Palovarotene

SOHONOS is indicated for the reduction in volume of new heterotopic ossification in adults and pediatric patients aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP). SOHONOS is a retinoid indicated for reduction in the volume of new heterotopic ossification in adults and children aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP).

In patients with FOP, abnormal bone formation, including heterotopic ossification (HO), is driven by a gain-of-function mutation in the bone morphogenetic protein (BMP) type I receptor ALK2 (ACVR1). Palovarotene is an orally bioavailable retinoic acid receptor agonist, with particular selectivity at the gamma subtype of RAR. Through binding to RARγ, palovarotene decreases the BMP/ALK2 downstream signaling pathway by inhibiting the phosphorylation of SMAD1/5/8, which reduces ALK2/SMAD-dependent chondrogenesis and osteocyte differentiation resulting in reduced endochondral bone formation.

Obtain a negative pregnancy test in females of reproductive potential before initiation of SOHONOS. Recommended dosage includes a chronic daily dose, which can be increased for flare-up symptoms. For adults and pediatric patients 14 years and older: Recommended dosage is 5 mg once daily, with an increase in dose at the time of a flare-up to 20 mg once daily for 4 weeks, followed by 10 mg once daily for 8 weeks for a total of 12 weeks (20/10 mg flare-up treatment). For pediatric patients under 14 years: Weight-adjusted for daily and flare-up dosing. Recommended daily dosage range from 2.5 to 5 mg. Refer to Table 2 in Full Prescribing Information for complete pediatric dosing. Take SOHONOS with food preferably at same time each day. Reduce the dose in the event of adverse reactions as appropriate. See Full Prescribing Information for complete dosing instructions

SOHONOS is contraindicated in the following patients: During Pregnancy. A history of allergy or hypersensitivity to retinoids, or to any component of SOHONOS. Anaphylaxis and other allergic reactions have occurred with other retinoids. Pregnancy. Hypersensitivity to retinoids or any component of SOHONOS

Boxed warning: is contraindicated in pregnancy. Because of the risk of teratogenicity and to minimize fetal exposure, SOHONOS is to be administered only if conditions for pregnancy prevention are met. SOHONOS causes premature epiphyseal closure in growing pediatric patients with FOP, close monitoring is recommended. Embryo-Fetal Toxicity SOHONOS is contraindicated in pregnancy. SOHONOS may cause fetal harm. Premature Epiphyseal Closure: Premature epiphyseal closure occurred with SOHONOS. Assess baseline skeletal maturity before SOHONOS therapy and monitor linear growth in growing pediatric patients. Mucocutaneous Adverse Reactions: Dry skin, lip dry, pruritus, rash, alopecia, erythema, skin exfoliation, and dry eye occurred with SOHONOS. Prevent or treat with skin emollients, sunscreen, artificial tears. Dosage reduction may be required in some patients.

The following clinically significant adverse reactions are described elsewhere in the labeling: Premature Epiphyseal Closure in Growing Pediatric Patients Mucocutaneous Adverse Reactions Metabolic Bone Disorders Psychiatric Disorders Night Blindness Most common adverse reactions (incidence ≥10%) are dry skin, lip dry, arthralgia, pruritus, pain in extremity, rash, alopecia, erythema, headache, back pain, skin exfoliation, nausea, musculoskeletal pain, myalgia, dry eye, hypersensitivity, peripheral edema, and fatigue

CYP3A4 Inhibitors: May increase SOHONOS exposure. Avoid concomitant use of strong/moderate CYP3A4 inhibitors. If concomitant use of moderate CYP3A4 inhibitors is unavoidable, reduce the dose of SOHONOS by half. CYP3A4 Inducers: May decrease SOHONOS exposure. Avoid concomitant use of strong/moderate CYP3A4 inducers. Vitamin A: May cause additive effects. Tetracyclines: Avoid concomitant use with SOHONOS. Systemic Corticosteroids: No clinically significant drug interaction is expected with concomitant use of SOHONOS

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F). 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. SOHONOS must be kept in the original carton to protect from light.