Everolimus

Registered South African indications:

• Organ rejection
• Renal cell carcinoma
• Giant cell astrocytoma associated with tuberous sclerosis
• Breast cancer
• Neuroendocrine tumours of pancreatic origin
• Tuberous sclerosis complex

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy 
• Breastfeeding
• Hepatic impairment
• Pre-existing infections
• Peri-surgical period
• High immunological risk
• Male fertility
• Exposure to sunlight and ultraviolet light
• Galactose intolerance
• Lapp lactase deficiency 
• Glucose-galactose malabsorption 
• History of hypersensitivity reactions 
• Stomatitis 
• Renal failure 
• Diabetes mellitus 
• Dyslipidaemia 
• Anaemia 

 

Forms avail. in SA and covered in this monograph: tab

Used for the treatment of

Kidney and heart transplant (additional agent required) 
- To reduce  the risk of organ rejection in patients at low to moderate immunological risk recieving an allogenic renal or cardiac transplant

• Oral (tab): 0.75mg, 12hrly; Treatment should be started as soon as possible after transplantation

Liver transplant (additional agent required)
Renal cell carcinoma
- Palliative treatment of patients with advanced renal cell carcinoma, who failed prior treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy

• Oral (tab): 1mg, 12hrly; Treatment should be started within 4 weeks of transplantation

Giant cell astrocytoma associated with tuberous sclerosis
Breast cancer (additional agent requires)
- Palliative treatment of postmenopausal women with oestrogen receptor positive, HER2/neu negative advanced breast cancer with recurrence or progression after prior treatment with a non-steroidal aromatase inhibitor
Advanced neuroendocrine tumours of pancreatic origin
Tuberous sclerosis complex
- With renal angiomyolipoma not requiring immediate surgery

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Consult specialist for dosages and regimens

Not established for use in children

Pregnancy 

• Caution: Not recommended
• There is no adequate data from the use of everolimus in pregnant women
• Studies in animals have shown reproductive toxicity effects including embryotoxicity and foetotoxicity
• The potential risk for humans is unknown
• Everolimus is not recommended during pregnancy and in women of childbearing potential not using contraception

Breastfeeding

• Caution; not recommended 
• It is not known whether everolimus is excreted in human breast milk. However, in rats, everolimus and/or its metabolites readily pass into the milk
• Therefore, women taking everolimus should not breastfeed during treatment and for 2 weeks after the last dose

Fertility

• The potential for everolimus to cause infertility in male and female patients is unknown, however amenorrhoea (secondary amenorrhoea and other menstrual irregularities) and associated luteinising hormone (LH)/ follicle stimulating hormone (FSH) imbalance has been observed in female patients
• Based on non-clinical findings, male and female fertility may be compromised by treatment with everolimus

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Caution; dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warning

Central Nervous System Disorders

• Insomnia
• Anxiety
• Dysgeusia
• Headache
• Ageusia
• Eyelid oedema
• Conjunctivitis
• Fatigue

Cardiovascular Disorders

• Congestive cardiac failure
• Pericardial effusion
• Tachycardia
• Haemorrhage 
• Hypertension
• Venous thromboembolic events
• Lymphocoele
• Epistaxis
• Renal graft thrombosis
• Flushing
• Deep vein thrombosis

Respiratory Disorders

• Pleural effusion
• Interstitial lung disease
• Pneumonitis
• Epistaxis
• Cough
• Dyspnoea
• Haemoptysis
• Pulmonary embolism
• Acute respiratory distress syndrome
• Upper respiratory tract infection
• Lower respiratory tract and lung infections 

Gastrointestinal Disorders

• Pancreatitis
• Stomatitis 
• Diarrhoea
• Nausea and vomiting
• Dry mouth
• Abdominal pain
• Mucosal inflammation
• Oral pain
• Dyspepsia
• Dysphagia

Hepatobiliary Disorders

• Increased aspartate aminotransferase 
• Increased alanine aminotransferase 
• Non infectious hepatitis
• Jaundice
• Abnormal hepatic enzymes

Genitourinary Disorders

• Erectile dysfunction
• Menstrual disorder
• Ovarian cyst
• Menstruation irregular
• Amenorrhoea
• Renal tubular necrosis
• Proteinuria
• Increased blood creatinine 
• Renal failure
• Increased daytime urination
• Acute renal failure
• Urinary tract infections

Endocrine and Metabolic Disorders

• Decreased appetite
• Hyperglycaemia
• Hypercholesterolaemia
• Hypertriglyceridaemia
• Hypophosphataemia
• Diabetes mellitus
• Hyperlipidaemia
• Hypokalaemia
• Dehydration
• Hypocalcaemia
• Hypogonadism male
• Decreased weight 

Musculoskeletal Disorders

• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Dry skin
• Nail disorders
• Mild alopecia
• Acne
• Erythema
• Onychoclasis
• Palmar-plantar erythrodysaesthesia syndrome
• Skin exfoliation
• Skin lesion
• Angioedema
• Peripheral oedema
• Healing impaired
• Wound infection

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Leukopaenia
• Thrombotic microangiopathies
• Anaemia
• Thrombocytopenia
• Neutropenia
• Leukopenia
• Lymphopenia
• Pancytopenia
• Pure red cell aplasia
• Pyrexia
• Malignant and unspecified skin neoplasms
• Lymphomas/post-transplant lymphoproliferative disorders 
• Infections (viral, bacterial, fungal)
• Sepsis

Others

• Incisional hernia
• Non-cardiac chest pain

• CYP3A4 inhibitors
• CYP3A4 inducers
• P-glycoprotein inhibitors
• CYP3A4 substrates 
• Live vaccines
• Thymoglobulin 
• Immunosuppressants
• Calcineurin inhibitor
• Octreotide 
• Ciclosporin 
• Angiotensin-converting enzyme inhibitors

• Renal function
• Blood glucose
• Lipid profile
• Hepatic function
• Full blood count with differential 
• Proteinuria
• Blood glucose

Drug levels

• Serum drug trough levels should be measured after 4-5 days after starting or after a dosing change. 
• Drug levels should be maintained between 3-8ng/ml

Missed everolimus dose

If a dose is missed, the patient should not take an additional dose, but take the next prescribed dose as usual

Everolimus, a rapamycin derivative, is a signal transduction inhibitor targeting mTOR (mammalian target of rapamycin), or more specifically, mTORC1 (mammalian 'target of rapamycin' complex 1). mTOR is a key serine-threonine kinase playing a central role in the regulation of cell growth, proliferation and survival. Inhibition of mTORC1 by everolimus has been shown to reduce cell proliferation, glycolysis and angiogenesis in solid tumours in vivo, both through direct antitumour cell activity and inhibition of the tumour stromal compartment.

Tablet 0.25mg

• Certican (Novartis) originator

Tablet 0.75mg

• Certican (Novartis) originator

Tablet 2.5mg

• Afinitor (Novartis) originator

Tablet 5mg

• Afinitor (Novartis) originator

Tablet 10mg

• Afinitor (Novartis) originator