Instructions Psotriol gel 50 mcg/g/0.5 mg/g bottle 30 g
Composition
active ingredients: calcipotriol, betamethasone;
1 g of gel contains 50 μg of calcipotriol (as calcipotriol monohydrate) and 0.5 mg of betamethasone (as betamethasone dipropionate);
Excipients: hydrogenated castor oil, polyoxypropylene stearyl ether (stabilized with butylhydroxytoluene), mineral oil.
Dosage form
Gel.
Main physicochemical properties: homogeneous, slightly cloudy and colorless gel, without foreign particles.
Pharmacotherapeutic group
Topical antipsoriatic agents. Other topical antipsoriatic agents. Calcipotriol, combinations.
ATX code D05A X52.
Pharmacological properties
Pharmacodynamics
Calcipotriol is a vitamin D analogue. In vitro data indicate that calcipotriol inhibits keratinocyte proliferation and promotes differentiation, a likely mechanism of action in psoriasis.
Like other topical corticosteroids, betamethasone dipropionate has anti-inflammatory, antipruritic, vasoconstrictor and immunosuppressive properties, but does not treat the primary disease. The use of occlusive dressings enhances the therapeutic effect by increasing penetration into the stratum corneum of the epidermis. In this regard, the frequency of adverse reactions may increase. In general, the mechanism of anti-inflammatory activity of topical steroids is not fully understood.
The adrenal response to adrenocorticotropic hormone (ACTH) was assessed by measuring serum cortisol levels in patients with widespread psoriasis of both the scalp and other body areas, using up to 106 g of a combination of calcipotriol + betamethasone dipropionate gel and calcipotriol + betamethasone dipropionate ointment per week. A marginal decrease in cortisol excretion in response to ACTH stimulation was observed in 5 of 32 patients (15.6%) after 4 weeks of treatment, and in 2 of 11 patients (18.2%) who continued treatment for up to 8 weeks. In all cases, serum cortisol levels were within normal limits 60 minutes after ACTH stimulation. No evidence of altered calcium metabolism was observed in these patients. Thus, with regard to suppression of the hypothalamic-pituitary-adrenal axis, this study provided some evidence that very high doses of gel and ointment containing calcipotriol + betamethasone dipropionate may have a weak effect on hypothalamic-pituitary-adrenal axis function.
The efficacy of calcipotriol + betamethasone dipropionate gel administered once daily was evaluated in two randomised, double-blind, 8-week clinical trials involving a total of over 2900 patients with scalp psoriasis of at least mild severity according to the Investigator's Global Assessment of Disease Severity (IGA). The comparators were betamethasone dipropionate gel vehicle, calcipotriol gel vehicle and (in one study) gel vehicle alone; all were administered once daily. The results for the primary endpoint of response to therapy (no or very mild disease severity according to the IGA at 8 weeks) demonstrated that calcipotriol + betamethasone dipropionate gel was statistically significantly more effective than the comparators. Results on rate of onset based on similar data at week 2 also demonstrated that the gel containing calcipotriol + betamethasone dipropionate was statistically significantly more effective than the comparator drugs.
| % of patients with no or very mild disease severity | Gel containing calcipotriol + betamethasone dipropionate (n=1108) | Betamethasone dipropionate (n=1118) | Calcipotriol (n=558) | Gel carrier (n=136) |
| Week 2 | 53.2% | 42.8%1 | 17.2 %1 | 11.8%1 |
| Week 8 | 69.8% | 62.5%1 | 40.1 %1 | 22.8%1 |
1Statistically significantly less effective than gel containing calcipotriol + betamethasone dipropionate (P
The efficacy of once-daily application of a gel containing calcipotriol + betamethasone dipropionate was evaluated in a randomized, double-blind, 8-week clinical study involving 296 patients with mild to moderate psoriasis vulgaris according to the IGA.
