Ammonium Lactate

ADVERSE REACTIONS In controlled clinical trials of patients with ichthyosis vulgaris, the most frequent adverse reactions in patients treated with ammonium lactate cream were rash (including erythema and irritation) and burning/stinging. Each was reported in approximately 10-15% of patients. In addition, itching was reported in approximately 5% of patients. In controlled clinical trials of patients with xerosis, the most frequent adverse reactions in patients treated with ammonium lactate cream were transient burning, in about 3% of patients, stinging, dry skin and rash, each reported in approximately 2% of patients.

CONTRAINDICATIONS Ammonium Lactate Cream, 12% is contraindicated in those patients with a history of hypersensitivity to any of the label ingredients.

DESCRIPTION *Ammonium Lactate Cream, 12% is a formulation of 12% lactic acid neutralized with ammonium hydroxide, as ammonium lactate with a pH of 4.4 - 5.4. Ammonium Lactate Cream, 12% also contains cetyl alcohol, glycerin, glyceryl stearate, laureth-4, light mineral oil, magnesium aluminum silicate, methylcellulose, methylparaben, PEG-100 stearate, polyoxyl 40 stearate, propylene glycol, propylparaben, and purified water. Lactic acid is a racemic mixture of 2-hydroxypropanoic acid and has the following structural formula: Ammonium Lactate Cream Structural Formula

DOSAGE AND ADMINISTRATION Apply to the affected areas and rub in thoroughly. Use twice daily or as directed by a physician.

INDICATIONS AND USAGE Ammonium Lactate Cream, 12% is indicated for the treatment of ichthyosis vulgaris and xerosis.

WARNING Use of this product should be discontinued if hypersensitivity to any of the ingredients is noted. Sun exposure to areas of the skin treated with ammonium lactate cream should be minimized or avoided (see PRECAUTIONS ).

CLINICAL PHARMACOLOGY Lactic acid is an alpha-hydroxy acid. It is a normal constituent of tissues and blood. The alpha-hydroxy acids (and their salts) are felt to act as humectants when applied to the skin. This property may influence hydration of the stratum corneum. In addition, lactic acid, when applied to the skin, may act to decrease corneocyte cohesion. The mechanism(s) by which this is accomplished is not yet known. An in vitro study of percutaneous absorption of ammonium lactate cream using human cadaver skin indicates that approximately 6.1% of the material was absorbed after 68 hours.

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Ammonium Lactate Ammonium Lactate AMMONIUM LACTATE LACTIC ACID CETYL ALCOHOL GLYCERIN GLYCERYL MONOSTEARATE LIGHT MINERAL OIL MAGNESIUM ALUMINUM SILICATE METHYLPARABEN PEG-100 STEARATE POLYOXYL 40 STEARATE PROPYLENE GLYCOL PROPYLPARABEN WATER LAURETH-4

Carcinogenesis, Mutagenesis, Impairment of Fertility - The topical treatment of CD-1 mice with 12%, 21% or 30% ammonium lactate formulations for two years did not produce a significant increase in dermal or systemic tumors in the absence of increased exposure to ultraviolet radiation. The maximum systemic exposure of the mice in this study was 0.7 times the maximum possible systemic exposure in humans. However, a long-term photocarcinogenicity study in hairless albino mice suggested that topically applied 12% ammonium lactate cream enhanced the rate of ultraviolet light-induced skin tumor formation. The mutagenic potential of ammonium lactate cream was evaluated in the Ames assay and in the mouse in vivo micronucleus assay, both of which were negative. In dermal Segment I and III studies with ammonium lactate cream, there were no effects observed in fertility or pre- or post-natal development parameters in rats at dose levels of 300 mg/kg/day (1800 mg/m 2 /day), approximately 0.4 times the human topical dose

ANDA075774

Ammonium Lactate

Ammonium Lactate

45802-493

HUMAN PRESCRIPTION DRUG

TOPICAL

Principal Display Panel NDC 45802-493-26 Rx Only Ammonium Lactate Cream, 12% For Dermatologic Use Only Not for Ophthalmic, Oral or Intravaginal Use NET WT 385 g The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation. label serialization-template.jpg

Rx Only For Dermatologic Use Only Not for Ophthalmic, Oral or Intravaginal Use

Information for Patients Patients using ammonium lactate cream should receive the following information and instructions: 1. This medication is to be used as directed by the physician, and should not be used for any disorder other than for which it was prescribed. It is for external use only. Avoid contact with eyes, lips, or mucous membranes. 2. Patients should minimize or avoid use of this product on areas of the skin that may be exposed to natural or artificial sunlight, including the face. If sun exposure is unavoidable, clothing should be worn to protect the skin. 3. This medication may cause stinging or burning when applied to skin with fissures, erosions, or abrasions (for example, after shaving the legs). 4. If the skin condition worsens with treatment, the medication should be promptly discontinued.

