Dabrafenib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of dabrafenib.
Drugs List
Therapeutic Indications
Uses
Advanced non-small cell lung cancer BRAFV600 mutation:Combination treatment
Treatment of unresectable or metastatic melanoma with BRAF V600 mutation
Melanoma
Monotherapy or in combination with trametinib in adults with unresectable or metastatic melanoma with a BRAF V600 mutation.
Adjuvant treatment of melanoma
In combination with trametinib in adults for the adjuvant treatment of patients with stage III melanoma with a BRAF V600 mutation, following complete resection.
Non-small cell lung cancer
In combination with trametinib in adults with advanced non-small cell lung cancer with a BRAF V600 mutation.
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 of dabrafenib is 150mg twice daily.
Treatment should continue until treatment no longer benefits patient or the development of unacceptable toxicity.
Additional Dosage Information
Missed Dose
If a dose is missed, it should not be taken if it is less than 6 hours until the next dose.
Dose modification
When modifying the dose of dabrafenib, consider if a reduction in the dose of trametinib may also be necessary.
Grade 1 or grade 2 (tolerable) adverse events
Continue treatment and monitor as clinically indicated.
Grade 2 (intolerable) or grade 3 adverse events
Interrupt therapy until toxicity is grade 0 to 1 and reduce by one dose level when resuming therapy.
Grade 4 adverse events
Discontinue permanently, or interrupt therapy until grade 0 to 1 and reduce by one dose level when resuming therapy.
Patients with uveitis that is controlled by local ocular therapies should remain on the normal dose regimen. If uveitis does not respond to local treatments suspend treatment until resolution and resume treatment at a dose reduced by one dose level.
Interrupt treatment with dabrafenib if fever occurs. Dabrafenib can be restarted once the fever resolves with appropriate prophylaxis using NSAIDs or paracetamol. If fever is associated with other severe signs and symptoms, dabrafenib should be restarted at a reduced dose once fever resolves and as clinically appropriate.
Dose modifications or interruptions are not recommended for adverse reactions of cutaneous squamous cell carcinoma or new primary melanoma.
Dose level reductions
Full dose: 150mg twice daily.
First dose reduction: 100mg twice daily.
Second reduction: 75mg twice daily.
Third reduction: 50mg twice daily.
Reductions below 50mg are not recommended.
Re-escalation
Once adverse reactions are under control, dose re-escalation following the same dosing levels as reduction may be considered.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Moderate hepatic impairment
RAS mutation associated cancer
Severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Confirm BRAF V600 mutation status of tumour prior to treatment
Consider use of corticosteroids if adverse reactions occur
CT scan recommended prior to and every 6 months during treatment
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Anal examination advised before, during and at end of treatment
Examine head and neck prior to and every 3 months during treatment
Pelvic examination advised before, during and at end of treatment
Monitor for skin lesions prior to, during and for 6 months after treatment
Monitor full blood count regularly
Monitor patient constantly for signs of new infection
Monitor serum creatinine
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report any blurred vision or any other eye symptoms
Advise patients to report symptoms of acute pancreatitis immediately
Consider pancreatitis in patients with unexplained abdominal pain
Discontinue or suspend treatment if grade 4 toxicities occur
Risk of pancreatitis
When fever resolves, use NSAID or paracetamol prophylactically
Discontinue if pulmonary embolism occurs
Interrupt treatment if patients temperature is 38 degrees C or more
Suspend treatment if grade 3 or intolerable grade 2 toxicities
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
May cause impaired fertility
Female: Contraception required during and for 2 weeks after treatment
Female: Effect of hormonal contraceptive may be reduced
Advise patient to inform physician of any skin changes immediately
An increased risk of non-cutaneous malignancies may be seen when dabrafenib is administered to patients with RAS mutations. Careful consideration of the benefits and risks must be carried out before administering dabrafenib to patients with prior or concurrent cancer associated with RAS mutations.
New primary melanoma should be excised but do not require treatment modification.
Monitoring for new or recurrent malignancies should continue for 6 months following discontinuation of treatment.
Patients with unexplained abdominal pain should be investigated for pancreatitis, including measurements of serum amylase and lipase. Closely monitor patients when re-starting dabrafenib after an episode of pancreatitis.
Pregnancy and Lactation
Pregnancy
Dabrafenib is contraindicated during pregnancy.
The manufacturer recommends that dabrafenib is not used during pregnancy unless the potential benefit to the mother outweighs any potential risk to the foetus. Animal studies have shown reproductive toxicity and embryofoetal developmental toxicities, including teratogenic effects.
Lactation
Dabrafenib is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues dabrafenib or discontinues breastfeeding. It is not known whether dabrafenib is excreted in breast milk. LactMed suggests the amount of dabrafenib present in breast milk is likely to be low. The effect on a breastfed infant is unknown, but a risk cannot be excluded.
Side Effects
Abdominal pain
Acneform changes
Acrochordon
Actinic keratosis
Acute renal failure
Alanine aminotransferase increased
Alopecia
Anaemia
Arthralgia
Aspartate aminotransferase increased
Asthenia
Basal cell carcinoma
Blurred vision
Bradycardia
Cellulitis
Chills
Chorioretinopathy
Colitis
Constipation
Cough
Creatine phosphokinase increased
Decreased appetite
Decreased ejection fraction
Dehydration
Diarrhoea
Dizziness
Dry mouth
Dry skin
Dyspnoea
Erythema
Facial oedema
Fatigue
Folliculitis
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal perforation
Haemorrhage
Headache
Hyperglycaemia
Hyperhidrosis
Hyperkeratosis
Hypersensitivity reactions
Hypertension
Hyponatraemia
Hypophosphataemia
Hypotension
Impaired vision
Increase in alkaline phosphatase
Infertility
Influenza-like symptoms
Keratosis
Leukopenia
Lymphoedema
Mucosal inflammation
Muscle spasm
Myalgia
Myocarditis
Nasopharyngitis
Nausea
Nephritis
Neutropenia
Night sweats
Painful extremities
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Panniculitis
Paronychia
Periorbital oedema
Peripheral oedema
Photosensitivity
Pneumonitis
Primary melanoma
Pruritus
Pustular rash
Pyrexia
Rash
Reduced left ventricular output
Renal failure
Retinal detachment
Skin fissures
Skin lesions
Skin papilloma
Squamous cell carcinoma
Stomatitis
Thrombocytopenia
Urinary tract infections
Uveitis
Vomiting
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: April 2019
Reference Sources
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 August 2019
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
Dabrafenib Last revised: 03 December 2018
Last accessed: 17 April 2019
Summary of Product Characteristics: Tafinlar 50mg and 75mg hard capsules. Novartis Pharmaceuticals UK Ltd. Revised May 2019.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.