Calcipotriene and Betamethasone Dipropionate Topical Suspension - Indication, Dosage, Precautions, and Pharmacological Aspects

Overview:

Psoriasis is caused by the immune system mistakenly attacking the body, influenced by genetics and environmental factors. It often runs in families, triggered by stress, infections, smoking, diet, and obesity—psoriasis results in red, itchy patches with silvery scales. Previously thought to affect only skin cells, it is now known that immune components like T-cells contribute. Despite advancements, topical treatments, like corticosteroids and vitamin D derivative Calcipotriene, remain primary. Combining Calcipotriene with steroids enhances effectiveness, leading to an FDA (Food and Drug Administration)-approved product. This review explores clinical evidence for this combination in treating psoriasis.

Drug Group:

Calcipotriene and Betamethasone dipropionate ointment, 0.005 percent or 0.064 percent, contains Calcipotriene hydrate and Betamethasone dipropionate for topical use. Calcipotriene hydrate is a synthetic vitamin D3 analog, while Betamethasone dipropionate is a synthetic corticosteroid. The ointment includes the below-mentioned ingredients in an off-white to yellow paraffin base.

1. Active Ingredients:

• Calcipotriene hydrates.

• Betamethasone dipropionate.

2. Inactive Ingredients:

• Mineral oil.

• PPG-15 stearyl ether.

• Dl-alpha tocopherol.

• White petrolatum.

Available Doses and Dosage Forms:

Doses are available in ointment form as 0.005 percent or 0.064 percent. Each gram contains 52.18 mcg (microgram) of Calcipotriene hydrate, which is equal to 50 mcg of Calcipotriene, and 0.643 mg of Betamethasone dipropionate which is equivalent to 0.5 mg (milligram) of Betamethasone in off-white to yellow paraffin ointment base.

• Put enough Calcipotriene and Betamethasone dipropionate topical ointment on affected areas once daily for up to four weeks.

• Do not use more than 100 grams per week or cover more than 30 percent of the body.

• Gently and thoroughly rub in the ointment, and wash the hands afterward.

• This ointment is not for use in the mouth, eyes, or vagina.

• The ointment comes in one strength, containing Calcipotriene and Betamethasone in a paraffin base.

For Patients

What Is Psoriasis?

Psoriasis is a persistent condition where the immune system becomes overly active, leading to the rapid multiplication of skin cells. This results in the development of scaly and inflamed patches on the skin, commonly found on the scalp, elbows, or knees. Other areas of the body may also be affected. While the exact cause of psoriasis is not entirely understood, scientists believe genetic and environmental factors influence it.

How Does Calcipotriene and Betamethasone Dipropionate Topical Suspension Work?

Betamethasone is a type of medicine that acts like cortisone or steroids. It aids in reducing redness, pain, itching, swelling, or other discomfort associated with specific skin issues. On the other hand, Calcipotriene is a form of Vitamin D. It operates by altering how skin cells are generated in the areas affected by psoriasis.

What Is the Dosage of Calcipotriene and Betamethasone Dipropionate Topical Suspension?

The amount of this medication will vary depending on the individual’s condition. Follow the doctor's instructions or the directions on the label carefully. The dosage is based on the strength of the medicine, how often it is used, and the duration of the treatment. Sticking to the prescribed dose is crucial unless the doctor advises otherwise.

For Cream:

• Plaque Psoriasis in Adults: Apply once daily to the affected skin for up to eight weeks until the area is clear or as directed by the doctor. Do not exceed 100 grams per week.

• Plaque Psoriasis in Children: The doctor will determine the appropriate use and dose.

For Foam:

• Plaque Psoriasis in Adults and Children (12 years and Older): Apply once daily to the affected skin for up to four weeks or until the area is clear and as directed by the doctor. Stay under 60 grams every four days.

• Children Under 12 years: The doctor will determine the appropriate use and dose.

For Ointment:

1. Plaque Psoriasis in Adults: Apply once daily to the affected skin for up to four weeks or until the area is clear, as the doctor directs. Do not exceed 100 grams per week.

