Overview
11 DESCRIPTION VIJOICE (alpelisib) is a kinase inhibitor. The chemical name of alpelisib is (2 S )- N 1 -[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide. Alpelisib is a white to almost white powder. The molecular formula for alpelisib is C 19 H 22 F 3 N 5 O 2 S and the relative molecular mass is 441.47 g/mol. The pH of a 1.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models. Activating mutations in PIK3CA have been found to induce a spectrum of overgrowths and malformations comprising a wide group of clinically recognizable disorders commonly known as PROS.
Indications
- 1 INDICATIONS AND USAGE VIJOICE is indicated for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Common Doses
- 50 mg
- 250 mg
- 125 mg
- 200 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended Dose: Pediatric patients (2 to less than 18 years of age): 50 mg taken orally once daily with food. ( 2.1 ) Adult patients: 250 mg taken orally once daily with food. ( 2.1 ) Administration: Swallow tablets whole. Do not chew, divide, or crush. ( 2.4 ) For patients who cannot swallow tablets whole, use tablets or oral granules to create a suspension or a mixture. ( 2.4 ) VIJOICE suspension made with water can be administered orally or via a nasogastric or gastric tube. ( 2.
Contraindications
- 4 CONTRAINDICATIONS VIJOICE is contraindicated in patients with severe hypersensitivity to alpelisib or any of its ingredients [see Warnings and Precautions (5.1)] . Severe hypersensitivity to VIJOICE or to any of its ingredients. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: Severe Hypersensitivity [see Warnings and Precautions (5.1)] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2)] Hyperglycemia [see Warnings and Precautions (5.3)] Pneumonitis [see Warnings and Precautions (5.4)] Diarrhea or Colitis [see Warnings and Precautions (5.5)] Most common adverse reactions (Grades 1 to 4, incidence ≥ 10%) were diarrhea, stomatitis, and hyperglycemia. ( 6.
Interactions
- 7 DRUG INTERACTIONS CYP3A4 Inducers : Avoid coadministration of VIJOICE 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 VIJOICE. If unable to use alternative drugs, closely monitor for increased adverse reactions. ( 7.1 ) 7.1 Effect of Other Drugs on VIJOICE CYP3A4 Inducers Avoid coadministration of VIJOICE with strong CYP3A4 inducers and consider an alternative concomitant drug with no or minimal potential...