The comparators were betamethasone dipropionate in a gel vehicle, calcipotriol in a gel vehicle, and the gel vehicle alone; all were applied once daily. The primary response criteria were controlled disease according to IGA at weeks 4 and 8. Controlled disease was defined as “clear skin” or “minimal disease” for patients with moderate disease at baseline or as “clear skin” for patients with mild disease at baseline. The relative change from baseline in the Psoriasis Area and Systemic Severity Index (PASI) at weeks 4 and 8 were secondary response criteria.
| Gel containing calcipotriol + betamethasone dipropionate (n=126) | Betamethasone dipropionate (n=68) | Calcipotriol (n=67) | Gel carrier (n=35) |
| Week 4 | 20.6% | 10.3 %1 | 4.5%1 | 2.9%1 |
| Week 8 | 31.7% | 19.1 %1 | 13.4 %1 | 0.0 %1 |
1Statistically significantly less effective than gel containing calcipotriol + betamethasone dipropionate (P
| % mean decrease in PASI (SD) | Gel containing calcipotriol + betamethasone dipropionate (n=126) | Betamethasone dipropionate (n=68) | Calcipotriol (n=67) | Gel carrier (n=35) |
| Week 4 | 50.2 (32.7) | 40.8 (33.3) 1 | 32.1 (23.6)1 | 17.0 (31.8)1 |
| Week 8 | 58.8 (32.4) | 51.8 (35.0) | 40.8 (31.9)1 | 11.1 (29.5)1 |
1Statistically significantly less effective than gel containing calcipotriol + betamethasone dipropionate (P
Another randomized, investigator-blinded clinical trial in 312 patients with scalp psoriasis of at least moderate severity according to the IGA evaluated the use of a gel containing calcipotriol + betamethasone dipropionate once daily compared with the use of a scalp solution containing calcipotriol + betamethasone dipropionate twice daily for up to 8 weeks. The results for the primary endpoint of response to therapy (absence or very mild disease severity according to the IGA after 8 weeks) demonstrated that the gel containing calcipotriol + betamethasone dipropionate was statistically significantly more effective than the scalp solution containing calcipotriol + betamethasone dipropionate.
| % of patients with no or very mild disease severity | Gel containing calcipotriol + betamethasone dipropionate (n=207) | Scalp solution containing calcipotriol + betamethasone dipropionate (n=105) |
| Week 8 | 68.6% | 31.4 %1 |
1Statistically significantly less effective than gel containing calcipotriol + betamethasone dipropionate (P
A randomized, double-blind, long-term clinical trial in 873 patients with at least moderate scalp psoriasis (according to IGA) evaluated the use of a gel containing calcipotriol + betamethasone dipropionate compared with calcipotriol in a gel vehicle. Both drugs were applied once daily, with breaks as needed, for up to 52 weeks. Adverse reactions possibly related to long-term use of corticosteroids on the scalp were identified by an independent, blinded panel of dermatologists. There was no difference in the percentage of patients who developed these adverse reactions between the treatment groups (2.6% in the calcipotriol + betamethasone dipropionate gel group and 3.0% in the calcipotriol group; P = 0.73). No cases of skin atrophy were reported.
Pediatric patients
The effect on calcium metabolism was evaluated in two open-label, uncontrolled, 8-week studies in 109 adolescents aged 12-17 years with scalp psoriasis who received up to 69 g of calcipotriol + betamethasone dipropionate gel per week. No cases of hypercalcemia and no clinically significant changes in urinary calcium levels were reported. The adrenal response to ACTH stimulation was evaluated in 30 patients; one patient had a reversible decrease in cortisol secretion in response to ACTH stimulation after 4 weeks of treatment, which was mild and did not cause clinical symptoms.
Pharmacokinetics
Systemic exposure to calcipotriol and betamethasone dipropionate following topical application of a gel containing calcipotriol and betamethasone is comparable to that of a calcipotriol and betamethasone ointment in rats and minipigs. Clinical studies using radiolabeled ointment indicate that systemic absorption of calcipotriol and betamethasone is less than 1% of the applied dose (2.5 g) when applied to intact skin (625 cm2) for 12 hours. Application to psoriatic plaques and under occlusive dressings may increase the absorption of topical corticosteroids. Absorption through damaged skin is approximately 24%.
Betamethasone is metabolized primarily in the liver, but also in the kidneys to form glucuronides and sulfoesters. The main route of excretion for calcipotriol is via the faeces (in rats and minipigs) and for betamethasone dipropionate is via the urine (in rats and mice). In rats, tissue distribution studies of radiolabelled calcipotriol and betamethasone dipropionate showed that the kidneys and liver had the highest levels of radioactivity.
