SOHONOS Capsule Ref.[107414] Active ingredients: Palovarotene

2.1 Pregnancy Testing Prior to Treatment with SOHONOS

For females of reproductive potential, obtain a negative pregnancy test within one week prior to initiating and periodically during SOHONOS therapy. If pregnancy occurs, stop SOHONOS treatment immediately and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity. [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)].

2.2 Recommended Dosage and Duration

Dosage Overview

Take SOHONOS with food preferably at the same time each day [see Dosage and Administration (2.3)]. The recommended dosing for SOHONOS includes a chronic daily dosage (daily dose) which can then be modified/increased in the event of FOP flare-up symptoms (flare-up dose).

Initiate flare-up treatment at the onset of the first symptom indicative of a FOP flare-up or substantial high-risk traumatic event likely to lead to a flare-up (e.g., surgery, intramuscular immunization, mandibular blocks for dental procedures, muscle fatigue, blunt muscle trauma from bumps, bruises, falls, or influenza-like viral illnesses). Symptoms of a FOP flare-up typically include but are not limited to localized pain, soft tissue swelling/inflammation, redness, warmth, decreased joint range of motion, and stiffness.

Recommended Dosage for Adults and Pediatric Patients 14 Years and Older

• Daily Dose: The recommended SOHONOS daily dosage for adults and pediatric patients 14 years and older is 5 mg daily. Stop daily dosing when flare-up dosing begins.
• Flare-up Dose:
  • The recommended SOHONOS flare-up dosage for adults and pediatric patients 14 years and older is 20 mg daily for 4 weeks, followed by 10 mg daily for 8 weeks (for a total of 12 weeks of flare-up treatment), even if symptoms resolve earlier, then return to daily dosing of 5 mg.
  • If during the course of flare-up treatment, the patient experiences marked worsening of the original flare-up site or another flare-up at a new location, restart the 12-week flare-up dosing at 20 mg daily.
  • For flare-up symptoms that have not resolved at the end of the 12-week period, the 10 mg daily dosage may be extended in 4-week intervals and continued until the flare-up symptoms resolve. If new flare-up symptoms occur after the 5 mg daily dosing is resumed, flare-up dosing may be restarted.

Recommended Dosage for Pediatric Patients Aged 8 to 13 Years for Females and Aged 10 to 13 Years for Males

• Daily Dose: The recommended SOHONOS daily dosage for patients under 14 years of age is weight-based ranging from 2.5 mg to 5 mg daily (see Table 1). Stop daily dosing when flare-up dosing begins.
• Flare-up Dose:
  • The recommended flare-up SOHONOS dosage for patients under 14 years of age is weight-based (see Table 1). Administer the initial flare-up dosage once daily for 4 weeks, then administer the lower flare-up dosage once daily for 8 weeks (for a total of 12 weeks of flare-up treatment), even if symptoms resolve earlier, then return to daily dosing (see Table 1).
  • If during the course of flare-up treatment, the patient experiences marked worsening of the original flare-up site or another flare-up at a new location, restart the 12-week flare-up dosing with the Week 1 to 4 dose.
  • For flare-up symptoms that have not resolved at the end of the 12-week period, the Week 5 to 12 flare-up dose may be extended in 4-week intervals and continued until the flare-up symptoms resolve. If new flare-up symptoms occur after daily dosing is resumed, flare-up dosing may be restarted.

Table 1. Recommended SOHONOS Weight-Based Dosage for Pediatric Patients Aged 8 to 13 Years for Females and 10 to 13 Years for Males*:

^* once daily

Missed Dose

If a dose of SOHONOS is missed, take the missed dose as soon as possible. If the dose has been missed by more than 6 hours, skip the missed dose, and continue with the next scheduled dose. Do not take two doses at the same time or in the same day.

2.3 Administration Instructions

Take SOHONOS with food preferably at the same time each day. SOHONOS may be swallowed whole, or capsules may be opened and the contents emptied onto one teaspoon (5 mL) of soft food (such as apple sauce, low-fat yogurt, or warm oatmeal) and taken within 1 hour of opening provided it was maintained at room temperature and not exposed to direct sunlight [see Clinical Pharmacology (12.3)]. Do not administer with grapefruit, pomelo, or juices containing these fruits.

2.4 Dosage Reduction for Adverse Reactions

If patients experience adverse reactions that require dosage reduction during either the SOHONOS daily dosing or flare-up dosing, reduce the daily dosage to the next lower dose as shown in Table 2 at the discretion of the healthcare provider; reduce the dosage further if adverse reactions do not improve. If the patient is already receiving the lowest possible tolerated dose, then consider discontinuing SOHONOS temporarily or permanently. Initiate subsequent flare-up dosing at the same reduced dose that was tolerated previously.

Table 2. Dose Reduction of SOHONOS for Flare-Up and Chronic Treatment:

2.5 Dosage Modifications for Drug Interactions

Moderate CYP3A Inhibitors

Avoid concomitant use of a moderate CYP3A inhibitor, if possible. If concomitant use will occur, reduce the dose of SOHONOS by half as shown in Table 3 when co-administered with moderate CYP3A inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Table 3. Dose Reduction of SOHONOS for Use with Moderate CYP3A Inhibitors:

^* All pediatric patients ≥14 years of age and adults should receive the dose in the ≥60 kg weight category.

No clinical experience with an overdose of SOHONOS has been reported. SOHONOS is a derivative of vitamin A. In case of accidental overdose, signs of hypervitaminosis A could appear, including severe headache, nausea or vomiting, drowsiness, irritability and pruritus. Any overdose should be treated with supportive care according to the signs and symptoms exhibited by the patient.

This package is child-resistant. Keep out of reach of children. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room temperature]. SOHONOS must be kept in the original carton to protect from light.

SOHONOS capsules may be opened and the contents emptied on a teaspoon of soft food and taken immediately. If not taken immediately, it can be taken after a maximum of one hour after the sprinkling, provided it was maintained at room temperature and not exposed to direct sunlight.