Palovarotene (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- SOHONOS
Indications and Usage
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).
Contraindications
SOHONOS is contraindicated in the following patients: During Pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. A history of allergy or hypersensitivity to retinoids, or to any component of SOHONOS. Anaphylaxis and other allergic reactions have occurred with other retinoids. [see Description (11)].
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Premature Epiphyseal Closure in Growing Pediatric Patients [see Warnings and Precautions (5.2)] Mucocutaneous Adverse Reactions [see Warnings and Precautions (5.3)] Metabolic Bone Disorders [see Warnings and Precautions (5.4)] Psychiatric Disorders [see Warnings and Precautions (5.5)] Night Blindness [see Warnings and Precautions (5.6)]
Mechanism of Action
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.
Overdosage
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.