Apremilast

Name: Apremilast

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

What Is Apremilast?

Apremilast inhibits an enzyme within your immune system that can affect certain cells and contribute to inflammation in the body.

Apremilast is used to treat the symptoms of active psoriatic arthritis in adults. Apremilast is also used to treat moderate to severe plaque psoriasis in people who may also receive phototherapy or other treatments for psoriasis.

Apremilast can relieve tenderness and swelling in and around the joints, but this medicine is not a cure for psoriatic arthritis.

Apremilast may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use apremilast if you are allergic to it.

To make sure apremilast is safe for you, tell your doctor if you have:

  • a history of depression or suicidal thoughts or actions;
  • kidney disease;
  • if you take seizure medication (such as carbamazepine, phenobarbital, phenytoin); or
  • if you take medicine to treat HIV/AIDS or tuberculosis.

Some people have depression or thoughts about suicide while taking apremilast. Your doctor will need to check your progress at regular visits while you are using apremilast. Your family or other caregivers should also be alert to changes in your mood or symptoms.

FDA pregnancy category C. It is not known whether apremilast will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether apremilast passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not give this medicine to anyone under 18 years old without medical advice.

Apremilast Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • unexplained weight loss, or if you lose a lot of weight;
  • mood changes, new or worsening depression; or
  • thoughts of suicide or hurting yourself.

Common side effects may include:

  • nausea, diarrhea;
  • headache; or
  • cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Is apremilast available as a generic drug?

GENERIC AVAILABLE: No

Apremilast Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • your kidney function
  • your age

The recommended dose of apremilast is 30 mg twice a day.

The recommended dose of apremilast in severe renal impairment is 30 mg once a day.

To reduce the risk of gastrointestinal symptoms, titrate to recommended dose of 30 mg twice daily according to the following schedule:

  • Day 1: 10 mg in the morning
  • Day 2: 10 mg in the morning and 10 mg in the evening
  • Day 3: 10 mg in the morning and 20 mg in the evening
  • Day 4: 20 mg in the morning and 20 mg in the evening
  • Day 5: 20 mg in the morning and 30 mg in the evening
  • Day 6 and thereafter: 30 mg twice daily

(In patients with severe renal impairment, titrate using only morning schedule listed and skip afternoon doses)

Other Requirements

  • Store apremilast tablets below 30°C (86°F).
  • Keep this and all medicines out of the reach of children.

What should I discuss with my healthcare provider before taking apremilast?

You should not use apremilast if you are allergic to it.

To make sure apremilast is safe for you, tell your doctor if you have:

  • a history of depression or suicidal thoughts or actions;

  • kidney disease;

  • if you take seizure medication (such as carbamazepine, phenobarbital, phenytoin); or

  • if you take medicine to treat HIV/AIDS or tuberculosis.

Some people have depression or thoughts about suicide while taking apremilast. Your doctor will need to check your progress at regular visits while you are using apremilast. Your family or other caregivers should also be alert to changes in your mood or symptoms.

FDA pregnancy category C. It is not known whether apremilast will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether apremilast passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not give this medicine to anyone under 18 years old without medical advice.

How should I take apremilast?

Follow all directions on your prescription label. Your doctor may occasionally change your dose or dosing schedule to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take apremilast with or without food.

Do not crush, chew, or break an apremilast tablet. Swallow it whole.

Keep track of your body weight while you are taking this medicine, and tell your doctor about any major weight loss.

Store at room temperature away from moisture and heat.

Apremilast dosing information

Usual Adult Dose for Psoriatic Arthritis:

Initial dose:
-Day 1: 10 mg orally once a day (AM)
-Day 2: 10 mg orally twice a day (AM and PM)
-Day 3: 10 mg orally once a day (AM); 20 mg orally once a day (PM)
-Day 4: 20 mg orally twice a day (AM and PM)
-Day 5: 20 mg orally once a day (AM); 30 mg orally once a day (PM)

Maintenance dose: 30 mg orally twice a day (AM and PM)

Comments: This titration is intended to reduce the gastrointestinal symptoms associated with initial therapy.

Use: Treatment of adult patients with active psoriatic arthritis

What other drugs will affect apremilast?

