Calcipotriene - Uses, Dosage, Precautions, and Side Effects.

Overview:

Plaque psoriasis is a prevalent chronic skin disorder characterized by red, raised, and scaly patches known as plaques, affecting millions of people worldwide. The condition not only causes physical discomfort but also significantly impacts individuals' emotional well-being and overall quality of life. As a result, there has been a growing need to explore effective treatment options that can alleviate symptoms and improve patients’ daily lives. In response to this demand, researchers and healthcare professionals have turned their attention to Calcipotriene, a synthetic vitamin D3 derivative formulated for topical use. With its unique mechanism of action and potential therapeutic benefits, Calcipotriene has emerged as a promising treatment for plaque psoriasis.

This article presents a comprehensive outline of Calcipotriene's role in the management of plaque psoriasis, shedding light on its mechanism of action, effectiveness, dosing considerations, safety considerations, and potential drug interactions. Calcipotriene received FDA approval in 2010. The approval was based on two clinical trials of eight weeks each that compared Calcipotriene with a placebo in patients with body psoriasis and one clinical trial of eight weeks that did the same for patients with scalp psoriasis. By understanding the characteristics and potential benefits of Calcipotriene, healthcare providers and patients can make informed decisions about its use in the management of this chronic skin condition. Through further research and clinical experience, Calcipotriene's role in psoriasis therapy can continue to be refined, offering hope and relief to individuals burdened by the challenges of living with plaque psoriasis.

Drug Group:

Calcipotriene belongs to the class of topical psoriasis agents or topical vitamin D analogs. Calcipotriene monohydrate is chemically described as (5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1α,3β,24-triol monohydrate, with the empirical formula C27H40O3•H2O and a molecular weight of 430.6.

Available Doses and Dosage Forms:

1. Calcipotriene Cream: Cream formulations are commonly available, and the concentration of calcipotriene can vary (e.g., 0.005 percent or 0.01 percent). Gently apply the cream directly to the affected areas of the skin.

2. Calcipotriene Ointment: Ointments are also widely used and may come in different strengths (e.g., 0.005 percent or 0.01 percent). Ointments are often preferred for areas of thickened or scaly skin.

3. Calcipotriene Solution: A liquid solution form of Calcipotriene may be available for certain applications.

4. Combination Products: Sometimes, Calcipotriene is combined with other active ingredients, such as topical corticosteroids, to enhance its effectiveness or address specific aspects of psoriasis treatment.

Calcipotriene cream, 0.005 percent, is offered in two convenient sizes:

1. 60-gram aluminum tubes.

2. 120-gram aluminum tubes.

For Patients:

What Is Plaque Psoriasis?

Plaque psoriasis is a common, chronic skin condition characterized by raised, red, and thickened patches of skin covered with silvery-white scales. It is the most prevalent form of psoriasis and occurs due to an overactive immune response, causing skin cells to grow at an accelerated rate.

The key features of plaque psoriasis include:

1. Red, Raised Patches: Plaque psoriasis typically appears as well-defined, red patches of skin that are slightly elevated above the surrounding skin.

2. Silvery-White Scales: The affected skin is covered with silver or white scales, which are a result of the rapid buildup of dead skin cells on the surface.

3. Itching and Discomfort: Plaque psoriasis patches can be itchy and may cause discomfort or irritation.

4. Common Locations: Plaque psoriasis commonly affects areas such as the elbows, knees, scalp, lower back, and the skin around the joints. However, it can appear on any part of the body.

5. Chronic Condition: Plaque psoriasis is a chronic condition, meaning it tends to persist over time, with periods of improvement and flare-ups.

Although the exact cause of plaque psoriasis remains unclear, it is thought to stem from an abnormal immune response. In this condition, the immune system erroneously targets healthy skin cells, triggering accelerated skin cell growth and the development of plaques.

It is crucial to note that plaque psoriasis is not contagious. Nevertheless, it can substantially affect an individual's quality of life, leading to physical discomfort, emotional distress, and self-consciousness about visible skin changes.

Treatment for plaque psoriasis aims to control symptoms, reduce inflammation, and slow down excessive skin cell growth. It may include topical creams, phototherapy (light therapy), systemic medications, and lifestyle changes.

How Does Calcipotriene Work?

• Calcipotriene works by modulating the growth and differentiation of skin cells, specifically targeting the abnormal processes associated with psoriasis.

