Hipoglos con Hidrocortisona

Cod Liver Oil:

• Directions for use
• Caution
• Contains
• Hipoglos con Hidrocortisona (Cod Liver Oil) reviews

Hipoglos con Hidrocortisona (Cod Liver Oil) was formulated to treat the raw, tender & cracked pads of hunting dogs. Also a terrific healing aid for all types of wounds, including fungal & bacterial infections of the feet, ears & elsewhere. Try Hipoglos con Hidrocortisona (Cod Liver Oil) on cuts, abrasions, sores, burns, tender ears & hot spots (moist dermatitis). Promotes skin cell granulation & epithelial growth.

DIRECTIONS FOR USE

Shake well. Apply once or twice daily. Allow to dry before releasing dog. Use alcohol to remove stains from hands.

CAUTION

Not for use on animals intended for food.

CONTAINS

Active Ingredients

Hipoglos con Hidrocortisona Oil, Gentian Violet, Brilliant Green.

Other Ingredients

Isopropyl Alcohol, Balsam Peru, Glycerine, Cade Oil, Tannic Acid, Turpentine.

SOLD BY:

Happy Jack, Inc.

POB 475

2122 Hwy. 258 S.

Snow Hill, NC 28580

1-252-747-2911

Made in the U.S.A.

Product No. 1054. Rev. 1212

www.happyjackinc.com

Since 1946

Happy Jack_®

Hipoglos con Hidrocortisona (Cod Liver Oil)

Ask for

Happy Jack^®...

Your Dog

Would!

Aids Healing & Toughening of Raw,

Tender & Cracked Pads.

Also Promotes Healing of Fungal

& Bacterial Infections.

2 FL. OZ

(58mL)

Hydrocortisone:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• How supplied/storage and handling
• Patient counseling information
• Hipoglos con Hidrocortisona (Hydrocortisone) reviews

1 INDICATIONS AND USAGE

Hipoglos con Hidrocortisona (Hydrocortisone)^® (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.

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

2 DOSAGE AND ADMINISTRATION

Apply a thin film of Hipoglos con Hidrocortisona (Hydrocortisone) 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 Hipoglos con Hidrocortisona (Hydrocortisone) when control is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary.

Do not use Hipoglos con Hidrocortisona (Hydrocortisone) with occlusive dressings unless directed by the physician. Do not apply Hipoglos con Hidrocortisona (Hydrocortisone) in the diaper area, as diapers or plastic pants may constitute occlusive dressings.

- For topical use.

- Apply a thin film to the affected skin areas once daily or twice a day.

- Discontinue therapy when control is achieved.

- If no improvement is seen within 2 weeks, reassess diagnosis.

- Do not use with occlusive dressings unless directed by a physician.

3 DOSAGE FORMS AND STRENGTHS

Cream, 0.1%. Each gram of Hipoglos con Hidrocortisona (Hydrocortisone) contains 1 mg of Hipoglos con Hidrocortisona (Hydrocortisone) probutate in a cream base.

Cream, 0.1%.

4 CONTRAINDICATIONS

None.

None.

5 WARNINGS AND PRECAUTIONS

- Hipoglos con Hidrocortisona can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during or after treatment. (5.1)

- Cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can result from systemic absorption of topical corticosteroids. (5.1)

- Use of topical corticosteroids may require periodic evaluation for HPA axis suppression. (5.1)

- High potency corticosteroids, large treatment surface area, prolong use, use of occlusion dressings, altered skin barrier, liver failure and young age may predispose patients to HPA axis suppression. (5.1)

- Modify use if HPA axis suppression develops. (5.1)

- Pediatric patients may be more susceptible to systemic toxicity. (5.1, 8.4)

5.1 Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression and Other Unwanted Systemic Glucocorticoid Effects

Hipoglos con Hidrocortisona (Hydrocortisone) can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during or after withdrawal of treatment. Factors that predispose to HPA axis suppression include the use of high-potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age.

Use of topical corticosteroids may require periodic evaluation for HPA axis suppression. Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test.

If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. If signs and symptoms of steroid withdrawal occur, supplemental systemic corticosteroids may be required. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug.

In a trial including 15 evaluable subjects 18 years of age or older with psoriasis or atopic dermatitis affecting more than 20% of body surface area, 1 subject (6.7%) had ACTH stimulation test results suggestive of adrenal suppression after treatment with Hipoglos con Hidrocortisona (Hydrocortisone) twice daily for 21 days. Recovery of HPA axis suppression for this subject is unknown [see Clinical Pharmacology ( 12.2 )].