Other drugs may interact with apremilast, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Interactions for Apremilast

Undergoes oxidative metabolism (mediated mainly by CYP3A4, with minor contributions from CYP1A2 and CYP2A6) with subsequent glucuronidation; also undergoes non-CYP-mediated hydrolysis.1 21

Does not inhibit CYP isoenzyme 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4 in vitro; does not induce CYP isoenzyme 1A2, 2B6, 2C9, 2C19, or 3A4 in vitro.1

A substrate but not an inhibitor of P-glycoprotein (P-gp) in vitro; neither a substrate nor inhibitor of organic anion transporters (OAT) 1 and 3, organic anion transporting polypeptides (OATP) 1B1 and 1B3, organic cation transporter (OCT) 2, or breast cancer resistance protein (BCRP) in vitro.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP inducers: Reduced systemic exposure and possible loss of efficacy of apremilast; concomitant use not recommended.1

Specific Drugs

Drug

Interaction

Comments

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Systemic exposure and efficacy of apremilast may be reduced1

Concomitant use not recommended1

Estrogens/progestins

Contraceptive containing ethinyl estradiol and norgestimate: No substantial pharmacokinetic interaction1 21

Ketoconazole

No clinically important effects on apremilast exposure1 21

Methotrexate

No substantial effects on pharmacokinetics of either drug1 21

Rifampin

Reduced apremilast AUC and peak plasma concentration; possible loss of apremilast efficacy1 21

Concomitant use not recommended1

Commonly used brand name(s)

In the U.S.

  • Otezla

Available Dosage Forms:

  • Tablet

Therapeutic Class: Musculoskeletal Agent

Pharmacologic Class: Phosphodiesterase Inhibitor

Uses For apremilast

Apremilast is used to treat active psoriatic arthritis. Psoriatic arthritis is a type of arthritis that causes pain and swelling of the joints and patches of scaly skin on some areas of the body. apremilast is also used to treat moderate to severe plaque psoriasis, which is a skin disease with red patches and white scales that do not go away.

apremilast is available only with your doctor's prescription.

What are some things I need to know or do while I take Apremilast?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • This medicine may cause weight loss. You will need to have your weight checked while taking apremilast. Talk with your doctor.
  • If you are 65 or older, use this medicine with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using apremilast while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is this medicine (Apremilast) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • Swallow whole. Do not chew, break, or crush.
  • To gain the most benefit, do not miss doses.
  • Keep taking apremilast as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Otezla: 30 mg

Tablet Therapy Pack, Oral:

Otezla: 10 & 20 & 30 mg (27 ea [DSC], 55 ea)

Pharmacologic Category

  • Phosphodiesterase-4 Enzyme Inhibitor

Special Populations Renal Function Impairment

The AUC and Cmax of apremilast increased by ~88% and 42%, respectively, in patients with severe renal impairment.

Dosing Adult

Active psoriatic arthritis or plaque psoriasis (moderate to severe): Oral: Initial: 10 mg in the morning. Titrate upward by additional 10 mg per day on days 2 to 5 as follows: Day 2: 10 mg twice daily; Day 3: 10 mg in the morning and 20 mg in the evening; Day 4: 20 mg twice daily; Day 5: 20 mg in the morning and 30 mg in the evening. Maintenance dose: 30 mg twice daily starting on day 6

Administration

Oral: Administer without regard to food. Do not crush, chew, or split tablets.

Warnings/Precautions

Concerns related to adverse effects:

• GI effects: Severe diarrhea, nausea, and vomiting have been reported, usually observed within the first few weeks of initiating therapy. Monitor patients who are more susceptible to complications of diarrhea or vomiting; use with caution in elderly patients (≥65 years) and patients taking medications that may lead to volume depletion or hypotension. Symptom improvement observed with dose reduction or discontinuation of therapy; consider dose reduction or suspension of therapy if severe symptoms occur.

• Neuropsychiatric effects: Neuropsychiatric effects (eg, depression, suicidal ideation, mood changes) have been reported. Use with caution in patients with a history of depression and/or suicidal thoughts /behavior. Instruct patients/caregivers to report worsening psychiatric symptoms and consider risks/benefits of continuation of therapy in such patients.

• Weight loss: May cause weight loss; monitor weight regularly. Discontinuation of therapy should be considered with unexplained or significant weight loss.

Disease-related concerns:

• Renal impairment: Use with caution in renal impairment. Systemic exposure is increased in patients with severe renal impairment (CrCl <30 mL/minute); dosage reduction is recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy Risk Factor C Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. A registry is available for women exposed to apremilast during pregnancy (877-311-8972).

Other Comments

Administration advice:
-Administer without regard to meals.
-Do not crush, split, or chew the tablets.

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