• In psoriasis, there is an overactive immune response that leads to the rapid production of skin cells. Normally, skin cells go through a process of growth and shedding in a balanced manner. However, in psoriasis, this process is disrupted, causing skin cells to multiply much faster than they can be shed. As a consequence, an accumulation of skin cells occurs on the skin's surface, giving rise to the characteristic plaques and scales commonly observed in psoriasis.

• Calcipotriene is a synthetic form of vitamin D3, which acts as a topical treatment for psoriasis. It binds to specific receptors on the skin cells known as vitamin D receptors. Once bound, Calcipotriene helps to regulate the growth and differentiation of skin cells.

• By targeting these vitamin D receptors, Calcipotriene normalizes the excessive cell growth seen in psoriasis. It will slow down the proliferation of skin cells and encourage their proper maturation and shedding. This leads to a reduction in the thickness of the plaques, the scaling, and the overall inflammation associated with psoriasis.

• Calcipotriene is typically used in combination with other treatments, such as topical corticosteroids, to enhance its effectiveness. The combination of Calcipotriene and corticosteroids provides a complementary approach that reduces inflammation and controls abnormal skin cell growth more effectively than either medication alone.

What Is the Dosage of Calcipotriene?

For topical use, Calcipotriene is typically available in cream, ointment, or solution forms, with concentrations ranging from 0.005 percent to 0.01 percent. The cream with a concentration of 0.005 percent is prescribed specifically for treating plaque psoriasis.

How Effective Is Calcipotriene?

Calcipotriene has been found to be effective in a significant number of psoriasis patients, especially in cases of mild to moderate plaque psoriasis. It is often considered a first-line treatment option for these types of psoriasis. However, for severe or resistant cases, other treatment approaches, such as systemic medications or biologics, may be necessary. The safety and efficacy of using topical calcipotriene for conditions other than psoriasis have not been established.

What Are the Things to Inform the Doctor Before Taking the Drug?

Before using calcipotriene, it is essential to take the following precautions:

1. Inform the doctor and pharmacist about any allergies the patient has, including allergies to Calcipotriene or other medications.

2. Share information with the doctor about all the prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products that the patient is currently taking or plans to take. The doctor may need to adjust the doses of the medications or closely monitor the patient for potential side effects.

3. Disclose any medical conditions the patient has or has had in the past.

4. If the patient is pregnant, have plans to conceive, or is currently breastfeeding, it is crucial to inform the doctor. Having an open discussion about the potential risks and benefits associated with using Calcipotriene during pregnancy or while breastfeeding is essential. If the patient has become pregnant while using Calcipotriene, contact the doctor promptly.

5. Take precautions to avoid unnecessary or prolonged exposure to sunlight. Calcipotriene can make the skin more sensitive to sunlight. It is necessary to wear protective clothing, such as a hat and sunglasses, and use sunscreen when outdoors.

How Is Calcipotriene Administered?

Patients using Calcipotriene cream should be provided with the following information and instructions:

• Prior to applying Calcipotriene, cleanse and dry the affected skin area. It is essential to have clean and dry skin for better absorption of the medication.

• Use the appropriate amount of Calcipotriene as prescribed by the healthcare professional. The amount of dosage can vary depending on the severity and extent of the patient’s psoriasis.

• Gently spread the Calcipotriene cream, ointment, or solution on the affected skin areas. Ensure an even application, covering the entire plaque and a small margin around it.

• Take care not to get the medication in the eyes or on the face. In case of accidental contact occurs, rinse thoroughly with water.

• After applying Calcipotriene, wash hands thoroughly to avoid inadvertently spreading the medication to other parts of the body or to others.

• It is necessary to follow the instructions provided by the healthcare professional and the guidelines on the product's label regarding the frequency and duration of use.

• Calcipotriene can increase the skin's sensitivity to sunlight, so it is essential to minimize sun exposure and use protective measures like wearing hats and protective clothing and applying sunscreen.

• Keep all follow-up appointments with the doctor to monitor the patient’s progress and adjust the treatment plan as needed.

Instructions for using the solution:

• Wash hands.

• Comb hair to remove any loose psoriasis scales.

• Part hair near the affected areas.

• Apply a small amount of the solution to the lesions. Take care to avoid contact with the forehead or other facial areas, especially near the eyes, nose, or mouth.

• Gently massage the solution into the lesions.

• Wash hands once more.

