Apremilast

On March 21, 2014, the FDA approved Apremilast for psoriatic arthritis. It is used to treat inflammatory conditions such as psoriatic arthritis, plaque psoriasis, and Bechet disease. It works by inhibiting an enzyme known as phosphodiesterase 4 (PDE4), which reduces inflammation and the immune system's overactive response that contributes to these diseases. 

BRAND NAMES: 

Apremilast Accord – The main active ingredient present in apremilast accord is apremilast. These are available in the form of film-coated tablets with strengths of 10mg, 20mg & 30mg. 

Otezla—Apremilast is the main active ingredient in the Otezla tablets, which helps relieve plaque psoriasis. These are available in oral tablets with strengths of 10mg, 20mg, and 30mg.

MECHANISM OF ACTION:

Apremilast is a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4), hindering the conversion of cyclic adenosine monophosphate, and further causing an intracellular accumulation of cyclic adenosine monophosphate. The inhibition of PDE4 is selective on the innate immune response causing a reduction in the production of inflammatory mediators such as CX-CL9, CX-CL10, IFN- γ, TNF- α, IL-2, IL-8, IL-2, and IL-23 and further decreasing the inflammatory response. The diminished inflammatory response by PDE4 inhibition is reported to confer a therapeutic benefit and clinical improvements in psoriatic arthritis, plaque psoriasis, and Bechet disease. Apremilast inhibitory effects on other phosphodiesterases, receptors, or enzymes are insignificant.

PHARMACOKINETICS:

Absorption: The bioavailability of apremilast oral dosage form is approximately 73%. Food intake does not affect apremilast absorption. 

Distribution: The average apparent volume of distribution is 87L.

Metabolism: The oral administration of apremilast is a major circulating component (45%) followed by inactive metabolite(39%), a glucuronide conjugate of O-demethylated apremilast. It is extensively metabolized in humans. Apremilast is metabolized by cytochrome oxidative metabolism with subsequent glucuronidation and non-CYP mediated hydrolysis. In vitro, CYP metabolism of apremilast is primarily mediated by CYP3A4, with minor contributions from CYPA2 and CYP2A6.

Excretion: In the excretion of apremilast for oral administration of radio-labeled apremilast, about 58% and 39% of the radioactivity is recovered in urine and feces, respectively, with about 3% and 7% of the radioactive dose recovered as apremilast in urine and feces, respectively.

PHARMACODYNAMICS:

Apremilast is a phosphodiesterase-4 (PDE4) inhibitor analog of thalidomide that has shown effectiveness in treating patients with PsA. Apremilast has immunomodulatory effects that result in the down-regulation of thalidomide and has shown effectiveness in treating patients with PsA. Apremilast has immunomodulatory effects that result in the downregulation of pro-inflammatory cytokines.

DOSAGE AND ADMINISTRATION: 

Apremilast is an oral dosage form available with strengths of 10mg, 20mg, and 30mg. The given dosage depends on the patient's health condition and age. It is usually taken twice a day. 

Dosage for Adults Suffering from Psoriatic Arthritis, Plaque Psoriasis, and Behcet’s Disease:

Day 1: 10mg once a day in the morning

Day 2: 10 mg twice a day morning and evening.

Day 3: 10mg in the morning and 20 mg in the evening

Day 4: 20mg twice in the morning and 20mg in the evening.

Day 5: 20mg in the morning and 30mg in the evening, then gradually the maintenance dose is recommended 30mg orally twice a day.

Dosage recommended for pediatric patients with moderate to severe plaque psoriasis:

Day -1: 10mg once a day in the morning

Day -2: 10mg twice a day both morning and evening.

Day -3: 10mg in the morning and 20mg in the evening.

Day -4: 20mg twice a day both morning and evening (for patients 20kg to less than 50kg)

              20mg twice a day both in the morning and evening (for patients 50kg or more)

Day -5: 20mg in the morning and 30mg in the evening (for patients 50kg or more).

Maintainance drug: 20mg daily in the morning and evening (for patients 20kg to less than 50kg)

Maintainance drug: 30mg daily in the morning and evening (for patients 50kg or more).

CONTRAINDICATIONS:

Apremilast is contraindicated in patients with hypersensitive to the drug and its formulations. Women who are breastfeeding are contraindicated to treatment.

DRUG INTERACTIONS:

Some medicines may interact with other medicines and lead to adverse effects. So before taking apremilast, it is better to discuss with the doctor if taking any other medicine for other health issues. Below are some medicines that contraindicate with apremilast.

• A diuretic is a water pill used to reduce edema and blood pressure.
• Medicines used to treat seizures or nerve pain – Carbamazepine, Carbatrol, Tegretol, and others.
• Medicines that control seizures like – phenytoin, Dilantin, phenytek, and other medicines.
• Tuberculosis medicines – Rifampin

ADVERSE EFFECTS:

• Upper respiratory tract infection
• Diarrhea
• Vomiting
• Nausea
• Headache
• Nasopharyngitis
• Upper abdominal pain
• Dyspepsia
• Insomnia
• Decreased appetite
• Arthralgia

Toxicity:

Taking medicine in over content than recommended can lead to many toxic effects leads as seizures, headaches, and vomiting.  It is recommended to take timely as prescribed if you miss the dose then take it as soon as possible or else if it is time for the next dose then can take the regular dose as scheduled.