Calcipotriene - Uses, Dosage, Precautions, and Side Effects

Overview:

Plaque psoriasis is a chronic skin disease that affects millions of people worldwide. This skin disease is aggravated by the presence of red, raised, and scaly patches on the skin, known as plaques. It not only causes physical pain but impacts people’s mental state and lowers their quality of life. Therefore, patients’ daily lives need to be made easier. This has resulted in an increased search for effective treatment methods. Healthcare providers and researchers have therefore turned their focus to Calcipotriene, a synthetic vitamin D3 derivative that patients can apply topically. Because of its unique mechanism of action and therapeutic properties, Calcipotriene has acquired significant attention as an efficacious treatment for plaque psoriasis.

Drug Approval:

Calcipotriene cream is used for the management of plaque psoriasis, and thus, knowing the mechanism, efficacy, dosing, safety, and drug interactions is crucial. The use of Calcipotriene was approved by the FDA (food and drug administration) in 2010. This was upon the completion of two clinical trials involving eight-week arms, where Calcipotriene was evaluated against placebo in patients with body and scalp psoriasis. Providers will need to know the specifics and possible advantages of Calcipotriene so that appropriate conclusions are made about its use for this chronic skin disease. After acquiring more clinical uses with Calcipotriene, the therapy approach of psoriasis can be further improved for better outcomes for patients suffering from 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:

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

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

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

• 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:

• 60-gram aluminum tubes.

• 120-gram aluminum tubes.

For Patients:

How Does Calcipotriene Work?

• Calcipotriene controls abnormal events connected with skin cell growth and the differentiation of these skin cells, which are responsible for the occurrence of psoriasis.

• It is characterized by a heightened immune reaction and active skin cell production. Newly produced skin cells get shed off but at a slower rate than they multiply. Psoriasis disturbs this balance, resulting in rapid and uncontrolled multiplication of skin cells, which accumulates on the skin surface, resulting in the scaling, plaques, and papules associated with the disease.

• Calcipotriene is used for topical application because of its effects on the skin. Psoriasis is a disease that occurs due to the overproliferation of skin cells, and it binds with the receptors located on skin cells called vitamin D receptors. Therapeutically, Calcipotriene is effective because it modifies the processes after coming into contact with the skin. Calcipotriene is a synthetic form of vitamin D3.

• Calcipotriene also helps normalize excessive cell growth by targeting these vitamin D receptors. This medicine slows the growth of skin cells and matures and sheds them properly, reducing the thickness of the plaques and the severity of the scaling and inflammation.

• Calcipotriene solution is typically used in combination with other treatments, such as topical corticosteroids, to enhance its effectiveness. This combination 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 is effective in a significant number of psoriasis patients, especially in 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 Calcipotriene?

While using Calcipotriene, the following measures should be taken into consideration:

• Notify your physician and pharmacist of any allergies you have, including Calcipotriene or any other medicines.

• Inform the physician about all prescription and over-the-counter drugs, vitamins, supplements, and herbal medication the patient will use or is using. There might be a need to change the doses of medication, and the patient might need to be checked for possible side effects.

• Mention any present or past illnesses of the patient.

• If the patient is expectant, intends to get pregnant, or is nursing, it is important to disclose this information to the physician. This enables the physician to provide detailed guidance on the hazards and benefits of using Calcipotriene in pregnancy and breastfeeding; if a patient gets pregnant while on Calcipotriene, immediately inform the physician.

• Avoid any unnecessary exposure to the sun or for a longer than needed time. Since Calcipotriene increases sensitivity to sunlight, it is important to put on protective clothing such as a hat and sunglasses and apply sunscreen while going out.

How Is Calcipotriene Administered?

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

• Prior to applying the Calcipotriene, cleanse and thoroughly dry the affected skin area, as skin moisture can hinder the medication's effect.

• As for dosage, always ensure that the amount of Calcipotriene prescribed by the healthcare professional is not exceeded. The dosage can differ based on the severity and scope of the patient's psoriasis.