What Are the Side Effects of Calcipotriene?

Calcipotriene may lead to side effects. If one experiences any of the following symptoms and they are severe or persist, inform the doctor:

• Itching.

• Redness.

• Worsening of psoriasis.

• Burning.

• Stinging or tingling of the skin.

• Dry skin.

Potential side effects of Calcipotriene include:

Rash or Irritation of the Treated or Nearby Skin Area: If someone experiences any unusual problems or if the symptoms worsen while using this medication, contact the doctor promptly. It is essential to communicate any adverse reactions to the healthcare provider to ensure the safe and effective use of Calcipotriene.

Dietary Considerations:

None.

Missed Dose:

The missed dose should be applied as soon as it is remembered. However, if it is almost time for the next scheduled dose, skip the missed dose and continue with the regular dosing schedule. Avoid applying extra cream or solution to compensate for the missed dose.

Overdose:

When applied topically, Calcipotriene can be absorbed sufficiently to cause systemic effects. Excessive use of topical Calcipotriene has been associated with elevated serum calcium levels. If an increase in serum calcium is observed, treatment should be discontinued until normal calcium levels are restored.

Storage:

Keep the medication at a controlled room temperature between 15 to 25 degrees Celsius (59 to 77 degrees Fahrenheit). Avoid freezing the medication.

For Doctors:

Indication:

The indication for Calcipotriene is the management of plaque psoriasis. It is applied topically to affected areas of the skin to reduce inflammation, scaling, and thickness of psoriasis plaques.

Dose:

The cream is formulated with a concentration of 0.005 percent, including Calcipotriene monohydrate.

Dosing Considerations:

When using Calcipotriene, there are several dosing considerations to keep in mind:

1. Dosage Form and Concentration: Calcipotriene is available in various dosage forms, such as creams, ointments, and solutions, with different concentrations (e.g., 0.005 percent or 0.01 percent). The specific formulation and concentration prescribed will depend on the severity and anatomical localization of the psoriasis.

2. Application Frequency: The recommended application frequency may vary based on individual factors and the severity of the psoriasis. Typically, Calcipotriene is applied once or twice daily to the affected skin areas.

3. Avoid Overuse: It is essential to use calcipotriene only as directed by the healthcare professional. Avoid applying more than the prescribed amount, as excessive use may increase the risk of side effects.

4. Combination Therapy: Calcipotriene is sometimes used in combination with other topical medications, such as corticosteroids, to enhance its effectiveness. Follow the doctor's instructions on how to use Calcipotriene in combination with other treatments.

5. Pregnancy and Breastfeeding: In the event of the patient being pregnant, planning to become pregnant, or breastfeeding, discuss with the doctor before using Calcipotriene. The safety of Calcipotriene during pregnancy and breastfeeding should be evaluated by the healthcare provider.

6. Adverse Reactions: Monitor for any signs of adverse reactions while using Calcipotriene. If one experiences unusual side effects or the symptoms worsen, contact the doctor promptly.

7. Sunlight Exposure: Calcipotriene can increase the skin's sensitivity to sunlight. Take precautions to avoid excessive sun exposure and use protective clothing and sunscreen when outdoors.

What Are the Pharmacological Aspects of Calcipotriene?

1. Pharmacodynamics:

The pharmacodynamics of Calcipotriene can be summarized as follows:

• Vitamin D Receptor Activation: Calcipotriene binds to the VDR (vitamin D receptor) in the skin cells, leading to receptor activation. The activated VDR complex then binds to specific regions of DNA, known as vitamin D response elements, within the cell nucleus.

• Regulation of Gene Expression: The binding of activated VDR to DNA initiates a series of intracellular events, ultimately resulting in the regulation of gene expression. This process influences the differentiation, proliferation, and function of skin cells.

• Normalization of Skin Cell Growth: Calcipotriene helps to normalize the growth and differentiation of skin cells, reducing the excessive proliferation of skin cells seen in psoriasis. This leads to a decrease in the thickness and scaling of psoriatic plaques, improving the overall appearance of the skin.

• Anti-Inflammatory Effects: Calcipotriene has anti-inflammatory properties, which help to reduce the inflammation associated with psoriasis. This contributes to the relief of symptoms such as redness and itching.

