Composition:
Utilisé dans le traitement:
Examiné médicalement par Militian Inessa Mesropovna, Pharmacie Dernière mise à jour le 04.04.2022
Attention! Information sur la page est réservée aux professionnels de la santé! Les informations sont collectées dans des sources ouvertes et peuvent contenir des erreurs significatives! Soyez prudent et revérifiez toutes les informations de cette page!
Top 20 des médicaments avec les mêmes ingrédients:
Top 20 des médicaments avec le même usage:
FABIOR Foam est contre-indiqué pendant la grossesse.
FABIOR Foam peut nuire au fœtus lorsqu'il est administré à une femme enceinte. Le tazarotène provoque des effets tératogènes et développementaux associés aux rétinoïdes après administration topique ou systémique chez le rat et le lapin.
Si ce médicament est utilisé pendant la grossesse ou si la patiente tombe enceinte pendant la prise de ce médicament, le traitement doit être interrompu et la patiente informée du danger potentiel pour le fœtus.
Les rétinoïdes peuvent nuire au fœtus lorsqu'ils sont administrés à une femme enceinte.
Chez le rat, 0,05% de tazarotène gel, administré topiquement pendant les jours de gestation, 6 à 17 à 0,25 mg / kg / jour (1,5 mg / m² / jour) ont entraîné une réduction du poids corporel fœtal et une réduction de l'ossification squelettique. Lapins dosés topiquement avec 0,25 mg / kg / jour (2,75 mg / m² de surface corporelle totale / jour), du gel de tazarotène pendant les jours de gestation 6 à 18 a été noté avec des incidences uniques de malformations rétinoïdes connues, y compris le spina bifida, l'hydrocéphalie et les anomalies cardiaques. Exposition quotidienne systémique (AUCde) à l'acide tazaroténique à des doses topiques de 0,25 mg / kg / jour de tazarotène dans une formulation de gel chez le rat et le lapin représentaient 0,62 et 6,7 fois, respectivement, l'ASC0-24h observée chez les patients psoriatiques traités avec 2 mg / cm² de gel de tazarotène 0,1% (extrapolé pour une application topique sur 20% de la surface corporelle) et 0,78 et 8,4 fois, respectivement, l'ASC0-24h maximum chez les patients souffrant d'acné traités avec 2 mg / cm² de gel de tazarotène 0,1% sur 15% (ciblé) surface corporelle.
Comme avec d'autres rétinoïdes, lorsque le tazarotène a été administré par voie orale à des animaux de laboratoire, des retards de développement ont été observés chez le rat, et des effets tératogènes et une perte post-implantation ont été observés chez le rat et le lapin à des valeurs d'AUCde qui étaient de 0,55 et 13,2 fois, respectivement, l'ASC0-24h observée chez les patients psoriatiques traités avec 2 mg / cm² de gel de tazarotène 0,1% (extrapolé pour une application topique sur 20% de la surface corporelle) et 0,68 et 16,4 fois, respectivement, l'ASC0-24h maximum chez les patients souffrant d'acné traités avec 2 mg / cm² de gel de tazarotène 0,1% sur 15% (ciblé) surface corporelle.
Dans une étude de l'effet du tazarotène oral sur la fertilité et le développement embryonnaire précoce chez le rat, diminution du nombre de sites d'implantation, diminution de la taille de la litière, diminution du nombre de fœtus vivants, et diminution du poids corporel fœtal, tous les effets de développement classiques des rétinoïdes, ont été observés lorsque des rats femelles ont été administrés 2 mg / kg / jour à partir de 15 jours avant l'accouplement jusqu'au jour de gestation 7. Une faible incidence de malformations liées aux rétinoïdes à cette dose aurait été liée au traitement. Cette dose a produit une AUCde qui était 1,7 fois l'ASC0-24h observée chez les patients psoriasiques traités avec 2 mg / cm² de gel de tazarotène 0,1% (extrapolé pour une application topique sur 20% de la surface corporelle) et 2,1 fois l'ASC0-24h maximale chez les patients souffrant d'acné traités avec 2 mg / cm² de gel de tazarotène 0,1% sur 15% (ciblé) surface corporelle.