• Spread the Calcipotriene cream, ointment, or solution carefully and smoothly on the affected areas. When applying the Calcipotriene medication, make sure you cover the entire plaque and a small margin surrounding it.

• Make sure that the medication does not touch the eyes or the face. Should any contact occur, wash the affected area with water.

• Remember to scrub your hands clean after applying the Calcipotriene so that medication does not accidentally get to other parts of the body or other people.

• Always obey the instructions given by your healthcare professional and the details provided on the product’s label regarding use frequency and duration.

• While using Calcipotriene, precautions must be taken as it can increase the chances of skin sunburn. Hence, minimizing direct contact with the sun, putting on hats and sunscreen lotion, and wearing sun-protective clothing are necessary.

• All follow-up visits with the doctor should be arranged to monitor the patient's progress.

Instructions for using the solution:

• Moisturize your palms.

• Gently comb hair. This will help with the loose psoriasis scales that may be left over.

• It is ideal to part the hair over the affected areas.

• Take a small quantity of the solution and apply it to the lesions (avoiding the forehead and facial area, eyes, nose, and mouth).

• Massage it gently over the lesions.

• Wash your hands again.

The Solution and Benefits:

• Calcipotriene is one of the most popular drugs in the treatment of psoriasis.

• It alleviates associated skin conditions such as redness, swelling, itching, and soreness rashes that emerge due to psoriasis.

• It neutralizes the burning sensation, dryness, irritation, and skin peeling and improves skin conditions.

• In such cases, Calcipotriene is of the utmost importance for alleviating psoriasis symptoms and improving skin health.

Adverse Effects:

Calcipotriene skin ointment is not known to have so many side effects but can have some complications. It is advisable to contact the physician if the symptoms mentioned below persist:

• Psoriasis itching.

• Redness on the skin.

• Psoriasis skin condition is worsening.

• Skin burning.

• A stinging or warm sensation on the skin.

• Drying of skin.

Calcipotriene side effects 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. Communicating any adverse reactions to the healthcare provider is essential to ensure the safe and effective use of Calcipotriene ointment.

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.

What Should I Do if I Accidentally Use Too Much Calcipotriene?

Seek medical help immediately if you suspect you have used too much Calcipotriene. Overdose symptoms will result in skin irritation in the form of burning, stinging, and redness. If you suspect an overdose, seek medical attention immediately.

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 and 25 degrees Celsius (59 and 77 degrees Fahrenheit). Avoid freezing it.

Who Should Not Use Calcipotriene?

Calcipotriene is contraindicated in patients who have:

• Hypercalcemia (elevated blood calcium levels).

• Higher vitamin D levels in the body psoriasis-related skin irritation.

For Doctors:

Instructions for Use: Calcipotriene is used to treat plaque psoriasis. It is applied externally to minimize inflammation, scaling, and plaque thickness.

Prescribing Patterns: The cream dosage form of 0.005 percent includes Calcipotriene monohydrate.

Dosing Considerations: When composing a dose for Calcipotriene, there are various things to take into account that pertain to dosage and dosing:

• Dosage Form and Concentration: Calcipotriene is available in several forms and strengths, including creams, ointments, and solutions with differing concentrations of 0.005 - 0.01 percent. The form and concentration used will depend on the degree of severity and the region of the body where the psoriasis is located.

• Frequency of Application: The degree of severity of the psoriasis may affect the frequency of application. Generally, the regimen includes one to two applications of Calcipotriene on the affected skin for a day.

• Avoid Overuse: Calcipotriene should only be applied in the recommended dose by the concerned health professional. Do not utilize more than the prescribed amounts, as it may lead to increased side effects.

• Combination Therapy: Calcipotriene is applied alongside other topical treatments, particularly corticosteroids, to increase its desired efficacy.

• Pregnancy and Breastfeeding: If the patient is pregnant, planning to become pregnant, or breastfeeding, discuss this with the doctor before using Calcipotriene. The healthcare provider should evaluate the safety of Calcipotriene during pregnancy and breastfeeding.