2. Mechanism:

Calcipotriene is an artificial derivative of vitamin D3 (cholecalciferol). When applied topically to the skin, Calcipotriene interacts with the vitamin D receptor (VDR) present in skin cells. As a result of this interaction, VDR gets activated, and it forms a complex with the retinoid X receptor (RXR). The VDR-RXR complex then binds to specific regions of DNA known as vitamin D response elements (VDREs) within the cell nucleus. Calcipotriene regulates the expression of genes involved in cell differentiation, proliferation, and immune responses by binding to VDREs. This helps to normalize the growth and differentiation of skin cells and reduces inflammation in psoriatic plaques. In psoriasis, where there is excessive proliferation and abnormal differentiation of skin cells, Calcipotriene's action leads to a decrease in the thickness and scaling of psoriatic plaques.

3. Pharmacokinetics:

The pharmacokinetics of Calcipotriene are as follows:

1. Absorption: Calcipotriene is primarily administered topically, and its absorption through the skin is relatively low. Clinical studies with radiolabeled Calcipotriene ointment have shown that approximately six percent of the applied dose is absorbed systemically when applied to psoriasis plaques and about five percent when applied to normal skin. The systemic absorption of the cream formulation has not been studied.

2. Distribution: Once absorbed, Calcipotriene and its metabolites may bind to specific plasma proteins and are transported in the bloodstream to various tissues, including the skin and liver.

3. Metabolism: In the body, Calcipotriene undergoes rapid metabolism, primarily in the liver. 1,25-dihydroxy vitamin D3 (calcitriol), the active form of vitamin D3, is formed through the metabolic conversion of Calcipotriene. It is crucial to highlight that a significant portion of the absorbed Calcipotriene undergoes conversion into inactive metabolites within 24 hours of application.

4. Excretion: The metabolites of Calcipotriene are excreted from the body through various routes, including urine and bile.

Toxicity:

The toxicity of Calcipotriene is mainly related to its potential for systemic absorption and its effects on calcium metabolism. If there is excessive systemic absorption of Calcipotriene, it may result in hypercalcemia, which is characterized by elevated levels of calcium in the bloodstream. Hypercalcemia can cause various symptoms, including:

1. Nausea and vomiting.

2. Increased thirst and frequent urination.

3. Constipation.

4. Fatigue and weakness.

5. Confusion and mental changes.

6. Kidney stones.

7. Bone pain and fractures.

Toxicity may also arise from interactions with other medications, particularly those that affect calcium levels or are metabolized by the same liver enzymes. Patients should inform their healthcare providers about all medications and supplements they are taking to minimize the risk of drug interactions. To minimize the risk of toxicity, patients using Calcipotriene cream, 0.005 percent, should follow the prescribed application instructions carefully, avoid applying it to large areas of the body, and avoid using it for extended periods without medical supervision. Patients should also be cautious about excessive sun exposure when using Calcipotriene, as it may increase the risk of skin irritation and potential toxicity.

Clinical Studies:

Clinical trials involving patients treated with Calcipotriene cream, 0.005 percent, have shown significant improvement, typically starting within two weeks of therapy. The positive progress continued, and around 50 percent of patients witnessed significant improvement in the signs and symptoms of psoriasis after undergoing an eight-week treatment. However, only around four percent of patients achieved complete clearing of psoriasis plaques.

What Are the Contraindications of Calcipotriene?

Contraindication for Calcipotriene (cream, 0.005 percent) is hypersensitivity or known allergy to Calcipotriene or any of its components. If a person has a history of experiencing severe allergic reactions, such as anaphylaxis, hives, or difficulty breathing, to Calcipotriene or related substances, they should avoid using this medication. Severe hypersensitivity reactions can be life-threatening and require immediate medical attention.

Warnings and Precautions:

The warning and precautions associated are:

1. Before using this medication, inform the doctor or pharmacist about any known allergies to the drug or its components. The product might encompass inert components that have the potential to incite allergic reactions or other related concerns. For more information, consult the pharmacist.

2. Prior to using this medication, disclose the medical history to the doctor or pharmacist, especially if one has a history of high calcium or vitamin D levels (hypercalcemia or hypervitaminosis D).

3. This medication may increase sensitivity to sunlight. To minimize sun exposure, refrain from using tanning booths and sunlamps, and make sure to apply sunscreen and wear protective clothing while outdoors. If one experiences sunburn or skin blisters/redness, promptly inform the doctor. The doctor may advise to restrict or avoid phototherapy while using this product. Please consult the doctor for specific details.

