Alpelisib
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From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
Renal Impairment The effect of severe renal impairment (CLcr < 30 mL/min) on alpelisib pharmacokinetics is unknown [see Clinical Pharmacology] . No dose adjustment is recommended for patients with mild to moderate renal impairment (CLcr 30 to < 90 mL/min).
Preparation and administration
Dosage and Administration The recommended dose of PIQRAY is 300 mg (two 150 mg film-coated tablets) taken orally, once daily, with food [see Clinical Pharmacology] . Continue treatment until disease progression or unacceptable toxicity occurs [see Dosage and Administration] . Patients should take their dose of PIQRAY at approximately the same time each day.
Swallow PIQRAY tablets whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact. If a dose of PIQRAY is missed, it can be taken with food within 9 hours after the time it is usually taken. After more than 9 hours, skip the dose for that day.
The next day, take PIQRAY at the usual time. If the patient vomits after taking the dose, advise the patient not to take an additional dose on that day, and to resume the dosing schedule the next day at the usual time. When given with PIQRAY, the recommended dose of fulvestrant is 500 mg administered on Days 1, 15, and 29, and once monthly thereafter.
Refer to the Full Prescribing Information for fulvestrant.
Drug interactions
Check alpelisib against a medication listLabel text (3 paragraphs)
7 DRUG INTERACTIONS CYP3A4 Inducers : Avoid coadministration of PIQRAY with a strong CYP3A4 inducer. Consider an alternative concomitant drug with no or minimal potential to induce CYP3A4. ( 7.1 ) Breast Cancer Resistance Protein (BCRP) Inhibitors : Avoid the use of BCRP inhibitors in patients treated with PIQRAY. If unable to use alternative drugs, closely monitor for increased adverse reactions. ( 7.1 )
7.1 Effect of Other Drugs on PIQRAY CYP3A4 Inducer Coadministration of PIQRAY with a strong CYP3A4 inducer decreases alpelisib concentration [see Clinical Pharmacology (12.3)] , which may reduce alpelisib efficacy. Avoid concomitant use of strong CYP3A4 inducers and consider an alternative concomitant drug with no or minimal potential to induce CYP3A4. Breast Cancer Resistance Protein Inhibitors Coadministration of PIQRAY with a breast cancer resistance protein (BCRP) inhibitor may increase alpelisib concentration [see Clinical Pharmacology (12.3)] , which may increase the risk of toxicities. Avoid the use of BCRP inhibitors in patients treated with PIQRAY.
If unable to use alternative drugs, when PIQRAY is used in combination with BCRP inhibitors, closely monitor for increased adverse reactions.
Contraindications
4 CONTRAINDICATIONS PIQRAY is contraindicated in patients with severe hypersensitivity to it or any of its components [see Warnings and Precautions (5.1)] . Severe hypersensitivity to PIQRAY or to any of its components. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
E*Likelihood score E*: Unproven but suspected rare cause of clinically apparent liver injury.
Alpelisib is an oral selective inhibitor of the phosphoinositol-3-kinase (PIK3) which is mutated in several forms of solid tumors and is approved for use in specific forms of advanced or metastatic breast cancer. Serum aminotransferase elevations are common during alpelisib therapy but clinically apparent liver injury with jaundice has not been reported with its use and must be rare, if it occurs at all.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary PIQRAY is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for pregnancy information. Based on animal data and mechanism of action, PIQRAY can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available data in pregnant women to inform the drug-associated risk.
In animal reproduction studies, oral administration of alpelisib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal mortality (post-implantation loss), reduced fetal weights, and increased incidences of fetal malformations at maternal exposures ≥ 0.8 times the exposure in humans based on AUC at the recommended dose of 300 mg/day (see Data) . Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
However, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of alpelisib up to 30 mg/kg/day during the period of organogenesis. In rats, oral administration of alpelisib resulted in maternal toxicity (body weight loss, low food consumption) and no viable fetuses (post-implantation loss) at 30 mg/kg/day (approximately 3 times the exposure in humans at the recommended dose of 300 mg/day based on AUC).
At a dose of 10 mg/kg/day (approximately 0.8 times the exposure in humans at the recommended dose of 300 mg/day based on AUC), toxicities included reduced fetal weight and increased incidences of skeletal malformations (bent scapula and thickened or bent long bones) and fetal variations (enlarged brain ventricle, decreased bone ossification). In a pilot embryo-fetal development study in rabbits, a dose of 30 mg/kg/day resulted in no viable fetuses (post-implantation loss). Doses ≥ 15 mg/kg/day resulted in increased embryo-fetal deaths, reduced fetal weights, and malformations, mostly related to the tail and head.
At 15 mg/kg/day in rabbits, the maternal exposure was approximately 5 times the exposure achieved at the recommended human dose of 300 mg/day based on AUC.
Breastfeeding (LactMed)
No information is available on alpelisib during breastfeeding. Because the drug is 89% protein bound, amounts in milk are likely to be low. Because of possible infant toxicity, the manufacturer recommends that breastfeeding be discontinued during alpelisib therapy and for 1 week after the final dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.