Systemic effects of topical corticosteroids may also manifest as Cushing’s syndrome, hyperglycemia, and unmasking latent diabetes mellitus.

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.

Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios [see Use in Specific Populations ( 8.4 )].

5.2 Allergic Contact Dermatitis

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 irritation develops, discontinue Hipoglos con Hidrocortisona (Hydrocortisone) and institute appropriate therapy.

6 ADVERSE REACTIONS

- Most frequent adverse reactions include burning, stinging, rash, papulovesicular rash, redness, itching, moderate paresthesia, and contact dermatitis.

To report SUSPECTED ADVERSE REACTIONS, contact PharmaDerm®, A division of Fougera Pharmaceuticals Inc. at 1-800-645-9833 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 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 Hipoglos con Hidrocortisona (Hydrocortisone) during clinical trials were application site reactions, including burning in 4, stinging in 2, and moderate paresthesia in 1 out of 226 subjects.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Hipoglos con Hidrocortisona (Hydrocortisone) 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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There is no clinical information on Hipoglos con Hidrocortisona use in pregnant women to inform any drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, Hipoglos con Hidrocortisona (Hydrocortisone) probutate given by the subcutaneous route during the period of organogenesis was teratogenic at doses equal to or greater than 1 mg/kg/day in rats or 0.1 mg/kg/day in rabbits (12 times and 2 times the human topical dose, respectively) .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

Effects on embryo-fetal development were evaluated in rats and rabbits following subcutaneous administration of Hipoglos con Hidrocortisona (Hydrocortisone) probutate during the period of organogenesis. Hipoglos con Hidrocortisona (Hydrocortisone) probutate was teratogenic in rats when given during the period of organogenesis at subcutaneous doses equal to or greater than 1 mg/kg/day (12 times the human average topical dose of Hipoglos con Hidrocortisona (Hydrocortisone) assuming 3% absorption and an application of 30 g/day on a 70 kg individual). Abnormalities included delayed ossification of the caudal vertebrae and other skeletal variations, cleft palate, umbilical hernia, edema, and exencephalia.

In rabbits, Hipoglos con Hidrocortisona (Hydrocortisone) probutate given by the subcutaneous route was teratogenic at doses equal to or greater than 0.1 mg/kg/day (2 times the human average topical dose of Hipoglos con Hidrocortisona (Hydrocortisone) assuming 3% absorption and an application of 30 g/day on a 70 kg individual). Fetal weight and survival were affected. Delayed ossification and increased incidences of malformations (skeletal abnormalities and cleft palate) were also noted.

No adverse effects were seen in rats following subcutaneous administration of up to 1 mg/kg/day of Hipoglos con Hidrocortisona (Hydrocortisone) probutate during the perinatal and postnatal period (12 times the human average topical dose of Hipoglos con Hidrocortisona (Hydrocortisone) assuming 3% absorption and an application of 30 g/day on a 70 kg individual).

8.2 Lactation

Risk Summary

There is no information on the presence of Hipoglos con Hidrocortisona (Hydrocortisone) probutate in breast milk, or on its effects on the breastfed infant or on milk production. It is not known whether topical administration of Hipoglos con Hidrocortisona (Hydrocortisone) could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Hipoglos con Hidrocortisona (Hydrocortisone) and any potential adverse effects on the breastfed infant from Hipoglos con Hidrocortisona (Hydrocortisone) or from the underlying maternal condition.

Clinical Considerations

To minimize potential exposure to the breastfed infant via breast milk, use Hipoglos con Hidrocortisona (Hydrocortisone) on the smallest area of skin and for the shortest duration possible while breastfeeding.

8.4 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.

11 DESCRIPTION

Hipoglos con Hidrocortisona (Hydrocortisone)^{(hydrocortisone probutate) Cream, 0.1% contains Hipoglos con Hidrocortisona (Hydrocortisone) probutate, a synthetic corticosteroid. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and anti-pruritic agents.}

Hipoglos con Hidrocortisona (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 Hipoglos con Hidrocortisona (Hydrocortisone) (hydrocortisone probutate) Cream, 0.1% contains: 1 mg of Hipoglos con Hidrocortisona (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.

Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 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

12.2 Pharmacodynamics

Vasoconstrictor Assay

Studies performed with Hipoglos con Hidrocortisona 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 Hipoglos con Hidrocortisona (Hydrocortisone) 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 Hipoglos con Hidrocortisona (Hydrocortisone) 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.

