Palovarotene Dosage

Medically reviewed by Drugs.com. Last updated on Oct 10, 2023.

Applies to the following strengths: 1 mg; 1.5 mg; 2.5 mg; 5 mg; 10 mg

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.