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

Duration of flare-up treatment: 12 weeks, even if symptoms resolve earlier

After 12-week flare-up treatment: dosing should 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 the emergence of a new flare-up at a different location, the 12-week flare-up dosing should restart at 20 mg daily.
For flare-up symptoms that persist beyond the 12-week period, the 10 mg daily dose can be extended in 4-week intervals and continued until the symptoms resolve; if new flare-up symptoms arise after resuming the 5 mg daily dosage, 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: Dosing should 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: Dosing should 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: Dosing should return to 4 mg orally once a day.

Weight 60 kg or more:

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: Dosing should 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: Dosing should return to 5 mg orally once a day.

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 the emergence of a new flare-up at a different 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, the Week 5 to 12 flare-up dose in patients younger than 14 years and the 10 mg daily dose in patients 14 years and older 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, the daily dosage should be reduced to the next lower dose as shown below at the discretion of the health care provider; the dosage should be reduced further if adverse reactions do not improve. If the patient is already receiving the lowest possible tolerated dose, then temporary or permanent discontinuation of this drug should be considered. Subsequent flare-up treatment should be started at the same reduced dose that was tolerated previously.

Dose Reduction for Chronic Treatment and Flare-Up:

Dose prescribed: 20 mg; Reduced dose: 15 mg
Dose prescribed: 15 mg; Reduced dose: 12.5 mg
Dose prescribed: 12.5 mg; Reduced dose: 10 mg
Dose prescribed: 10 mg; Reduced dose: 7.5 mg
Dose prescribed: 7.5 mg; Reduced dose: 5 mg
Dose prescribed: 6 mg; Reduced dose: 4 mg
Dose prescribed: 5 mg; Reduced dose: 2.5 mg
Dose prescribed: 4 mg; Reduced dose: 2 mg
Dose prescribed: 3 mg; Reduced dose: 1.5 mg
Dose prescribed: 2.5 mg; Reduced dose: 1 mg

DOSE REDUCTION FOR DRUG INTERACTIONS:
Moderate CYP450 3A Inhibitors:

Concomitant use of a moderate CYP450 3A inhibitor should be avoided, if possible.
In cases where concomitant usage is unavoidable, the dose should be reduced by half when coadministered with moderate CYP450 3A inhibitors.

Dose reduction:

Weight 10 to 19.9 kg:
Daily dosage: 1 mg
Week 1 to 4 flare-up dosage: 5 mg
Week 5 to 12 flare-up dosage: 2.5 mg
Weight 20 to 39.9 kg:
Daily dosage: 1.5 mg
Week 1 to 4 flare-up dosage: 6 mg
Week 5 to 12 flare-up dosage: 3 mg
Weight 40 to 59.9 kg:
Daily dosage: 2 mg
Week 1 to 4 flare-up dosage: 7.5 mg
Week 5 to 12 flare-up dosage: 4 mg
Weight 60 kg or more:
Daily dosage: 2.5 mg
Week 1 to 4 flare-up dosage: 10 mg
Week 5 to 12 flare-up dosage: 5 mg

All patients 14 years and older should be dosed based on the 60 kg or more weight category.

Precautions

US BOXED WARNINGS:

EMBRYOFETAL TOXICITY: This drug is contraindicated in pregnancy. This drug may cause fetal harm. This drug should only be administered if the conditions for preventing pregnancy are met, because of the risk of teratogenicity and to minimize fetal exposure.
PREMATURE EPIPHYSEAL CLOSURE: This drug has been shown to cause premature epiphyseal closure in growing pediatric patients. 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 capsule whole.
If unable to swallow the capsule whole, open and empty the capsule contents onto a teaspoon of soft food (such as apple sauce, low-fat yogurt, or warm oatmeal) and take immediately; if not taken immediately, it can be taken up to 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.
Caregivers should wear disposable gloves when handling this drug to avoid unintended exposure.

Storage requirements:

Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).
Keep blister strip in the 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 indicating 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: Pregnancy testing in patients of childbearing potential (monthly)
Musculoskeletal: For problems with normal bone growth
Psychiatric: For signs of depression; for signs/symptoms of mental health problems

Patient advice:

Read the US FDA-approved patient labeling (Medication Guide).
This treatment carries the risk of causing harm to a developing fetus and is contraindicated during pregnancy.
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 (i.e., intrauterine device) or 2 effective methods (i.e., 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.
This drug has been associated with premature epiphyseal closure in growing pediatric patients with FOP and discuss the proposed monitoring plan with the patient and caregiver.
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.
This drug has been linked to reduced vertebral bone mineral content, density, strength, and an increased risk of radiographically detected vertebral fractures.
Regular radiological assessments of the spine is advised.
Monitor for signs of depression and seek appropriate treatment as needed.
There is a risk of night blindness with the use of this drug.
Inform your health care provider about all concomitant medications, including prescription drugs, over-the-counter products, and herbal supplements.
Take this capsule with food. If swallowing the capsule is difficult, empty the capsule contents onto soft food.
If a dose is missed, take the missed dose as soon as possible; if it has been more than 6 hours, skip the missed dose and continue with the next scheduled dose. Do not take 2 doses simultaneously or in the same day.