Calcipotriol and betamethasone dipropionate levels were below the lower limit of quantification in all blood samples from 34 patients treated for 4 or 8 weeks with either a gel containing calcipotriol + betamethasone dipropionate or an ointment containing calcipotriol + betamethasone dipropionate for extensive psoriasis on both the body and the scalp. One metabolite of calcipotriol and one metabolite of betamethasone dipropionate were quantifiable in some patients.
Indication
Topical treatment of scalp psoriasis. Topical treatment of mild to moderate plaque psoriasis vulgaris, other than scalp psoriasis, in adults.
Contraindication
Hypersensitivity to the active substances or to any of the excipients of the medicinal product listed in the "Composition" section.
The use of the drug Psotriol®, gel, is contraindicated in patients with psoriatic erythroderma, exfoliative and pustular psoriasis.
Due to the content of calcipotriol, Psotriol® gel is contraindicated in patients with known disorders of calcium metabolism (see section "Special instructions").
Due to the content of the corticosteroid Psotriol®, gel is contraindicated in the following diseases: skin lesions of viral etiology (e.g. herpes or chickenpox), fungal or bacterial skin infections, parasitic infections, skin manifestations of tuberculosis, perioral dermatitis, skin atrophy, atrophic skin stripes, increased vascular fragility, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wounds (see the section "Peculiarities of use").
Interaction with other medicinal products and other types of interactions
No drug interaction studies have been conducted with Psotriol®, gel.
Application features
Impact on the endocrine system
Psotriol®, gel, contains a potent Group III steroid. Concomitant treatment with other steroids should be avoided. Adverse reactions that develop in connection with treatment with systemic corticosteroids, such as suppression of adrenal function or effects on the metabolic control of diabetes mellitus, may also develop during treatment with topical corticosteroids, due to systemic absorption. Application of the drug under an occlusive dressing should be avoided, as this increases the systemic absorption of corticosteroids.
Application to large areas of damaged skin or mucous membranes or in skin folds should be avoided as this increases systemic absorption of corticosteroids (see section "Adverse reactions").
In a study of patients with both widespread psoriasis of the scalp and widespread psoriasis of other parts of the body who used a combination of a gel containing calcipotriol + betamethasone dipropionate at high doses (application of the drug to the skin of the scalp covered with hair) and an ointment containing calcipotriol + betamethasone dipropionate at high doses (application of the drug to other parts of the body), a marginal decrease in cortisol excretion in response to ACTH stimulation was recorded in 5 of 32 patients after 4 weeks of treatment (see section "Pharmacodynamics").
Vision impairment
Visual impairment may occur with systemic or topical corticosteroids. If a patient presents with symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist to determine possible causes, which may include cataracts, glaucoma, or a rare condition called central serous chorioretinopathy (CSCR), which has been reported following the use of systemic and topical corticosteroids.
Effect on calcium metabolism
Due to the content of calcipotriol, hypercalcemia may develop if the maximum daily dose (15 g) is exceeded. Serum calcium levels return to normal upon discontinuation of treatment. The risk of hypercalcemia is minimal if the recommendations for calcipotriol are followed. The drug should not be applied to skin areas exceeding 30% of the body surface (see section "Method of administration and dosage").
Local adverse reactions
Psotriol® gel contains a potent Group III steroid. Concomitant treatment with other steroids at the same site should be avoided.
The skin of the face and genitals is very sensitive to corticosteroids. The drug should not be used on these areas. The patient should be instructed in the correct use of the drug to prevent application or accidental contact with the face, mouth or eyes. Hands should be washed after each application of the drug to prevent accidental contact with these areas of the body.
If the lesions are complicated by secondary infection, antibacterial therapy should be administered. However, if the infection worsens, corticosteroid treatment should be discontinued (see Contraindications).
Therapy withdrawal
When treating psoriasis with topical corticosteroids, there is a risk of generalized pustular psoriasis or rebound effects upon drug withdrawal. Therefore, continued medical supervision is necessary after discontinuation of the drug.
