Silkis - Product Information
|Class:||Antipsoriatics, Topical non-steroidal anti-inflammatories|
|Form:||Cream, gel, liniment or balm, lotion, ointment, etc|
|Ingredients:||Calcitriol, vitamin E (dl-α tocopherol) added as an antioxidant, mineral oil, and white petrolatum|
Summary Product Information
|Route of Administration||Dosage Form / Strength||Clinically Relevant Nonmedicinal Ingredients|
|Topical||Ointment 3 μg/g||None
For a complete listing see Dosage Forms,
Composition and Packaging section.
Indications and Clinical Use
Silkis (calcitriol) ointment 3 µg/g is indicated for:
- Topical treatment of mild to moderate plaque type psoriasis (psoriasis vulgaris) with up to 35% body surface area involvement.
Geriatrics (> 65 years of age)
Clinical studies of Silkis ointment did not include sufficient numbers of subjects 65 years and older to determine whether they respond differently from younger subjects. See Warnings and Precautions.
Pediatrics (< 18 years of age):
Silkis is not recommended for pediatric use. Safety and effectiveness in pediatric patients have not been established.
- Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.
- NOT FOR OPHTHALMIC or INTERNAL USE.
- Patients with hypercalcemia and patients known to suffer from abnormal calcium metabolism.
- Patients on systemic treatment of calcium homeostasis.
- Patients with severe renal impairment or end-stage renal disease.
Warnings and Precautions
Serum calcium levels should be monitored at regular intervals if risk factors for hypercalcemia are present. If the serum calcium level becomes elevated, calcitriol therapy should be discontinued and the serum calcium level monitored in these patients until it returns to normal.
Due to the potential effect of Vitamin D and its metabolites on calcium metabolism, substances that may increase the absorption of calcitriol must not be added to the ointment or used concomitantly with the ointment.
Silkis ointment must not be covered with an occlusive dressing.
Silkis is not recommended for severe, extensive psoriasis (i.e., involvement of more than 35% of the body surface).
Silkis should not be applied to the eyes, lips or facial skin.
Silkis is not approved for use in other clinical forms of psoriasis.
No more than 30 g of Silkis ointment should be used per day.
Carcinogenesis and Mutagenesis
Animal data suggest that the vehicle of Silkis ointment may enhance the ability of ultraviolet radiation (UVR) to induce skin tumours (see Toxicology - Carcinogenicity). Patients who apply Silkis ointment to exposed skin should avoid excessive exposure of the treated areas to either natural or artificial sunlight, including tanning booths and sun lamps. Physicians may wish to limit or avoid using phototherapy in patients who use Silkis ointment.
Endocrine and Metabolism
If abnormal serum calcium levels are observed, treatment with calcitriol should be discontinued.
Silkis is not recommended in patients with reduced liver function.
Silkis is not recommended in patients with mild to moderate renal impairment.
Hands should be washed after applying Silkis in order to avoid unintentional application to other areas. In case of severe irritation or a contact allergic reaction, treatment with Silkis should be discontinued.
There are no adequate and well-controlled studies in pregnant women, although studies in experimental animals have not shown teratogenic effects. Silkis should be used during pregnancy only if the anticipated benefit clearly outweighs the potential risk (see Toxicology - Reproduction).
It is not known whether calcitriol is excreted in human milk. Silkis has been found in the milk of lactating rats. Calcitriol should be used by nursing women only if the anticipated benefit clearly outweighs the potential risk (see Toxicology – Reproduction).
Geriatrics (> 65 years of age)
Of the total number of subjects in clinical studies of Silkis, 14% were 65 and over. The incidence of drug-related adverse events, serious adverse events, and adverse events leading to discontinuation were higher in subjects 65 or older than in subjects 18 to < 65. In general, use in elderly patients should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Pediatrics (< 18 years of age)
There are insufficient data in patients under 18 years of age to determine the safety and efficacy in this population. Silkis is not recommended in pediatric patients.
Monitoring and Laboratory Tests
Serum calcium levels should be monitored at regular intervals if risk factors for hypercalcemia are present. If serum calcium becomes elevated, treatment with calcitriol should be discontinued.
Adverse Drug Reaction Overview
The clinical trial adverse reaction data for Silkis is largely based on two 8-week randomized, vehicle-controlled trials as well as one long term (1 year) safety study. These data provide information on twice daily exposure in 743 patients, including 239 exposed for 6 months and 116 exposed for at least one year. The most common adverse reactions experienced were laboratory test abnormality, skin discomfort, pruritus, and psoriasis.
Clinical Trial Adverse Drug Reactions
Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
Silkis was studied in two vehicle-controlled 8 week studies with 419 patients treated with Silkis twice daily. Drug-related adverse reactions that occurred in at least 1% of patients in the Silkis group are shown in the following table:
|Calcitriol ointment 3 μg/g
|Calcitriol vehicle ointment
|Total number of AEs||58||71|
|Total number of subjects with AEs||36 (8.6%)||45 (10.7%)|
|SKIN AND APPENDAGES|
|Discomfort skin||11 (2.6%)||9 (2.1%)|
|Pruritus||6 (1.4%)||4 (1%)|
|LAB TEST ABNORMAL|
|Lab test abnormality||14 (3.3%)||15 (3.6%)|
In these two studies, among subjects having laboratory monitoring, hypercalcemia (albumin-adjusted calcium above the upper limit of normal) at any post-baseline point during the 8 week trials, was observed in 24% (18/74) of calcitriol-exposed subjects compared to 16% (13/79) of vehicle-exposed subjects. No subject had an albumin-adjusted calcium result over the alert level (10% above the upper limit of the normal range) at any time-point throughout the study. Hypercalcemia was not reported as an adverse event during either study.
