1. Home
  2. Labeler Index
  3. Lupin Pharmaceuticals, Inc.
  4. 68180-153
  5. Label Information: Desloratadine

FDA Label for Desloratadine

View Indications, Usage & Precautions

Table of Contents

    1. OTHER
    2. DESCRIPTION
    3. CLINICAL PHARMACOLOGY
    4. PHARMACOKINETICS
    5. INDICATIONS AND USAGE
    6. CONTRAINDICATIONS
    7. GENERAL
    8. INFORMATION FOR PATIENTS
    9. LABORATORY TESTS
    10. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
    11. PREGNANCY CATEGORY C.
    12. NURSING MOTHERS
    13. PEDIATRIC USE
    14. GERIATRIC USE
    15. ADVERSE REACTIONS
    16. OVERDOSAGE
    17. DOSAGE AND ADMINISTRATION
    18. HOW SUPPLIED
    19. 1 INDICATIONS AND USAGE
    20. 1.1 SEASONAL ALLERGIC RHINITIS
    21. 2 DOSAGE AND ADMINISTRATION
    22. 2.1 ADULTS AND ADOLESCENTS 12 YEARS OF AGE AND OVER
    23. 2.5 ADULTS WITH HEPATIC OR RENAL IMPAIRMENT
    24. 3 DOSAGE FORMS AND STRENGTHS
    25. 4 CONTRAINDICATIONS
    26. 5 WARNINGS AND PRECAUTIONS
    27. 5.1 HYPERSENSITIVITY REACTIONS
    28. 6 ADVERSE REACTIONS
    29. 6.1 CLINICAL TRIALS EXPERIENCE
    30. 6.2 POST-MARKETING EXPERIENCE
    31. 7.1 INHIBITORS OF CYTOCHROME P450 3A4
    32. 7.2 FLUOXETINE
    33. 7.3 CIMETIDINE
    34. 8 USE IN SPECIFIC POPULATIONS
    35. 8.1 PREGNANCY
    36. 8.2 LACTATION
    37. 8.3 FEMALES AND MALES OF REPRODUCTIVE POTENTIAL
    38. 8.4 PEDIATRIC USE
    39. 8.5 GERIATRIC USE
    40. 8.6 RENAL IMPAIRMENT
    41. 8.7 HEPATIC IMPAIRMENT
    42. THERE IS NO INFORMATION TO INDICATE THAT ABUSE OR DEPENDENCY OCCURS WITH DESLORATADINE TABLETS.
    43. 12.1 MECHANISM OF ACTION
    44. 12.2 PHARMACODYNAMICS
    45. 12.3 PHARMACOKINETICS
    46. 13.1 CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
    47. 14.1 SEASONAL ALLERGIC RHINITIS
    48. 14.2 PERENNIAL ALLERGIC RHINITIS
    49. 16 HOW SUPPLIED/STORAGE AND HANDLING
    50. 17.1 INFORMATION FOR PATIENTS
    51. CLOBETEX CLOBETASOL PROPIONATE CREAM USP, 0.05% (60 GM TUBE) DESLORATADINE TABLETS USP, 5MG (100 TABLETS)

Desloratadine Product Label

The following document was submitted to the FDA by the labeler of this product Lupin Pharmaceuticals, Inc.. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.

Other



Rx only

FOR TOPICAL DERMATOLOGIC USE ONLY - NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.

Desloratadine tablets may be taken without regard to meals.

Desloratadine tablets USP, 5 mg are light blue, circular, biconvex, film-coated tablets, debossed "LU" on one side and "S71" on other side.

Desloratadine tablets are contraindicated in patients who are hypersensitive to this medication or to any of its ingredients or to loratadine [see WARNINGS AND PRECAUTIONS (5.1) and ADVERSE REACTIONS (6.2)].

The following adverse reactions are discussed in greater detail in other sections of the label:

Hypersensitivity reactions. [See WARNINGS AND PRECAUTIONS (5.1).]

In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Desloratadine and 3-hydroxydesloratadine are not eliminated by hemodialysis.

Information regarding acute overdosage is limited to experience from post-marketing adverse event reports and from clinical trials conducted during the development of the desloratadine product. In a dose-ranging trial, at doses of 10 mg and 20 mg/day somnolence was reported.

In another study, no clinically relevant adverse events were reported in normal male and female volunteers who were given single daily doses of desloratadine 45 mg for 10 days [See CLINICAL PHARMACOLOGY (12.2)].

Desloratadine tablets USP, 5 mg are light blue, circular, biconvex, film-coated tablets debossed "LU" on one side and "S71" on other side, containing 5 mg desloratadine, an antihistamine, to be administered orally. Desloratadine tablets USP also contain the following excipients: anhydrous lactose, colloidal silicon dioxide, FD&C Blue#2/Indigo Carmine Aluminium Lake, hydrogenated vegetable oil, hypromellose, microcrystalline cellulose, polyethylene glycol, pregelatinised starch and titanium dioxide.

Desloratadine is a white to off-white crystalline powder that is freely soluble in dichloromethane and in methanol. It has an empirical formula: C19H19ClN2 and a molecular weight of 310.8. The chemical name is 8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine and has the following structure:

Metabolism Desloratadine (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of 3-hydroxydesloratadine have not been identified. Data from clinical trials indicate that a subset of the general population has a decreased ability to form 3-hydroxydesloratadine, and are poor metabolizers of desloratadine. In pharmacokinetic studies (n=3748), approximately 6% of subjects were poor metabolizers of desloratadine (defined as a subject with an AUC ratio of 3-hydroxydesloratadine to desloratadine less than 0.1, or a subject with a desloratadine half-life exceeding 50 hours). These pharmacokinetic studies included subjects between the ages of 2 and 70 years, including 977 subjects aged 2 to 5 years, 1575 subjects aged 6 to 11 years, and 1196 subjects aged 12 to 70 years. There was no difference in the prevalence of poor metabolizers across age groups. The frequency of poor metabolizers was higher in Blacks (17%, n=988) as compared to Caucasians (2%, n=1,462) and Hispanics (2%, n=1,063). The median exposure (AUC) to desloratadine in the poor metabolizers was approximately 6-fold greater than in the subjects who are not poor metabolizers. Subjects who are poor metabolizers of desloratadine cannot be prospectively identified and will be exposed to higher levels of desloratadine following dosing with the recommended dose of desloratadine. In multidose clinical safety studies, where metabolizer status was identified, a total of 94 poor metabolizers and 123 normal metabolizers were enrolled and treated with desloratadine oral solution for 15 to 35 days. In these studies, no overall differences in safety were observed between poor metabolizers and normal metabolizers. Although not seen in these studies, an increased risk of exposure-related adverse events in patients who are poor metabolizers cannot be ruled out.

Elimination

The mean plasma elimination half-life of desloratadine was approximately 27 hours. Cmax and AUC values increased in a dose proportional manner following single oral doses between 5 and 20 mg. The degree of accumulation after 14 days of dosing was consistent with the half-life and dosing frequency. A human mass balance study documented a recovery of approximately 87% of the 14C-desloratadine dose, which was equally distributed in urine and feces as metabolic products. Analysis of plasma 3-hydroxydesloratadine showed similar Tmax and half-life values compared to desloratadine.

Special Populations

Geriatric Subjects:

In older subjects (≥65 years old; n=17) following multiple-dose administration of desloratadine tablets, the mean Cmax and AUC values for desloratadine were 20% greater than in younger subjects (<65 years old). The oral total body clearance (CL/F) when normalized for body weight was similar between the two age groups. The mean plasma elimination half-life of desloratadine was 33.7 hr in subjects ≥65 years old. The pharmacokinetics for 3-hydroxydesloratadine appeared unchanged in older versus younger subjects. These age-related differences are unlikely to be clinically relevant and no dosage adjustment is recommended in elderly subjects.

Pediatric Subjects:

In subjects 6 to 11 years old, a single dose of 5 mL of desloratadine oral solution containing 2.5 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg desloratadine tablet. In subjects 2 to 5 years old, a single dose of 2.5 mL of desloratadine oral solution containing 1.25 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg desloratadine tablet. However, the Cmax and AUC of the metabolite (3-hydroxydesloratadine) were 1.27 and 1.61 times higher for the 5 mg dose of oral solution administered in adults compared to the Cmax and AUC obtained in children 2 to 11 years of age receiving 1.25 to 2.5 mg of desloratadine oral solution.

A single dose of either 2.5 mL or 1.25 mL of desloratadine oral solution containing 1.25 mg or 0.625 mg, respectively, of desloratadine was administered to subjects 6 to 11 months of age and 12 to 23 months of age. The results of a population pharmacokinetic analysis indicated that a dose of 1 mg for subjects aged 6 to 11 months and 1.25 mg for subjects 12 to 23 months of age is required to obtain desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg dose of desloratadine oral solution.

Renally Impaired:

Desloratadine pharmacokinetics following a single dose of 7.5 mg were characterized in patients with mild (n=7; creatinine clearance 51 to 69 mL/min/1.73 m2), moderate (n=6; creatinine clearance 34 to 43 mL/min/1.73 m2), and severe (n=6; creatinine clearance 5 to 29 mL/min/1.73 m2) renal impairment or hemodialysis dependent (n=6) patients. In patients with mild and moderate renal impairment, median Cmax and AUC values increased by approximately 1.2- and 1.9-fold, respectively, relative to subjects with normal renal function. In patients with severe renal impairment or who were hemodialysis dependent, Cmax and AUC values increased by approximately 1.7- and 2.5-fold, respectively. Minimal changes in 3-hydroxydesloratadine concentrations were observed. Desloratadine and 3-hydroxydesloratadine were poorly removed by hemodialysis. Plasma protein binding of desloratadine and 3-hydroxydesloratadine was unaltered by renal impairment. Dosage adjustment for patients with renal impairment is recommended [see DOSAGE AND ADMINISTRATION (2.5)].

Hepatically Impaired:

Desloratadine pharmacokinetics were characterized following a single oral dose in patients with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment as defined by the Child-Pugh classification of hepatic function and 8 subjects with normal hepatic function. Patients with hepatic impairment, regardless of severity, had approximately a 2.4-fold increase in AUC as compared with normal subjects. The apparent oral clearance of desloratadine in patients with mild, moderate, and severe hepatic impairment was 37%, 36%, and 28% of that in normal subjects, respectively. An increase in the mean elimination half-life of desloratadine in patients with hepatic impairment was observed. For 3-hydroxydesloratadine, the mean Cmax and AUC values for patients with hepatic impairment were not statistically significantly different from subjects with normal hepatic function. Dosage adjustment for patients with hepatic impairment is recommended [see DOSAGE AND ADMINISTRATION (2.5)].

Gender:

Female subjects treated for 14 days with desloratadine tablets had 10% and 3% higher desloratadine Cmax and AUC values, respectively, compared with male subjects. The 3-hydroxydesloratadine Cmax and AUC values were also increased by 45% and 48%, respectively, in females compared with males. However, these apparent differences are not likely to be clinically relevant and therefore no dosage adjustment is recommended.

Race:

Following 14 days of treatment with desloratadine tablets, the C max and AUC values for desloratadine were 18% and 32% higher, respectively, in Blacks compared with Caucasians. For 3-hydroxydesloratadine there was a corresponding 10% reduction in C max and AUC values in Blacks compared to Caucasians. These differences are not likely to be clinically relevant and therefore no dose adjustment is recommended.

Drug Interactions:

In two controlled crossover clinical pharmacology studies in healthy male (n=12 in each study) and female (n=12 in each study) volunteers, desloratadine 7.5 mg (1.5 times the daily dose) once daily was coadministered with erythromycin 500 mg every 8 hours or ketoconazole 200 mg every 12 hours for 10 days. In three separate controlled, parallel group clinical pharmacology studies, desloratadine at the clinical dose of 5 mg has been coadministered with azithromycin 500 mg followed by 250 mg once daily for 4 days (n=18) or with fluoxetine 20 mg once daily for 7 days after a 23-day pretreatment period with fluoxetine (n=18) or with cimetidine 600 mg every 12 hours for 14 days (n=18) under steady-state conditions to normal healthy male and female volunteers. Although increased plasma concentrations (C max and AUC 0 to 24 hrs) of desloratadine and 3-hydroxydesloratadine were observed (see Table 2), there were no clinically relevant changes in the safety profile of desloratadine, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs, and adverse events.

Table 2 Changes in Desloratadine and 3-Hydroxydesloratadine Pharmacokinetics in Healthy Male and Female Volunteers
Desloratadine
3-Hydroxydesloratadine
C max
AUC

0 to 24 hrs
C max
AUC

0 to 24 hrs
Erythromycin

(500 mg Q8h)
+ 24%
+ 14%
+ 43%
+ 40%
Ketoconazole

(200 mg Q12h)
+ 45%
+ 39%
+ 43%
+ 72%
Azithromycin

(500 mg day 1, 250 mg

QD x 4 days)
+ 15%
+ 5%
+ 15%
+ 4%
Fluoxetine

(20 mg QD)
+ 15%
+ 0%
+ 17%
+ 13%
Cimetidine

(600 mg Q12h)
+ 12%
+ 19%
- 11%
- 3%

Genotoxicity Studies

In genotoxicity studies with desloratadine, there was no evidence of genotoxic potential in a reverse mutation assay (Salmonella/E. coli mammalian microsome bacterial mutagenicity assay) or in 2 assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay).

Impairment of Fertility

In a female fertility study, desloratadine was given to female rats orally 14 days prior to and throughout mating until Gestation Day 7 at doses of 6, 12 and 24 mg/kg/day. An increase in preimplantation loss and a decrease in number of implantations and fetuses noted at 24 mg/kg (approximately 200 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD) was likely due to maternal toxicities including reduced body weight gain and food consumption. In a male fertility study in rats, desloratadine was given orally to male rats for 70 days prior to mating and throughout the mating period (total dosing period 106 to 108 days) at doses of 3, 12 and 40 mg/kg/day. Reduced body weight gain, food consumption, and absolute organ weights of testes, epididymis, and cauda epididymis were noted at 40 mg/kg/day. A male-specific decrease in fertility, demonstrated by reduced female conception rates, decreased sperm numbers and motility, and histopathologic changes in testes and epididymis, occurred at a dose of 12 mg/kg or greater (approximately 65 times or greater than the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Desloratadine had no effect on male fertility in rats at 3 mg/kg/day (approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD).

Desloratadine tablets USP, 5 mg are light blue, circular, biconvex, film-coated tablets, debossed "LU" on one side and "S71" on other side. They are supplied as follows:

NDC 68180-153-06 Bottles of 30

NDC 68180-153-01 Bottles of 100

NDC 68180-153-02 Bottles of 500

NDC 68180-153-03 Bottles of 1000

NDC 68180-153-12 3x10's unit dose blisters

NDC 68180-153-13 10x10's unit dose blisters

Storage:

Store at 25°C (77°F); excursions permitted to 15° to 30° C (59° to 86° F) [see USP Controlled Room Temperature].

Heat Sensitive.

Avoid exposure at or above 30°C (86°F).

Dispense in tight, light-resistant container as defined in the USP using a child-resistant closure.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

PATIENT INFORMATION LEAFLET

DESLORATADINE (DES-lor-A-ta-deen)

TABLETS USP

Rx only

Read the Patient Information that comes with desloratadine tablets before you start taking it and each time you get a refill. There may be new information. This leaflet is a summary of the information for patients. Your doctor or pharmacist can give you additional information. This leaflet does not take the place of talking to your doctor about your medical condition or treatment.

What are desloratadine tablets?

Desloratadine tablets are prescription medicine that contains the medicine desloratadine (an antihistamine).

Desloratadine tablets are used to help control the symptoms of:

seasonal allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in people 12 years of age and older.
perennial allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in people 12 years of age and older.

Desloratadine tablets are not for children younger than 12 years of age.

Who should not take desloratadine tablets?

Do not take desloratadine tablets if you:

are allergic to desloratadine or any of the ingredients in desloratadine tablets. See the end of this leaflet for a complete list of ingredients.
are allergic to loratadine (Alavert, Claritin).

Talk to your doctor before taking this medicine if you have any questions about whether or not to take this medicine.

What should I tell my doctor before taking desloratadine tablets?

Before you take desloratadine tablets, tell your doctor if you:

have liver or kidney problems.
have any other medical conditions.
are pregnant or plan to become pregnant. It is not known if desloratadine tablets will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
are breast-feeding or plan to breast-feed. Desloratadine can pass into your breast milk . Talk to your doctor about the best way to feed your baby if you take desloratadine tablets.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Desloratadine tablets may affect the way other medicines work, and other medicines may affect how desloratadine works. Especially tell your doctor if you take:

ketoconazole (Nizoral)
erythromycin (Ery-tab, Eryc, PCE)
azithromycin (Zithromax, Zmax)
antihistamines
fluoxetine (Prozac)
cimetidine (Tagamet)

Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

How should I take desloratadine tablets?

Take desloratadine tablets exactly as your doctor tells you to take it.
Do not change your dose of desloratadine tablets or take more often than prescribed.
Desloratadine tablets can be taken with or without food.
If you take too much desloratadine tablets, call your doctor or get medical attention right away.

What are the possible side effects of desloratadine tablets?

Desloratadine tablets may cause serious side effects, including:

• Allergic reactions. Stop taking desloratadine tablets and call your doctor right away or get emergency help if you have any of these symptoms:

rash
itching
hives
swelling of your lips, tongue, face, and throat
shortness of breath or trouble breathing

The most common side effects of desloratadine tablets in adults and children 12 years of age and older with allergic rhinitis include:

sore throat
dry mouth
muscle pain
tiredness
sleepiness
menstrual pain

Increased sleepiness or tiredness can happen if you take more desloratadine tablets than your doctor prescribed to you.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of desloratadine tablets. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to Lupin Pharmaceuticals, Inc at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

How should I store desloratadine tablets?

• Store at 25° C (77° F); excursions permitted to 15° to 30° C (59° to 86° F).

• Desloratadine tablets are sensitive to heat. Do not store above 30°C (86°F).

• Protect desloratadine tablets from moisture.

Keep desloratadine tablets and all medicines out of the reach of children.

General information about desloratadine tablets

Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use desloratadine tablets for a condition for which it was not prescribed. Do not give desloratadine tablets to other people, even if they have the same condition you have. It may harm them.

This Patient Information leaflet summarizes the most important information about desloratadine tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about desloratadine tablets that is written for health professionals.

What are the ingredients in desloratadine tablets?

Active ingredient: desloratadine

Inactive ingredients in desloratadine tablets: anhydrous lactose, colloidal silicon dioxide, FD&C Blue#2/Indigo Carmine Aluminium Lake, hydrogenated vegetable oil, hypromellose, microcrystalline cellulose, polyethylene glycol, pregelatinised starch and titanium dioxide.

The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Goa 403 722

INDIA

Revised: December 2019 ID#: 263068


Description



Clobetasol Propionate Cream USP, 0.05% contains the active compound clobetasol propionate, a synthetic corticosteroid, for topical dermatologic use. Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity.

Chemically, clobetasol propionate is (11ß,16ß)-21-chloro-9- fluoro-11-hydroxy-16-methyl-17-(1-oxopropoxy)-pregna-1,4- diene-3,20-dione, and it has the following structural formula:

structural formula - structural formula

structural formula - structural formula

Clobetasol propionate has the molecular formula C 25H 32CIFO 5 and a molecular weight of 467. It is a white to cream-colored crystalline powder insoluble in water.

Clobetasol propionate cream contains clobetasol propionate 0.5 mg/g in a cream base composed of cetyl alcohol, citric acid, glycol stearate, lanolin oil, methylparaben, PEG-8 stearate, polysorbate 60, propylene glycol, propylparaben, purified water, sodium citrate, stearyl alcohol, and white petrolatum. Sodium hydroxide may be used to adjust pH.


Clinical Pharmacology



Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A 2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A 2.


Pharmacokinetics



The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusive dressing with hydrocortisone for up to 24 hours has not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

Studies performed with clobetasol propionate cream indicate that it is in the super-high range of potency as compared with other topical corticosteroids.


Indications And Usage



Clobetasol propionate cream is a super-high potency corticosteroid formulation indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment beyond 2 consecutive weeks is not recommended, and the total dosage should not exceed 50 g/week because of the potential for the drug to suppress the hypothalamicpituitary- adrenal (HPA) axis. Use in pediatric patients under 12 years of age is not recommended.

As with other highly active corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary.


Contraindications



Clobetasol Propionate Cream, USP, 0.05% is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparations.


