Letrozole oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of letrozole.
Drugs List
Therapeutic Indications
Uses
Adjuvant therapy postmenop. women for hormone receptor+ early breast cancer
Advanced breast cancer (post-menopausal) after anti-oestrogen failed
Advanced hormone dependent breast cancer in post menopausal women
Early invasive breast cancer in postmenop women prev treated with tamoxifen
Hormone receptor +ve, HER2 -ve breast cancer in post menopausal women
Adjuvant treatment of postmenopausal women with hormone receptor positive invasive early breast cancer.
Extended adjuvant treatment of early invasive breast cancer in postmenopausal women, who have received prior standard adjuvant tamoxifen therapy (5 years).
Advanced breast cancer in post-menopausal women after other anti-oestrogen therapy has failed.
First-line treatment in post-menopausal women with hormone-dependent advanced breast cancer.
Neo-adjuvant therapy in post-menopausal women with hormone receptor positive, HER-2 negative breast cancer where chemotherapy is not suitable and immediate surgery is not indicated.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
The recommended dose is 2.5mg once daily.
Due to a lack of long term data, the optimal duration of therapy has not yet been established.
Extended adjuvant setting: Continue letrozole for 5 years or until tumour relapse occurs, whichever comes first.
Adjuvant setting: Continue letrozole for 5 years or until tumour relapse occurs, whichever comes first. A sequential treatment schedule may be considered (letrozole 2 years and tamoxifen 3 years).
In metastatic or advanced disease: Treatment with letrozole should continue until tumour progression is evident.
Neo-adjuvant setting: Treat with letrozole for 4 to 8 months for optimal tumour reduction. Discontinue if the response is inadequate.
Additional Dosage Information
Advise patient that if a dose is missed, it should be taken as soon as possible. However, if it is less than 3 hours until the next scheduled dose, the missed dose should be skipped and the normal dosing schedule resumed.
Contraindications
Children under 18 years
Premenopausal females
Breast cancer in males
Breastfeeding
Galactosaemia
Pregnancy
Precautions and Warnings
Glucose-galactose malabsorption syndrome
Lactose intolerance
Osteoporosis
Renal impairment - creatinine clearance below 10ml/minute
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Advise ability to drive/operate machinery may be affected by side effects
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Define menopause biochemically if in doubt about hormonal status
Monitor closely patient with Child-Pugh C hepatic impairment
Patients at risk of osteoporosis should have bone density assessed
Advise patient to rest affected limb if tendonitis occurs
May cause loss of bone mineral density
Treatment or prophylaxis of osteoporosis should be started as appropriate
Female: Ensure adequate contraception during treatment
In patients whose post-menopausal status seems unclear, LH, FSH and/or estradiol levels must be assessed before initiating treatment in order to establish menopausal status.
Despite a clear post-menopausal status, there are reports of woman regaining ovarian function. Adequate contraception should be discussed where necessary.
Letrozole is a potent oestrogen lowering agent and reductions in bone mineral density can be anticipated. During adjuvant treatment with letrozole, women with osteoporosis or at risk of osteoporosis and those at risk of bone fractures should have their bone mineral density formally assessed by bone densitometry at the commencement of treatment and at regular intervals thereafter. Treatment for osteoporosis should be initiated as appropriate and patients should be carefully monitored.
Pregnancy and Lactation
Pregnancy
Letrozole is contraindicated during pregnancy.
The manufacturer states that letrozole is contraindicated during pregnancy. Letrozole is thought to cause congenital malformations when administered during pregnancy. Briggs (2015) suggests this may be due to letrozole's inhibition of estrogen synthesis in all tissues.
Animal studies have shown reproductive toxicity. An increased incidence of developmental abnormalities and foetal resorptions were observed, however it is not known whether this was an indirect consequence of inhibition of oestrogen biosynthesis, or a direct drug effect.
Lactation
Letrozole is contraindicated during breastfeeding.
The manufacturer recommends that letrozole is contraindicated during breastfeeding.
At the time of writing, there is no data on the transfer of letrozole or its metabolites into human breast milk.
The molecular weight, low plasma protein binding and long terminal elimination half-life suggest it is likely that letrozole will be excreted into breast milk.
LactMed (2017) states that some manufacturers recommend that breastfeeding is discontinued during treatment, and for 3 weeks after the last dose.
Side Effects
Abdominal pain
Alopecia
Anaphylactic reaction
Angina pectoris
Angioedema
Anorexia
Anxiety
Arterial thrombosis
Arthralgia
Arthritis
Asthenia
Blurred vision
Bone pain
Breast pain
Cardiac failure
Carpal tunnel syndrome
Cataracts
Cerebrovascular accident
Constipation
Cough
Depression
Diarrhoea
Dizziness
Dry mouth
Dry mucous membranes
Dry skin
Dysaesthesia
Dyspepsia
Dyspnoea
Endometrial hyperplasia
Erythema multiforme
Eye irritation
Fatigue
Fractures
Headache
Hepatitis
Hot flushes
Hypercholesterolaemia
Hypertension
Hypoaesthesia
Impaired memory
Increased appetite
Increased sweating
Increased urinary frequency
Increases in hepatic enzymes
Insomnia
Irritability
Leukopenia
Malaise
Myalgia
Myocardial infarction
Myocardial ischaemia
Nausea
Nervousness
Night sweats
Oedema
Osteopenia
Osteoporosis
Ovarian cysts
Palpitations
Paraesthesia
Peripheral oedema
Pruritus
Pulmonary embolism
Pyrexia
Rash
Somnolence
Stomatitis
Stroke
Tachycardia
Taste disturbances
Tendon inflammation
Tendon rupture
Thirst
Thromboembolic disorders
Thrombophlebitis
Toxic epidermal necrolysis
Transient ischaemic attack
Trigger finger
Tumour pain
Urinary retention
Urinary tract infections
Urticaria
Vaginal bleeding
Vaginal discharge
Vaginal dryness
Vomiting
Weight gain
Weight loss
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: March 2018
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Femara 2.5 mg Tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2019.
Summary of Product Characteristics: Letrozole 2.5 mg Dr. Reddy's Laboratories UK Ltd. Revised October 2019.
Summary of Product Characteristics: Letrozole 2.5 mg film-coated tablets. Teva UK Ltd. Revised October 2017.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Letrozole Last revised: 10 October 2017
Last accessed: 27 March 2018
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 23 March 2018
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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