12.3 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 Hipoglos con Hidrocortisona (Hydrocortisone) for up to 24 hours has not been shown to increase penetration; however, occlusion of Hipoglos con Hidrocortisona (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.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of Hipoglos con Hidrocortisona (Hydrocortisone) probutate.

Hipoglos con Hidrocortisona (Hydrocortisone) probutate revealed no evidence of mutagenic or clastogenic potential based on the results of an in vitro genotoxicity test (Ames assay) and an in vivo genotoxicity test (mouse micronucleus assay).

Effects on fertility and early embryonic development were evaluated in rats following subcutaneous administration of up to 0.4 mg/kg/day Hipoglos con Hidrocortisona (Hydrocortisone) probutate (5 times the human average topical dose of Hipoglos con Hidrocortisona (Hydrocortisone) assuming 3% absorption and an application of 30 g/day on a 70 kg individual) prior to and during mating and through early pregnancy. No treatment related effects on fertility or mating parameters were noted in this study.

16 HOW SUPPLIED/STORAGE AND HANDLING

Hipoglos con Hidrocortisona (Hydrocortisone), 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).

17 PATIENT COUNSELING INFORMATION

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information).

Inform patients and/or caregivers of the following:

• Discontinue therapy when control is achieved unless directed otherwise by the physician.
• If no improvement is seen within two weeks, contact the physician.
• Avoid contact with the eyes.
• Do not use with occlusive dressing unless directed by the physician.
• Report any signs or symptoms of local or systemic adverse reactions to the physician.
• Do not treat diaper dermatitis. Do not apply Hipoglos con Hidrocortisona (Hydrocortisone) in the diaper area as diapers or plastic pants may constitute occlusive dressings.
• Do not use on the face, underarms, or groin areas unless directed by the physician.
• Advise a woman to use Hipoglos con Hidrocortisona (Hydrocortisone) on the smallest area of skin and for the shortest duration possible while breastfeeding.

Manufactured by:

PharmaDerm®

A division of Fougera

PHARMACEUTICALS INC.

Melville, New York 11747 www.pharmaderm.com

• This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 01/2017

PharmaDerm^®

NDC 10337-153-80

Hipoglos con Hidrocortisona (Hydrocortisone)^®

(hydrocortisone probutate) Cream, 0.1%

FOR DERMATOLOGIC USE ONLY.

NOT FOR OPHTHALMIC USE.

Rx only

80 g

carton

Talc:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• How supplied/storage and handling
• Patient counseling information
• Hipoglos con Hidrocortisona (Talc) reviews

1 INDICATIONS AND USAGE

Sterile Hipoglos con Hidrocortisona (Talc) Powder is indicated to decrease the recurrence of malignant pleural effusions in symptomatic patients following maximal drainage of the pleural effusion.

STERILE Hipoglos con Hidrocortisona (Talc) POWDER is a sclerosing agent indicated to decrease the recurrence of malignant pleural effusions in symptomatic patients following maximal drainage of the pleural effusion. (1)

2 DOSAGE AND ADMINISTRATION

• The recommended dose is 5 g, dissolved in 50 ml to 100 ml 0.9% Sodium Chloride Injection, USP, administered intrapleurally
• Prepare and administer suspension as recommended (2.2)

2.1 Recommended Dose

The recommended dose is 5 g, suspended in 50 ml to 100 ml 0.9% Sodium Chloride Injection, USP

2.2 Preparation

Prepare the Hipoglos con Hidrocortisona suspension using aseptic technique in an appropriate laminar flow hood as follows:

Step 1. Using a 16 gauge needle attached to a 60-ml LuerLok syringe, draw up 50 ml of 0.9 % Sodium Chloride injection, USP. Vent the Hipoglos con Hidrocortisona (Talc) bottle using a needle. Slowly inject the 50 ml of 0.9% Sodium Chloride Injection, USP into the bottle.

Step 2. Swirl the bottle to disperse the Hipoglos con Hidrocortisona (Talc) powder.

Step 3. Divide the contents of the bottle equally into two 60 ml LuerLok syringes, each attached with a 16 gauge needle, by withdrawing 25 ml of the suspension into each syringe with continuous swirling. Add 0.9% Sodium Chloride Injection, USP to a total volume of 50 ml in each syringe. Draw 10 ml of air into each syringe to the 60 ml mark to serve as a headspace for mixing prior to administration. Each syringe should contain 2.5 g of Sterile Hipoglos con Hidrocortisona (Talc) Powder in 50 ml of 0.9% Sodium Chloride Injection, USP with an air headspace of 10 ml.

