calcipotriene/betamethasone

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action: 

• calcipotriene: calcipotriene acts as a vitamin D receptor agonist. It binds to the skin cells’ vitamin D receptors, regulating gene expression. calcipotriene modulates the growth and differentiation of keratinocytes, reduces inflammation, and normalizes the excessive skin cell proliferation seen in psoriasis. 
• betamethasone: betamethasone is a potent corticosteroid with anti-inflammatory, immunosuppressive, and antiproliferative properties. It exerts its effects by binding to cytoplasmic glucocorticoid receptors in various cell types, including immune and skin cells. betamethasone regulates gene expression, inhibits the release of inflammatory mediators, and suppresses the immune response involved in psoriasis. 

Spectrum of Activity: 

calcipotriene/betamethasone is primarily indicated for the topical treatment of plaque psoriasis in adults. Plaque psoriasis is a chronic autoimmune skin condition characterized by red, scaly patches of skin. The combination of calcipotriene and betamethasone provides a synergistic effect by targeting different aspects of the disease: 

• Anti-inflammatory Activity: betamethasone, as a corticosteroid, helps to reduce inflammation, redness, and itching associated with psoriasis. 
• Antiproliferative Activity: calcipotriene helps to normalize the excessive growth and differentiation of skin cells (keratinocytes) seen in psoriasis, thus reducing the thickening and scaling of the skin. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Topical cream, adults 

Nausea (13%) 

Headache (20%)  

Topical cream, 7 years and older 

Nausea (17%) 

Vomiting (16%) 

Decreased appetite (8%) 

Enuresis (18%) 

Headache (16%) 

Weight decreased (12%) 

Dizziness (6%)  

1-10% 

Topical cream 

Decreased appetite (8%) 

Diarrhea (6%) 

Anxiety (5%) 

Fatigue (4%) 

Depressed mood (4%) 

Dizziness (10%) 

Parasomnia (6%) 

Hyperhidrosis (6%) 

Vomiting (5%) 

Dry mouth (4%)  

Topical suspension 

Burning (1%) 

Folliculitis (1%) 

Topical ointment H4 

Psoriasis (3.4%) 

Skin atrophy (1.9%) 

Pruritus (7.2%) 

Pruritus (2.8%)  

<1% 

Topical foam, adults 

Application site pruritus (<1%) 

Skin hypopigmentation (<1%) 

Urticaria (<1%) 

Application site irritation (<1%) 

Folliculitis (<1%) 

Hypercalcemia (<1%)  

Topical ointment 

Erythema (0.4%) 

Burning sensation (0.2%) 

Application site pruritus (0.5%) 

Skin irritation (0.4%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Skin Irritation: calcipotriene/betamethasone may cause skin irritation, including burning, stinging, itching, or redness at the application site. 
• Hypersensitivity Reactions: Hypersensitivity reactions, including allergic contact dermatitis, may occur using calcipotriene/betamethasone.  
• Skin Atrophy: Prolonged and excessive use of corticosteroids, such as betamethasone, can lead to skin atrophy, thinning, and fragility.  
• Systemic Effects: Although the systemic absorption of calcipotriene/betamethasone is low, excessive, or prolonged use, application to large areas of the body or use under occlusion can increase the risk of systemic effects associated with corticosteroids.  
• Use on the Face and Intertriginous Areas: The use of calcipotriene/betamethasone on the face, groin, or axillae should be done with caution due to the increased risk of skin atrophy, perioral dermatitis, or other adverse effects associated with corticosteroids. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• calcipotriene acts as a synthetic vitamin D3 receptor agonist. It binds to the vitamin D receptor in keratinocytes and modulates gene expression, normalizing skin cell growth and differentiation. It has antiproliferative and anti-inflammatory effects, helping to reduce the thickness and scaling of psoriatic lesions. 
• betamethasone is a potent corticosteroid that acts by binding to cytoplasmic glucocorticoid receptors. It modulates gene expression, producing anti-inflammatory, immunosuppressive, and vasoconstrictive effects. It helps reduce inflammation, itching, and redness associated with psoriasis. 

Pharmacodynamics: 

The combination of calcipotriene and betamethasone in calcipotriene/betamethasone offers synergistic effects in the treatment of psoriasis: 

• calcipotriene addresses the abnormal cellular proliferation and differentiation in psoriasis lesions. 
• betamethasone provides potent anti-inflammatory effects, reducing the inflammation associated with psoriasis. 

Pharmacokinetics: 

Absorption 

When applied topically, calcipotriene is minimally absorbed through the skin. The peak plasma concentration of calcipotriene occurs at approximately 30 pg/mL at Week 4. When applied topically, betamethasone is absorbed through the skin. The peak plasma concentration of betamethasone occurs at approximately 22 pg/mL at Week 4. 

Distribution 

After absorption, calcipotriene is distributed to the site of action in the skin. It primarily acts locally on the keratinocytes within the epidermis. betamethasone is distributed systemically following absorption. It can reach various tissues throughout the body but has a higher affinity for glucocorticoid receptors in target tissues.  

Metabolism 

Following systemic uptake, calcipotriene undergoes rapid metabolism in the liver. It is metabolized to MC1046, which is further metabolized to MC1080, the major metabolite in plasma. MC1080 is slowly metabolized to calcitroic acid. The primary metabolites of calcipotriene are less potent than the parent compound. betamethasone is metabolized by hydrolysis to betamethasone 17-propionate and betamethasone, including the 6ß-hydroxy derivatives. betamethasone 17-propionate (B17P) is the primary metabolite. 

Elimination and Excretion 

The metabolites of calcipotriene are primarily excreted in the urine.The metabolites of betamethasone are excreted primarily in the urine, with a small portion being eliminated in the feces. 

Adminstartion

Administration: 

Topical administration 

• Not to be used intravenously, orally, or topically  
• Avoid using it on the face, axillae, or groin if the treatment location has skin atrophy.  
• Without a doctor’s prescription, avoid using occlusive dressings.  
• Wash your hands after using. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: calcipotriene/betamethasone 

Why do we use calcipotriene/betamethasone? 

calcipotriene and betamethasone are combined in a medication primarily used to treat psoriasis. Combining these two active ingredients offers synergistic effects in managing the symptoms associated with psoriasis.  

• Psoriasis: calcipotriene/betamethasone is primarily indicated for the topical treatment of plaque psoriasis in adult patients. It is used when psoriasis involves up to 30% of the body’s surface area.