Dosing & Administration

TAFINLAR + MEKINIST is the first and only oral treatment for pediatric patients with BRAF V600E+ low-grade glioma who require systemic therapy

Oral Dosing

TAFINLAR + MEKINIST is available in 2 forms of oral dosing.^1,2

Capsule & Tablet Dosing

The recommended dosage for TAFINLAR (capsules) and MEKINIST (tablets) in pediatric patients is based on body weight, beginning at 26 kg. (Note: This applies to capsule and tablet dosing only.) A recommended dose for TAFINLAR + MEKINIST has not been established in patients who weigh less than 26 kg.^1,2

If vomiting occurs after administration of TAFINLAR or MEKINIST, do not take an additional dose. Take the next dose at its scheduled time^1,2

Weight-based oral dosing for TAFINLAR + MEKINIST^1,2

TAFINLAR		MEKINIST
Body Weight	Recommended Pediatric Dose (Capsules)	Body Weight	Recommended Pediatric Dose (Tablets)
26 to 37 kg	75 mg (one 75-mg capsule) orally BID	26 to 37 kg	1 mg (two 0.5-mg tablets) orally QD
38 to 50 kg	100 mg (two 50-mg capsules) orally BID	38 to 50 kg	1.5 mg (three 0.5-mg tablets) orally QD
≥51 kg	150 mg (two 75-mg capsules) orally BID	≥51 kg	2 mg (one 2-mg tablet) orally QD

BID, twice daily; QD, once daily.

Treatment is recommended until disease progression or unacceptable toxicity^1,2
The number of TAFINLAR capsules and MEKINIST tablets included in the chart above are an example. TAFINLAR and MEKINIST are also available in other strengths. TAFINLAR is available as 50-mg and 75-mg capsules, and MEKINIST is available as 0.5-mg and 2-mg tablets^1,2

Liquid Formulation Dosing

TAFINLAR + MEKINIST can be administered as a liquid formulation for patients who may have difficulty swallowing or are unable to swallow.⁴ Ensure caregivers are properly trained to administer TAFINLAR + MEKINIST in liquid form by reviewing the TAFINLAR Instructions for Use and MEKINIST Instructions for Use with them.

TAFINLAR oral suspension is prepared by dissolving TAFINLAR tablets in 5 to 10 mL of water. MEKINIST is provided as an oral solution by your patient's pharmacy.^1,2

How to prepare liquid formulation infographic.

Weight-based dosing for TAFINLAR tablets for oral suspension and MEKINIST for oral solution^1,2

TAFINLAR Total Daily Dose		MEKINIST Total Daily Dose
Body Weight	Recommended Dosage (# of 10-mg Tablets for Oral Suspension BID)	Body Weight	Recommended Dosage (Total Volume of Oral Solution QD)
8 to 9 kg	20 mg (2 tablets)	8 kg	6 mL (0.3 mg)
8 to 9 kg	20 mg (2 tablets)	9 kg	7 mL (0.35 mg)
10 to 13 kg	30 mg (3 tablets)	10 kg	7 mL (0.35 mg)
		11 kg	8 mL (0.4 mg)
		12 to 13 kg	9 mL (0.45 mg)
14 to 17 kg	40 mg (4 tablets)	14 to 17 kg	11 mL (0.55 mg)
18 to 21 kg	50 mg (5 tablets)	18 to 21 kg	14 mL (0.7 mg)
22 to 25 kg	60 mg (6 tablets)	22 to 25 kg	17 mL (0.85 mg)
26 to 29 kg	70 mg (7 tablets)	26 to 29 kg	18 mL (0.9 mg)
30 to 33 kg	80 mg (8 tablets)	30 to 33 kg	20 mL (1 mg)
34 to 37 kg	90 mg (9 tablets)	34 to 37 kg	23 mL (1.15 mg)
38 to 41 kg	100 mg (10 tablets)	38 to 41 kg	25 mL (1.25 mg)
42 to 45 kg	110 mg (11 tablets)	42 to 45 kg	28 mL (1.4 mg)
46 to 50 kg	130 mg (13 tablets)	46 to 50 kg	32 mL (1.6 mg)
≥51 kg	150 mg (15 tablets)	≥51 kg	40 mL (2 mg)

BID, twice daily; QD, once daily.