4. Older adults may be more susceptible to the side effects of this medication.

5. If the patient is pregnant, use this medication only if clearly necessary. Before proceeding with the treatment, it is essential to have a discussion with the doctor about the potential risks and benefits involved.

What Are the Drug Interactions of Calcipotriene?

Using Calcipotriene cream may have an impact on the effectiveness of other medications or potentially increase the risk of experiencing serious side effects. It is essential to be aware of potential drug interactions, although this document may not cover all possible interactions. For the safety of the patient, it is crucial to maintain a comprehensive list of all products they are using, including prescription and non-prescription medications, as well as herbal products. This information should be shared with the healthcare provider and pharmacist. Before making any changes to one’s medication regimen, such as starting, stopping, or adjusting dosages, always seek approval from the doctor. Specifically, be cautious when using Calcipotriene cream with other products containing vitamin D, as they may interact and lead to unforeseen consequences. Keeping the healthcare team informed about all the medications allows them to provide the best guidance and minimize the risk of potential drug interactions.

Specific Considerations:

Carcinogenesis, Mutagenesis, Impairment of Fertility:

In studies where calcipotriene was topically applied to mice for up to 24 months at dosages of three, 10, and 30 mcg/kg/day (equivalent to nine, 30, and 90 mcg/m2/day), there were no significant changes in tumor incidence compared to control. However, in a study involving albino hairless mice exposed to both ultraviolet radiation (UVR) and topically applied Calcipotriene, there was a reduction in the time required for UVR to induce skin tumors (statistically significant in males only). This suggests that calcipotriene may enhance the effect of UVR in inducing skin tumors. Patients using Calcipotriene cream, 0.005 percent, on exposed skin areas should take caution to avoid excessive exposure to natural or artificial sunlight, including tanning booths and sunlamps. Physicians may consider limiting or avoiding phototherapy in patients using Calcipotriene cream, 0.005 percent.

Calcipotriene did not show mutagenic effects in several mutagenicity assays, including the Ames mutagenicity assay, mouse lymphoma TK locus assay, human lymphocyte chromosome aberration assay, and micronucleus assay conducted in mice.

Research conducted on rats exposed to doses of up to 54 mcg/kg/day (equivalent to 324 mcg/m2/day) of Calcipotriene revealed no negative impacts on fertility or general reproductive performance.

Pregnancy:

Studies on teratogenicity were conducted orally, where bioavailability was expected to be approximately 40 to 60 percent of the administered dose. Increased maternal and fetal toxicity was observed in rabbits at 12 mcg/kg/day (132 mcg/m2/day), while rabbits exposed to 36 mcg/kg/day (396 mcg/m2/day) showed a significant increase in the incidence of certain fetal skeletal abnormalities. During a rat study, administration of oral doses of 54 mcg/kg/day (318 mcg/m2/day) resulted in a higher incidence of skeletal abnormalities, primarily enlarged fontanelles and extra ribs. These enlarged fontanelles are likely due to the effect of Calcipotriene on calcium metabolism. The calculated no-effect exposures observed in both rat and rabbit studies are approximately equivalent to the anticipated human systemic exposure level (18.5 mcg/m2/day) resulting from dermal application. As there are no sufficient and well-controlled studies conducted on pregnant women, the use of Calcipotriene cream, 0.005 percent, during pregnancy should only be contemplated if the prospective advantages surpass the potential hazards to the fetus.

Nursing Mothers:

Research indicates that maternal 1,25-dihydroxy vitamin D3 (calcitriol) might enter fetal circulation, but it remains ambiguous whether it is secreted in human milk. The systemic behavior of Calcipotriene is anticipated to resemble that of naturally present vitamin D. Caution should be exercised when administering calcipotriene cream, 0.005 percent, to nursing women as many drugs are excreted in human milk.

Pediatric Use:

The safety and effectiveness of Calcipotriene cream, 0.005 percent, in pediatric patients have not been established. Pediatric patients might have a higher risk than adults of encountering systemic adverse effects when treated with topical medication due to their higher skin surface area to body mass ratio.

Geriatric Use:

Approximately 15 percent of patients in clinical studies of Calcipotriene cream were 65 or older, with approximately three percent being 75 and over. No substantial disparities in adverse events were noted between subjects aged over 65 years and those under 65 years of age. However, the increased sensitivity of older individuals cannot be ruled out.