Management of patients with BRAF positive melanoma

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Tafinlar (dabrafenib) + Mekinist (trametinib) is an all-oral regimen^1,2

Advice for patients on how to take Tafinlar + Mekinist

Image of a glass of water, two Tafinlar tablets and one Mekinist tablet alongside advice for patients on how to take Tafinlar and Mekinist

How to take Tafinlar and Mekinist^1,2
	Tafinlar	Mekinist
How much to take	The usual dose is 150 mg (two 75 mg capsules) twice daily.	The usual dose is 2 mg (one tablet) once a day.
When to take	Taflinar should be taken twice a day in the morning and in the evening, about 12 hours apart. The morning and evening doses of Taflinar should be taken at similar times every day.	Mekinist should be taken once a day, at about the same time each day, either with the morning or with the evening dose of Taflinar.
How to take	Taflinar should be taken on an empty stomach, either 1 hour before, or 2 hours after, a meal.	Mekinist should be taken on an empty stomach, either 1 hour before, or 2 hours after, a meal.
What to do in certain situations when taking Tafinlar and Mekinist
	Tafinlar	Mekinist
If a patient forgets to take Tafinlar or Mekinist:	If the missed dose is less than 6 hours late, the patient must take it as soon as they remember. If the missed dose is more than 6 hours late, the patient should skip that dose and take the next dose at the usual time. Then carry on taking the capsules at regular times as usual. The patient mustn’t take a double dose to make up for a missed dose.	If the missed dose is less than 12 hours late, the patient must take it as soon as they remember. If the missed dose is more than 12 hours late, the patient should skip that dose and take the next dose at the usual time. Then carry on taking the capsules at regular times as usual. The patient mustn’t take a double dose to make up for a missed dose.
If a patient cannot remember if they have taken Tafinlar or Mekinist:	The patient mustn’t take any Tafinlar capsules in case they have already taken some. The patient must take next dose at the usual scheduled time. Then carry on taking the tablets at regular times as usual.	The patient mustn’t take a Mekinist tablet in case they have already taken one. The patient must take next dose at the usual scheduled time. Then carry on taking the tablets at regular times as usual.
If a patient vomits after taking Tafinlar or Mekinist:	The patient mustn’t take the capsules or tablet again, but wait until next dose is due and take it at the normal time.
If a patient has taken more than the prescribed number of Tafinlar capsules, Mekinist tablets, or other medicines:	The patient must consult a doctor, pharmacist or nurse immediately, and take the medicine(s) and its packaging.

Dose reduction schedule for Tafinlar + Mekinist

. Icon of three tablets alongside the words 'Two TAFINLAR capsule strengths (50 mg and 75 mg) and two MEKINIST tablet strengths (0.5 mg and 2 mg) are available to manage dose modifications'

Recommended dose level reductions^1,2
Dose Level	Tafinlar dose	Mekinist dose
Starting dose	150 mg twice daily	2 mg once daily
1st dose reduction	100 mg twice daily	1.5 mg once daily
2nd dose reduction	75 mg twice daily	1 mg once daily
3rd dose reduction	50 mg twice daily	1 mg once daily

Mekinist must be stored in a refrigerator (2–8°C) before opening.

Management of pyrexia

Pyrexia was the most common adverse event observed in Phase III clinical trials of Tafinlar + Mekinist.^3,4

~50% of first occurrences happen in the first month of therapy and the majority of cases are mild to moderate^1,5
Patients may respond well to dose interruption and/or dose reduction and supportive care for management of pyrexia, allowing later re-initiation of treatment¹

Guidance for managing pyrexia in patients receiving Tafinlar + Mekinist

Three-step guidance for managing pyrexia (≥38.5°C)^1,2
1. INTERRUPT	2. MANAGE	3. REINITIATE
Interrupt TAFINLAR Continue MEKINIST at the same dose	Evaluate for infection, and, if necessary, treat in accordance with local practice Initiate antipyretics such as ibuprofen or paracetamol Consider oral corticosteroids where antipyretics are insufficient	Upon resolution of pyrexia, restart TAFINLAR with appropriate antipyretic prophylaxis: At the same dosage if the pyrexia was a first occurrence and was not accompanied by other severe signs and symptoms At a reduced dosage if the pyrexia was recurrent and/or was accompanied by other severe signs and symptoms

Diagram showing three-step guidance for managing pyrexia and Infographic showing three-step guidance for managing pyrexia

In the TAFINLAR + MEKINIST clinical studies, management of pyrexia was implemented at ≥38.5°C. Local treatment protocols may define pyrexia differently.

NSAID, non-steroidal anti-inflammatory drug.

References

Tafinlar (dabrafenib) Summary of Product Characteristics.
Mekinist (trametinib) Summary of Product Characteristics.
Robert C et al. N Engl J Med 2019;381:626–636.
Long GV et al. N Engl J Med 2017;377:1813–1823.
Long GV et al. N Engl J Med 2014;371:1877–1888.
Welsh SJ, Corrie PG. Ther Adv Med Oncol 2015;1–15.
Common Terminology Criteria for Adverse Events (CTCAE) V4.0.

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IE154653 November 2021

Oncology

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Reporting of side effects
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk profile of the medicinal product. All suspected adverse reactions should be reported to HPRA Pharmacovigilance, website www.hpra.ie. Adverse events can also be reported to Novartis preferably at www.novartis.com/report, by emailing [email protected] or by calling (01) 2080 612.

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Management of patients with BRAF positive melanoma