Treatment is recommended until disease progression or unacceptable toxicity^1,2

TAFINLAR + MEKINIST liquid formulation can be administered in multiple ways^1,2:

Methods of liquid formulation administration graphic

For complete administration instructions, please see the full Prescribing Information for the appropriate medications. Please share the Instructions for Use with your patients.

Capsule & Tablet Dose Reductions

The overall management of certain adverse reactions may require treatment interruption, dose reduction, or treatment discontinuation, depending on severity.^1,2

Dose reductions for TAFINLAR capsules and MEKINIST tablets^1,2

TAFINLAR

Recommended Pediatric Dose Reductions (Capsules)

MEKINIST

Recommended Pediatric Dose Reductions (Tablets)

Body Weight: 26 to 37 kg

Recommended dose: 75 mg (one 75-mg capsule) orally BID

First dose reduction: 50 mg (one 50-mg capsule) BID
Subsequent modification: Permanently discontinue TAFINLAR if unable to tolerate 50 mg BID

Recommended dose: 1 mg (two 0.5-mg tablets) orally QD

First dose reduction: 0.5 mg (one 0.5-mg tablet) QD
Permanently discontinue MEKINIST tablets if unable to tolerate a maximum of 2 dose reductions

Body Weight: 38 to 50 kg

Recommended dose: 100 mg (two 50-mg capsules) orally BID

First dose reduction: 75 mg (one 75-mg capsule BID
Second dose reduction: 50 mg (one 50-mg capsule) BID
Subsequent modification: Permanently discontinue TAFINLAR if unable to tolerate 50 mg BID

Recommended dose: 1.5 mg (three 0.5-mg tablets) orally QD

First dose reduction: 1 mg (two 0.5-mg tablets) QD
Second dose reduction: 0.5 mg (one 0.5-mg tablet) QD
Permanently discontinue MEKINIST tablets if unable to tolerate a maximum of 2 dose reductions

Body Weight: ≥51 kg

Recommended dose: 150 mg (two 75-mg capsules) orally BID

First dose reduction: 100 mg (two 50-mg capsules) BID
Second dose reduction: 75 mg (one 75-mg capsule) BID
Third dose reduction: 50 mg (one 50-mg capsule) BID
Subsequent modification: Permanently discontinue TAFINLAR if unable to tolerate 50 mg BID

Recommended dose: 2 mg (one 2-mg tablet) orally QD

First dose reduction: 1.5 mg (three 0.5-mg tablets) QD
Second does reduction: 1 mg (two 0.5-mg tablets) QD
Permanently discontinue MEKINIST tablets if unable to tolerate a maximum of 2 dose reductions

BID, twice daily; QD, once daily.

The number of TAFINLAR capsules and MEKINIST tablets included in the chart above are an example. TAFINLAR and MEKINIST are also available in other strengths. TAFINLAR is available as 50-mg and 75-mg capsules, and MEKINIST is available as 0.5-mg and 2-mg tablets^1,2

Liquid Dose Reductions

Dose reductions for TAFINLAR + MEKINIST liquid formulation^1,2

TAFINLAR Total Daily Dose (Oral Suspension)					MEKINIST Total Daily Dose (Oral Solution)
Body Weight	Recommended Dosage BID	Dose Reduction^a			Body Weight	Recommended Dosage QD	Dose Reduction
Body Weight	Recommended Dosage BID	1st	2nd	3rd	Body Weight	Recommended Dosage QD	1st	2nd
8 to 9 kg	20 mg	1	0	0	8 kg	6 mL (0.3 mg)	5 mL	3 mL
8 to 9 kg	20 mg	1	0	0	9 kg	7 mL (0.35 mg)	5 mL	4 mL
10 to 13 kg	30 mg	2	1	0	10 kg	7 mL (0.35 mg)	5 mL	4 mL
					11 kg	8 mL (0.4 mg)	6 mL	4 mL
					12 to 13 kg	9 mL (0.45 mg)	7 mL	5 mL
14 to 17 kg	40 mg	3	2	1	14 to 17 kg	11 mL (0.55 mg)	8 mL	6 mL
18 to 21 kg	50 mg	3	2	1	18 to 21 kg	14 mL (0.7 mg)	11 mL	7 mL
22 to 25 kg	60 mg	4	3	2	22 to 25 kg	17 mL (0.85 mg)	13 mL	9 mL
26 to 29 kg	70 mg	5	4	2	26 to 29 kg	18 mL (0.9 mg)	14 mL	9 mL
30 to 33 kg	80 mg	5	4	3	30 to 33 kg	20 mL (1 mg)	15 mL	10 mL
34 to 37 kg	90 mg	6	5	3	34 to 37 kg	23 mL (1.15 mg)	17 mL	12 mL
38 to 41 kg	100 mg	7	5	3	38 to 41 kg	25 mL (1.25 mg)	19 mL	13 mL
42 to 45 kg	110 mg	7	6	4	42 to 45 kg	28 mL (1.4 mg)	21 mL	14 mL
46 to 50 kg	130 mg	9	7	4	46 to 50 kg	32 mL (1.6 mg)	24 mL	16 mL
≥51 kg	150 mg	10	8	5	≥51 kg	40 mL (2 mg)	30 mL	20 mL

Permanently discontinue MEKINIST for oral solution if unable to tolerate a maximum of 2 dose reductions.²

BID, twice daily; QD, once daily.
^aNumber of 10-mg tablets for oral suspension BID.¹

