VIJOICE® (alpelisib) tablets

Gafacom April 11, 2023

VIJOICE® (alpelisib) tablets

VIJOICE® (alpelisib) tablets are indicated for the treatment of pediatric and adult patients with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy. This rare genetic disorder is characterized by the overgrowth of various tissues and can lead to a range of symptoms and complications. VIJOICE® works by inhibiting the activity of PI3K, a protein involved in cell growth and division.

VIJOICE (alpelisib) is a kinase inhibitor. The chemical name of alpelisib is (2S)-N1-[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 C19H22F3N5O2S and the relative molecular mass is 441.47 g/mol.

VIJOICE® (alpelisib) tablets


VIJOICE film-coated tablets are supplied for oral administration with three strengths that contain 50 mg, 125 mg and 200 mg of alpelisib. The tablets also contain hypromellose, magnesium stearate, mannitol, microcrystalline cellulose, and sodium starch glycolate. The film-coating contains hypromellose, iron oxide red (applicable only to 50 mg and 200 mg strengths), iron oxide yellow, macrogol/polyethylene glycol (PEG) 4000, talc, and titanium dioxide.

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).

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.

In an inducible mouse model of Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal syndrome (CLOVES), a phenotype of PROS, alpelisib inhibition of the PI3K pathway resulted in the prevention or improvement of organ abnormalities associated with the disease, depending on when alpelisib treatment was started. These findings were reversed after withdrawal of alpelisib.

DOSAGE AND ADMINISTRATION

Adult Patients: The recommended dosage of VIJOICE in adult patients is 250 mg orally, once daily, administered as recommended until disease progression or unacceptable toxicity.

Pediatric Patients (2 to less than 18 years of age): The recommended initial dosage of VIJOICE in pediatric patients is 50 mg orally, once daily, administered as recommendeduntil disease progression or unacceptable toxicity.

Consider a dose increase to 125 mg once daily in pediatric patients ≥ 6 years old for response optimization (clinical/radiological) after 24 weeks of treatment with VIJOICE at 50 mg once daily. When a pediatric patient turns 18 years old, consider a gradual dose increase up to 250 mg.

Administration

Take VIJOICE with food at approximately the same time each day.

No tablet should be used if it is broken, cracked, or otherwise damaged at the time of opening the blister pack.

Swallow VIJOICE tablets whole. Do not split or chew.

If a dose of VIJOICE 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 VIJOICE 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.

For patients who are not able to swallow tablets, administer VIJOICE as an oral suspension with food

  • Place VIJOICE tablets in a glass containing 2 to 4 ounces of water and let it stand for approximately 5 minutes. Make the suspension with water only.
  • Crush the tablets with a spoon and stir until an oral suspension is obtained.
  • Administer the oral suspension immediately after preparation. Discard the oral suspension if it is not administered within 60 minutes after preparation.
  • After administration of the oral suspension, add approximately 2 to 3 tablespoons of water to the same glass. Stir with the same spoon to re-suspend any remaining particles and administer the entire contents of the glass.

Repeat if particles remain.

CONTRAINDICATIONS

VIJOICE is contraindicated in patients with severe hypersensitivity to alpelisib or any of its ingredients.

WARNINGS AND PRECAUTIONS

Severe Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have occurred in adult patients treatedwith alpelisib in the oncology setting and may occur in patients treated with VIJOICE. VIJOICE is not approved for use inthe oncology setting.

Permanently discontinue VIJOICE in the event of severe hypersensitivity.

Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), erythema multiforme (EM),toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have occurred inadult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE. VIJOICE isnot approved for use in the oncology setting.

If signs or symptoms of SCARs occur, interrupt VIJOICE until the etiology of the reaction has been determined.

Consultation with a dermatologist is recommended.

If a SCAR is confirmed, permanently discontinue VIJOICE.

If a SCAR is not confirmed, VIJOICE may require dose modifications, topical corticosteroids, or oral antihistamine treatment.

Hyperglycemia: Severe hyperglycemia, in some cases associated with hyperglycemic hyperosmolar non-ketotic syndrome (HHNKS) orfatal cases of ketoacidosis, has occurred in adult patients treated with alpelisib in the oncology setting and may occur inpatients treated with VIJOICE. VIJOICE is not approved for use in the oncology setting.

Pneumonitis: Severe pneumonitis, including acute interstitial pneumonitis and interstitial lung disease, has occurred in adult patientstreated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE. VIJOICE is not approvedfor use in the oncology setting.

In patients who have new or worsening respiratory symptoms or are suspected to have developed pneumonitis, interrupt VIJOICE immediately and evaluate the patient for pneumonitis. Consider a diagnosis of non-infectious pneumonitis in patients presenting with non-specific respiratory signs and symptoms, such as hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams and in whom infectious, neoplastic, and other causes have been excluded by means of appropriate investigations.

Permanently discontinue VIJOICE in all patients with confirmed pneumonitis.

Diarrhea: Severe diarrhea, including cases resulting in dehydration and acute kidney injury, has occurred in adult patients treatedwith alpelisib in the oncology setting and may occur in patients treated with VIJOICE. VIJOICE is not approved for use inthe oncology setting.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, VIJOICE can cause fetal harm when administered to apregnant woman. In animal reproduction studies, oral administration of alpelisib to pregnant animals duringorganogenesis caused adverse developmental outcomes, including embryo-fetal mortality (post-implantation loss),reduced fetal weights, and increased incidences of fetal malformations at doses that were approximately equivalent to therecommended pediatric and adult doses. Advise pregnant women and females of reproductive potential of the potentialrisk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VIJOICE and

for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use condoms and effective contraception during treatment with VIJOICE and for 1 week after the last dose

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data and mechanism of action, VIJOICE can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Inanimal reproduction studies, oral administration of alpelisib to pregnant rats and rabbits during organogenesis causedadverse developmental outcomes, including embryo-fetal mortality (post-implantation loss), reduced fetal weights, andincreased incidences of fetal malformations. Advise pregnant women of the potentialrisk to a fetus.

Lactation: There are no data on the presence of alpelisib in human milk, its effects on milk production, or the breastfed child.Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeedduring treatment with VIJOICE and for 1 week after the last dose.

Pediatric Use: The safety and effectiveness of VIJOICE have been established in pediatric patients 2 to less than 18 years of age withPROS based on results from a single-arm clinical study of VIJOICE (EPIK-P1) that enrolled 39 pediatric patients: 11patients aged 2 to 5 years, 12 patients aged 6 to 11 years, and 16 patients aged 12 to less than 18 years of age.

The safety and effectiveness of VIJOICE in pediatric patients below the age of 2 years have not been established.

Although there were no new safety signals observed in pediatric patients, there is insufficient data to determine whether VIJOICE has an adverse impact on growth and development in pediatric patients with PROS.

Geriatric Use: There were no adult patients aged 65 years of age or older who received VIJOICE in EPIK-P1.

OVERDOSAGE

There is limited experience of overdose with alpelisib in clinical trials.

In cases where accidental overdosage of alpelisib was reported in the clinical studies, the adverse reactions associated with the overdose were consistent with the known safety profile of alpelisib and included hyperglycemia, nausea, asthenia, and rash.

Initiate general symptomatic and supportive measures in all cases of overdosage where necessary. There is no known antidote for VIJOICE.

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