• Adverse Reactions: It is important for the healthcare provider to check for any signs or symptoms of adverse reactions during the course of Calcipotriene. If any individual experiences side effects, prompt medical attention is necessary.

• Sunlight Exposure: Calcipotriene can make the skin sensitive to sunlight. Therefore, it is crucial to avoid too much sun exposure and always cover the sun-exposed skin with protective clothing and SPF (sun protection factor).

Tips for Managing Skin Conditions With Calcipotriene:

To use Calcipotriene appropriately in treating skin conditions:

Combination Therapy: Calcipotriene with nicotinamide may enhance the efficacy of treatment for psoriasis.

1. Long-Term Use: Calcipotriene and Betamethasone dipropionate are effective in treating psoriasis vulgaris and scalp psoriasis when given once daily over a long term.

2. Safety: The topical Calcipotriene has a very minimal negative impact on calcium and bone metabolism and is safe and effective for the treatment of plaque psoriasis.

3. Sequential Therapy: For effective treatment of scalp psoriasis, consider a sequential therapy regimen using Clobetasol solution and Calcipotriene.

4. Efficacy: Calcipotriene outperforms Fluocinonide in treating plaque psoriasis compared to Fluocinonide, thus yielding favorable outcomes for scaling, erythema, and overall disease severity.

What Are the Pharmacological Aspects of Calcipotriene?

Pharmacodynamics:

The pharmacodynamics of Calcipotriene can be summarized as follows:

1. Calcipotriene Pleiotropically Activates the Vitamin D Receptor: Calcipotriene has an affinity for VDR, which leads to skin cells' VDR activation. The activated VDR then forms a complex that recognizes and binds to certain regions of the DNA in the cell nucleus known as Vitamin D response elements.

2. Regulated Gene Expression: The VDR-activated processes in psoriatic tissue involve the sequential binding of a number of proteins to the responsive DNA region. Polymerase allows transcriptional processes to take place, which results in the synthesis of mRNA and proteins. This, in turn, alters and controls the rate and increase or decrease of skin cell activity.

3. Calcipotriene Restores Normal Skin Cell Growth: The main goal of anti-psoriasis treatment is to lower the magnitude of the constant multiplication of skin cells. Calcipotriene, thus, helps reduce the scale in thickness and the amount of visible psoriatic plaques, making the skin surface appear better.

4. Calcipotriene Has Anti-Inflammatory Effects: Psoriasis is associated with inflammation. Thus, the anti-inflammatory activity of Calcipotriene helps reduce the inflammation responsible for red skin lesions and itching discomfort.

Mechanism:

Calcipotriene is a synthetic form of calcitriol. Once applied to the skin, it gets into the skin cells and starts working on the vitamin D receptor (VDR). When Calcipotriene performs this function, the VDR becomes activated and forms a complex with the retinoid X receptor RXR. This VDR-RXR complex then attaches to certain sections of the DNA that are located in the nucleus of the cell and are called vitamin D response elements (VDREs). With the help of Calcipotriene, the expression of genes that have to do with cell growth and division, as well as immune response, is decreased in order to bind with the VDREs. This activity is useful for providing a balance in the overactive and inflamed state of psoriatic skin plaques where there is overgrowing, as well as for dealing with skin cells. In psoriasis, there is an overstimulation and some abnormal changes in skin cell structures. With the help of Calcipotriene, the waves of inflammation responses decrease, and as a result, the thickness and scaling of psoriatic plaques decrease.

Pharmacokinetics:

These are the pharmacokinetics of Calcipotriene ointment as illustrated in the diagrams:

Absorption: The ointment is primarily used topically, so it has a low absorption through the skin. Clinical research on the use of radiolabeled Calcipotriene ointment indicates that around six percent of the prescribed amount is absorbed whenever the ointment is spread on plaques of psoriasis and around five percent whenever it is spread on normal skin.

Distribution: Once absorbed, receptors for Calcipotriene and its metabolites bind with specific plasma proteins and are transported through the bloodstream to the liver and skin tissues.

