Usual Adult Dose for Hutchinson-Gilford Syndrome

Initial dose: 115 mg/m2 orally twice a day

• After 4 months increase to 150 mg/m2 orally twice a day

Maintenance dose: 115 mg/m2 or 150 mg/m2 twice a day

Comments:

• The total daily dose should be rounded to the nearest 25 mg increment.
• For patients unable to tolerate a dose of 150 mg/m2 twice a day due to repeated episodes of vomiting and/or diarrhea resulting in dehydration or weight loss, may decrease dose to 115 mg/m2.
• See Administration Advice for preparation and administration instructions.
• Limitations of Use: Not indicated for other Progeroid Syndromes or processing-proficient Progeroid Laminopathies since based upon its mechanism of action, it would not be expected to be effective.

Uses:

• To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS).
• For the treatment of processing deficient Progeroid Laminopathies with either:
• Heterozygous LMNA mutation with progerin-like protein accumulation
• Homozygous or compound heterozygous ZMPSTE24 mutations

Usual Pediatric Dose for Hutchinson-Gilford Syndrome

12 months and older with a Body Surface Area (BSA) of 0.39 m2 and above:

Initial dose: 115 mg/m2 orally twice a day

• After 4 months increase to 150 mg/m2 orally twice a day

Maintenance dose: 115 mg/m2 or 150 mg/m2 twice a day

Comments:

• The total daily dose should be rounded to the nearest 25 mg increment.
• For patients unable to tolerate a dose of 150 mg/m2 twice a day due to repeated episodes of vomiting and/or diarrhea resulting in dehydration or weight loss, may decrease dose to 115 mg/m2.
• See Administration Advice for preparation and administration instructions.
• Limitations of Use: Not indicated for other Progeroid Syndromes or processing-proficient Progeroid Laminopathies since based upon its mechanism of action, it would not be expected to be effective.

Uses:

• To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS).
• For the treatment of processing deficient Progeroid Laminopathies with either:
• Heterozygous LMNA mutation with progerin-like protein accumulation
• Homozygous or compound heterozygous ZMPSTE24 mutations

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

CYP450 3A Inhibitors:

• Contraindicated with strong or moderate CYP450 3A inhibitors
• If coadministration with a weak CYP450 3A inhibitor is unavoidable, reduce lonafarnib dose to 115 mg/m2 or continue with lonafarnib dose of 115 mg/m2 twice a day
• Following discontinuation of weak CYP450 3A inhibitor, previous lonafarnib dose should be resumed after 14 days

Concomitant Midazolam Use:

• Temporarily discontinue lonafarnib use for 10 to 14 days before and 2 days after midazolam administration

Precautions

CONTRAINDICATIONS:

• Strong or moderate CYP450 3A inhibitors or inducers
• Midazolam
• Lovastatin, simvastatin, or atorvastatin

Safety and efficacy have not been established in patients younger than 12 months.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally twice a day with morning and evening meals
• Swallow capsules with an adequate amount of water; do not chew capsules

If Unable to Swallow Capsules: Mix capsule contents with Ora Blend SR, Ora Plus, orange juice, or applesauce as follows:

• To mix with Ora Blend SR, Ora Plus, or orange juice: For each capsule, empty contents into container containing 5 to 10 mL of liquid, mix thoroughly with a spoon, consume entire serving
• To mix with applesauce: For each capsule, empty contents of capsule into a container containing 1 teaspoonful to 2 teaspoonfuls of applesauce, mix thoroughly with a spoon, consume entire serving
• Do not mix with juice containing grapefruit juice or Seville oranges
• Prepared mixture must be taken within 10 minutes of mixing

MISSED DOSE: If a dose is missed, take as soon as possible with food up to 8 hours prior to the next scheduled dose; if less than 8 hours remains before next scheduled dose, skip the missed dose, and resume regular schedule

General:

• BSA-based dosage recommendation tables are available in the manufacturer's product labeling (PI). These tables provide total daily dosage rounded to nearest 25 mg for BSAs ranging from 0.39 to 1 m2.

Monitoring:

• Periodically monitor electrolytes, complete blood counts, and liver enzymes
• Monitor renal function at regular intervals
• Perform ophthalmological evaluation at regular intervals and with any new visual changes

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information and Instructions of Use).
• Patients and caregivers should be instructed to report use of all prescription and nonprescription medications, including nutritional supplements and vitamins to their healthcare provider as this drug may interact with many drugs.
• Patients and caregivers should understand that gastrointestinal adverse reactions are common, however, they should contact their healthcare provider if they are persistent.
• Patients and caregivers should be advised to report symptoms of hypertension and/or any visual changes.
• Patients should understand that this drug may cause embryo-fetal toxicity and impaired fertility; males and females of reproductive potential should discuss use with their healthcare provider.