Dose Modifications

Severity of Adverse Reaction^a	TAFINLAR^1,b	MEKINIST^2,c
Hemorrhage
Grade 3	See Other Adverse Reactions (Including Hemorrhage for TAFINLAR)	Withhold MEKINIST If improved, resume MEKINIST at lower dose If not improved, permanently discontinue MEKINIST
Grade 4	See Other Adverse Reactions (Including Hemorrhage for TAFINLAR)	Permanently discontinue MEKINIST
New Primary Malignancies
Noncutaneous RAS-mutation–positive malignancies	Permanently discontinue TAFINLAR	No dose modifications recommended for MEKINIST
Venous Thromboembolism
Uncomplicated DVT or PE	No dose modifications recommended for TAFINLAR	Withhold MEKINIST for up to 3 weeks If improved to grade 0/1, resume MEKINIST at lower dose If not improved, permanently discontinue MEKINIST
Life-threatening PE	No dose modifications recommended for TAFINLAR	Permanently discontinue MEKINIST
Cardiomyopathy
Asymptomatic, absolute decrease in LVEF of 10% or greater from baseline and is below institutional LLN from pretreatment value	No dose modifications recommended for TAFINLAR	Withhold MEKINIST for up to 4 weeks If improved to normal LVEF value, resume MEKINIST at lower dose If not improved to normal LVEF value, permanently discontinue MEKINIST
Symptomatic cardiomyopathy or congestive heart failure Absolute decrease in LVEF of greater than 20% from baseline that is below LLN	Withhold TAFINLAR until LVEF improves to at least the institutional LLN and absolute decrease to less than or equal to 10% compared to baseline, then resume at same dose	Permanently discontinue MEKINIST
Ocular Toxicities
Retinal pigment epithelial detachment	No dose modifications recommended for TAFINLAR	Withhold MEKINIST for up to 3 weeks If improved, resume MEKINIST at same or lower dose If not improved, permanently discontinue MEKINIST or resume MEKINIST at lower dose
Retinal vein occlusion	No dose modifications recommended for TAFINLAR	Permanently discontinue MEKINIST
Uveitis (including iritis and iridocyclitis) that is mild or moderate but does not respond to ocular therapy Severe uveitis	Withhold TAFINLAR for up to 6 weeks If improved to grade 0/1, then resume TAFINLAR at same or lower dose If not improved, permanently discontinue TAFINLAR	No dose modifications recommended for MEKINIST
Pulmonary
Interstitial lung disease/pneumonitis	No dose modifications recommended for TAFINLAR	Permanently discontinue MEKINIST
Febrile Reactions
Fever of 100.4 °F to 104 °F (or first symptoms in case of recurrence)	Withhold TAFINLAR until fever resolves, then resume at same or lower dose	Withhold MEKINIST until fever resolves, then resume MEKINIST at same or lower dose
Fever higher than 104 °F Fever complicated by rigors, hypotension, dehydration, or renal failure	Withhold TAFINLAR until febrile reactions resolve for at least 24 hours, then resume at lower dose Or Permanently discontinue TAFINLAR	Withhold MEKINIST until febrile reactions resolve for at least 24 hours, then resume MEKINIST at lower dose Or Permanently discontinue MEKINIST
Skin Toxicities
Intolerable grade 2 Grade 3 or 4	Withhold TAFINLAR for up to 3 weeks If improved, resume TAFINLAR at lower dose If not improved, permanently discontinue TAFINLAR	Withhold MEKINIST for up to 3 weeks If improved, resume MEKINIST at lower dose If not improved, permanently discontinue MEKINIST
Severe cutaneous adverse reactions	Permanently discontinue TAFINLAR	Permanently discontinue MEKINIST
Other Adverse Reactions (Including Hemorrhage for TAFINLAR)
Intolerable grade 2 Any grade 3	Withhold TAFINLAR If improved to grade 0/1, resume TAFINLAR at lower dose If not improved, permanently discontinue TAFINLAR	Withhold MEKINIST If improved to grade 0/1, resume MEKINIST at lower dose If not improved, permanently discontinue MEKINIST
First occurrence of any grade 4	Withhold TAFINLAR until adverse reaction improves to grade 0/1. Then resume at a lower dose Or Permanently discontinue TAFINLAR	Withhold MEKINIST until adverse reaction improves to grade 0/1. Then resume at a lower dose Or Permanently discontinue MEKINIST
Recurrent grade 4	Permanently discontinue TAFINLAR	Permanently discontinue MEKINIST

DVT, deep venous thromboembolism; LLN, lower limit of normal; LVEF, left ventricular ejection fraction; PE, pulmonary embolism; RAS, monomeric G protein.
^aNational Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.^1,2
^bDose modifications are not recommended for TAFINLAR when administered with MEKINIST for the following adverse reactions of MEKINIST: retinal vein occlusion, retinal pigment epithelial detachment, interstitial lung disease/pneumonitis, and uncomplicated venous thromboembolism. Dose modification of TAFINLAR is not required for new primary cutaneous malignancies.^1,2
^cDose modifications are not recommended for MEKINIST when administered with TAFINLAR for the following adverse reactions of TAFINLAR: noncutaneous malignancies and uveitis. Dose modification of MEKINIST is not required for new primary cutaneous malignancies.^1,2

NEXT: About BRAF V600E

References: 1. Tafinlar. Prescribing information. Novartis Pharmaceuticals Corp. 2. Mekinist. Prescribing information. Novartis Pharmaceuticals Corp. 3. Packer RJ, Ater J, Allen J, et al. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg. 1997;86(5):747-754. doi:10.3171/jns.1997.86.5.0747 4. Data on file. Primary analysis of a phase II trial of dabrafenib + trametinib in BRAF V600−mutant pediatric low-grade glioma. Novartis Pharmaceuticals Corp; 2022.

Dosing & Administration

IMPORTANT SAFETY INFORMATION

INDICATION