Nursing Mothers - Although lactic acid is a normal constituent of blood and tissues, it is not known to what extent this drug affects normal lactic acid levels in human milk. Because many drugs are excreted in human milk, caution should be exercised when ammonium lactate cream is administered to a nursing woman.

Pediatric Use - The safety and efficacy of Ammonium Lactate Cream, 12% has been established in patients as young as 2 years old.

Pregnancy: Teratogenic Effects: Pregnancy Category B - Animal reproduction studies have been performed in rats and rabbits at doses up to 0.7 and 1.5 times the human dose, respectively (600 mg/kg/day, corresponding to 3600 mg/m 2 /day in the rat and 7200 mg/m 2 /day in the rabbit) and have revealed no evidence of impaired fertility or harm to the fetus due to ammonium lactate cream. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ammonium lactate cream should be used during pregnancy only if clearly needed.

HOW SUPPLIED Ammonium Lactate Cream, 12% is available as follows: 385 g bottle (NDC 45802- 493 -26) 280 g carton (NDC 45802- 493 -83) containing two 140 g tubes (NDC 45802- 493 -98) STORAGE Store at 20-25°C (68-77°F) [see USP Controlled Room Temperature]. Manufactured By Padagis Minneapolis, MN 55427 www.padagis.com Rev 12-21

STORAGE Store at 20-25°C (68-77°F) [see USP Controlled Room Temperature]. Manufactured By Padagis Minneapolis, MN 55427 www.padagis.com Rev 12-21

General - For external use only. Stinging or burning may occur when applied to skin with fissures, erosions, or that is otherwise abraded (for example, after shaving the legs). Caution is advised when used on the face because of the potential for irritation. The potential for post-inflammatory hypo- or hyperpigmentation has not been studied.

PRECAUTIONS General - For external use only. Stinging or burning may occur when applied to skin with fissures, erosions, or that is otherwise abraded (for example, after shaving the legs). Caution is advised when used on the face because of the potential for irritation. The potential for post-inflammatory hypo- or hyperpigmentation has not been studied. Information for Patients Patients using ammonium lactate cream should receive the following information and instructions: 1. This medication is to be used as directed by the physician, and should not be used for any disorder other than for which it was prescribed. It is for external use only. Avoid contact with eyes, lips, or mucous membranes. 2. Patients should minimize or avoid use of this product on areas of the skin that may be exposed to natural or artificial sunlight, including the face. If sun exposure is unavoidable, clothing should be worn to protect the skin. 3. This medication may cause stinging or burning when applied to skin with fissures, erosions, or abrasions (for example, after shaving the legs). 4. If the skin condition worsens with treatment, the medication should be promptly discontinued. Carcinogenesis, Mutagenesis, Impairment of Fertility - The topical treatment of CD-1 mice with 12%, 21% or 30% ammonium lactate formulations for two years did not produce a significant increase in dermal or systemic tumors in the absence of increased exposure to ultraviolet radiation. The maximum systemic exposure of the mice in this study was 0.7 times the maximum possible systemic exposure in humans. However, a long-term photocarcinogenicity study in hairless albino mice suggested that topically applied 12% ammonium lactate cream enhanced the rate of ultraviolet light-induced skin tumor formation. The mutagenic potential of ammonium lactate cream was evaluated in the Ames assay and in the mouse in vivo micronucleus assay, both of which were negative. In dermal Segment I and III studies with ammonium lactate cream, there were no effects observed in fertility or pre- or post-natal development parameters in rats at dose levels of 300 mg/kg/day (1800 mg/m 2 /day), approximately 0.4 times the human topical dose Pregnancy: Teratogenic Effects: Pregnancy Category B - Animal reproduction studies have been performed in rats and rabbits at doses up to 0.7 and 1.5 times the human dose, respectively (600 mg/kg/day, corresponding to 3600 mg/m 2 /day in the rat and 7200 mg/m 2 /day in the rabbit) and have revealed no evidence of impaired fertility or harm to the fetus due to ammonium lactate cream. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ammonium lactate cream should be used during pregnancy only if clearly needed. Nursing Mothers - Although lactic acid is a normal constituent of blood and tissues, it is not known to what extent this drug affects normal lactic acid levels in human milk. Because many drugs are excreted in human milk, caution should be exercised when ammonium lactate cream is administered to a nursing woman. Pediatric Use - The safety and efficacy of Ammonium Lactate Cream, 12% has been established in patients as young as 2 years old. Geriatric Use - Clinical studies of ammonium lactate cream, 12% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious.