ALIQOPA
Clinical safety rating
cautionComprehensive clinical and safety monograph for ALIQOPA (ALIQOPA).
ALIQOPA (copanlisib) is a phosphatidylinositol 3-kinase (PI3K) inhibitor with inhibitory activity predominantly against PI3K-α and PI3K-δ isoforms. It induces apoptosis and inhibits proliferation in malignant B-cell lines.
| Metabolism | Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily fecal (88%) and renal (8%) as unchanged drug and metabolites; biliary excretion contributes significantly. |
| Half-life | Terminal elimination half-life of approximately 39 hours in patients with hematologic malignancies; supports twice-daily dosing. |
| Protein binding | 84% bound to human plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution approximately 217 L in patients, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability approximately 34% under fasted conditions; food increases exposure (AUC) by 34% but decreases Cmax by 11%. |
| Onset of Action | Oral administration: evidence of target inhibition (PI3K pathway) within 24 hours; clinical response typically seen after 2–4 weeks of continuous dosing. |
| Duration of Action | Duration of action approximately 12 hours; clinical effect maintained with twice-daily dosing; continuous inhibition required for efficacy. |
| Molecular Weight | 480.57 |
60 mg intravenously over 1 hour on days 1, 8, and 15 of a 28-day cycle.
| Dosage form | POWDER |
| Renal impairment | For GFR ≥ 30 mL/min: no adjustment. For GFR < 30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce to 40 mg; Child-Pugh C: avoid use. |
| Pediatric use | Safety and efficacy not established; no recommended dose. |
| Geriatric use | No specific dose adjustment; monitor for increased toxicity due to age-related renal impairment. |
| 1st trimester | Avoid due to potential for teratogenicity and embryofetal toxicity based on animal studies. ALIQOPA (copanlisib) is a PI3K inhibitor, and PI3K inhibition has been associated with fetal harm. |
| 2nd trimester | Avoid. No human data; animal studies show embryofetal toxicity including decreased fetal weight and malformations. |
| 3rd trimester | Avoid. Risk of fetal harm; may also cause neonatal myelosuppression and other toxicities if administered near term. |
Clinical note
Comprehensive clinical and safety monograph for ALIQOPA (ALIQOPA).
| Placental transfer | Likely crosses placenta based on molecular weight (<500 Da) and preclinical studies demonstrating embryofetal toxicity. |
| Breastfeeding | No human data on presence in breast milk; however, due to molecular weight and potential for serious adverse effects (e.g., myelosuppression, immunosuppression), breastfeeding is not recommended during treatment and for at least 1 month after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | ALIQOPA (copanlisib) is a PI3K inhibitor. Based on its mechanism of action and animal studies, it can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, copanlisib was teratogenic and embryotoxic at maternal exposures below the recommended human dose. First trimester: High risk of structural anomalies. Second and third trimesters: Risk of fetal growth restriction and oligohydramnios; potential for fetal PI3K pathway disruption. Advise women of childbearing potential to use effective contraception during treatment and for at least 1 month after the last dose. |
| Fetal Monitoring | Monitor pregnant women exposed to ALIQOPA for fetal growth, amniotic fluid volume, and fetal anatomy via ultrasound. Perform serial growth scans if exposed in second/third trimester. Monitor maternal blood glucose and blood pressure due to potential drug-induced hyperglycemia and hypertension. Closely monitor for signs of infection. Consult maternal-fetal medicine specialist. |
| Fertility Effects | Based on animal studies, copanlisib may impair male and female fertility. In female rats, decreased numbers of corpora lutea, implantation sites, and viable embryos were observed. In male dogs, testicular tubular degeneration occurred at clinically relevant exposures. Reversibility of these effects is unknown. Advise patients of potential impact on fertility. |
■ FDA Black Box Warning
Fatal and serious toxicities including infections, hyperglycemia, hypertension, non-infectious pneumonitis, and severe cutaneous reactions have occurred.
| Serious Effects |
Hypersensitivity to copanlisib or any excipientConcurrent use with strong CYP3A4 inhibitors (if cannot be avoided)
| Precautions | Monitor for infections; manage hyperglycemia and hypertension; monitor for pneumonitis symptoms; avoid in patients with severe hepatic impairment. |
| Food/Dietary | Avoid grapefruit, grapefruit juice, and Seville oranges as they may increase drug exposure. No other specific food interactions reported. |
| Clinical Pearls | ALIQOPA (copanlisib) is a PI3K inhibitor with significant toxicity including hyperglycemia, hypertension, and infections. Monitor blood glucose and blood pressure closely during infusion. Premedicate with antihistamines and corticosteroids to reduce infusion-related reactions. Consider Pneumocystis jirovecii pneumonia prophylaxis due to immunosuppression. |
| Patient Advice | Report any signs of infection (fever, cough, burning urination) immediately. · Monitor blood sugar levels regularly as this drug can cause high blood sugar. · Check blood pressure at home and report elevations. · Avoid grapefruit and Seville oranges during treatment. · Use effective contraception during treatment and for 1 month after last dose. |
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