What does Otezla do to the body?

Key Points

• Otezla blocks the action of the PDE4 enzyme to help control inflammatory symptoms like pain, redness, and swelling.

• Otezla is FDA-approved to treat plaque psoriasis, psoriatic arthritis and oral ulcers associated with Behçet’s disease.

• Otezla is associated with a wide variety of side effects, drug interactions, and dosing precautions.

Otezla (apremilast) works by blocking the phosphodiesterase type 4 (PDE4) enzyme located inside cells to lower inflammation in the body. The PDE4 enzyme is a type of immune system protein. By inhibiting PDE4 in the cell, an increase in cyclic adenosine monophosphate (cAMP) levels occurs. cAMP is an important molecule used in many different biological actions including regulation of inflammation.

Otezla is classified as a small molecule phosphodiesterase 4 (PDE4) inhibitor and is approved by the FDA for the treatment of plaque psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s Disease. Lowering PDE4 activity is thought to help reduce the overactive inflammation seen with these conditions. Exactly how Otezla works is not fully known; however, Otezla is not classified as a biologic agent.

Otezla, from Amgen, is taken as an oral tablet and was first approved by the FDA in 2014. You may start to see an improvement in your symptoms within the first few weeks of treatment. Patients usually see therapeutic results within 12 to 16 weeks.

• Plaque psoriasis: In plaque psoriasis, overactive inflammation leads to a build-up of skin cells. Eventually, your skin can develop raised silvery plaques that can be flaky, red, and itchy. Psoriasis is a long-lasting disease and can occur in many areas of the body, including hands, feet, elbows, scalp or genitals. Otezla works inside the cell to block PDE4 activity and reduce the inflammation that leads to the plaques and symptoms of psoriasis.

• Psoriatic arthritis: In psoriatic arthritis, PDE4 activity can lead to inflammation inside the joints and cause tenderness, swelling and pain. Psoriatic arthritis often occurs in association with plaque psoriasis. Otezla can reduce these symptoms by its PDE4 inhibitory action.

• Behçet’s Disease: Behçet’s Disease is a rare, chronic inflammatory disorder that can cause recurrent ulcers in the mouth, on the genitals, and inflammation in the eye. It can also lead to arthritis, skin lesions, bowel disease, inflammation in the brain and spinal cord, and eventual blindness and stroke.

Otezla is not the only drug approved that blocks the PDE4 enzyme. Other PDE4 inhibitors are approved for different conditions involved with inflammation. For example, Daliresp (roflumilast) is approved to lower inflammation in the lungs of patients with chronic obstructive pulmonary disease (COPD), and Eucrisa (crisaborole) is available to treat eczema (atopic dermatitis) on the skin. Blocking PDE4 is a common mechanism for many different drugs.

Related Questions

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• Do you need to take Otezla forever?
• Can you drink alcohol while taking Otezla?

Side effects in your body

Otezla can also lead to different types of side effects in your body. It is important that you review all side effects with your doctor before you start treatment.

Stomach side effects with Otezla

• Slowly increasing your dose of Otezla over the first 5 days when you first start treatment will help to reduce the gastrointestinal (stomach) symptoms, such as diarrhea, nausea, vomiting and stomach pain.
• For example, in plaque psoriasis studies, about 17% of patients experienced diarrhea and nausea as compared to roughly 6% to 7% of those taking an inactive placebo pill.
• Most stomach side effects due to Otezla occur within the first weeks of starting treatment. However, some of these side effects may lead to hospitalization if they are serious.
• In addition, weight loss can be a significant side effect with Otezla. Your doctor will monitor your body weight regularly, and decide if it is safe for you to remain on Otezla.

Other common side effects that can occur with Otezla are upper respiratory tract infections, headache, and tension headaches. Over time, many of these side effects will subside.

Drug interactions and CYP450

In the body, Otezla undergoes oxidative metabolism. Metabolism is how drugs are broken down for excretion from the body. An enzyme family known as the cytochrome P450 3A4 is responsible for this action and can lead to important drug interactions with Otezla.

Have your pharmacist or doctor review for Otezla drug interactions, as some medications that greatly boost the action of CYP450 3A4 enzymes (known as “CYP inducers”) may lower the effectiveness of Otezla. Use of Otezla with these types of drugs is not recommended.

Examples include:

• carbamazepine
• phenobarbital
• phenytoin
• rifampin

Dosage Adjustment in Kidney Disease

Otezla is partially eliminated from your body through the kidney. If you have a severe level of kidney disease, you may need to take a lower dose of Otezla.

Be sure to tell your doctor if you have kidney disease or a history of kidney disease. Your doctor can determine your level of kidney disease and if you need a dose adjustment.

Bottom Line

• Otezla (apremilast) is a phosphodiesterase 4 (PDE4) inhibitor available as an oral tablet used to treat plaque psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s Disease.
• In your body, Otezla helps to control inflammatory symptoms like redness, swelling and pain in these conditions.
• Otezla is started gradually to help minimize stomach side effects such as diarrhea and nausea.
• Talk to your doctor and pharmacist about drug interactions and if you need a lower dose if you have kidney disease.