Pandel

Patient Information

PANDEL^®
(pan-del)
(hydrocortisone probutate) Cream

Important: PANDEL is for use on skin only (topical). Avoid using PANDEL near or around your eyes.

What is PANDEL?

PANDEL is a prescription corticosteroid medicine used on the skin (topical) for the relief of inflammation and itching caused by certain skin conditions in people 18 years of age or older.

It is not known if PANDEL is safe and effective in children.

Before using PANDEL tell your healthcare provider about all of your medical conditions, including if you:

• have adrenal gland problems
• have liver problems
• have diabetes
• have thinning skin (atrophy) at the site to be treated.
• are pregnant or plan to become pregnant. It is not known if PANDEL will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if PANDEL can pass into your breast milk and harm your baby.
  • If you breastfeed during treatment with PANDEL, clean the treated area of skin on and near your breast, and your nipple before breastfeeding. This will help prevent contact of PANDEL with your baby’s skin.
  • You should use PANDEL on the smallest area of skin and for the shortest time possible while breastfeeding.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I use PANDEL?

• Use PANDEL exactly as your healthcare provider tells you to use it.
• Apply a thin film to the affected skin area. Gently rub PANDEL into your skin until it disappears.
• Tell your healthcare provider if your symptoms do not improve after 2 weeks of treatment.
• Do not bandage, cover, or wrap the treated area unless your healthcare provider tells you to.
• Do not apply PANDEL in the diaper area or use with plastic pants.
• Do not use PANDEL on your face, underarms (armpits) or groin areas unless your healthcare provider tells you to.
• Wash your hands after applying PANDEL, unless your hands are being treated.

What are possible side effects with PANDEL?

PANDEL may cause serious side effects, including:

• PANDEL can pass through your skin and may cause adrenal gland problems. This is more likely to happen if you use PANDEL for too long, use it over a large treatment area, use it with other topical medicines that contain corticosteroids, cover the treated area, or have liver failure. Your healthcare provider may do blood tests to check your adrenal gland function during and after treatment with PANDEL.
• Skin problems, including skin reactions or thinning of your skin (atrophy), skin infections, and allergic reactions (allergic contact dermatitis) at the treatment site. Tell your healthcare provider if you get any skin reactions such as pain, tenderness, swelling, or healing problems.

The most common side effects of PANDEL include burning and stinging and moderate tingling or prickling feeling. These are not all the possible side effects with PANDEL. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store PANDEL?

• Store PANDEL between 68°F to 77°F (20°C to 25°C).

Keep PANDEL and all medicines out of the reach of children.

General information about the safe and effective use of PANDEL.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PANDEL for a condition for which it was not prescribed. Do not give PANDEL to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about PANDEL that is written for health professionals.

What are the ingredients in PANDEL?

Active ingredient: hydrocortisone probutate

Inactive ingredients: propylene glycol, white petrolatum, light mineral oil, stearyl alcohol, polysorbate 60, sorbitan monostearate, glyceryl monostearate, PEG-20 stearate, glyceryl stearate SE, methylparaben, butylparaben, citric acid, sodium citrate anhydrous, and purified water.

Description

PANDEL (hydrocortisone probutate) Cream, 0.1% contains hydrocortisone probutate, a synthetic corticosteroid. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and anti-pruritic agents.

Hydrocortisone probutate is a tasteless and odorless white crystalline powder practically insoluble in hexane or water, slightly soluble in ether, and very soluble in dichloromethane, methanol and acetone. Chemically, it is 11β,17,21-trihydroxypregn-4-ene-3,20-dione 17-butyrate 21-propionate. The structural formula is:

Molecular Formula: C₂₈H₄₀O₇     Molecular Weight: 488.62

Each gram of PANDEL (hydrocortisone probutate) Cream, 0.1% contains: 1 mg of hydrocortisone probutate in a cream base of propylene glycol, white petrolatum, light mineral oil, stearyl alcohol, polysorbate 60, sorbitan monostearate, glyceryl monostearate, PEG-20 stearate, glyceryl stearate SE, methylparaben, butylparaben, citric acid, sodium citrate anhydrous, and purified water.

Indications

PANDEL^® (hydrocortisone probutate) Cream, 0.1% is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 18 years of age or older.

Dosage And Admintisration

Apply a thin film of PANDEL to the affected area once or twice a day depending on the severity of the condition. Massage gently until the medication disappears.

Occlusive dressings may be used for the management of refractory lesions of psoriasis and other deep-seated dermatoses, such as localized neurodermatitis (lichen simplex chronicus).

Discontinue PANDEL when control is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary.

Do not use PANDEL with occlusive dressings unless directed by the physician. Do not apply PANDEL in the diaper area, as diapers or plastic pants may constitute occlusive dressings.

How Supplied

Dosage Forms And Strengths

Cream, 0.1%. Each gram of PANDEL contains 1 mg of hydrocortisone probutate in a cream base.

Storage And Handling

PANDEL, a white to off-white opaque cream is supplied as follows:

45 g tubes NDC 10337-153-46
80 g tubes NDC 10337-153-80

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Manufactured by: PharmaDerm^® A division of Fougera Pharmaceuticals Inc. Melville, New York 11747. Revised: Jan 2017.

Side Effects

Clinical Trials Experience

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 clinical practice.

The most frequent adverse reactions reported for PANDEL during clinical trials were application site reactions, including burning in 4, stinging in 2, and moderate paresthesia in 1 out of 226 subjects.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of PANDEL because these reactions were 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.

These adverse reactions are as follows:

Skin and Subcutaneous Tissue Disorders:rash, papulovesicular rash

Application Site Reactions: dryness, erythema, pruritus, allergic contact dermatitis.

The following local adverse reactions are reported with topical corticosteroids, and they may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infections, skin atrophy, striae, and miliaria.

Drug Interactions

No Information Provided

WarningS

No information provided.

Preauctions

General: Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment.Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical cor-ticosteroids while on treatment.

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 or urinary free cortisol tests.

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 steroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corti-costeroids. 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, Pandel (hydrocortisone probutate cream) Cream, 0.1% 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 observed with most topical products not containing corticosteroids.

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 Pandel (hydrocortisone probutate cream) Cream, 0.1% should be discontinued until the infection has been adequately controlled.

Laboratory Tests

The following tests may be helpful in evaluating if HPA axis suppression does occur:

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

Carcinogenesis, Mutagenesis and Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids.

In two mutagenicity experiments using hydrocortisone probutate, negative responses were observed in the occurrence of micronuclei in the bone marrow of mice and in the Ames reverse mutation test bacterial assay – with and without metabolic activation.

Pregnancy

Teratogenic Effects – 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.

Hydrocortisone probutate has not been tested for teratogenicity when applied topically; however, it is absorbed percutaneously, and studies in Wistar rats using the subcutaneous route resulted in teratogenicity at dose levels equal to or greater than 1 mg/kg. This dose is approximately 12 times the human average topical dose of Pandel (hydrocortisone probutate cream) Cream, 0.1% assuming 3% absorption and an application of 30 g/day on a 70 kg individual. Abnormalities seen included delayed ossification of the caudal vertebrae and other skeletal variations, cleft palate, umbilical hernia, edema, and exencephalia.

In rabbits, hydrocortisone probutate given by the subcutaneous route was teratogenic at doses equal to or greater than 0.1 mg/kg. This dose is approximately 2 times the human average topical dose of Pandel (hydrocortisone probutate cream) Cream, 0.1% assuming 3% absorption and an application of 30 g/day on a 70 kg individual. Abnormalities seen included delayed ossification of the cau-dal vertebrae and other skeletal abnormalities, cleft palate and increased fetal mortality.

The differences between the doses used in animal studies and the proposed human dose may not fully predict the human outcome. The animals received a bolus subcutaneous dose, whereas humans receive a dermal application, where absorption is lower and highly dependent on various factors (e.g., vehicle, integrity of epidermal barrier, occlusion).

There are no adequate and well-controlled studies of the teratogenic potential of hydrocortisone probutate in pregnant women. Although human epidemiological studies do not indicate an increased incidence of teratogenicity with the use of topical corticosteroids, Pandel (hydrocortisone probutate cream) Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mother

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 Pandel (hydrocortisone probutate cream) Cream, 0.1% is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. 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’s syndrome when they are treated with topical corticosteroids. They are therefore also at a greater risk of adrenal insufficiency during and/or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.

Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s 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.

Overdose

No Information Provided

Contraindications

None.

Mechanism Of Action

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in corticosteroid responsive dermatoses is unknown.

Pharmacodynamics

Vasoconstrictor Assay

Studies performed with PANDEL indicate that it is in the medium range of potency as demonstrated in vasoconstrictor trials in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

In an open label HPA axis suppression trial, 19 adult subjects (ages 23 to 82 years) with atopic dermatitis or plaque psoriasis covering greater than 20% Body Surface Area (BSA) were treated with PANDEL twice daily for 21 days and were assessed for HPA axis suppression. At baseline, the mean disease BSA involvement was 36%. The criterion for HPA axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter at 30-minutes after cosyntropin stimulation. Of these subjects, 15 were considered evaluable with respect to their adrenal axis function post-treatment. One of the evaluable subjects (6.7%) showed laboratory evidence of suppression on Day 22. This subject had psoriasis covering 48% of BSA at baseline and was reported to have received 98% of the twice-daily applications of PANDEL over the 21 day treatment period. It is not known if this subject had recovery of adrenal function because follow-up testing was not performed.

Pharmacokinetics

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