L'EXPOSITION SYSTÉMIQUE À L'ACIDE TAZAROTÉNIQUE EST DÉPENDANTE SUR L'EXTENTION DE LA ZONE DE SURFACE CORPORELLE TRAITÉE. DANS LES PATIENTS TRAITÉ TOPIQUEMENT SUR LA ZONE DE SURFACE CORPOREL SUFFICACE, L'EXPOSITION POURRAIT ÊTRE DANS LA MÊME COMMANDE DE MAGNITUDE COMME DANS CES ANIMAUX TRAITÉS ORALEMENT. Bien qu'il puisse y avoir moins d'exposition SYSTÉMIQUE dans le TRAITEMENT DE L'ACNE DU VISAGE SEUL EN RAISON DE MOINS DE SURFACE POUR L'APPLICATION, TAZAROTENE EST UNE SUBSTANCE TERATOGÉNIQUE, ET IL N'EST PAS CONNU QUEL NIVEAU D'EXPOSITION EST OBLIGATOIRE POUR LA TERATOGÉNICITÉ EN HUMAINS (VOIR
La mousse de tazoskin est contre-indiquée pendant la grossesse.
La mousse de tazoskin peut nuire au fœtus lorsqu'elle est administrée à une femme enceinte. Le tazarotène provoque des effets tératogènes et développementaux associés aux rétinoïdes après administration topique ou systémique chez le rat et le lapin.
Si ce médicament est utilisé pendant la grossesse ou si la patiente tombe enceinte pendant la prise de ce médicament, le traitement doit être interrompu et la patiente informée du danger potentiel pour le fœtus.
Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Tazarotenic acid was highly bound to plasma proteins (greater than 99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones, and other polar metabolites which were eliminated through urinary and fecal pathways.
Systemic exposure following topical application of FABIOR Foam 0.1% was evaluated in one trial. Patients aged 15 years and older with moderate-to-severe acne applied approximately 3.7 grams of FABIOR Foam 0.1% (N = 13) to approximately 15% body surface area (face, upper chest, upper back, and shoulders) once daily for 22 days. On Day 22, the mean (±SD) tazarotenic acid Cmax was 0.43 (±0.19) ng/mL, the AUC0-24h - was 6.98 (±3.56) ng·h/mL, and the half-life was 21.7 (±15.7) hours. The median Tmax was 6 hours (range: 4.4 to 12 hours). The AUC0-24h for tazarotenic acid was approximately 50-fold higher compared with the parent compound tazarotene. The mean (±SD) half-life of tazarotene was 8.1 (±3.7) hours.
Accumulation was observed upon repeated once-daily dosing as the tazarotenic acid predose concentrations were measurable in the majority of subjects. Steady state was attained within 22 days of daily application. Once-daily dosing resulted in little to no accumulation of tazarotene as predose concentrations were mostly below the quantitation limit throughout the study.
Nursing Mothers
After single topical doses of 14C-tazarotene to the skin of lactating rats, radioactivity was detected in milk, suggesting that there would be transfer of drug-related material to the offspring via milk. It is not known whether this drug is excreted in human milk. Caution should be exercised when tazarotene is administered to a nursing woman.
Pediatric Use
The safety and efficacy of tazarotene have not been established in pediatric patients under the age of 12 years.
Geriatric Use
Of the total number of subjects in clinical studies of tazarotene gels, 0.05% and 0.1% for plaque psoriasis, 163 were over the age of 65. Subjects over 65 years of age experienced more adverse events and lower treatment success rates after 12 weeks of use of Tazoskin® (tazarotene gel) Gel compared with those 65 years of age and younger. Currently there is no other reliable clinical experience on the differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals can not be ruled out. Tazarotene gel for the treatment of acne has not been clinically evaluated in persons over the age of 65.
Overdosage & ContraindicationsOVERDOSE
Excessive topical use of Tazoskin® (tazarotene gel) Gel may lead to marked redness, peeling, or discomfort (see PRECAUTIONS: General).
Tazoskin® (tazarotene gel) Gels 0.05% and 0.1% are not for oral use. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of Vitamin A (hypervitaminosis A) or other retinoids. If oral ingestion occurs, the patient should be monitored, and appropriate supportive measures should be administered as necessary.
CONTRAINDICATIONS
Retinoids may cause fetal harm when administered to a pregnant woman.
In rats, tazarotene 0.05% gel, administered topically during gestation days 6 through 17 at 0.25 mg/kg/day (1.5 mg/m²/day) resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day (2.75 mg/m² total body surface area/day) tazarotene gel during gestation days 6 through 18 were noted with single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. Systemic daily-exposure (AUCde) to tazarotenic acid at topical doses of 0.25 mg/kg/day tazarotene in a gel formulation in rats and rabbits represented 0.62 and 6.7 times, respectively, the AUC0-24h observed in psoriatic patients treated with 2 mg/cm² of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 0.78 and 8.4 times, respectively, the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) body surface area.
