palovarotene (Sohonos)

Indications

• reduction in volume of heterotopic ossification
• males with fibrodysplasia ossificans progressiva

Contraindications

• pregnancy

Dosage

• 5 mg PO QD
  • increase to 20 mg PO QD with flare for 4 weeks
  • taper to 10 mg PO QD for 8 weeks.

Capsules: 1 mg, 1,5 mg, 2.5 mg, 5 mg, 10 mg

Adverse effects

• headache, back pain
• premature epiphyseal closure
• decreased vertebral bone mineral conted
• dry skin, dry lips, pruritus, rash, alopecia, skin exfoliation, dry eye
• depression, anxiety
• night blindness

Drug interactions

• CYP3A4 inhibitors may increase palovarotene exposure
• CYP3A4 inducers may decrease palovarotene exposure
• avoid concurrent use of tetracyclnes
• vitamin A may have additive effects

Mechanism of action

• retinoic acid receptor agonist, with particular selectivity for RAR-gamma
• through binding of RAR-gamma, palovarotene decreases BMP/ALK2 downstream signaling by inhibiting phosphorylation of SMAD1/5/8
• this reduces ALK2/SMAD-dependent chondrogenesis & osteocyte differentiation resulting in reduced endochondral bone formation

More general terms

• metabolic agent (metabolic modifier)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=10295295