic BP from baseline to 2 hours post-infusion on Cycle 1 Day 1 was 16.8 mmHg and 7.8 mmHg, respectively. The mean BP started decreasing approximately 2 hours post-infusion; BP remained elevated for 6 to 8 hours after the start of the ALIQOPA infusion. Optimal BP control should be achieved before starting each ALIQOPA infusion. Monitor BP pre- and post-infusion. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of hypertension.
Non-infectious Pneumonitis: Non-infectious pneumonitis occurred in 5% of 317 patients treated with ALIQOPA monotherapy. Withhold ALIQOPA and conduct a diagnostic examination of a patient who is experiencing pulmonary symptoms such as cough, dyspnea, hypoxia, or interstitial infiltrates on radiologic exam. Patients with pneumonitis thought to be caused by ALIQOPA have been managed by withholding ALIQOPA and administration of systemic corticosteroids. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of non-infectious pneumonitis.
Neutropenia: Grade 3 or 4 neutropenia occurred in 24% of 317 patients treated with ALIQOPA monotherapy. Serious neutropenic events occurred in 1.3%. Monitor blood counts at least weekly during treatment with ALIQOPA. Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of neutropenia.
Severe Cutaneous Reaction: Grade 3 and 4 cutaneous reactions occurred in 2.8% and 0.6% of 317 patients treated with ALIQOPA monotherapy respectively. Serious cutaneous reaction events were reported in 0.9%. The reported events included dermatitis exfoliative, exfoliative rash, pruritus, and rash (including maculo-papular rash). Withhold, reduce dose, or discontinue ALIQOPA depending on the severity and persistence of severe cutaneous reactions.
Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ALIQOPA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of copanlisib to pregnant rats during organogenesis caused embryo-fetal death and fetal abnormalities in rats at maternal doses as low as 0.75 mg/kg/day (4.5 mg/m2/day body surface area) corresponding to approximately 12% the recommended dose for patients. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least one month after the last dose.
Adverse Drug Reactions: Serious adverse reactions were reported in 44 (26%) patients. The most frequent serious adverse reactions that occurred were pneumonia (8%), pneumonitis (5%) and hyperglycemia (5%). Adverse reactions resulted in dose reduction in 36 (21%) and discontinuation in 27 (16%) patients. The most frequently observed adverse drug reactions (≥20%) in ALIQOPA-treated patients were: hyperglycemia (54%), leukopenia (36%), diarrhea (36%), decreased general strength and energy (36%), hypertension (35%), neutropenia (32%), nausea (26%), thrombocytopenia (22%), and lower respiratory tract infections (21%).
Drug Interactions: Avoid concomitant use with strong CYP3A inducers. Reduce the ALIQOPA dose to 45 mg when concomitantly administered with strong CYP3A inhibitors.
Lactation: Advise women not to breastfeed. Advise a lactating woman not to breastfeed during treatment with ALIQOPA and for at least 1 month after the last dose.
For important risk and use information about Aliqopa, please see the full Prescribing Information.
You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
For Bayer products you can report these directly to Bayer by clicking here.
1. Aliqopa (copanlisib) for injection [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; September 2017.