As with other retinoids, when tazarotene was given orally to experimental animals, developmental delays were seen in rats, and teratogenic effects and post-implantation loss were observed in rats and rabbits at AUCde values that were 0.55 and 13.2 times, respectively, the AUC0-24h observed in psoriatic patients treated with 2 mg/cm² of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 0.68 and 16.4 times, respectively, the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) body surface area.
In a study of the effect of oral tazarotene on fertility and early embryonic development in rats, decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights, all classic developmental effects of retinoids, were observed when female rats were administered 2 mg/kg/day from 15 days before mating through gestation day 7. A low incidence of retinoid-related malformations at that dose was reported to be related to treatment. This dose produced an AUCde that was 1.7 times the AUC0-24h observed in psoriatic patients treated with 2 mg/cm² tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area) and 2.1 times the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) body surface area.
SYSTEMIC EXPOSURE TO TAZAROTENIC ACID IS DEPENDENT UPON THE EXTENT OF THE BODY SURFACE AREA TREATED. IN PATIENTS TREATED TOPICALLY OVER SUFFICIENT BODY SURFACE AREA, EXPOSURE COULD BE IN THE SAME ORDER OF MAGNITUDE AS IN THESE ORALLY TREATED ANIMALS. ALTHOUGH THERE MAY BE LESS SYSTEMIC EXPOSURE IN THE TREATMENT OF ACNE OF THE FACE ALONE DUE TO LESS SURFACE AREA FOR APPLICATION, TAZAROTENE IS A TERATOGENIC SUBSTANCE, AND IT IS NOT KNOWN WHAT LEVEL OF EXPOSURE IS REQUIRED FOR TERATOGENICITY IN HUMANS (SEE CLINICAL PHARMACOLOGY: Pharmacokinetics).
There were thirteen reported pregnancies in patients who participated in clinical trials for topical tazarotene. Nine of the patients were found to have been treated with topical tazarotene, and the other four had been treated with vehicle. One of the patients who was treated with tazarotene cream elected to terminate the pregnancy for non-medical reasons unrelated to treatment. The other eight pregnant women who were inadvertently exposed to topical tazarotene during clinical trials subsequently delivered apparently healthy babies. As the exact timing and extent of exposure in relation to the gestation times are not certain, the significance of these findings is unknown.
Tazoskin® (tazarotene gel) Gel is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued and the patient apprised of the potential hazard to the fetus. Women of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when Tazoskin® (tazarotene gel) Gel is used. The possibility that a woman of childbearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test having a sensitivity down to at least 50 mIU/mL for human chorionic gonadotropin (hCG) should be obtained within 2 weeks prior to Tazoskin® (tazarotene gel) Gel therapy, which should begin during a normal menstrual period (see also PRECAUTIONS: Pregnancy: Teratogenic Effects).
Tazoskin® (tazarotene gel) Gel is contraindicated in individuals who have shown hypersensitivity to any of its components.
Clinical PharmacologyCLINICAL PHARMACOLOGY
Tazarotene is a retinoid prodrug which is converted to its active form, the cognate carboxylic acid of tazarotene (AGN 190299), by rapid deesterification in animals and man. AGN 190299 (“tazarotenic acid”) binds to all three members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ but shows relative selectivity for RARβ, and RARγ and may modify gene expression. The clinical significance of these findings is unknown.
Psoriasis
The mechanism of tazarotene action in psoriasis is not defined. Topical tazarotene blocks induction of mouse epidermal ornithine decarboxylase (ODC) activity, which is associated with cell proliferation and hyperplasia. In cell culture and in vitro models of skin, tazarotene suppresses expression of MRP8, a marker of inflammation present in the epidermis of psoriasis patients at high levels. In human keratinocyte cultures, it inhibits cornified envelope formation, whose build-up is an element of the psoriatic scale. Tazarotene also induces the expression of a gene which may be a growth suppressor in human keratinocytes and which may inhibit epidermal hyperproliferation in treated plaques. However, the clinical significance of these findings is unknown.
Acne
The mechanism of tazarotene action in acne vulgaris is not defined. However, the basis of tazarotene's therapeutic effect in acne may be due to its anti-hyperproliferative, normalizing-of-differentiation and antiinflammatory effects. Tazarotene inhibited corneocyte accumulation in rhino mouse skin and cross-linked envelope formation in cultured human keratinocytes. The clinical significance of these findings is unknown.
Pharmacokinetics
Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Little parent compound could be detected in the plasma. Tazarotenic acid was highly bound to plasma proteins ( ≥ greater than 99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways. The half-life of tazarotenic acid was approximately 18 hours, following topical application of tazarotene to normal, acne or psoriatic skin.
