Prescription Drug Information: Taclonex
TACLONEX — calcipotriene hydrate and betamethasone dipropionate ointment
Physicians Total Care, Inc.
1 INDICATIONS AND USAGE
1.1 Indication
Taclonex® (calcipotriene and betamethasone dipropionate) Ointment is indicated for the topical treatment of psoriasis vulgaris in adults 18 years of age and older for up to 4 weeks.
1.2 Limitations of Use
- Taclonex® Ointment should not be applied to the face, axillae or groin.
- Taclonex® Ointment should not be used if there is skin atrophy at the treatment site.
2 DOSAGE AND ADMINISTRATION
2.1 Usual Dosage and Administration
Apply an adequate layer of Taclonex® Ointment to the affected area(s) once daily for up to 4 weeks. The maximum weekly dose should not exceed 100 g. Treatment of more than 30% body surface area is not recommended. Taclonex® Ointment should be rubbed in gently and completely. Patients should wash their hands after applying Taclonex® Ointment.
Taclonex® Ointment is not for oral, ophthalmic, or intravaginal use.
3 DOSAGE FORMS AND STRENGTHS
Ointment. Soft white (off white to yellow) paraffin based ointment with calcipotriene 0.005% and betamethasone dipropionate 0.064%.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Effects on Calcium Metabolism
Hypercalcemia and hypercalciuria have been reported with use of Taclonex®. If hypercalcemia or hypercalciuria develop, treatment should be discontinued until parameters of calcium metabolism have normalized. In the trials that included assessment of the effects of Taclonex® Ointment on calcium metabolism, such testing was done after 4 weeks of treatment. The effects of Taclonex® Ointment on calcium metabolism following treatment durations of longer than 4 weeks have not been evaluated.
5.2 Effects on Endocrine System
Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid.
HPA axis suppression has been observed with Taclonex® Ointment [see Clinical Pharmacology (12.2) ]. The effects of Taclonex® Ointment on the HPA axis following treatment durations of longer than 4 weeks have not been adequately studied.
In a study of 32 subjects concomitantly treated with Taclonex® Scalp Topical Suspension on the scalp and Taclonex® Ointment on the body, adrenal suppression was identified in 5 of 32 subjects (15.6%) after 4 weeks of treatment [see CLINICAL PHARMACOLOGY Pharmacodynamics (12.2) ].
Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure.
An ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.
Cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.
Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.
Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids [see Use in Specific Populations (8.4) ].
5.3 Local Adverse Reactions with Topical Corticosteroids
Local adverse reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible.
5.4 Allergic Contact Dermatitis with Topical Corticosteroids
Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.
5.5 Allergic Contact Dermatitis with Topical Calcipotriene
Allergic contact dermatitis has been observed with use of topical calcipotriene. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.
5.6 Concomitant Skin Infections
Concomitant skin infections should be treated with an appropriate antimicrobial agent. If the infection persists, Taclonex® Ointment should be discontinued until the infection has been adequately treated.
5.7 Skin Irritation
If irritation develops, treatment with Taclonex® Ointment should be discontinued and appropriate therapy instituted.
5.8 Unevaluated Uses
The safety and efficacy of Taclonex® Ointment in patients with known or suspected disorders of calcium metabolism have not been evaluated.
The safety and efficacy of Taclonex® Ointment in patients with erythrodermic, exfoliative, or pustular psoriasis have not been evaluated.
The safety and efficacy of Taclonex® Ointment in patients with severe renal insufficiency or severe hepatic disorders have not been evaluated.
5.9 Ultraviolet Light Exposure
Patients who apply Taclonex® Ointment to exposed skin should avoid excessive exposure to either natural or artificial sunlight, including tanning booths, sun lamps, etc. Physicians may wish to limit or avoid use of phototherapy in patients who use Taclonex® Ointment.
