Palovarotene Dosage

Medically reviewed by Drugs.com. Last updated on May 6, 2025.

Usual Adult Dose for Progressive Myositis Ossificans

Daily dose: 5 mg orally once a day
Flare-up dose: 20 mg orally once a day for 4 weeks, followed by 10 mg orally once a day for 8 weeks

• Total duration of flare-up treatment: 12 weeks, even if symptoms resolve earlier

After 12-week flare-up treatment: Return to 5 mg orally once a day.

Comments:

• Chronic treatment (daily dose) should stop when initiating flare-up treatment and restart after completing flare-up treatment.
• If, during the flare-up treatment, there is a marked worsening of the original flare-up site or another flare-up at a new location, the 12-week flare-up dosing should be restarted at 20 mg daily.
• For flare-up symptoms that persist beyond the 12-week period, 10 mg/day may be extended in 4-week intervals and continued until the symptoms resolve.
• If new flare-up symptoms arise after resuming 5 mg/day, flare-up dosing may be restarted.

Use: For the reduction in volume of new heterotopic ossification in patients with fibrodysplasia ossificans progressiva (FOP)

Usual Pediatric Dose for Progressive Myositis Ossificans

Female Patients 8 to 13 Years and Male Patients 10 to 13 Years:
Weight 10 to 19.9 kg:

• Daily dose: 2.5 mg orally once a day
• Week 1 to 4 flare-up dose: 10 mg orally once a day
• Week 5 to 12 flare-up dose: 5 mg orally once a day
• After 12-week flare-up treatment: Return to 2.5 mg orally once a day.

Weight 20 to 39.9 kg:

• Daily dose: 3 mg orally once a day
• Week 1 to 4 flare-up dose: 12.5 mg orally once a day
• Week 5 to 12 flare-up dose: 6 mg orally once a day
• After 12-week flare-up treatment: Return to 3 mg orally once a day.

Weight 40 to 59.9 kg:

• Daily dose: 4 mg orally once a day
• Week 1 to 4 flare-up dose: 15 mg orally once a day
• Week 5 to 12 flare-up dose: 7.5 mg orally once a day
• After 12-week flare-up treatment: Return to 4 mg orally once a day.

Weight at least 60 kg:

• Daily dose: 5 mg orally once a day
• Week 1 to 4 flare-up dose: 20 mg orally once a day
• Week 5 to 12 flare-up dose: 10 mg orally once a day
• After 12-week flare-up treatment: Return to 5 mg orally once a day.

Female and Male Patients 14 Years and Older:

• Daily dose: 5 mg orally once a day
• Flare-up dose: 20 mg orally once a day for 4 weeks, followed by 10 mg orally once a day for 8 weeks
• After 12-week flare-up treatment: Return to 5 mg orally once a day.

Total Duration of Flare-Up Treatment: 12 weeks, even if symptoms resolve earlier

Comments:

• Chronic treatment (daily dose) should stop when initiating flare-up treatment and restart after completing flare-up treatment.
• If, during the flare-up treatment, there is a marked worsening of the original flare-up site or another flare-up at a new location, the 12-week flare-up dosing should be restarted (with the Week 1 to 4 dose in patients younger than 14 years and at 20 mg daily in patients 14 years and older).
• For flare-up symptoms that persist beyond the 12-week period:
• In patients younger than 14 years, the Week 5 to 12 flare-up dose may be extended in 4-week intervals and continued until the symptoms resolve.
• In patients 14 years and older, 10 mg/day may be extended in 4-week intervals and continued until the symptoms resolve.
• If new flare-up symptoms arise after resuming the daily dose, flare-up dosing may be restarted.

Use: For the reduction in volume of new heterotopic ossification in patients with FOP

Renal Dose Adjustments

Mild to moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended
Severe renal dysfunction (CrCl 15 to 29 mL/min): Not recommended

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh A): No adjustment recommended
Moderate or severe liver dysfunction (Child-Pugh B or C): Not recommended

Dose Adjustments

DOSE REDUCTION FOR ADVERSE REACTIONS:

• If adverse reactions that require dose reduction develop during daily dosing or flare-up dosing, reduce the daily dosage to the next lower dose as shown below at the discretion of the health care provider; reduce the dosage further if adverse reactions do not improve.
• If the patient is already receiving the lowest possible tolerated dose, then consider stopping this drug temporarily or permanently.
• Start subsequent flare-up dosing at the same reduced dose that was tolerated previously.

Dose Reduction for Chronic and Flare-Up Treatment:

• For prescribed dose of 20 mg: Reduce dose to 15 mg.
• For prescribed dose of 15 mg: Reduce dose to 12.5 mg.
• For prescribed dose of 12.5 mg: Reduce dose to 10 mg.
• For prescribed dose of 10 mg: Reduce dose to 7.5 mg.
• For prescribed dose of 7.5 mg: Reduce dose to 5 mg.
• For prescribed dose of 6 mg: Reduce dose to 4 mg.
• For prescribed dose of 5 mg: Reduce dose to 2.5 mg.
• For prescribed dose of 4 mg: Reduce dose to 2 mg.
• For prescribed dose of 3 mg: Reduce dose to 1.5 mg.
• For prescribed dose of 2.5 mg: Reduce dose to 1 mg.