• Children (12 to 17 Years): Apply once daily to the affected skin for up to four weeks or until the area is clear, as the doctor directs. Do not exceed 60 grams per week.

• Children Under 12 Years: The doctor will determine the appropriate use and dose.

For Suspension:

1. Plaque Psoriasis of the Body in Adults and Children: Apply once daily to the affected skin for up to eight weeks or until the area is clear, as the doctor directs. Do not exceed 100 grams per week.

2. Plaque Psoriasis of the Scalp:

• Adults: Apply once daily to the affected scalp area for up to eight weeks or until the area is clear, as the doctor directs. Do not exceed 100 grams per week.

• Children (12 to 17 Years): Apply once daily to the affected scalp area for up to eight weeks or until the area is clear, as directed by the doctor. Do not exceed 60 grams per week.

• Children Under 12 Years: The doctor will determine the appropriate use and dose.

How Effective Is Calcipotriene and Betamethasone Dipropionate?

After two weeks of treatment, Calcipotriene and Betamethasone dipropionate can change the skin. The skin will slowly get better over time. The overall benefit is about 12 weeks of treatment.

What Are the Things to Inform the Doctor Before Taking the Calcipotriene and Betamethasone Dipropionate Topical Suspension?

Before using this product, inform the doctor or pharmacist if the person is allergic to Betamethasone or Calcipotriene or if a person has any other allergies. This product may contain inactive ingredients that could trigger allergic reactions or other issues.

How Is Calcipotriene and Betamethasone Dipropionate Topical Suspension Administered?

• Shake the bottle before using.

• Apply Calcipotriene and Betamethasone dipropionate topical suspension to affected areas on the scalp and body once daily for up to eight weeks.

• Stop using the product when the condition has been controlled.

• If the person is between the ages of 12 to 17, do not use more than 60 grams per week.

• If the person is an adult, do not use more than 100 grams weekly.

• Avoid using occlusive dressings unless directed by a healthcare provider.

• Do not use it on the face, groin, or axillae or if skin atrophy is present at the treatment site.

• This product is not meant for oral, ophthalmic, or intravaginal use.

What Are the Side Effects of Calcipotriene and Betamethasone Dipropionate Topical Suspension?

• A person might experience itching, burning, redness, or skin irritation. If these effects persist or worsen, inform the doctor.

• This medication is prescribed because its benefits are considered greater than the risks for most people. Many users do not experience serious side effects.

• Contact the doctor immediately if a person notices severe side effects such as skin thinning, discoloration, "stretch marks," small red bumps (folliculitis), or worsening psoriasis.

• In rare cases, the medication may increase calcium levels in the blood or urine, leading to serious effects like mood changes, unexplained constipation, pink or bloody urine, or painful urination.

• Absorption into the bloodstream is rare but can lead to corticosteroid side effects. This is likely to occur more in children or over large skin areas due to long-term use. Watch for unusual tiredness, weight loss, headache, swelling, increased thirst or urination, or vision problems.

• A severe allergic reaction is rare but requires immediate medical attention and may include rash, itching, or swelling (especially of the face, tongue, or throat), severe dizziness, or trouble breathing.

• This is not a complete list of possible side effects, so contact the doctor or pharmacist for any unlisted effects.

Dietary Considerations:

Some medications may not be suitable to take with or around meals or specific types of food, as this could lead to interactions. Additionally, consuming alcohol or tobacco while taking certain medications may also result in interactions. It is important to talk to the healthcare provider about how to use the medication concerning meals, alcohol, or tobacco.

Missed Dose:

If a person needs to remember to take a dose, they should take it as soon as they remember. If it is almost time for the next dose, skip the missed one. Take the next dose at the usual scheduled time. Do not take double the dose to make up for the missed one.

Overdose:

Calcipotriene and Betamethasone dipropionate topical suspension, if swallowed, may be harmful if someone has swollen and overdosed and has serious symptoms such as passing out or having breathing trouble.

Storage:

• Store the medication at room temperature.

• There is no necessity to store it in the fridge.

• When not using, keep the bottle in the box it came in.

• Throw away any unused product six months after the bottle is opened.

• Make sure to keep all medications out of reach of kids and pets.