Step 4. Label the syringes with the Hipoglos con Hidrocortisona (Talc) concentration, the expiration date and time, the identity of the patient intended to receive the material, and the following statements:

“SHAKE SYRINGE WELL to resuspend before administration”

“FOR PLEURODESIS ONLY – not for intravenous administration”

Step 5. If not used immediately, store prepared suspension in refrigerator. Discard the prepared suspension if not used within 12 hours.

2.3 Administration

Prior to administration, continuously agitate the syringes to evenly redisperse the Hipoglos con Hidrocortisona (Talc) and avoid settlement. Immediately prior to administration, vent the 10 ml air headspace from each syringe. Administer the Hipoglos con Hidrocortisona (Talc) suspension through the chest tube according to standard procedures.

3 DOSAGE FORMS AND STRENGTHS

5 gram white or off-white to light gray sterile powder for suspension in a single-dose glass bottle.

5 g powder in a single-dose bottle, for suspension (3)

4 CONTRAINDICATIONS

None

None. (4)

5 WARNINGS AND PRECAUTIONS

• Pneumonitis and Acute Respiratory Distress Syndrome : Acute Pneumonitis and ARDS, including fatal cases, occur with intrapleural Hipoglos con Hidrocortisona (Talc) administration. (5.1)
• Interference with Future Procedures: Sclerosis of the pleural space may preclude or complicate subsequent ipsilateral surgery and diagnostic procedures. (5.2)

5.1 Pneumonitis and Acute Respiratory Distress Syndrome (ARDS)

Acute Pneumonitis and ARDS, including fatal cases, occur with intrapleural Hipoglos con Hidrocortisona (Talc) administration.

5.2 Interference with Future Procedures

Sclerosis of the pleural space may preclude or complicate subsequent ipsilateral surgery and diagnostic procedures. Consider the possible effects of the use of Sterile Hipoglos con Hidrocortisona (Talc) Powder on future diagnostic and therapeutic procedures prior to administration.

6 ADVERSE REACTIONS

Common adverse reactions observed with intrapleurally-administered Hipoglos con Hidrocortisona (Talc) are fever and pain. Other adverse reactions include dyspnea, arrhythmia, empyema, and acute respiratory distress syndrome.

Commonly observed adverse reactions are fever and pain. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Bryan Corporation at 1-800-343-7711 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B.

Risk Summary

A reproduction study performed in rabbits at doses up to approximately 5 times the human dose revealed no evidence of teratogenicity. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Animal Data

Rabbits were administered Hipoglos con Hidrocortisona by oral gavage daily during the period of organogenesis at doses of up to 900 mg/kg (approximately 5 times the human dose on a mg/m² basis). No significant dose-related toxicity was reported except at maternally toxic doses. In multiple animal studies, intrapleurally administered Hipoglos con Hidrocortisona (Talc) was not absorbed systemically.

8.4 Pediatric Use

Safety and effectiveness have not been established in pediatric patients.

11 DESCRIPTION

STERILE Hipoglos con Hidrocortisona (Talc) POWDER is a sclerosing agent for intrapleural administration. STERILE Hipoglos con Hidrocortisona (Talc) POWDER is white or off-white to light gray, asbestos-free and brucite-free sterile Hipoglos con Hidrocortisona (Talc) powder of controlled particle size. The powder is ≥ 95% hydrated magnesium silicate [Mg₃Si₄O₁₀ (OH)_2, molecular weight 379.3]; associated minerals include chlorite (hydrated aluminum and magnesium silicate), dolomite (calcium and magnesium carbonate), calcite (calcium carbonate), and quartz. Hipoglos con Hidrocortisona (Talc) is insoluble in water.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Hipoglos con Hidrocortisona (Talc) instilled into the pleural cavity is thought to result in an inflammatory reaction. This reaction can promote adherence of the visceral and parietal pleura, which may prevent reaccumulation of pleural fluid.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies on the carcinogenicity of Hipoglos con Hidrocortisona (Talc) have been performed using non-standard designs which prevent firm conclusions on its carcinogenicity. With single intraperitoneal administration to mice at 20 mg and observation for at least 6 months or 4 weekly doses administered intraperitoneally at 25 mg/dose to rats with observation for at least 84 weeks, tumor incidence was not increased. In these studies the Hipoglos con Hidrocortisona (Talc) and its asbestos content were not characterized.