6 ADVERSE REACTIONS
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
6.1 Clinical Study Experience
The data described below reflect exposure to Taclonex® Ointment in 2448 subjects, including 1992 exposed for 4 weeks, and 289 exposed for 8 weeks. Taclonex® Ointment was studied primarily in placebo- and active-controlled trials (N = 1176, and N = 1272, respectively). The population was 15-97 years old, 61% males and 39% females, mostly white (97%) and had a baseline disease severity ranging from mild to very severe. Most subjects received once daily application, and the median weekly dose was 24.5 g.
The percentage of subjects reporting at least one adverse event was 27.1% in the Taclonex® Ointment group, 33.0% in the calcipotriene group, 28.3% in the betamethasone group, and 33.4% in the vehicle group.
Table 1
Adverse Events Reported by ≥1% of Subjects by Preferred Term
| Taclonex® OintmentN = 2448 | CalcipotrieneN = 3197 | Betamethasone dipropionateN = 1164 | VehicleN = 470 | |
| Any Adverse Event | 663 (27.1) | 1055 (33.0) | 329 (28.3) | 157 (33.4) |
| Preferred Term | # of subjects (%) | |||
| Pruritis | 75 (3.1) | 183 (5.7) | 38 (3.3) | 43 (9.1) |
| Headache | 69 (2.8) | 75 (2.3) | 44 (3.8) | 12 (2.6) |
| Nasopharyngitis | 56 (2.3) | 77 (2.4) | 34 (2.9) | 9 (1.9) |
| Psoriasis | 30 (1.2) | 47 (1.5) | 14 (1.2) | 5 (1.1) |
| Rash scaly | 30 (1.2) | 40 (1.3) | 0 (0.0) | 1 (0.2) |
| Influenza | 23 (0.9) | 34 (1.1) | 14 (1.2) | 6 (1.3) |
| Upper respiratory tract infection | 20 (0.8) | 19 (0.6) | 12 (1.0) | 3 (0.6) |
| Erythema | 15 (0.6) | 54 (1.7) | 3 (0.3) | 5 (1.1) |
| Application site pruritus | 13 (0.5) | 24 (0.8) | 10 (0.9) | 6 (1.3) |
| Skin irritation | 11 (0.4) | 60 (1.9) | 8 (0.7) | 5 (1.1) |
| Pain | 7 (0.3) | 12 (0.4) | 3 (0.3) | 5 (1.1) |
| Burning sensation | 6 (0.2) | 30 (0.9) | 3 (0.3) | 6 (1.3) |
A lesional/perilesional adverse event was generally defined as an adverse event located ≤ 2 cm from the lesional border.
Table 2
Lesional/Perilesional Adverse Events Reported by ≥1% of Subjects
| Taclonex® OintmentN = 2448 | CalcipotrieneN = 3197 | Betamethasone dipropionateN = 1164 | VehicleN = 470 | |
| Any Adverse Event | 213 (8.7) | 419 (13.1) | 85 (7.3) | 76 (16.2) |
| Preferred Term | # of subjects (%) | |||
| Pruritis | 69 (2.8) | 170 (5.3) | 31 (2.7) | 41 (8.7) |
| Rash scaly | 29 (1.2) | 38 (1.2) | 0 (0.0) | 0 (0.0) |
| Application site pruritus | 12 (0.5) | 24 (0.8) | 10 (0.9) | 6 (1.3) |
| Erythema | 9 (0.4) | 36 (1.1) | 2 (0.2) | 4 (0.9) |
| Skin irritation | 9 (0.4) | 51 (1.6) | 8 (0.7) | 5 (1.1) |
| Burning sensation | 6 (0.2) | 25 (0.8) | 3 (0.3) | 5 (1.1) |
For subjects who reported lesional/perilesional adverse events, the median time to onset was 7 days for Taclonex® Ointment, 7 days for calcipotriene, 5 days for betamethasone dipropionate, and 3 days for vehicle.