• Do not flush the medication down the toilet or pour it down the drain unless told to.

• Dispose of the product correctly when it is expired or no longer needs it.

• Ask the pharmacist or local waste disposal company for guidance.

For Doctors

Indication:

Calcipotriene and betamethasone dipropionate topical ointment treat psoriasis in adults 18 years and older.

Dose:

Calcipotriene and Betamethasone dipropionate topical ointment comes as a cream with a concentration of 0.005 percent Calcipotriene hydrate and 0.064 percent Betamethasone dipropionate. In simpler terms, each gram of the ointment contains specific amounts of these active ingredients in a base resembling off-white to yellow paraffin.

Dosing Considerations:

Apply a sufficient amount of Calcipotriene and Betamethasone dipropionate topical suspension to the affected areas once a day for up to four weeks. The maximum amount per week should be at most 100 grams. Avoid treating more than 30 percent of the body surface. Gently and thoroughly rub in the ointment, and remember to wash your hands afterward.

What Are the Pharmacological Aspects of Calcipotriene and Betamethasone Dipropionate Topical Suspension?

Pharmacodynamics:

• Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression: In a study involving 109 adolescents aged 12 to 17 years with scalp plaque psoriasis treated with the once-daily application of Calcipotriene and Betamethasone dipropionate topical suspension for up to eight weeks, there were no reported cases of hypercalcemia or clinically significant changes in urinary calcium levels.

• HPA Axis Suppression - Trial C: In trial C, HPA axis suppression was assessed in pediatric subjects aged 12 to 17 years with scalp plaque psoriasis (involving at least 20 percent of the scalp area). They received a once-daily application of Calcipotriene and Betamethasone dipropionate topical suspension for up to eight weeks. Adrenal suppression, indicated by a 30-minute post-stimulation cortisol level ≤18 mcg/dL, was observed in one of 30 subjects (3.3 percent) after four weeks of treatment, with no instances noted in subjects continuing treatment for eight weeks.

• Effects on Calcium Metabolism: The impact on calcium metabolism was investigated in 109 pediatric subjects aged 12 to 17 years with scalp plaque psoriasis (involving at least ten percent of the scalp area). They underwent once-daily application of Calcipotriene and Betamethasone dipropionate topical suspension to the scalp for up to eight weeks. No occurrences of hypercalcemia or clinically significant alterations in urinary calcium were reported.

Mechanism of Action:

Calcipotriene and Betamethasone dipropionate topical suspension integrate the pharmacological actions of Calcipotriene hydrate, a synthetic vitamin D3 analog, and Betamethasone dipropionate, a synthetic corticosteroid. Despite well-established pharmacologic and clinical effects, the precise mechanisms of their actions in plaque psoriasis remain undisclosed.

Pharmacokinetics:

The systemic impact of Calcipotriene and Betamethasone dipropionate topical ointment in extensive psoriasis was examined. Serum levels of Calcipotriene and Betamethasone dipropionate, along with their major metabolites, were assessed after four and eight weeks of once-daily application on the body and scalp. While Calcipotriene and Betamethasone dipropionate were mostly undetectable in serum, a significant metabolite of Calcipotriene (MC1080) was observed in some subjects. The primary metabolites of Calcipotriene, especially MC1080, were quantifiable, with concentrations ranging from 20 to 75 pg/mL. The clinical significance of these findings remains uncertain.

Metabolism:

Calcipotriene undergoes rapid hepatic metabolism, producing less potent metabolites. It transforms into MC1046, an alpha, beta-unsaturated ketone analog, which further metabolizes into MC1080, a saturated ketone analog. MC1080 is the major plasma metabolite, gradually converting to calcitroic acid.

Betamethasone dipropionate is metabolized into Betamethasone 17-propionate (B17P) and Betamethasone, including their 6 beta-hydroxy derivatives, through hydrolysis. B17P is the primary metabolite.

Toxicity:

Topical Calcipotriene in mice (3, 10, 30 mcg/kg/day (microgram per kilogram per day)) for 24 months had no notable tumor changes. However, in UV-exposed albino hairless mice, Calcipotriene reduced UVR-induced skin tumors, particularly in males, suggesting it may enhance UVR's carcinogenic effect.