General



Clobetasol propionate cream should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.

Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from treatment. Manifestations of Cushing syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on therapy.

Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol tests. Patients receiving super-potent corticosteroids should not be treated for more than 2 weeks at a time, and only small areas should be treated at any one time due to the increased risk of HPA suppression.

Clobetasol propionate cream produced HPA axis suppression when used at doses as low as 2 g/day for 1 week in patients with eczema.

If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur that require supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.

Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios (see PRECAUTIONS: Pediatric Use).

If irritation develops, clobetasol propionate cream should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of clobetasol propionate cream should be discontinued until the infection has been adequately controlled.


Information For Patients



Patients using topical corticosteroids should receive the following information and instructions:

  • This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.
  • This medication should not be used for any disorder other than that for which it was prescribed.
  • The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician.
  • Patients should report any signs of local adverse reactions to the physician.

Laboratory Tests



The following tests may be helpful in evaluating patients for HPA axis suppression:

  • ACTH stimulation test
  • A.M. plasma cortisol test
  • Urinary free cortisol test

Carcinogenesis, Mutagenesis, Impairment Of Fertility



Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.

Studies in the rat following subcutaneous administration at dosage levels up to 50 mcg/kg/day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

Clobetasol propionate was nonmutagenic in 3 different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test.


Pregnancy Category C.



Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals.

Clobetasol propionate has not been tested for teratogenicity when applied topically; however, it is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent.

Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 1.4 and 0.04 times, respectively, the human topical dose of clobetasol propionate cream and ointment. Abnormalities seen included cleft palate and skeletal abnormalities.

In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of clobetasol propionate cream and ointment. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.

There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clobetasol propionate cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


Nursing Mothers



Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when clobetasol propionate cream is administered to a nursing woman.


Pediatric Use



Safety and effectiveness of clobetasol propionate cream in pediatric patients have not been established. Use in pediatric patients under 12 years of age is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.

HPA axis suppression, Cushing syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids.



Manifestations of adrenal suppression in children include low plasma cortisol levels and an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.


Geriatric Use



A limited number of patients at or above 65 years of age have been treated with clobetasol propionate cream (n = 231) in US and non-US clinical trials. While the number of patients is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger patients. Based on available data, no adjustment of dosage of clobetasol propionate cream in geriatric patients is warranted.

In studies where geriatric patients (65 years of age or older, see PRECAUTIONS) have been treated with clobetasol propionate cream, safety did not differ from that in younger patients; therefore, no dosage adjustment is recommended.


Adverse Reactions



In controlled clinical trials, the most frequent adverse reactions reported for clobetasol propionate cream were burning and stinging sensation in 1% of treated patients. Less frequent adverse reactions were itching, skin atrophy, and cracking and fissuring of the skin.

Cushing syndrome has been reported in infants and adults as a result of prolonged use of topical clobetasol propionate formulations.

The following additional local adverse reactions have been reported with topical corticosteroids, and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in an approximately decreasing order of occurrence: dryness, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, irritation, striae, and miliaria.

To report SUSPECTED ADVERSE REACTIONS, contact Teligent Pharma, Inc. at 1-856-697-1441 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.


Overdosage



Topically applied clobetasol propionate cream can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS ).


Dosage And Administration



Apply a thin layer of clobetasol propionate cream to the affected skin areas twice daily and rub in gently and completely (see INDICATIONS AND USAGE).

Clobetasol propionate cream is a super-high potency topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks and amounts greater than 50 g/week should not be used.

As with other highly active corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

Clobetasol propionate cream should not be used with occlusive dressings.


How Supplied



Clobetasol Propionate Cream USP, 0.05% is supplied in tubes containing:



15 grams tube NDC 52565-051-15

30 grams tube NDC 52565-051-30

45 gram tubes NDC 52565-051-45

60 grams tube NDC 52565-051-60

Store cream between 15° and 30°C (59° and 86°F).

Clobetasol propionate cream should not be refrigerated. Do not use if you see separation into a liquid and semi-solid state.

Rx only

Manufactured by:

Teligent Pharma, Inc.

Buena, NJ 08310

C101281

PI-051-00

Rev 07/2019


* Please review the disclaimer below.