Metabolism: Calcipotriene is rapidly absorbed and metabolized through the body, primarily in the liver. Within 24 hours post application, a significant portion of absorbed Calcipotriene transforms into inactive metabolites. Within the body, Calcipotriene gets transformed into the active form of Vitamin D 3 known as 1,25-dihydroxy Vitamin D 3 (Calcitriol).

Excretion: The body metabolizes Calcipotriene’s active metabolites and excretes them through bile and urine.

Toxicity: The toxicity of Calcipotriene is mainly related to its potential for systemic absorption and its effects on calcium metabolism. An increased amount of Calcipotriene absorbed could lead to hypercalcemia or an increased amount of calcium in the blood. Hypercalcemia could lead to symptoms like:

• Increased urination or constipation.

• Frequent nauseous feelings or vomiting.

• Bone fractures.

• Confusion or changes in mental state.

• An ache in the kidneys and bones

• Exhaustion.

Toxic reactions could also stem from overdosage or intake of medication affecting calcium concentration or liver enzymes.

What Are the Contraindications of Calcipotriene?

The contraindication for Calcipotriene (cream, 0.005 percent) is hypersensitivity or a 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:

• Please inform the doctor or pharmacist of any allergies you may have prior to using this medication. The active ingredients might contain components that could cause an allergic reaction or similar complications. It is best to contact a pharmacist for more clarity.

• Before you begin taking this medication, make sure to tell the physician or the pharmacist if you have any preexisting diseases, such as renal diseases, dehydration, or other medical issues that might put you at risk of having too much calcium or vitamin D in your system (hypercalcemia or hypervitaminosis D).

• This medication may enhance the subject's vulnerability to direct sunlight. To lessen exposure without sunscreen, try to avoid the sun, tanning beds, and sun lamps. Be sure to wear protective clothing when going outside. Please inform the doctor immediately if sunburn or skin blisters arise. The doctor will likely recommend stopping or limiting the use of phototherapy while taking this medicine. Be sure to ask the doctor about it for more details.

• Elderly patients might be at a higher risk of the possible unwanted effects of this medication.

• If the patient is in the course of pregnancy, then this medication should be used if it is essential. One of the first steps before treatment is to talk to the doctor regarding the advantages and disadvantages of medication.

What Are the Drug Interactions of Calcipotriene?

The use of Calcipotriene cream may diminish the effectiveness of other treatments or increase the likelihood of serious adverse impacts. Although this document may not determine all the interactions, it is important to mention that there are many possible interactions. It is also critical for the health of the patient that an accurate list of all the items they are taking, prescription and non-prescription medications, and herbal medicines is maintained. This information should be provided to the relevant medical personnel and the pharmacist. Always consult the doctor before initiating treatment with a new drug, stopping treatment, or making dosage adjustments. Additionally, exercise particular care when applying other vitamin D-containing medications together with Calcipotriene cream. 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:

Studies on topical Calcipotriene on mice did not indicate any statistical increase in tumor incidence in the 24-month study. However, Calcipotriene increased the risk of inducing skin tumors in males by reducing the dose of UVR ultraviolet radiation required. Therefore, Calcipotriene users are advised to avoid exposure directly to the sun or in tanning booths.

In various assays, Calcipotriene did not exhibit any mutagenic activity. Studies in rats revealed that a constant dosage of 53 mcg does not affect fertility or mating ability.

Pregnancy: The animal studies raised the possibility of potential harm to the fetus, including some skeletal deformities on higher doses. Because there are no controlled studies in human pregnancy, Calcipotriene should only be administered during pregnancy when the benefits outweigh the risks.

Nursing Mothers: It is not known whether calcipotriene is excreted in milk, and therefore, nursing women are advised to exercise caution.

Pediatric Use: No data exist on the safety and efficacy of Calcipotriene in children. Given their relatively higher skin-to-body mass ratio, they may be prone to greater systemic effects.

Geriatric Use: Clinical studies of the elderly show that patients over the age of 65 and patients under the age of 65 have no significant difference in the adverse effects suffered.