Long-term use of the drug
The risk of local or systemic adverse reactions increases with long-term use of corticosteroids. The drug should be discontinued if adverse reactions associated with long-term use of corticosteroids occur (see section "Adverse reactions").
Application not evaluated
There is no experience with the use of the drug Psotriol®, gel, in patients with guttate psoriasis.
Concomitant treatment and UV irradiation
Calcipotriol + betamethasone dipropionate ointment has been used in combination with calcipotriol + betamethasone dipropionate gel for the treatment of psoriatic lesions on the scalp, but experience with the combination of calcipotriol + betamethasone dipropionate with other antipsoriatic medicinal products for topical application to the same area, with other antipsoriatic medicinal products used systemically, or with phototherapy is limited.
Patients are advised to limit or avoid excessive exposure to natural or artificial light while using Psotriol® Gel. Topical calcipotriol should not be used with UVA unless the physician and patient consider that the expected benefit outweighs the potential risk.
Adverse reactions to excipients
Psotriol®, gel, contains butylhydroxytoluene as an excipient, which may cause local skin reactions (e.g. contact dermatitis) or irritation of the eyes and mucous membranes.
Use during pregnancy or breastfeeding
Pregnancy
There are no adequate data on the use of Psotriol®, gel in pregnant women. Animal studies with glucocorticosteroids have shown reproductive toxicity, but a number of epidemiological studies (less than 300 pregnancy outcomes) have not revealed any congenital anomalies in infants born to mothers exposed to corticosteroids during pregnancy. The potential risk to humans has not yet been determined. Therefore, Psotriol®, gel should be used during pregnancy only if the expected benefit justifies the potential risk.
Breastfeeding period
Betamethasone passes into breast milk, but adverse reactions in the infant are unlikely when the drug is used in therapeutic doses. There are no clinical data on the excretion of calcipotriol into breast milk. Psotriol® gel should be prescribed to women during breastfeeding with caution. Patients should not apply Psotriol® gel to the mammary glands during breastfeeding.
Fertility
Studies in rats with oral administration of calcipotriol or betamethasone dipropionate did not reveal any reduction in male or female fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Psotriol®, gel, has no or negligible influence on the ability to drive or use machines.
Method of administration and doses
Doses
Psotriol®, gel, should be applied to the affected areas of the skin once a day.
The recommended treatment period is 4 weeks for scalp areas and 8 weeks for other areas of the body. If after 4 weeks it is necessary to continue or restart the use of the medicinal product, this should be done after consultation with a doctor and under regular medical supervision.
When using medicinal products containing calcipotriol, the maximum daily dose should not exceed 15 g. The area of application of medicinal products containing calcipotriol should not exceed 30% of the body surface (see section "Special instructions").
When applied to the scalp
Psotriol® gel can be applied to all affected areas of the scalp. Usually, 1 to 4 g per day is sufficient to treat the scalp (4 g corresponds to one teaspoon).
Method of administration and doses
Psotriol®, gel, should not be applied directly to the face or eyes. For optimal results, it is not recommended to shower or bathe or wash your hair immediately after applying the gel to the scalp. Psotriol®, gel, should be left on the skin overnight or during the day.
Shake the bottle before use and apply Psotriol® gel to the affected area. Wash your hands after using the gel.
Special patient groups
Patients with renal and hepatic impairment
The safety and efficacy of Psotriol® gel in patients with severe renal impairment or severe liver disease have not been established.
Children
The safety and efficacy of Psotriol® gel in children under 18 years of age have not been established. The data available to date on the use of the medicinal product in children aged 12 to 17 years are described in the sections “Pharmacodynamics” and “Adverse reactions”, but no dosage recommendations can be made.
Overdose
The use of the drug in doses exceeding the recommended dose may cause an increase in serum calcium levels, which resolves upon discontinuation of treatment. Symptoms of hypercalcemia include polyuria, constipation, muscle weakness, confusion and coma.
Excessive prolonged use of topical corticosteroids may suppress pituitary-adrenal function with the development of secondary adrenal insufficiency, which is usually reversible. In such cases, symptomatic treatment is indicated.
In case of chronic toxicity, corticosteroids should be gradually withdrawn.