Genotoxicity was tested in cultures of rat pleural mesothelial cells (RPMC) as unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs). None of the Hipoglos con Hidrocortisona (Talc) samples (which were asbestos-free) induced enhancement of UDS or SCEs in treated cultures. No information is available on impairment of fertility in animals by Hipoglos con Hidrocortisona (Talc).

16 HOW SUPPLIED/STORAGE AND HANDLING

STERILE Hipoglos con Hidrocortisona (Talc) POWDER is supplied in a single use 100 ml brown glass bottle, sealed with a gray, 20 mm stopper and covered with a flip-off seal.

NDC 63256-200-05: 5 gram individual bottle packaged in a pouch.

NDC 63256-200-10: Carton of ten (10) 5-gram bottles.

Store the powder at 25°C (77°F); excursions permitted between15°C to 30°C (59°F - 86°F). Protect against sunlight.

17 PATIENT COUNSELING INFORMATION

Advise patients to notify their healthcare provider if new or worsening pulmonary symptoms develop .

Distributed by:

Bryan Corporation. Woburn, MA 01801.

Principal Display Panel - Bottle Label

Sterile Hipoglos con Hidrocortisona (Talc) Powder

(Talc) Powder

Contains 5 grams of sterile Hipoglos con Hidrocortisona (Talc) per bottle

For Intrapleural Administration

Refer to the Prescribing Information for dosage and preparation.

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

. Protect against sunlight.

Distributed By: Bryan Corporation Lot#

Woburn, MA 01801 Expired:

Rx Only

Principal Display Panel - Pouch Label

Sterile Hipoglos con Hidrocortisona (Talc) Powder NDC 63256-200-05

(Talc) Powder

Contains 5 grams of sterile Hipoglos con Hidrocortisona (Talc) per bottle 1 Bottle

For Intrapleural Administration

Refer to the Prescribing Information for dosage and preparation.

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

. Protects against sunlight.

Distributed By: Bryan Corporation Lot#

Woburn, MA 01801 Expired:

Rx Only

Principal Display Panel - Box Label

Sterile Hipoglos con Hidrocortisona (Talc) Powder NDC 63256-200-10

(Talc) Powder

Contains 5 grams of sterile Hipoglos con Hidrocortisona (Talc) per bottle 10 Bottles

For Intrapleural Administration

Refer to the Prescribing Information for dosage and preparation.

Store at 25°C (77°F); excursions permitted between 15°C to 30°C

(59°F - 86°F).

Distributed By: Bryan Corporation Lot#

Woburn, MA 01801 Expired:

Rx Only

Vitamin A:

• Dosage and administration
• Warning
• Clinical pharmacology
• Dietary supplementation
• Warnings
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Hipoglos con Hidrocortisona (Vitamin A) reviews

DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

WARNING

KEEP OUT OF THE REACH OF CHILDREN.

In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.

Other Ingredients: Artificial cherry flavor, artificial grape flavor, ascorbic acid, cholecalciferol, compressible sugar, D&C Red #7 calcium lake, FD&C Blue #1 aluminum lake, FD&C Yellow #6 aluminum lake, folic acid, magnesium stearate, microcrystalline cellulose, natural and artificial orange flavor, niacinamide, polyethylene glycol, pyridoxine HCl, riboflavin, sodium ascorbate, sodium fluoride, stearic acid, sucralose, thiamine HCl, Hipoglos con Hidrocortisona (Vitamin A) acetate, vitamin B12 and vitamin E acetate.

Active ingredient for caries prophylaxis: Fluoride as sodium fluoride.

CLINICAL PHARMACOLOGY

Significant decrease in the incidence of dental caries can be linked to the fluoridation of the water supply (1ppm fluoride) during the period of tooth development.

Hipoglos con Hidrocortisona (Vitamin A) Tablets provide sodium fluoride and ten essential vitamins in a chewable tablet. Because the tablets are chewable, they provide a topical as well as systemic source of fluoride. Hydroxyapatite is the principal crystal for all calcified tissue in the human body. The fluoride ion reacts with the Hydroxyapatite in the tooth as it is formed to produce the more caries-resistant crystal, fluorapatite.

