Acella Hydrocortisone Acetate - Pramoxine Singles

DESCRIPTION: Hydrocortisone Acetate 2.5%-Pramoxine HCl 1% Cream is a topical preparation containing Hydrocortisone Acetate 2.5% w/w and Pramoxine HCl 1% w/w in a hydrophilic base containing Purified Water, Petrolatum, PEG 40 Stearate, Mineral Oil, Ceresin Wax, Cetostearyl Alcohol, Stearic Acid, TEA-Lauryl Sulfate, Isopropyl Palmitate, Carbomer 940, Methyl Paraben, Propyl Paraben, Citric Acid, Sodium Citrate and Triethanolamine. Topical corticosteroids are anti-inflammatory and anti-pruritic agents. The structural formula, the chemical name, molecular formula and molecular weight for active ingredients are presented below.

CLINICAL PHARMACOLOGY: Topical corticosteroids share anti-inflammatory, anti-pruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. Pramoxine hydrochloride is a topical anesthetic agent which provides temporary relief from itching and pain. It acts by stabilizing the neuronal membrane of nerve endings with which it comes into contact.

Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. (See DOSAGE AND ADMINISTRATION.) Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

INDICATIONS AND USAGE: Topical corticosteroids are indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

CONTRAINDICATIONS: Topical corticosteroids are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

PRECAUTIONS: General: Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing’s syndrome, hyperglycemia and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use and the addition of occlusive dressings. Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area and under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation 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 corticosteroids. Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. (See Precautions-Pediatric Use.) If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted. In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.

Information for the patient: Patients using topical corticosteroids should receive the following information and instructions:
1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with eyes.
2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed.
3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.
4. Patients should report any signs of local adverse reactions especially under occlusive dressings.
5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings.

Laboratory Tests: Urinary free cortisol test and ACTH stimulation test may be helpful in evaluating the HPA axis suppression.

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. Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results.

Pregnancy: Teratogenic Effects: Pregnancy Category C: Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant patients, in large amounts or for prolonged periods of time.

Nursing Mothers: It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable amounts in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities NOT likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to a nursing woman.

Pediatric Use: Pediatric patients may demonstrate greater susceptibility to topical corticosteroids induced HPA axis suppression and Cushing’s syndrome than mature patients because of larger skin surface area to body weight ratio. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

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

OVERDOSAGE: Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects (See PRECAUTIONS.)

DOSAGE AND ADMINISTRATION: Topical corticosteroids are generally applied to the affected area as a thin film three to four times daily depending on the severity of the condition. Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions. If an infection develops, the use of occlusive dressings should be discontinued and appropriate antimicrobial therapy instituted.

HOW SUPPLIED: Hydrocortisone Acetate 2.5%-Pramoxine HCl 1% Cream Singles are supplied in 30 x 4 gram tubes (NDC 42192-108-04).

Storage Conditions: Store at 20° - 25°C (68° - 77°F); excursions permitted to 15° - 30°C (59° - 86°F) [see USP Controlled Room Temperature].

Rx Only

Manufactured for:
Acella Pharmaceuticals, LLC
9005 Westside Parkway                                                                         L700
Alpharetta, GA 30009                                                                             Rev.0310

NDC 42192-108-04                     Rx Only                     Net Wt. 4 g

Hydrocortisone Acetate 2.5% -
Pramoxine HCl 1% Cream

CONTAINS: Hydrocortisone Acetate 2.5% and Pramoxine HCl 1% in a hydrophilic base containing Purified Water, Petrolatum, PEG 40 Stearate, Mineral Oil, Ceresin Wax, Cetostearyl Alcohol, Stearic Acid, TEA-Lauryl Sulfate, Isopropyl Palmitate, Carbomer Homopolymer Type C, Methyl Paraben, Propyl Paraben, Citric Acid, Sodium Citrate and Triethanolamine.

USUAL DOSAGE: Apply to affected area 3 - 4 times daily. See enclosed package insert for full prescribing information.

FOR EXTERNAL USE ONLY. NOT FOR OPTHALMIC USE.

Store at controlled room temperature 15 degree - 30 degree C (59 degree - 86 degree F) Keep tightly closed.

TO OPEN: Remove cap and use point to puncture foil seal.

MANUFACTURED FOR: Acella Pharmaceuticals, LLC                            L697
Alpharetta, GA 30009                                                                           Rev. 0610

- Helps relieve itching, burning and inflammation.

- 2.5% Hydrocortisone Acetate: Treats inflammation and itching while maintaining an excellent safety profile.

- 1% Pramoxine HCl: Provides fast, soothing relief from pain and itching.

                                                                                              NDC 42192-108-04

Hydrocortisone Acetate 2.5% -
Pramoxine HCl 1% Cream Singles

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

FOR EXTERNAL USE ONLY. NOT FOR OPHTHALMIC USE.

CONTAINS: Hydrocortisone Acetate 2.5% and Pramoxine HCl 1% in a hydrophilic base containing Purified Water, Petrolatum, PEG 40 Stearate, Mineral Oil, Ceresin Wax, Cetostearyl Alcohol, Stearic Acid, TEA-Lauryl Sulfate, Isopropyl Palmitate, Carbomer 940, Methyl Paraben, Propyl Paraben, Citric Acid, Sodium Citrate and Triethanolamine.