DOSE REDUCTION FOR DRUG INTERACTIONS:
Moderate CYP450 3A Inhibitors: Avoid concomitant use, if possible.

• If concomitant use is unavoidable: Reduce the dose by half when coadministered with moderate CYP450 3A inhibitors.

Dose Reduction for Use with Moderate CYP450 3A Inhibitors:
Weight 10 to 19.9 kg:

• Daily dose: 1 mg orally once a day
• Week 1 to 4 flare-up dose: 5 mg orally once a day
• Week 5 to 12 flare-up dose: 2.5 mg orally once a day

Weight 20 to 39.9 kg:

• Daily dose: 1.5 mg orally once a day
• Week 1 to 4 flare-up dose: 6 mg orally once a day
• Week 5 to 12 flare-up dose: 3 mg orally once a day

Weight 40 to 59.9 kg:

• Daily dose: 2 mg orally once a day
• Week 1 to 4 flare-up dose: 7.5 mg orally once a day
• Week 5 to 12 flare-up dose: 4 mg orally once a day

Weight at least 60 kg:

• Daily dose: 2.5 mg orally once a day
• Week 1 to 4 flare-up dose: 10 mg orally once a day
• Week 5 to 12 flare-up dose: 5 mg orally once a day

All patients at least 14 years of age should receive the same dose as patients weighing at least 60 kg.

Precautions

US BOXED WARNINGS:

• EMBRYOFETAL TOXICITY: This drug is contraindicated in pregnancy; it may cause fetal harm. This drug should only be administered if conditions for preventing pregnancy are met due to the risk of teratogenicity and to minimize fetal exposure.
• PREMATURE EPIPHYSEAL CLOSURE: Premature epiphyseal closure occurs in growing pediatric patients treated with this drug; close monitoring is recommended.

CONTRAINDICATIONS:

• Pregnancy
• History of allergy or hypersensitivity to retinoids or any of the ingredients of this product

Safety and efficacy have not been established in female patients younger than 8 years and male patients younger than 10 years; this drug is not recommended for use in these patients.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For patients of childbearing potential, obtain a negative pregnancy test within 1 week before starting and periodically during therapy; if pregnancy occurs, stop this drug at once and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity.
• Administer with food, preferably at the same time each day.
• Swallow the capsule whole.
• Alternatively, open and empty the capsule contents onto a teaspoon (5 mL) of soft food (e.g., apple sauce, low-fat yogurt, warm oatmeal) and administer immediately; if not administered immediately, it can be administered within 1 hour after sprinkling, as long as it was kept at room temperature and not exposed to direct sunlight.
• Do not administer with grapefruit, pomelo, or juices containing these fruits.
• If a dose is missed, administer the missed dose as soon as possible; if it has been missed by more than 6 hours, skip the missed dose and continue with the next scheduled dose. Do not take 2 doses simultaneously or within the same day.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).
• Keep in the original carton to protect from light.

General:

• Recommended dosing includes a chronic daily dosage (daily dose) which can be modified/increased for FOP flare-up symptoms (flare-up dose).
• Flare-up treatment should be started at the onset of the first symptom indicative of FOP flare-up or substantial high-risk traumatic event likely to lead to a flare-up (e.g., surgery, IM immunization, mandibular blocks for dental procedures, muscle fatigue, blunt muscle trauma from bumps/bruises/falls, or influenza-like viral illnesses).
• Symptoms of FOP flare-up generally include (but are not limited to) localized pain, soft tissue swelling/inflammation, redness, warmth, decreased joint range of motion, and stiffness.

Monitoring:

• General: For pregnancy in patients of childbearing potential (before starting therapy, periodically during therapy, and 1 month after the last dose)
• Musculoskeletal: Linear growth in growing pediatric patients (before starting therapy, then every 6 to 12 months until skeletal maturity/final adult height reached); radiography of the spine (periodically)
• Psychiatric: For new/worsening psychiatric symptoms (during therapy); for signs of depression

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Verify you are not pregnant before starting therapy, periodically during therapy, and 1 month after the last dose.
• Patients of childbearing potential:
• Avoid pregnancy during therapy and for at least 1 month after the last dose.
• Use at least 1 highly effective method of contraception (e.g., intrauterine device) or 2 effective methods (e.g., combined hormonal contraception with another method of contraception [e.g., barrier method]) during therapy.
• Immediately stop this drug if you become pregnant during therapy; rapidly consult health care provider if there is a risk of pregnancy or you might be pregnant.
• Do not donate blood during therapy and for 1 week after the last dose to avoid blood donation to a pregnant patient and fetus.
• Do not breastfeed during therapy and for at least 1 month after the last dose.
• Use prophylactic measures (e.g., skin emollients, sunscreen, lip moisturizers, artificial tears) to minimize risk and/or treat mucocutaneous adverse reactions (e.g., dry skin, dry lip, pruritus, rash, alopecia, erythema, skin exfoliation, dry eye).
• Minimize exposure to sunlight and artificial ultraviolet light.
• Be cautious when driving or operating any vehicle at night; seek medical attention if vision impairment occurs.

See also:

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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