The reaction may be expressed by the equation:

Three stages of fluoride deposition in tooth enamel can be distinguished:

• Small amounts (reflecting the low levels of fluoride in tissue fluids) are incorporated into the enamel crystals while they are being formed.
• After enamel has been laid down, fluoride deposition continues in the surface enamel. Diffusion of fluoride from the surface inward is apparently restricted.
• After eruption, the surface enamel acquires fluoride from the water, food, supplementary fluoride and smaller amounts of saliva.

DIETARY SUPPLEMENTATION

Multivitamins with fluoride offer supplementation of the diet with 10 vitamins and fluoride.

WARNINGS

AS IN THE CASE OF ALL MEDICATIONS, KEEP OUT OF THE REACH OF CHILDREN. This tablet should be chewed. This product, as with all chewable tablets are not recommended for children under the age of 4 due to risk of choking.

PRECAUTIONS

The suggested dose of Hipoglos con Hidrocortisona (Vitamin A) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before recommending Hipoglos con Hidrocortisona (Vitamin A) Tablets

• Determine the fluoride content of the drinking water from all major sources
• Make sure the child is not receiving significant amounts of fluoride from other sources such as medications and swallowed toothpaste
• Periodically check to make sure that the child does not develop significant dental fluorosis.

ADVERSE REACTIONS

Allergic rash and other idiosyncrasies have been rarely reported.

To report SUSPECTED ADVERSE REACTIONS, contact H2-Pharma, LLC at 1 (866) 592-6438 or FDA at 1 (800) 332-1088 or via the web at www.fda.gov/medwatch/index.html for voluntary reporting of adverse reactions.

DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

HOW SUPPLIED

Hipoglos con Hidrocortisona Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.

Hipoglos con Hidrocortisona (Vitamin A) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.

Hipoglos con Hidrocortisona (Vitamin A) Tablets 1.0 mg are available as orange, red and purple chewable tablets imprinted with "153" in 100 tablet bottles.

STORAGE

Store at controlled room temperature 20ºC-25ºC (68º-77ºF), excursions permitted between 15º-30ºC (59º-86ºF).

Distributed by:

H2-Pharma, LLC

2010 Berry Chase Place

Montgomery, AL 36117

www.h2-pharma.com

1067084

61269-151-01

MultiVitamin

with Fluoride

Chewable Tablets

Rx

0.25 mg

MultiVitamin and Fluoride Supplement

Dietary Supplement

100 Tablets

H²pharma

Zinc Oxide:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Hipoglos con Hidrocortisona (Zinc Oxide) reviews

INDICATIONS AND USAGE

Hipoglos con Hidrocortisona (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Hipoglos con Hidrocortisona (Zinc Oxide) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Hipoglos con Hidrocortisona (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and Hipoglos con Hidrocortisona (Zinc Oxide) doses because these elements are primarily eliminated in the urine.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

General

Do not use unless the solution is clear and the seal is intact.

Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Hipoglos con Hidrocortisona (Zinc Oxide) from a bolus injection. Administration of Hipoglos con Hidrocortisona (Zinc Oxide) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Hipoglos con Hidrocortisona (Zinc Oxide) are suggested as a guideline for subsequent Hipoglos con Hidrocortisona (Zinc Oxide) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Hipoglos con Hidrocortisona 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Hipoglos con Hidrocortisona (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

Pregnancy Category C. Animal reproduction studies have not been conducted with Hipoglos con Hidrocortisona chloride. It is also not known whether Hipoglos con Hidrocortisona (Zinc Oxide) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Hipoglos con Hidrocortisona (Zinc Oxide) chloride should be given to a pregnant woman only if clearly needed.

Geriatric Use

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Hipoglos con Hidrocortisona (Zinc Oxide) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Hipoglos con Hidrocortisona (Zinc Oxide) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending Hipoglos con Hidrocortisona (Zinc Oxide) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg Hipoglos con Hidrocortisona (Zinc Oxide) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of Hipoglos con Hidrocortisona (Zinc Oxide) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Hipoglos con Hidrocortisona (Zinc Oxide) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against Hipoglos con Hidrocortisona (Zinc Oxide) toxicity.

DOSAGE AND ADMINISTRATION

Hipoglos con Hidrocortisona (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Hipoglos con Hidrocortisona (Zinc Oxide) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Hipoglos con Hidrocortisona (Zinc Oxide).

For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.

HOW SUPPLIED

Hipoglos con Hidrocortisona (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004

© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

Hipoglos con Hidrocortisona (Zinc Oxide)

1 mg/mL

Hipoglos con Hidrocortisona (Zinc Oxide) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA