Active Ingredient: Lonafarnib
Lonafarnib is indicated for the treatment of patients 12 months of age and older with a genetically confirmed diagnosis of Hutchinson-Gilford progeria syndrome or a processing-deficient progeroid laminopathy associated with either a heterozygous LMNA mutation with progerin-like protein accumulation or a homozygous or compound heterozygous ZMPSTE24 mutation.
For this indication, competent medicine agencies globally authorize below treatments:
Oral
75 - 225 mg per m² of body surface area (BSA)
From 37.5 To 112.5 mg per m² of body surface area (BSA) 2 time(s) per day every day
115 mg per m² of body surface area (BSA)
150 mg per m² of body surface area (BSA)
For all indications, the recommended starting dose is 115 mg/m² twice daily. The Du Bois formula was used in clinical trials and should be used to calculate body surface area for dosing. All total daily doses should be rounded to the nearest 25 mg increment and divided into two equal, or near equal, doses (see Table 1). Doses should be taken approximately 12 hours apart from one another (morning and evening).
Table 1. Recommended starting dose and administration schedule for 115 mg/m² body surface area-based dosing:
| Body surface area (m²) | Total daily dose rounded to nearest 25 mg | Morning dose number of capsule(s) | Evening dose number of capsule(s) | ||
|---|---|---|---|---|---|
| lonafarnib 50 mg | lonafarnib 75 mg | lonafarnib 50 mg | lonafarnib 75 mg | ||
| 0.30 – 0.38 | 75 | 1* | 1* | ||
| 0.39 – 0.48 | 100 | 1 | 1 | ||
| 0.49 – 0.59 | 125 | 1 | 1 | ||
| 0.6 – 0.7 | 150 | 1 | 1 | ||
| 0.71 – 0.81 | 175 | 2 | 1 | ||
| 0.82 – 0.92 | 200 | 2 | 2 | ||
| 0.93 – 1 | 225 | 1 | 1 | 2 | |
* For patients with a body surface area of 0.30 m² to 0.38 m², the contents of a 75 mg capsule must be mixed with 10 mL of orange juice. Half of the mixture (5 mL) equates to a 37.5 mg dose of lonafarnib. This dose will be prepared and consumed twice daily.
After 4 months of treatment using the starting dose of 115 mg/m² twice daily, the dose should be increased to the maintenance dose of 150 mg/m² twice daily (morning and evening). All total daily doses should be rounded to the nearest 25 mg increment and divided into two equal, or near equal, doses (see Table 2).
Table 2. Recommended maintenance dose and administration schedule for 150 mg/m² body surface area-based dosing:
| Body surface area (m²) | Total daily dose rounded to nearest 25 mg | Morning dose number of capsule(s) | Evening dose number of capsule(s) | ||
|---|---|---|---|---|---|
| lonafarnib 50 mg | lonafarnib 75 mg | lonafarnib 50 mg | lonafarnib 75 mg | ||
| 0.30 – 0.37 | 100 | 1 | 1 | ||
| 0.38 – 0.45 | 125 | 1 | 1 | ||
| 0.46 – 0.54 | 150 | 1 | 1 | ||
| 0.55 – 0.62 | 175 | 2 | 1 | ||
| 0.63 – 0.7 | 200 | 2 | 2 | ||
| 0.71 – 0.79 | 225 | 1 | 1 | 2 | |
| 0.8 – 0.87 | 250 | 1 | 1 | 1 | 1 |
| 0.88 – 0.95 | 275 | 2 | 1 | 1 | |
| 0.96 – 1 | 300 | 2 | 2 | ||
If a dose is missed, the dose should be taken as soon as possible, up to 8 hours prior to the next scheduled dose with food. If less than 8 hours remain before the next scheduled dose, the missed dose should be skipped and the dose regimen should be resumed at the next scheduled dose.
Patients will need to receive a daily dose of 75 mg (37.5 mg twice daily). The contents of a lonafarnib 75 mg capsule should be mixed with 10 mL of orange juice. Only half of the 10-mL mixture will be consumed.
For patients who have increased their dose to 150 mg/m² twice daily and are experiencing repeated episodes of vomiting and/or diarrhoea resulting in dehydration or weight loss, the dose can be reduced to the starting dose of 115 mg/m² twice daily. All daily doses should be rounded to the nearest 25 mg increment and divided into two equal, or near equal, doses (see Table 1).
Prevention or treatment of vomiting and/or diarrhoea with an anti-emetic and/or anti-diarrhoeal medicinal product can be considered.
Concomitant use of midazolam is contraindicated. Patients requiring parenteral midazolam for a surgical procedure should discontinue lonafarnib for 14 days before and 2 days after administration of midazolam.
Lonafarnib is intended for oral use. The capsule should be swallowed whole. The capsule should not be chewed. Each dose is to be taken with food.
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