Copanlisib – Uses, Dosage, Side Effects, Interactions

Before receiving copanlisib injection,

• tell your doctor and pharmacist if you are allergic to copanlisib, any other medications, or any of the ingredients in copanlisib injection. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements and herbal products you are taking or plan to take. Be sure to mention any of the following: boceprevir (Victrelis); carbamazepine (Carbatrol, Equetro, Tegretol, others), clarithromycin (Biaxin, in Prevpac), cobicistat (Tybost, in Evotaz, Genvoya, Prezcobix, Stribild), conivaptan (Vaprisol), diltiazem (Cardizem, Cartia XT, Diltzac, others), efavirenz (Sustiva), enzalutamide (Xtandi), idelalisib (Zydelig), indinavir (Crixivan) with ritonavir; itraconazole (Sporonox, Onmel), and ketoconazole, lopinavir with ritonavir (in Kaletra); mitotane (Lysodren), nefazodone, nelfinavir (Viracept), nevirapine (Viramune), paritaprevir, ritonavir, ombitasvir, and/or dasabuvir (Viekira Pak); phenobarbital, phenytoin (Dilantin, Phenytek), posaconazole (Noxafil), rifabutin (Mycobutin), rifampin (Rifadine, in Rifamate, Rifater), ritonavir (Norvir, in Kaletra, Technivie, Viekira Pak), saquinavir (Invirase), and tipranavir (Aptivus) with ritonavir; and voriconazole (Vfend). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with copanlisib injection, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor what herbal products you are taking, especially St. John’s wort.
• tell your doctor if you have an infection or if you have or have ever had high blood sugar, diabetes, lung or breathing problems, high blood pressure, or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or plan to father a child. You should not become pregnant while you are receiving copanlisib injection. You will need to have a negative pregnancy test before you begin receiving this medication. Use effective birth control during your treatment with copanlisib injection and for 1 month after your final dose. If you are a male and your partner can become pregnant, you should use effective birth control during your treatment and for 1 month after your final dose. If you or your partner become pregnant while receiving copanlisib, call your doctor.
• tell your doctor if you are breastfeeding. You should not breastfeed while you are receiving copanlisib injection, and for 1 month after your final dose.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of receiving copanlisib injection.

Warning

Serious infection has occurred in patients receiving copanlisib therapy; some cases were fatal. Monitor patients for signs and symptoms of infection; hold therapy for grade 3 or higher infection. Serious pneumocystis jiroveci pneumonia (PJP) has occurred with copanlisib use; consider PJP prophylaxis in at-risk patients before initiating therapy. Hold therapy if PJP is suspected. If PJP diagnosis is confirmed, treat the infection until resolution and then resume copanlisib at the previous dose and give PJP prophylaxis for the duration of therapy.

Severe hyperglycemia, elevated HbA1c, and infusion-related hyperglycemia have occurred with copanlisib therapy; additionally, serious hyperglycemic events have been reported. Monitor blood glucose levels before and after the copanlisib infusion. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop hyperglycemia. Blood glucose levels typically peak at 5 to 8 hours post infusion and then decline to baseline levels in most patients. Use copanlisib with caution in patients with diabetes mellitus. Initiate copanlisib therapy only after these patients have achieved optimal blood glucose control; monitor blood glucose levels in these patients closely.

Severe hypertension and infusion-related hypertension have occurred with copanlisib therapy; use copanlisib with caution in patients with pre-existing hypertension. Monitor blood pressure before and after the copanlisib infusion; optimal blood pressure control should be achieved prior to each dose. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop hypertension. A mean increase in systolic (+16.8 mmHg) and diastolic (+7.8 mmHg) blood pressure was observed at 2 hours post infusion on day 1 of cycle 1 of copanlisib therapy; blood pressure typically remained elevated for 6 to 8 hours after the start of the infusion.

Non-infectious pneumonitis has occurred with copanlisib therapy; use copanlisib with caution in patients with pre-existing pulmonary disease. Hold therapy and evaluate patients who experience signs or symptoms of pneumonitis (e.g., cough, dyspnea, hypoxia, and interstitial infiltrates on X-ray exam). Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop pneumonitis. The use of systemic corticosteroid may be beneficial in these patients.

Severe hematologic toxicity including neutropenia and thrombocytopenia has occurred with copanlisib therapy. Monitor complete blood counts at least weekly during treatment. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop severe neutropenia or thrombocytopenia.

Severe cutaneous reactions (e.g., serious rash) have occurred with copanlisib therapy. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop severe skin reactions.

Reduce the dose of copanlisib in patients with moderate hepatic disease/impairment (Child-Pugh class B). Copanlisib has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Evaluate liver function tests at baseline and as clinically appropriate during therapy.

Geriatric patients with follicular lymphoma or other hematologic malignancies had a higher incidence of serious adverse reactions compared with patients aged less than 65 years (30% vs. 23%) after treatment with single-agent copanlisib in a pooled analysis from clinical trials (n = 168). However, an initial dose adjustment is not necessary in patients 65 years or older.

Copanlisib can cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant while receiving copanlisib. Advise patients to notify their healthcare provider immediately if they become pregnant or if pregnancy is suspected during treatment. Embryo-fetal toxicities including embryo-fetal death and fetal abnormalities (e.g., domed head, malformed eyeballs or eyeholes, hydrocephalus internus, ventricular septal defects, major vessel malformations, dysplastic forelimb bones, malformed ribs and vertebrae, and pelvis shift) were observed when copanlisib was administered to pregnant rats during organogenesis at doses corresponding to approximately 12% the recommended dose in humans.

Counsel patients about the reproductive risk and contraception requirements during copanlisib treatment. Pregnancy testing prior to starting therapy is recommended for females of reproductive potential. These patients should avoid pregnancy and use highly effective contraception during therapy and for 1 month after the last copanlisib dose. Due to the risk of male-mediated teratogenicity, men with female partners of reproductive potential should avoid fathering a child and use effective contraception during and for 1 month after copanlisib therapy. Adverse effects on male and female reproduction (e.g., infertility) are expected based on findings from animal studies.

It is not known whether copanlisib or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because of the potential for serious adverse reactions in nursing infants, women should discontinue breast-feeding during copanlisib therapy and for 1 month after the last dose.