Apremilast

Apremilast is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) used for the treatment of active psoriatic arthritis and moderate to severe plaque psoriasis. It works by blocking the action of certain chemical messengers responsible for inflammation, thereby reducing the signs and symptoms of these conditions.

PDE4 inhibition results in increased intracellular cAMP levels, which inhibits the production of multiple proinflammatory mediators including TNF-alpha, interleukin-2 (IL-2), interferon-gamma, leukotrienes, and nitric oxide synthase.

Common side effects include nausea, diarrhea, and vomiting. To reduce gastrointestinal symptoms, the dose is gradually titrated over the first 5 days.

• Active psoriatic arthritis
• Moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy

Apremilast is a novel, orally available small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4). PDE-4 is a cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase that is predominantly located in inflammatory cells.

By inhibiting PDE-4, apremilast increases intracellular levels of cAMP and thereby inhibits the production of multiple proinflammatory mediators including TNF-alpha, interleukin-2 (IL-2), interferon-gamma, leukotrienes, and nitric oxide synthase.

Apremilast inhibits the phosphodiesterase 4 (PDE4) enzyme, leading to increased intracellular cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP reduces the production of proinflammatory cytokines and other inflammatory mediators, which helps decrease inflammation and symptoms associated with psoriasis and psoriatic arthritis.

Recommended Dose Titration (to reduce GI symptoms):

Maintenance Dose: 30 mg twice daily from Day 6

Severe Renal Impairment (CrCl <30 mL/min): Reduce dose to 30 mg once daily. Use only morning schedule; skip evening doses.

Hepatic Impairment: No dosage adjustment required.

Take this medicine in the dose and duration as advised by your doctor. Swallow the tablet whole - do not chew, crush or break. May be taken with or without food, but take at a fixed time.

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.

Common (>10%):

• Nausea
• Diarrhea
• Headache

Other (1-10%):

• Upper respiratory tract infection
• Vomiting
• Nasopharyngitis
• Abdominal pain
• Hypersensitivity
• Gastroesophageal reflux disease
• Dyspepsia
• Fatigue
• Decreased appetite
• Cough
• Rash
• Insomnia

Weight Loss: 5-10% body weight loss reported during treatment.

Serious Precautions:

• Inform your doctor immediately if you experience new or worsened depression, suicidal thoughts, or other mood changes
• Monitor weight regularly - apremilast may cause weight loss
• Caution during pregnancy - animal studies have shown harmful effects on the developing baby
• Caution during breastfeeding - apremilast was detected in milk of lactating mice
• Dose adjustment needed in severe renal impairment
• Mild stomach upset may occur early during treatment but usually resolves

• Known hypersensitivity to apremilast or any excipient

• Strong CYP enzyme inducers (e.g., rifampin, carbamazepine, phenobarbital, phenytoin): Decrease apremilast systemic exposure and may result in loss of efficacy → coadministration not recommended

[CAUTION] Caution is advised when consuming alcohol with Apremilast. Please consult your doctor.

[CONSULT YOUR DOCTOR] Apremilast may be unsafe to use during pregnancy (Pregnancy Category C). Animal studies have shown harmful effects on the developing baby. Your doctor will weigh the benefits and potential risks before prescribing.

[CONSULT YOUR DOCTOR] It is not known whether apremilast or its metabolites are present in human milk; however, apremilast was detected in milk of lactating mice. Caution should be exercised when administered to a nursing woman.

Safety and effectiveness in pediatric patients less than 18 years of age have not been established.

No specific dose adjustment needed for elderly patients.

[CAUTION] Severe renal impairment (CrCl <30 mL/min): Reduce dose to 30 mg once daily. Mild-to-moderate renal impairment: No dosage adjustment required.

[SAFE IF PRESCRIBED] Safe to use in patients with liver disease. No dose adjustment recommended.

There is no known specific antidote for apremilast overdose. In the event of an overdose, undertake general supportive measures.

Store at cool & dry place below 30°C, protected from light & moisture. Keep out of reach of children.