Palbociclib

Registered South African indications:

• Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Coadministration with preparations containing St. John's Wort
• Porphyria

Cautions

• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment
• Moderate to severe hepatic impairment (Child-Pugh Classes B&C)
  - Patients on haemodialysis
• Females of reproductive potential
• Males of reproductive potential
• Pre- or perimenopausal women
• Critical visceral disease
• Coadministration with endocrine therapy 
• Coadministration with strong CYP3A inhibitors or inducers (See additional prescribing points)
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive or operate machinery

Forms avail in SA and covered in this monograph: cap

Used for the treatment of

• Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer (additional agent required)

Consult specialist for dosages and regimens

Not established for use in children below 18 years

Pregnancy

• Caution; not recommended
• There are no or limited amount of data from the use of palbociclib in pregnant women. Studies in animals have shown reproductive toxicity
• Palbociclib is not recommended during pregnancy and in woman of childbearing potential not using contraception
• Females of childbearing potential who are receiving this medicinal product, or their male partners should use adequate contraceptive methods (e.g. double-barrier contraception) during therapy and for at least 3 weeks or 14 weeks after completing therapy for females and males, respectively

Breastfeeding

• Caution; not recommended 
• No studies have been conducted in humans or animals to assess the effect of palbociclib on milk production, its presence in breast milk or its effects on the breastfed child
• It is unknown whether palbociclib is excreted in human milk
• Patients receiving palbociclib should not breastfeed

Fertility

• There were no effects on oestrous cycle (female rats) or mating and fertility in rats (male or female) in non-clinical reproductive studies. However, no clinical data have been obtained on fertility in humans
• Based on male reproductive organ findings (seminiferous tubule degeneration in testis, epididymal hypospermia, lower sperm motility and density, and decreased prostate secretion) in nonclinical safety studies, male fertility may be compromised by treatment with palbociclib. Thus, men may consider sperm preservation prior to beginning therapy with palbociclib

Renal impairment

• Mild: No dose adjustment recommended
• Moderate to severe; Caution; no dose adjustment recommended
  Closely monitor for signs of toxicity
  Insufficient data are available in patients requiring haemodialysis to provide any dose adjustment recommendation

Hepatic impairment

• Mild (Child-Pugh Class A): No dose adjustment recommended
• Moderate (Child-Pugh Class B): Caution; no dose adjustment recommended
  Closely monitor for signs of toxicity
• Severe (Child-Pugh Class C): Caution; dose adjustment recommended
  Closely monitor for signs of toxicity
  Consult specialist for dosages and regimens

Elderly

• No dose adjustment recommended

Porphyria Information

• Possibly porphyrinogenic (PSP) 

Drugs in Sport

• Permitted - No warnings (monotherapy)
  Palbociclib is permitted and available on prescription only. However, in postmenopausal women, palbociclib may be given in combination with a hormonal medicine, such as letrozole or fulvestrant, which are both prohibited in and out of competition

Central Nervous System Disorders

• Fatigue

Respiratory Disorders

• Epistaxis
• Interstitial lung disease/ pneumonitis

Gastrointestinal Disorders

• Stomatitis
  - Apthous stomatitis
  - Cheilitis
  - Glossitis
  - Glossodynia
  - Mouth ulceration
  - Mucosal inflammation
  - Oral pain
  - Oropharyngeal discomfort
  - Oropharyngeal pain
• Nausea and vomiting
• Diarrhoea

Hepatobiliary Disorders

• Increased alanine aminotransaminases
• Increased aspartate aminotransferase

Endocrine and Metabolic Disorders

• Decreased appetite

Skin and Subcutaneous Tissue Disorders

• Rash
  - Maculopapular
  - Pruritic
  - Erythematous
  - Papular
  - Dermatitis
  - Acneiform dermatitis
  - Toxic skin eruption
• Aloplecia
• Dry skin

Immune, Blood and Lymphatic System Disorders

• Infections
• Neutropenia
  - Decreased neutrophil count
• Leukopenia
  - Decreased white blood cell count
• Anaemia
  - Decreased haemoglobin
  - Decreased haematocrit
• Thrombocytopenia
  - Decreased platelet count
• Febrile neutropenia
• Fever

Sensory Disorders

• Dysgeusia
• Blurred vision
• Increased lacrimation
• Dry eye

• CYP3A inhibitors
• Clarithromycin
• Indinavir
• Itraconazole
• Ketoconazole
• Lopinavir/ ritonavir
• Nefazodone
• Nelfinavir
• Posaconazole
• Saquinavir
• Telapravir
• Telithromycin
• Voriconazole
• CYP3A inducers
• Carbamazepine
• Enzalutamide
• Phenytoin
• Rifampicin
• Modafinil
• Rabeprazole
• Midazolam
• Alfentanil
• Ciclosporine
• Dihydroergotamine
• Ergotamine
• Everolimus
• Fentanyl
• Pimozide
• Quinidine
• Sirolimus
• Tacrolimus
• P-glycoprotein substrates
• Digoxin
• Dabigatran
• Colchicine
• Breast cancer resistance protein substrates
• Pravastatin
• Rosuvastatin
• Sulfasalazine
• Organic cationic transporter substrates
• Metformin

Other

• St. John's Wort
• Grapefruit or grapefruit juice

• Full blood count

Specific cases may require

• Pregnancy test (prior to initiation)

Additional observations

• Signs and symptoms of:
  - Interstitial lung disease/ pneumonitis
  - Infection

Administration instructions

• Palbociclib should be taken with food, preferably a meal to ensure consistent palbociclib exposure
• Capsules should be swallowed whole (should not be chewed, crushed, or opened prior to swallowing). No capsule should be ingested if it is broken, cracked, or otherwise not intact

Coadministration with inhibitors or inducers of CYP3A4

• Strong inhibitors of CYP3A4 may lead to increased toxicity. Concomitant use of strong CYP3A inhibitors during treatment with palbociclib should be avoided. Coadministration should only be considered after careful evaluation of the potential benefits and risks. If coadministration with a strong CYP3A inhibitor is unavoidable, reduce the palbociclib dose to 75mg once daily. When the strong inhibitor is discontinued, increase the dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor
• Coadministration of CYP3A inducers may lead to decreased palbociclib exposure and consequently a risk for lack of efficacy. Therefore, concomitant use of palbociclib with strong CYP3A4 inducers should be avoided. No dose adjustments are required for coadministration of palbociclib with moderate CYP3A inducers

Palbociclib is a highly selective, reversible inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Cyclin D1 and CDK4/6 are downstream of multiple signalling pathways which lead to cellular proliferation. Through inhibition of CDK4/6, palbociclib reduced cellular proliferation by blocking progression of the cell from G1 into S phase of the cell cycle. 

Capsule 75mg

• Palbociclib Pfizer 75mg (Pfizer Laboratories) originator

Capsule 100mg

• Palbociclib Pfizer 100mg (Pfizer Laboratories) originator

Capsule 125mg

• Palbociclib Pfizer 150mg (Pfizer Laboratories) originator