A one -year multi-center, open -label, non-comparative study enrolled 324 patients with psoriasis. Silkis was applied twice daily for up to 52 weeks. The most common adverse events were laboratory test abnormality (8%), urine test abnormality (4%), psoriasis (4%), flu syndrome (4%), hypercalciuria (3%), pruritus (3%) and skin infection (3%). There were 10 cases (3%) of hypercalcemia (defined as an albumin-adjusted serum total calcium concentration above the upper limit of the reference range (2.15 to 2.55 mmol/L). With one exception (2.72 mmol/L), all other albumin-adjusted serum total calcium concentrations were less than 5% above the upper limit of normal. There were 3 subjects with reported kidney stones.
Less Common Clinical Trial Adverse Drug Reactions (<1%)
Skin and Appendages psoriasis (0.2%)
Post-Market Adverse Drug Reactions
Because post-market adverse drug reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following post-market adverse reactions have been reported with the use of Silkis ointment: acute blistering dermatitis, erythema, pruritus, skin burning sensation, and skin discomfort. Two serious, unexpected related reports have been received which describe skin atrophy (1) and blisters over the body, burning sensation and extensive flare-up of weepy eczema (2).
Silkis (calcitriol) ointment 3 µg/g must be used with caution in patients receiving medications known to increase serum calcium levels, such as thiazide diuretics, or medications with pharmacological effects impacted by a change in calcium levels, such as digoxin. Caution must also be exercised in patients receiving calcium supplements or high doses of vitamin D.
Silkis has a slight irritant potential, and therefore it is possible that concomitant use of peeling agents, astringents, or irritant products may produce an additive irritant effect.
Interactions with food have not been established.
Interactions with herbal products have not been established.
Interactions with laboratory tests have not been established.
Dosage And Administration
- Silkis is for TOPICAL USE ONLY and not for oral, ophthalmic or intravaginal use.
- There is no clinical trial experience with the use of Silkis in children and there is limited experience with the use of Silkis in the elderly (see Warnings and Precautions).
- Silkis should be used in pregnant or nursing women only if the benefit versus risk is favourable (see Warnings and Precautions).
- Silkis is contraindicated in patients with severe renal impairment or end-stage renal disease.
- Silkis is not recommended in patients with mild to moderate renal impairment or in patients with liver dysfunction (see Warnings and Precautions).
Recommended Dose and Dosage Adjustment
Silkis (calcitriol) ointment 3 µg/g should be applied to the areas affected with psoriasis twice daily, morning and evening, after washing and gentle drying. No more than 30 g of Silkis ointment should be used daily. No more than 35% of the body can be treated.
No additional therapeutic benefit has been demonstrated with higher doses or more frequent application.
If a dose of Silkis is missed, it should be applied as soon as the patient remembers and further dosing resumed as usual.
The affected area should be washed and dried gently. The ointment should be applied and rubbed in gently until the medication is no longer visible. The treated area should not be bandaged or occluded in any way.
Hands should be washed thoroughly with soap and water after each application.
After satisfactory improvement has occurred, the drug should be discontinued. If recurrence takes place after discontinuation, the treatment may be reinstituted.
The accidental ingestion of Silkis (calcitriol) ointment 3 µg/g may produce symptoms that are consistent with vitamin D toxicity and hypercalcemia. The initial clinical signs (polyuria, polydypsia, dyspepsia) should be confirmed with a serum analysis of calcium levels prior to initiating treatment for hypercalcemia.
Topically applied calcitriol can be absorbed in sufficient amounts to produce systemic effects. If signs of hypercalcemia occur with the prescribed use of Silkis, treatment should be discontinued.
Action And Clinical Pharmacology
Mechanism of Action
Calcitriol (1 -25-dihydroxyvitamin D3) is the naturally occurring and biologically active metabolite of vitamin D3, primarily produced in the skin by exposure to the ultraviolet rays of the sun. Vitamin D3 must be metabolically activated in the liver and the kidney before it is fully active at target tissues as calcitriol.
Calcitriol primarily regulates systemic calcium and phosphate homeostasis by effects on the gastrointestinal tract, bone, and kidney. The mechanism of action of calcitriol in the treatment of psoriasis has not been established.
The systemic exposure of calcitriol ointment 3 µg/g was assessed in 23 patients with chronic plaque psoriasis over 21 days with a total of 30 g/day application to 35% body surface area. At Day 21, the geometric mean plasma concentration values of Cmax increased by 36% over baseline and the geometric mean value of AUC(0-12hr) increased by 44%. There was no correlation between the observed elevated calcitriol levels and the pharmacodynamic parameters of serum albumin adjusted calcium, serum phosphorus, urinary calcium and urinary phosphorus.
Considerable inter-subject variability in calcitriol permeation through the skin is observed.
Storage and Stability
Store at room temperature (15° - 30° C).
Dosage Forms, Composition And Packaging
Silkis (calcitriol) ointment 3 μg/g is available in collapsible aluminium tubes coated internally with an epoxy-phenolic resin and fitted with a white high density polyethylene or polypropylene screw cap. Tubes contain 5 g or 60 g of ointment.
Silkis is a white, translucent, ointment containing 3 μg/g (0.0003% w/w) of calcitriol. Other components of the ointment are vitamin E (dl-α tocopherol) added as an antioxidant, mineral oil, and white petrolatum.