USUAL DOSAGE: Apply to affected area 3 - 4 times daily or as directed by a physician. See enclosed package Insert for full prescribing information. Store at 20 degree - 25 degree C (68 degree - 77 degree F) ; excursions permitted to 15 degree - 30 degree C (59 degree - 86 degree F) [see USP Controlled Room Temperature].

                                         Acella Pharmaceuticals, LLC

                                                                                              NDC 42192-108-04
Hydrocortisone Acetate 2.5% -
Pramoxine HCl 1% Cream Singles

DIRECTIONS FOR USE WITH APPLICATOR:
1. Remove the cap and use point to puncture foil seal. Do not peel foil seal away.
2. Attach applicator to the tube.
3. Squeeze the tube to fill applicator and lubricate the tip with cream.
4. Gently insert only the tip of the applicator into the anus and squeeze again to
    force contents of tube into the anal canal.
5. Discard empty tube and applicator.

MANUFACTURED FOR:
Acella Pharmaceuticals, LLC
Alpharetta, GA 30009                                                                           L701
1-800-541-4902                                                                                    Rev. 0310

                                                                                              NDC 42192-108-04
Hydrocortisone Acetate 2.5% -
Pramoxine HCl 1% Cream Singles

                                                 4 gram Single Use Tubes

                                                             Rx Only

                            Contents: 30 Single Use 4 gram Tubes and Applicators


                                               Acella Pharmaceuticals, LLC

Acella Hydrocortisone Acetate - Pramoxine Singles  hydrocortisone acetate, pramoxine cream

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:42192-108 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HYDROCORTISONE ACETATE (HYDROCORTISONE) HYDROCORTISONE ACETATE 2.5 g  in 100 g PRAMOXINE (PRAMOXINE) PRAMOXINE 1 g  in 100 g

Inactive Ingredients Ingredient Name Strength WATER   PETROLATUM   MINERAL OIL   CETOSTEARYL ALCOHOL   STEARIC ACID   TROLAMINE LAURYL SULFATE   ISOPROPYL PALMITATE   CARBOMER HOMOPOLYMER TYPE C   METHYLPARABEN   CITRIC ACID MONOHYDRATE   SODIUM CITRATE   TROLAMINE

Packaging # Item Code Package Description 1 NDC:42192-108-04 30 TUBE, WITH APPLICATOR (TUBE) in 1 CARTON 1 4 g in 1 TUBE, WITH APPLICATOR

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 11/08/2010

Labeler - Acella Pharmaceuticals, LLC (825380939)

Revised: 12/2010   Acella Pharmaceuticals, LLC

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of a weak adrenal gland like a very bad upset stomach or throwing up, very bad dizziness or passing out, muscle weakness, feeling very tired, mood changes, not hungry, or weight loss.
• Signs of Cushing's disease like weight gain in the upper back or belly, moon face, very bad headache, or slow healing.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Irritation where this drug is used.
• Skin changes (pimples, stretch marks, slow healing, hair growth).
• Thinning of the skin.

Rectal cream, rectal lotion, topical cream, topical foam, topical lotion: Apply a thin film to the affected area 3 to 4 times a day, depending on severity of condition.

Comments:
-Should only be used externally
-Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions; should discontinue use of occlusive dressings if an infection develops.
-For cleansing the anogenital area, the rectal lotion should be applied with a tissue or cotton ball.
-If redness, pain, irritation, or swelling persists, the topical foam should be discontinued; not for prolonged use.

Rectal foam: Apply to affected area 3 to 4 times a day.

Comments:
-The applicator supplied should be used for anal administration.
-For perianal use, a small amount should be transferred to a tissue and gently rubbed in.
-If no clinical improvement within 2 or 3 weeks after starting therapy, or if patient's condition worsens, the rectal foam should be discontinued.

Approved indications:
-Rectal cream, rectal lotion, topical cream, topical foam, topical lotion: For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses
-Rectal foam: For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses of the anal region

Rectal cream, rectal lotion, topical cream, topical foam, topical lotion: Apply a thin film to the affected area 3 to 4 times a day, depending on severity of condition.

Comments:
-Should only be used externally
-Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions; should discontinue use of occlusive dressings if an infection develops.
-For cleansing the anogenital area, the rectal lotion should be applied with a tissue or cotton ball.
-If redness, pain, irritation, or swelling persists, the topical foam should be discontinued; not for prolonged use.

Rectal foam: Apply to affected area 3 to 4 times a day.

Comments:
-The applicator supplied should be used for anal administration.
-For perianal use, a small amount should be transferred to a tissue and gently rubbed in.
-If no clinical improvement within 2 or 3 weeks after starting therapy, or if patient's condition worsens, the rectal foam should be discontinued.

Approved indications:
-Rectal cream, rectal lotion, topical cream, topical foam, topical lotion: For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses
-Rectal foam: For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses of the anal region

Data not available

Hydrocortisone-pramoxine topical has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence that the more potent corticosteroids have been teratogenic after dermal application. Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. There are no controlled data in human pregnancy. Hydrocortisone-pramoxine topical should only be given during pregnancy when benefits outweigh risks. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.