Sohonos Generic Name & Formulations
Mechanism of Action
Palovarotene is an orally bioavailable retinoic acid receptor (RAR) 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.
For reduction in the volume of new heterotopic ossification in adults and children aged ≥8yrs (females) and aged ≥10yrs (males) with fibrodysplasia ossificans progressiva (FOP).
Sohonos Dosage and Administration
Adults and Children
<8yrs (females) and <10yrs (males): not established. Take with food. Swallow caps whole, or may be opened and the contents emptied onto 1 tsp of soft food (eg, apple sauce, low-fat yogurt, warm oatmeal); consume within 1hr of opening. 8–13yrs (females) and 10–13yrs (males): weight-based dose ranging from 2.5–5mg once daily (see full labeling); stop daily dosing when flare-up dosing begins. Flare-up: give initial flare-up dose (weight-based; see full labeling) once daily for 4 weeks, followed by lower flare-up dose once daily for 8 weeks (for total of 12 weeks of flare-up treatment), then return to daily dosing. Restart the 12-week flare-up dosing (Week 1–4), if marked worsening of the original flare-up site or another flare-up at a new location occurs during the course of the flare-up treatment. May extend the Week 5–12 flare-up dose in 4-week intervals for flare-up symptoms that have not resolved at the end of the 12-week period, and continued until resolved. If new flare-up symptoms occur after daily dosing is resumed, flare-up dosing may be restarted. ≥14yrs: 5mg once daily; stop daily dosing when flare-up dosing begins. Flare-up: 20mg once daily for 4 weeks, followed by 10mg once daily for 8 weeks (for total of 12 weeks of flare-up treatment), then return to 5mg daily. Restart the 12-week flare-up dosing at 20mg once daily, if marked worsening of the original flare-up site or another flare-up at a new location occurs during the course of the flare-up treatment. May extend the 10mg once daily dose in 4-week intervals for flare-up symptoms that have not resolved at the end of the 12-week period, and continued until resolved. If new flare-up symptoms occur after the 5mg once daily dosing is resumed, flare-up dosing may be restarted. Dosage modifications for adverse reactions, drug interactions: see full labeling.
Sohonos Boxed Warnings
Embryo-fetal toxicity. Premature epiphyseal closure in growing pediatric patients.
Embryo-fetal toxicity. Females of reproductive potential: obtain a negative pregnancy test within 1 week prior to initiation and periodically during therapy. Discontinue immediately if pregnancy occurs; refer to ob/gyn. Advise females of reproductive potential to use effective contraception at least 1 month prior to therapy, during, and for 1 month after the last dose. Do not donate blood during and for 1 week after discontinuation. Risk for premature epiphyseal closure in growing pediatric patients; monitor linear growth. Assess baseline skeletal maturity in all growing children prior to initiation and continue monitoring every 6–12 months until skeletal maturity or final adult height is reached. Increased risk for mucocutaneous adverse reactions, skin/soft tissue infections, paronychia and decubitus ulcer. Phototoxicity. Avoid excessive exposure to sun or artificial UV light. Metabolic bone disorders (eg, bone mineral density and fracture, hyperostosis). Obtain periodic radiological assessment of the spine. Monitor for new or worsening psychiatric symptoms during treatment. History of psychiatric illness. Severe renal impairment (CrCl 15–29mL/min): not recommended. Moderate or severe hepatic impairment: not recommended. Elderly. Nursing mothers: not recommended (during and for at least 1 month after the last dose).
Median time to achieve peak concentration (Tmax): 3.0–4.0 hours, across the chronic dose of 5 mg to flare-up dose of 10 and 20 mg. Palovarotene mean AUC and mean Cmax increased by approximately 40% and 16%, respectively; Tmax was delayed by approximately 2 hours with a high-fat, high-calorie meal (800–1000 calories, 15% protein, 25% carbohydrate, and 50–60% fat).
Mean (SD) apparent volume of distribution (Vd/F): 237 (± 90.1) L. Protein bound: 97.9–99.6% in vitro. Mean blood-to-plasma ratio: 0.62.
Fecal (97.1%), renal (3.2%). Mean elimination half-life: 8.7 hours with a standard breakfast (800–1000 calories, 15% protein, 25% carbohydrate, and 50–60% fat). Apparent total body clearance: 19.9 L/h.
Avoid concomitant grapefruit, pomelo, or juices containing these fruits. Potentiated by moderate or strong CYP3A4 inhibitors; avoid concomitant use. If moderate CYP3A4 inhibitor is unavoidable, reduce Sohonos dose by half. Antagonized by moderate or strong CYP3A4 inducers; avoid concomitant use. Avoid concomitant Vit. A (w. doses > recommended daily allowance) and/or other oral retinoids due to the risk for hypervitaminosis A. Avoid concomitant tetracycline derivatives (increased risk for pseudotumor cerebri).
Sohonos Adverse Reactions
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, fatigue; premature epiphyseal closure, hepatotoxicity, night blindness.
Sohonos Clinical Trials
Sohonos Patient Counseling