PIQRAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PIQRAY (PIQRAY).
PIQRAY (alpelisib) is a phosphatidylinositol-3-kinase (PI3K) inhibitor with inhibitory activity predominantly against PI3Kα. It inhibits the PI3K/AKT/mTOR signaling pathway, reducing cell proliferation and survival in PIK3CA-mutated cancer cells.
| Metabolism | Primarily metabolized by CYP3A4. Minor contributions from other CYP enzymes and glucuronidation. |
| Excretion | Following a single oral dose of [14C]-PIQRAY, 81% of the radioactivity was recovered in feces (70% unchanged) and 14% in urine (7% unchanged). |
| Half-life | The terminal elimination half-life is 12 hours (range 9-17 hours), supporting twice-daily dosing. |
| Protein binding | 84% bound to plasma proteins (mainly albumin and α1-acid glycoprotein). |
| Volume of Distribution | Apparent volume of distribution is 2,200 L (approximately 31 L/kg for a 70 kg individual), indicating extensive extravascular distribution. |
| Bioavailability | Absolute bioavailability is 37% (range 30-47%). Oral bioavailability is increased by 2-fold when taken with food (high-fat meal). |
| Onset of Action | Onset of clinical effect (tumor response) is typically observed within 2-4 weeks of starting therapy, based on clinical trials. |
| Duration of Action | Duration of action is approximately 12 hours, consistent with twice-daily dosing. Continuous dosing is required for sustained effect. |
300 mg orally twice daily with food, taken as two 150 mg tablets.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): 250 mg orally twice daily. Moderate hepatic impairment (Child-Pugh B): 200 mg orally twice daily. Severe hepatic impairment (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment required for elderly patients. Clinical studies included patients ≥65 years; no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PIQRAY (PIQRAY).
| Breastfeeding | It is not known whether alpelisib is excreted in human milk. However, due to the potential for serious adverse reactions in breastfed infants, women should not breastfeed during treatment with PIQRAY and for at least 1 week after the last dose. The M/P ratio is unknown. |
| Teratogenic Risk | PIQRAY (alpelisib) is contraindicated in pregnancy. Based on its mechanism of action and animal studies, alpelisib 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, alpelisib caused embryofetal toxicity and teratogenicity at exposures below the recommended human dose. The risk is present throughout all trimesters. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of severe hypersensitivity to alpelisib or any of its excipients","Inherited severe combined immunodeficiency (SCID)","Concomitant use with strong CYP3A4 inducers","Concomitant use with strong CYP3A4 inhibitors (if unable to reduce dose)"]
| Precautions | ["Severe hypersensitivity reactions","Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS)","Hyperglycemia (monitor blood glucose prior to and during treatment)","Pneumonitis","Diarrhea (may be severe)","Pancreatitis","Risk of fetal harm","Monitor for osteonecrosis of the jaw"] |
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| Fetal Monitoring | Women of reproductive potential should have a pregnancy test prior to initiating PIQRAY. Use effective contraception during treatment and for at least 3 weeks after the last dose. Monitor for hyperglycemia, which is a common adverse effect, and manage appropriately. No specific fetal monitoring is recommended beyond standard prenatal care. |
| Fertility Effects | Based on animal studies, alpelisib may impair fertility in females and males. In female rats, ovarian and uterine atrophy were observed. In male rats, testicular degeneration and reduced sperm count were noted. The effects on human fertility are unknown. |