Topical Betamethasone dipropionate in CD-1 mice (1.3, 4.2, 8.5 mcg/kg/day in females, 1.3, 4.2, 12.9 mcg/kg/day in males) for 24 months showed no significant tumor changes. Oral Betamethasone dipropionate in rats (20, 60, 200 mcg/kg/day) for 24 months exhibited no significant tumor changes.

Calcipotriene, in genotoxicity tests (Ames assay, mouse lymphoma assay, chromosome aberration test, micronucleus test), showed no adverse effects. Similarly, Betamethasone dipropionate, in genotoxicity tests (Ames assay, mouse lymphoma assay, rat micronucleus test), displayed no adverse effects.

In fertility studies with rats, oral Calcipotriene doses up to 54 mcg/kg/day and Betamethasone dipropionate doses up to 200 mcg/kg/day in male rats, and 1000 mcg/kg/day in female rats showed no negative impact on fertility or reproductive performance.

Clinical Studies:

The data reflects the exposure of 2448 subjects to Calcipotriene and Betamethasone dipropionate topical ointment, with 1992 exposed for four weeks and 289 for eight weeks. Studied in placebo- and active-controlled trials (N = 1176 and N = 1272), the population ranged from 15-97 years, comprising 61 percent males and 39 percent females, predominantly white (97 percent), with baseline disease severity from mild to severe. Most applied the ointment once daily, with a median weekly dose of 24.5 g.

Adverse event reporting percentages were 27.1 percent (Calcipotriene and Betamethasone dipropionate topical ointment), 33.0 percent (Calcipotriene), 28.3 percent (Betamethasone), and 33.4 percent (vehicle). Lesional/perilesional events had median onset times of seven days (Calcipotriene and Betamethasone dipropionate topical suspension), seven days (Calcipotriene), five days (Betamethasone), and three days (vehicle).

Less common reactions (0.1 - one percent) included folliculitis, rash papular, rash pustular, and skin hypopigmentation, with infrequent reports of skin atrophy, telangiectasia, and hyperpigmentation (0.1 percent).

In a separate trial with subjects (N = 207) of at least moderate disease severity, intermittent "as needed" Calcipotriene and Betamethasone dipropionate topical ointment used for up to 52 weeks (median 15.4 g/week (gram per week)) occurred. Effects on calcium metabolism and the HPA axis needed to be adequately studied. Adverse reactions reported by ≥ one percent included pruritus (7.2 percent), psoriasis (3.4 percent), skin atrophy (1.9 percent), folliculitis (1.4 percent), burning sensation (1.4 percent), skin depigmentation (1.4 percent), ecchymosis (1.0 percent), erythema (1.0 percent), and hand dermatitis (1.0 percent). A serious psoriasis flare-up case was reported.

Warnings and Precautions:

• Calcium Metabolism Effects: Calcipotriene and Betamethasone dipropionate topical suspension use may lead to hypercalcemia and hypercalciuria. If observed, discontinue treatment until calcium metabolism normalizes. Calcium metabolism effects were evaluated after four weeks. Longer durations were not assessed.

• Endocrine System Impact: Topical corticosteroids, including Calcipotriene and Betamethasone dipropionate topical ointment, may cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, potentially resulting in clinical glucocorticosteroid insufficiency during treatment or withdrawal. HPA axis suppression was noted in a trial involving 32 subjects after four weeks. Evaluate patients periodically for HPA axis suppression, considering factors such as potency, surface area, duration, occlusion, skin barrier alterations, and liver failure. ACTH (Adrenocorticotropic hormone) stimulation tests can aid in evaluation. If suppression is confirmed, gradual withdrawal or reduced application frequency may be attempted, with consideration for less potent steroids. Adrenal insufficiency manifestations may necessitate systemic corticosteroids. Cushing's syndrome, hyperglycemia, and unmasking latent diabetes mellitus may result from systemic corticosteroid absorption. Concurrent use of multiple corticosteroid products may increase systemic exposure. Pediatric patients may be more susceptible to systemic toxicity.

