Pimecrolimus

Approved Indication:

• Mild to Moderate Atopic Dermatitis (Eczema):
  Indicated for the treatment of mild to moderate atopic dermatitis in non-immunocompromised patients aged 2 years and older. It is suitable for intermittent long-term use to manage and prevent flares.

Important Off-Label (Clinically Accepted) Uses:

• Facial Seborrheic Dermatitis:
  Especially effective on sensitive skin areas where corticosteroids are contraindicated.
• Contact Dermatitis (Allergic or Irritant):
  Applied when inflammation affects delicate areas like the face or flexures.
• Lichen Planus:
  Used in mucosal or cutaneous forms, especially genital or oral lichen planus.
• Vitiligo (Early Lesions):
  Topical immunomodulatory role in facial or intertriginous vitiligo.
• Inverse Psoriasis / Genital Psoriasis:
  Used on areas where steroids may be inappropriate for long-term use.
• Perioral Dermatitis & Rosacea (Sensitive Areas):
  Applied with caution for anti-inflammatory benefit on perinasal or perioral lesions.

Route: Topical
Formulation: 1% cream

Adults and Children (≥2 years):

• Apply a thin layer of Pimecrolimus 1% cream to the affected area twice daily.
• Continue treatment until signs and symptoms resolve.
• May be used intermittently or long-term to prevent recurrence.

Pediatrics (<2 years):

• Not approved for use due to insufficient safety data.

Elderly (≥65 years):

• No specific dosage adjustment needed; monitor for skin sensitivity.

Renal or Hepatic Impairment:

• No adjustment required due to negligible systemic absorption.

Administration Notes:

• Apply only to intact skin.
• Do not use with occlusive dressings unless directed.
• Avoid contact with eyes, mucous membranes, and broken/infected skin.
• Wash hands after application.
• Limit exposure of treated skin to sunlight or UV therapy.

Pimecrolimus is a topical calcineurin inhibitor that selectively inhibits the enzyme calcineurin in T-lymphocytes. This inhibition prevents dephosphorylation of nuclear factor of activated T-cells (NFAT), thereby suppressing transcription of inflammatory cytokines such as IL-2, IL-4, and IFN-γ. By inhibiting T-cell activation and cytokine release, Pimecrolimus effectively reduces inflammation, erythema, and itching associated with inflammatory dermatoses, especially atopic dermatitis. Unlike corticosteroids, it does not cause skin atrophy, making it suitable for long-term use on delicate areas like the face or folds.

• Absorption:
  Minimal systemic absorption through intact skin.
  Plasma levels typically undetectable or very low, even with long-term use.
• Distribution:
  Not systemically relevant; binds to skin proteins locally.
• Metabolism:
  If absorbed, metabolized hepatically via CYP3A4 enzymes.
• Elimination:
  Excreted mainly through bile/feces; renal clearance is negligible.
• Half-life:
  Not clinically meaningful for topical route due to limited absorption.
• Steady-State:
  No accumulation seen with repeated topical application.

• Pregnancy:
• Category C (FDA)
• Animal studies show embryotoxicity at high doses.
• No adequate human data available.
• Should only be used during pregnancy if the potential benefit justifies potential risk.
• Lactation:
• Unknown if pimecrolimus is excreted in human milk.
• Avoid applying on nipple or breast area to prevent infant exposure.
• Use cautiously during breastfeeding under medical supervision.

• Primary Class: Topical Immunomodulator
• Subclass: Calcineurin Inhibitor (Non-steroidal anti-inflammatory agent)

• Hypersensitivity to Pimecrolimus or any cream excipients
• Presence of active cutaneous infections (bacterial, viral, fungal)
• Use in immunocompromised patients (e.g., post-transplant, HIV/AIDS)
• Children under 2 years of age

• Malignancy Risk:
  Rare cases of skin cancer and lymphoma reported in patients using topical calcineurin inhibitors. A direct causal link has not been proven, but prolonged use on large surface areas is discouraged.
• Phototoxicity & Sun Sensitivity:
  Avoid sun exposure and phototherapy on treated skin. Use sun protection.
• Local Reactions:
  Burning or stinging may occur, especially in the first few days of use.
• Secondary Infection:
  Do not apply to infected skin. Treat infection first or co-administer appropriate antimicrobials.
• Use in Pediatrics (<2 years):
  Not recommended due to immature immune system and unknown long-term effects.

Common (≥1%):

• Dermatologic:
• Burning sensation
• Pruritus
• Skin redness
• Irritation
• Infections:
• Localized viral infections (e.g., herpes simplex, molluscum contagiosum)

Less Common:

• Folliculitis
• Acneiform eruptions
• Rash
• Dry skin

Rare but Serious:

• Skin malignancy (very rare; causal link unproven)
• Lymphoma
• Hypersensitivity reactions (e.g., urticaria)

Onset:
Local reactions generally appear within first week and diminish over time.
Most systemic side effects are not dose-dependent due to minimal absorption.

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin):
  Theoretical risk of increased systemic pimecrolimus levels if absorbed.
• Vaccines:
  Avoid use on days of live vaccinations; immunomodulatory effects may blunt vaccine response.
• Topical Corticosteroids:
  Can be co-administered on different areas; avoid combining on same site without physician direction.
• Alcohol (Topical):
  May exacerbate skin irritation if applied concurrently.

• Long-term safety reviews continue to support intermittent use as needed for flare control.
• Regulatory agencies (e.g., FDA, EMA) advise periodic reassessment during long-term treatment.
• Updated pediatric safety data remain limited for <2 years; use still contraindicated in that group.
• Guidelines for atopic dermatitis (e.g., from AAD, EADV) confirm pimecrolimus as a preferred non-steroidal alternative for facial, intertriginous, and maintenance therapy.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Permissible Range: 15°C to 30°C (59°F to 86°F)
• Humidity: Keep container tightly closed to protect from moisture
• Light: Store away from direct light exposure
• Handling Instructions:
• Do not freeze
• Keep out of reach of children
• Do not use after the expiration date