The human in vivo studies described below were conducted with tazarotene gel applied topically at approximately 2 mg/cm² and left on the skin for 10 to 12 hours. Both the peak plasma concentration (Cmax) and area under the plasma concentration time curve (AUC) refer to the active metabolite only.
Two single, topical dose studies were conducted using 14C-tazarotene gel. Systemic absorption, as determined from radioactivity in the excreta, was less than 1% of the applied dose (without occlusion) in six psoriatic patients and approximately 5% of the applied dose (under occlusion) in six healthy subjects. One non-radiolabeled single-dose study comparing the 0.05% gel to the 0.1% gel in healthy subjects indicated that the Cmax and AUC were 40% higher for the 0.1% gel.
After 7 days of topical dosing with measured doses of tazarotene 0.1% gel on 20% of the total body surface without occlusion in 24 healthy subjects, the Cmax for tazarotenic acid was 0.72 RMG 0.58 ng/mL (mean RMG SD) occurring 9 hours after the last dose, and the AUC0-24hr for tazarotenic acid was 10.1 RMG 7.2 ng·hr/mL. Systemic absorption was 0.91 RMG 0.67% of the applied dose.
In a 14-day study in five psoriatic patients, measured doses of tazarotene 0.1% gel were applied daily by nursing staff to involved skin without occlusion (8 to 18% of total body surface area; mean RMG SD: 13 RMG 5%). The Cmax for tazarotenic acid was 12.0 RMG 7.6 ng/mL occurring 6 hours after the final dose, and the AUC0-24hr for tazarotenic acid was 105 RMG 55 ng·hr/mL. Systemic absorption was 14.8 RMG 7.6% of the applied dose. Extrapolation of these results to represent dosing on 20% of total body surface yielded estimates for tazarotenic acid with Cmax of 18.9 RMG 10.6 ng/mL and AUC0-24hr of 172 RMG 88 ng·hr/mL.
An in vitro percutaneous absorption study, using radiolabeled drug and freshly excised human skin or human cadaver skin, indicated that approximately 4 to 5% of the applied dose was in the stratum corneum (tazarotene: tazarotenic acid = 5:1) and 2 to 4% was in the viable epidermis-dermis layer (tazarotene:tazarotenic acid = 2:1) 24 hours after topical application of the gel.
Clinical Studies
Psoriasis
In two large vehicle-controlled clinical studies, tazarotene 0.05% and 0.1% gels applied once daily for 12 weeks were significantly more effective than vehicle in reducing the severity of the clinical signs of stable plaque psoriasis covering up to 20% of body surface area. In one of the studies, patients were followed up for an additional 12 weeks following cessation of therapy with Tazoskin® (tazarotene gel) Gel. Mean baseline scores and changes from baseline (reductions) after treatment in these two studies are shown in the following table:
Plaque Elevation, Scaling and Erythema in Two Controlled Clinical Trials for Psoriasis
Tazoskin® 0.05% Gel | Tazoskin® 0.1% Gel | Vehicle | Gel | ||||||||||
Trunk/Arm/Leg Lesions | Knee/Elbow Lesions | Trunk/Arm/Leg Lesions | Knee/Elbow Lesions | Trunk/Arm/Leg Lesions | Knee/Elbow Lesions | ||||||||
N=108 | N=111 | N=108 | N=111 | N=108 | N=112 | N=108 | N=112 | N=108 | N=113 | N=108 | N=113 | ||
Plaque | B* | 2.5 | 2.6 | 2.6 | 2.6 | 2.5 | 2.6 | 2.6 | 2.6 | 2.4 | 2.6 | 2.6 | 2.6 |
Elevation | C-12* | -1.4 | -1.3 | -1.3 | -1.1 | -1.4 | -1.4 | -1.5 | -1.3 | -0.8 | -0.7 | -0.7 | -0.6 |
C-24* | -1.2 | -1.1 | -1.1 | -1.0 | -0.9 | -0.7 | |||||||
Scaling | B* | 2.4 | 2.5 | 2.5 | 2.6 | 2.4 | 2.6 | 2.5 | 2.7 | 2.4 | 2.6 | 2.5 | 2.7 |
C-12* | -1.1 | -1.1 | -1.1 | -0.9 | -1.3 | -1.3 | -1.2 | -1.2 | -0.7 | -0.7 | -0.6 | -0.6 | |
C-24* | -0.9 | -0.8 | -1.0 | -0.8 | -0.8 | -0.7 | |||||||
Erythema | B* | 2.4 | 2.7 | 2.2 | 2.5 | 2.4 | 2.8 | 2.3 | 2.5 | 2.3 | 2.7 | 2.2 | 2.5 |