• Local Reactions: Occlusive, prolonged, or high-potency corticosteroid use may increase the likelihood of local adverse reactions, including atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some reactions may be irreversible.

• Allergic Contact Dermatitis with Corticosteroids: Allergic contact dermatitis to corticosteroid components is diagnosed by delayed healing. Clinical confirmation is achieved through patch testing.

• Allergic Contact Dermatitis with Calcipotriene: Topical Calcipotriene use may lead to allergic contact dermatitis, confirmed through patch testing.

• Concomitant Skin Infections: Treat concomitant skin infections with appropriate antimicrobials. If persistent, discontinue Calcipotriene and Betamethasone dipropionate topical ointment until the infection is adequately treated.

• Skin Irritation: Discontinue Calcipotriene and Betamethasone dipropionate topical ointment if irritation occurs, initiating appropriate alternative therapy.

• Ultraviolet Light Exposure: Patients applying Calcipotriene and Betamethasone dipropionate topical ointment to exposed skin should avoid excessive natural or artificial sunlight exposure. Physicians may consider limiting phototherapy in such patients.

What Are the Drug Interactions of Calcipotriene and Betamethasone Dipropionate Topical Suspension?

While certain medications are not recommended to be used concurrently, there are instances where two different medications may be prescribed together despite the potential for interaction. The healthcare provider may adjust the dosage or implement other precautions in such cases. It is crucial to inform the healthcare professional about all the medicines a person takes. The following interactions have been highlighted for their potential significance but may only cover some possibilities. This medication is not advised to be used with the following medicines. The doctor may choose not to treat the patient with this medication or may modify other medications they are taking:

• Desmopressin: While using this medication with the following medicines is generally not recommended, it may be necessary in some cases. If both drugs are prescribed, the doctor may adjust the dosage or frequency of one or both medications.

Using this medication with the following medicines may elevate the risk of specific side effects, but the combination may be the most effective treatment. If both drugs are prescribed together, the doctor may adjust the dosage or frequency of one or both medications:

• Alcuronium.

• Atracurium.

• Auranofin.

• Fosphenytoin.

• Gallamine.

• Hexafluorenium.

• Licorice.

• Metocurine.

• Phenobarbital.

• Phenytoin.

• Primidone.

• Rifampin.

• Rifapentine.

• Saiboku-To.

Specific Considerations:

• Pregnancy: Calcipotriene and Betamethasone dipropionate topical ointment fall under pregnancy category C due to a lack of well-controlled studies in pregnant women. Its use during pregnancy should be considered only if the potential benefit justifies the potential fetal risk. Animal studies indicate Calcipotriene's fetotoxicity and Betamethasone dipropionate's teratogenicity when given systemically.

• Nursing Mothers: Systemically administered corticosteroids may appear in human milk, posing risks to the infant's growth and endogenous corticosteroid production. The extent of Calcipotriene or corticosteroid absorption into human milk through topical administration is unknown. Caution is advised when administering Calcipotriene and Betamethasone dipropionate topical ointment to nursing mothers.

• Pediatric Use: The safety and efficacy of Calcipotriene and Betamethasone dipropionate Topical Ointment in pediatric patients, particularly those under twelve, have not been studied. Children may be at an increased risk of systemic adverse effects due to a higher ratio of skin surface area to body mass. Reported effects in children receiving topical corticosteroids include HPA axis suppression, Cushing's syndrome, growth retardation, delayed weight gain, and intracranial hypertension.

• Geriatric Use: Approximately 14 percent of the subjects in Calcipotriene and Betamethasone dipropionate topical ointment clinical studies were 65 years and older, with three percent aged 75 and over. No significant differences in safety or effectiveness were observed between elderly and younger subjects. Other clinical experiences did not identify variations in response between age groups.

• Unevaluated Uses: The safety and efficacy of Calcipotriene and Betamethasone dipropionate topical ointment have not been evaluated in patients with known or suspected calcium metabolism disorders, erythrodermic, exfoliative, or pustular psoriasis. Additionally, its use in patients with severe renal insufficiency or severe hepatic disorders has not been assessed.