Zypram Cream

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.

Directions for Using ZyPram™

Remove cleansing wipe from package and gently clean the affected area. Discard wipe after use (it is flushable). Remove cap from tube and puncture foil. Attach the provided applicator. Squeeze tube until the applicator is full. Gently insert the tip of the filled applicator approximately ½ inch into the anal area and squeeze the tube, applying ZyPram™ cream to the anus and the peri-anal area. Do not insert the applicator any additional length into the anus or into the rectum. Remove the applicator and tube. Thoroughly clean the applicator. If directed by a physician, a small amount of cream may be applied to the anal area using a fingertip.

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

Use in Pregnancy

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 corticosteroid induced HPA axis suppression and Cushing's syndrome than mature patients because of a 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.

ZyPram™ NDC 68025-040-30, contains 1 tube 30 g, 2 wipes, 1 applicator and insert.

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

Storage Conditions

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

05/09

Rx Only

Manufactured For:
Vertical Pharmaceuticals, Inc.
Sayreville, NJ 08872

Lipid Base Delivery System
QuSomes™
U.S. Patent No. 6,610,322
U.S. Patent No. 6,958,160
U.S. Patent No. 7,150,883
2 Other patents pending

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.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dry skin.
• Burning.
• Itching.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Applies to hydrocortisone / pramoxine topical: rectal cream, rectal foam, rectal kit, rectal lotion, topical cream, topical foam, topical gel, topical lotion, topical ointment

Dermatologic

Dermatologic side effects including burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria have been reported.[Ref]

Hypersensitivity

Hypersensitivity side effects including allergic contact dermatitis have been reported.[Ref]

Some side effects of Zypram may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.