It has been reported that, as a result of incorrect use of the medicinal product, one patient with widespread erythrodermic psoriasis, who was treated with 240 g of calcipotriol + betamethasone dipropionate ointment weekly (corresponding to a daily dose of approximately 34 g) for 5 months (the maximum recommended dose is 15 g per day), developed Cushing's syndrome during treatment and subsequently pustular psoriasis after abrupt discontinuation of treatment.
Adverse reactions
The assessment of the frequency of adverse reactions is based on a generalized analysis of clinical trial data, including post-marketing safety studies and spontaneous reports.
The most commonly reported adverse reaction during treatment is pruritus.
Adverse reactions are listed according to MedDRA system organ class (SOC) and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
| Infectious and parasitic diseases |
| Uncommon (≥1/1000 to | Skin reactions*, folliculitis |
| On the part of the immune system |
| Rare (≥1/10,000 to | Increased sensitivity |
| From the organs of vision |
| Uncommon (≥1/1000 to | Eye irritation |
| Frequency not known (cannot be estimated from the available data) | Blurred vision***** |
| Skin and subcutaneous tissue disorders |
| Common (≥1/100 to | Itch |
| Uncommon (≥1/1000 to | Psoriasis flare-ups Dermatitis Erythema Rash** Acne Burning sensation of the skin Skin irritation Dry skin |
| Rare (≥1/10,000 to | Stretch marks on the skin Peeling skin |
| Frequency not known (cannot be estimated from the available data) | Hair color changes*** |
| General disorders and administration site conditions |
| Uncommon (≥1/1000 to | Pain at the site of application of the drug **** |
| Rare (≥1/10,000 to | The ricochet effect |
*Skin infections, including bacterial, fungal, and viral skin infections, have been reported.
**Various types of rashes have been reported, such as exfoliative rash, papular rash, and pustular rash.
*** Temporary hair discoloration at the site of application on the scalp to a yellowish color on light or gray hair has been reported.
**** Burning sensation at the site of application of the drug is included in application site pain.
*****See section "Application features"
The adverse reactions listed below are considered to be related to the pharmacological classes of calcipotriol and betamethasone, respectively.
Calcipotriol
Adverse reactions include application site reactions, pruritus, skin irritation, burning and stinging sensation, dry skin, erythema, rash, dermatitis, eczema, exacerbation of psoriasis, photosensitivity and hypersensitivity reactions which may include in very rare cases angioedema and facial oedema.
Very rarely, systemic reactions may occur after topical application, leading to hypercalcemia or hypercalciuria (see section "Special warnings and precautions for use").
Betamethasone (as dipropionate)
After topical application, reactions at the application site may develop, especially during prolonged use, including the development of skin atrophy, telangiectasias, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation and colloid degeneration of the skin.
Systemic reactions associated with topical corticosteroids are rare in adults. However, they may be severe. Adrenal suppression, cataracts, infections, effects on metabolic control of diabetes mellitus, and increased intraocular pressure may occur, especially after long-term use of the drug. Systemic reactions are more likely to occur with the use of occlusive dressings (plastic, skin folds), when the drug is applied to large areas, and during long-term treatment (see section "Special instructions").
Pediatric patients
No new adverse events or new adverse reactions were identified in 109 adolescents aged 12-17 years treated with this medicinal product containing calcipotriol + betamethasone dipropionate for 8 weeks for scalp psoriasis. However, the size of this study does not allow for definitive conclusions to be drawn regarding the safety profile of calcipotriol + betamethasone dipropionate gel when used in adolescents compared to adults (see section 5.1).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions during post-marketing surveillance is very important. This allows monitoring of the benefit-risk balance of medicinal products. Healthcare professionals should report any suspected adverse reactions.
Expiration date
36 months. After first opening – 6 months.
Storage conditions
Store at a temperature not exceeding 30. Keep out of the reach of children.
Packaging
30 g in a bottle with a dropper and a screw cap; 1 bottle in a pack.
Vacation category
According to the recipe.
Producer
mibe GmbH Arcnaymittel.
Location of the manufacturer and its address of place of business.
Münchenerstrasse 15, Brena, Saxony-Anhalt, 06796, Germany.