Other less common reactions (less than 1% but more than 0.1%) were, in decreasing order of incidence, folliculitis, rash papular, rash pustular, and skin hypopigmentation. Skin atrophy, telangiectasia and skin hyperpigmentation were reported infrequently (0.1%).
In a separate study, subjects (N = 207) with at least moderate disease severity were given Taclonex® Ointment intermittently on an “as needed” basis for up to 52 weeks. The median use was 15.4 g per week. The effects of Taclonex® Ointment on calcium metabolism were not studied and the effects on the HPA axis were not adequately studied. The following adverse reactions were reported by 1% or more of the subjects: pruritus (7.2%), psoriasis (3.4%), skin atrophy (1.9%), folliculitis (1.4%), burning sensation (1.4%), skin depigmentation (1.4%), ecchymosis (1.0%), erythema (1.0%) and hand dermatitis (1.0%). One case of serious flare-up of psoriasis was reported.
6.2 Post-marketing Experience
The following adverse reactions associated with the use of Taclonex® Ointment have been identified post-approval: pustular psoriasis and rebound effect.
Because these 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.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic Effects: Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Pregnant women were excluded from the clinical studies conducted with Taclonex® Ointment. Taclonex® Ointment should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus. Animal reproduction studies have not been conducted with Taclonex® Ointment. Taclonex® Ointment contains calcipotriene that has been shown to be fetotoxic and betamethasone dipropionate that has been shown to be teratogenic in animals when given systemically.
Teratogenicity studies with calcipotriene were performed by the oral route in rats and rabbits. In rabbits, increased maternal and fetal toxicity were noted at a dosage of 12 mcg/kg/day (144 mcg/m2 /day); a dosage of 36 mcg/kg/day (432 mcg/m2 /day) resulted in a significant increase in the incidence of incomplete ossification of the pubic bones and forelimb phalanges of fetuses. In a rat study, a dosage of 54 mcg/kg/day (324 mcg/m2 /day) resulted in a significantly increased incidence of skeletal abnormalities (enlarged fontanelles and extra ribs). The enlarged fontanelles are most likely due to the effect of calcipotriene upon calcium metabolism. The estimated maternal and fetal no-adverse effect levels (NOAEL) in the rat (108 mcg/m2 /day) and rabbit (48 mcg/m2 /day) derived from oral studies are lower than the estimated maximum topical dose of calcipotriene in man (460 mcg/m2 /day).
Betamethasone dipropionate has been shown to be teratogenic in mice and rabbits when given by the subcutaneous route at doses of 156 mcg/kg/day (468 mcg/m2 /day) and 2.5 mcg/kg/day (30 mcg/m2 /day), respectively. Those dose levels are lower than the estimated maximum topical dose in man (about 5950 mcg/m2 /day). The abnormalities observed included umbilical hernia, exencephaly and cleft palate.
Two oral peri- and post-natal development studies were conducted with rats:
Pregnant Wistar rats were dosed daily with calcipotriene at exposures of 0, 6, 18 or 54 mcg/kg/day from gestation day 15 through day 20 postpartum. No remarkable effects were observed on any parameter, including survival, behavior, body weight, litter parameters, or the ability to nurse or rear pups.
Betamethasone dipropionate was evaluated for effects when orally administered to pregnant rats from gestation day 6 through day 20 postpartum at dosages of 0, 100, 300, and 1000 mcg/kg/day. Mean maternal body weight was significantly reduced on gestation day 20 in animals dosed at 300 and 1000 mcg/kg/day. The mean duration of gestation was slightly, but statistically significantly, increased at 100, 300, and 1000 mcg/kg/day. The mean percentage of pups that survived to day 4 was reduced in relation to dosage. On lactation day 5, the percentage of pups with a reflex to right themselves when placed on their back was significantly reduced at 1000 mcg/kg/day. No effects on the ability of pups to learn were observed, and the ability of the offspring of treated rats to reproduce was not affected.
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