Alpelisib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of alpelisib.
Drugs List
Therapeutic Indications
Uses
Hormone receptor +ve, HER2 -ve locally advanced or metastatic breast cancer
In combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative, locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy.
Dosage
Adults
300mg once daily.
Alpelisib should be co-administered with fulvestrant. The recommended dose of fulvestrant is 500mg via intramuscular injection of days 1, 15 and 29, and once monthly thereafter.
Additional Dosage Information
Dose modifications of alpelisib
Starting dose: 300mg/day
First dose reduction: 250mg/day
Second dose reduction: 200mg/day
Dose modifications for hyperglycaemia management
Fasting glucose levels greater than ULN to 160 mg/dl or greater than ULN to 8.9 mmol/l: Initiate or intensify oral antidiabetic treatment.
Fasting glucose levels greater than 160 to 250 mg/dl or greater than 8.9 to 13.9 mmol/l: Initiate or intensify oral antidiabetic treatment. If fasting glucose does not decrease to less than or equal to 160 mg/dl or 8.9 mmol/l within 21 days with oral antidiabetic treatment, reduce alpelisib dose by 1 dose level.
Fasting glucose levels greater than 250 to 500 mg/dl or 13.9 to 27.8 mmol/l: Interrupt alpelisib. Initiate or intensify oral antidiabetic treatment and consider additional antidiabetic treatment (such as insulin) for 1 to 2 days until hyperglycaemia resolves. Administer adequate hydration and ensure electrolyte/ketoacidosis/hyperosmolar disturbances are treated. If fasting glucose decreases to less than or equal to 160 mg/dl or 8.9 mmol/l within 3 to 5 days under appropriate antidiabetic treatment, resume alpelisib at next lower dose level. If fasting glucose does not decrease to less than or equal to 160 mg/dl or 8.9 mmol/l within 3 to 5 days under appropriate antidiabetic treatment, consultation with a healthcare professional with expertise in the treatment of hyperglycaemia is recommended. If fasting glucose does not decrease to less than or equal to 160 mg/dl or 8.9 mmol/l within 21 days antidiabetic treatment, permanently discontinue alpelisib treatment.
Fasting glucose levels greater than 500 mg/dl or greater than or equal to 27.8 mmol/l: Interrupt alpelisib. Initiate or intensify oral antidiabetic treatment and administer adequate hydration and ensure electrolyte/ketoacidosis/hyperosmolar disturbances are treated. Re-check within 24 hours and as clinically indicated. If fasting glucose decreases to less than or equal to 500 mg/dl or 27.8 mmol/l, then follow fasting glucose value specific recommendations for less than 500 mg/dl. If fasting glucose is still greater than 500 mg/dl or greater than or equal to 27.8 mmol/l after 24 hours, then permanently discontinue alpelisib treatment.
Dose modifications for rash management
Grade 1 (less than 10% body surface area (BSA) with active skin toxicity): Initiate topical corticosteroid treatment. Consider oral antihistamines to manage symptoms.
Grade 2 (10% to 30% BSA with active skin toxicity): Initiate or intensify topical corticosteroid and oral antihistamine treatment. Consider low-dose oral corticosteroid treatment.
Grade 3 (greater than 30% BSA with active skin toxicity): Interrupt treatment until rash is grade 1 or lower. Initiate or intensify topical/oral corticosteroid and antihistamine treatment. Once rash has improved to grade 1 or lower, then resume alpelisib at the same dose level for first occurrence of rash and at next lower dose level, in case of second occurrence.
Grade 4 (any % BSA associated with extensive superinfection, with intravenous antibiotics indicated; life threatening consequences): Permanently discontinue alpelisib.
Dose modifications for diarrhoea management
Grade 1: Initiate appropriate medical therapy and monitor as clinically indicated.
Grade 2: Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Interrupt alpelisib until recovery to grade 1 or lower, then resume alpelisib at the same dose level.
Grade 3 or 4: Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Interrupt alpelisib until recovery to grade 1 or lower, then resume alpelisib at the next lower dose level.
Dose modifications for other toxicity management (excluding hyperglycaemia, rash and diarrhoea)
Grade 1 or 2: Initiate appropriate medical therapy and monitor as clinically indicated.
Grade 3: Interrupt alpelisib until improvement to grade 1 or lower, then resume at the next dose level.
Grade 4: Permanently discontinue alpelisib.
Grade 2 or 3 pancreatitis: Interrupt alpelisib until recovery to grade 1 or lower and resume at the next lower dose level. If toxicity recurs, permanently discontinue alpelisib treatment.
Grade 2 bilirubin elevation: Interrupt alpelisib until recovery to grade 1 or lower and resume at the same dose level if resolved within 14 days or resume at the next lower dose level if resolved in more than 14 days.
Missed doses
If a dose of alpelisib is missed, it can be taken immediately following food and within 9 hours after the time it is usually administered. After 9 hours, the dose should be skipped for that day. On the next day, the dose of alpelisib should be taken at the regular time.
Contraindications
Children under 18 years
Breastfeeding
History of severe cutaneous adverse reactions
Osteonecrosis of the jaw
Pregnancy
Precautions and Warnings
Impaired glucose tolerance
Obese patients with a BMI greater than 30kg/m2
Patients over 75 years
Diabetes mellitus
Severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Consider use of corticosteroids if adverse reactions occur
Maintain adequate hydration of patient prior / during treatment
Must be used as part of combination therapy
Premedication with antihistamine recommended
Treatment to be initiated by specialist
Advise patient to take with or after food
Consult local policy on the safe use of oral anti-cancer drugs
Ensure patient has adequate fluid intake
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor fasting serum glucose prior to and periodically during treatment
Diabetic control may need adjustment
Monitor antidiabetic drug treatment
Monitor blood glucose closely in patients with diabetes mellitus
Monitor HbA1c before treatment, after 4 weeks and every 3 months thereafter
Monitor periodically for signs or symptoms of hyperglycaemia
Monitor serum electrolytes
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report diarrhoea
Suspend treatment if pneumonitis is suspected
Consider discontinuing treatment if grade 4 toxicity occurs
Consider suspending treatment if grade 2 or 3 toxicity occurs
Discontinue and do not restart if severe cutaneous adverse reactions occur
Discontinue if treatment related pneumonitis is diagnosed
Discontinue permanently if severe hypersensitivity reactions occur
Suspend treatment if patients experience worsening of respiratory symptoms
May cause impaired fertility
Female: Contraception required during and for 1 week after treatment
Male & female: Two methods of contraception required (including barrier)
Male: Contraception required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment
Advise patient to report any dental mobility, pain or swelling
Advise patients to report skin rash
Severe cutaneous reactions
Patients should be advised of the signs and symptoms of severe cutaneous reactions (e.g. a prodrome of fever, flu-like symptoms, mucosal lesions or progressive skin rash). If signs and symptoms of severe cutaneous reactions occur, alpelisib should be interrupted until the aetiology of the reaction has been determined. If a severe cutaneous reaction is confirmed, alpelisib should be permanently discontinued. If a severe cutaneous reaction is not confirmed, alpelisib may require treatment interruption, dose reduction or treatment discontinuation.
Pneumonitis
A diagnosis of non-infectious pneumonitis should be considered in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, cough, dyspnoea, or interstitial infiltrates on a radiological examination and in whom infectious, neoplastic and other causes have been excluded by means of appropriate investigations.
Pregnancy and Lactation
Pregnancy
Alpelisib is contraindicated during pregnancy.
The manufacturer recommends that alpelisib is not used in pregnancy and in women of childbearing potential not using contraception. There is no data in the use in pregnant women, however animal studies have shown reproductive toxicity.
Lactation
Alpelisib is contraindicated during breastfeeding.
The manufacturer recommends that women should not breastfeed during treatment and for at least 1 week following the last dose. It is unknown whether alpelisib is excreted in animal or human breast milk, however there is the potential for serious adverse reactions in the breast-fed infant.
Side Effects
Abdominal pain
Acute kidney injury
Ageusia
Alanine aminotransferase increased
Allergic dermatitis
Alopecia
Anaemia
Aphthous ulcers
Asthenia
Blurred vision
Cheilitis
Decreased appetite
Decreased blood glucose
Decreased serum albumin
Dehydration
Dermatitis
Dermatitis acneiform
Diabetic ketoacidosis
Diarrhoea
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry eyes
Dry mouth
Dry skin
Dryness of nasal mucosa
Dysgeusia
Dyspepsia
Elevated serum lipase
Erythema
Erythema multiforme
Eyelid oedema
Facial oedema
Fatigue
Gamma glutamyl transferase (GGT) increased
Gingival pain
Gingivitis
Headache
Hypersensitivity reactions
Hypertension
Hypocalcaemia
Hypogeusia
Hypokalaemia
Hypomagnesaemia
Increase in serum glucose
Increased glycated haemoglobin (HbA1c) levels
Increased partial thromboplastin time
Insomnia
Interstitial lung disease
Ketoacidosis
Lymphoedema
Macular rash
Maculopapular rash
Mouth ulcers
Mucosal inflammation
Muscle spasm
Myalgia
Nausea
Oedema
Osteonecrosis (primarily of the jaw)
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Peripheral oedema
Pneumonitis
Pruritic rash
Pruritus
Pyrexia
Rash
Reduced lymphocyte count
Reduced platelet count
Serum creatinine increased
Skin fissures
Stevens-Johnson syndrome
Stomatitis
Tooth ache
Urinary tract infections
Urosepsis
Vaginal dryness
Vomiting
Weight loss
Xeroderma
Xerosis
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: January 2021
Reference Sources
Summary of Product Characteristics: Piqray 50mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised July 2020.
Summary of Product Characteristics: Piqray 150mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised July 2020.
Summary of Product Characteristics: Piqray 200mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised July 2020.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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