C-12* | -1.0 | -0.8 | -0.9 | -0.8 | -1.0 | -1.1 | -1.0 | -0.8 | -0.6 | -0.5 | -0.5 | -0.5 | |
C-24* | -1.1 | -0.7 | -0.9 | -0.8 | -0.7 | -0.6 | |||||||
Plaque elevation, scaling and erythema scored on a 0-4 scale with 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe. B*=Mean Baseline Severity: C-12*=Mean Change from Baseline at end of 12 weeks of therapy: C-24*=Mean Change from Baseline at week 24 (12 weeks after the end of therapy). |
Global improvement over baseline at the end of 12 weeks of treatment in these two studies is shown in the following table:
Tazoskin® 0.05% Gel | Tazoskin® 0.1% Gel | Vehicle Gel | ||||
N=81 | N-93 | N=79 | N=69 | N=84 | N=91 | |
100% improvement | 2 (2%) | 1 (1%) | 0 | 0 | 1 (1%) | 0 |
≥ 75% improvement | 23 (28%) | 17 (18%) | 30 (38%) | 17 (25%) | 10 (12%) | 9 (10%) |
≥ 50% improvement | 42 (52%) | 39 (42%) | 51 (65%) | 36 (52%) | 28 (33%) | 21 (23%) |
1-49% improvement | 21 (26%) | 32 (34%) | 18 (23%) | 23 (33%) | 27 (32%) | 32 (35%) |
No change or worse | 18 (22%) | 22 (24%) | 10 (13%) | 10 (14%) | 29 (35%) | 38 (42%) |
The 0.1% gel was more effective than the 0.05% gel, but the 0.05% gel was associated with less local irritation than the 0.1% gel (see ADVERSE REACTIONS section).
Acne
In two large vehicle-controlled studies, tazarotene 0.1% gel applied once daily was significantly more effective than vehicle in the treatment of facial acne vulgaris of mild to moderate severity. Percent reductions in lesion counts after treatment for 12 weeks in these two studies are shown in the following table:
Reduction in Lesion Counts after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Acne
Tazoskin® 0.1% Gel | Vehicle Gel | |||
N=150 | N=149 | N=148 | N=149 | |
Noninflammatory lesions | 55% | 43% | 35% | 27% |
Inflammatory lesions | 42% | 47% | 30% | 28% |
Total lesions | 52% | 45% | 33% | 27% |
Global improvement over baseline at the end of 12 weeks of treatment in these two studies is shown in the following table:
Tazoskin® 0.1% Gel | Vehicle Gel | |||
N=105 | N=117 | N=117 | N=110 | |
100% improvement | 1 (1%) | 0 | 0 | 0 |
≥ 75% improvement | 40(38%) | 21(18%) | 23(20%) | 11(10%) |
≥ 50% improvement | 71(68%) | 56(48%) | 47(40%) | 32(29%) |
1-49% improvement | 23(22%) | 49(42%) | 48(41%) | 46(42%) |
No change or worse | 11(10%) | 12(10%) | 22(19%) | 32(29%) |
Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Tazarotenic acid was highly bound to plasma proteins (greater than 99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones, and other polar metabolites which were eliminated through urinary and fecal pathways.
Systemic exposure following topical application of Tazoskin Foam 0.1% was evaluated in one trial. Patients aged 15 years and older with moderate-to-severe acne applied approximately 3.7 grams of Tazoskin Foam 0.1% (N = 13) to approximately 15% body surface area (face, upper chest, upper back, and shoulders) once daily for 22 days. On Day 22, the mean (±SD) tazarotenic acid Cmax was 0.43 (±0.19) ng/mL, the AUC0-24h - was 6.98 (±3.56) ng·h/mL, and the half-life was 21.7 (±15.7) hours. The median Tmax was 6 hours (range: 4.4 to 12 hours). The AUC0-24h for tazarotenic acid was approximately 50-fold higher compared with the parent compound tazarotene. The mean (±SD) half-life of tazarotene was 8.1 (±3.7) hours.
Accumulation was observed upon repeated once-daily dosing as the tazarotenic acid predose concentrations were measurable in the majority of subjects. Steady state was attained within 22 days of daily application. Once-daily dosing resulted in little to no accumulation of tazarotene as predose concentrations were mostly below the quantitation limit throughout the study.
However, we will provide data for each active ingredient