Salicylic Acid

PruGen, Inc.

Salicylic Acid 6% Cream

FULL PRESCRIBING INFORMATION

Salicylic Acid 6% Cream contains 6% salicylic acid 
USP incorporated into a specially formulated oil
in water emulsion vehicle containing ammonium
lactate, cetearyl alcohol, cetearyl alcohol and
PEG-3 distearoylamidoethylmonium methosulfate
and polysorbate 60, cetyl alcohol, dimethicone
350, disodium EDTA, glycerine, glyceryl stearate
SE, methyl paraben, mineral oil, PEG-100 stearate,
phenoxyethanol, propyl paraben, purified water
and trolamine.
Salicylic acid is the 2-hydroxy derivative of benzoic
acid having the following structure:

This formulation has been shown to provide gradual
and prolonged release of the active ingredient into 
the skin.


Salicylic acid has been shown to produce 
desquamation of the horny layer of skin while not 
effecting qualitative or quantitative changes in the
structure of the viable epidermis. The mechanism of 
action has been attributed to a dissolution of
 intercellular cement substance. In a study of the
percutaneous absorption of salicylic acid in a 6%
 salicylic acid gel in four patients with extensive
 active psoriasis, Taylor and Halprin showed that the
peak serum salicylate levels never exceeded 5
mg/100 mL even though more than 60% of the 
applied salicylic acid was absorbed. Systemic toxic
reactions are usually associated with much higher 
serum levels (30 to 40 mg/100 mL). Peak serum 
levels occurred within five hours of the topical
application under occlusion. The sites were 
occluded for 10 hours over the entire body surface 
below the neck. Since salicylates are distributed in 
the extracellular space, patients with a contracted 
extracellular space due to dehydration or diuretics 
have higher salicylate levels than those with a
normal extracellular space. (See PRECAUTIONS.)
 The major metabolites identified in the urine after 
topical administration are salicyluric acid (52%),
salicylate glucuronides (42%) and free salicylic acid 
(6%). The urinary metabolites after percutaneous 
absorption differ from those after oral salicylate 
administration; those derived from percutaneous 
absorption contain more salicylate glucuronides 
and less salicyluric and salicylic acid. Almost 95%
 of a single dose of salicylate is excreted within 24
 hours of its entrance into the extracellular space.
 Fifty to eighty percent of salicylate is protein bound
 to albumin. Salicylates compete with the binding 
of several drugs and can modify the action of these 
drugs; by similar competitive mechanisms other 
drugs can influence the serum levels of salicylate. 
(See PRECAUTIONS.)

Uses

For Dermatologic Use: Salicylic Acid 6% Cream is
 a topical aid in the removal of excessive keratin in 
hyperkeratotic skin disorders, including verrucae,
 and the various ichthyoses (vulgaris, sex-linked
and lamellar), keratosis palmaris and plantaris, 
keratosis pilaris, pityriasis rubra pilaris, and
psoriasis (including body, scalp, palms and soles). 
For Podiatric Use: Salicylic Acid 6% Cream is a 
topical aid in the removal of excessive keratin on
dorsal and plantar hyperkeratotic lesions. Topical 
preparations of 6% salicylic acid have been
 reported to be useful adjunctive therapy for verrucae
plantares.

Salicylic Acid 6% Cream should not be used in any
 patient known to be sensitive to salicylic acid or any 
other listed ingredients. Salicylic Acid 6% Cream
 should not be used in children under 2 years of age.

Prolonged and repeated daily use over large areas, 
especially in children and those patients with 
significant renal or hepatic impairment, could result
in salicylism. Patients should be advised not to apply 
occlusive dressings, clothing or other occlusive topical 
products such as petrolatum-based ointments 
to prevent excessive systemic exposure to salicylic 
acid. Excessive application of the product other than
 is needed to cover the affected area will not result
in a more rapid therapeutic benefit. Concomitant use of other drugs which may contribute to elevated
 serum salicylate levels should be avoided where the
 potential for toxicity is present. In children under 12
 years of age and those patients with renal or hepatic
impairment, the area to be treated should be 
limited and the patient monitored closely for signs 
of salicylate toxicity: nausea, vomiting, dizziness,
loss of hearing, tinnitus, lethargy, hyperpnea,
 diarrhea, and psychic disturbances. In the event
of salicylic acid toxicity, the use of Salicylic Acid 
6% Cream should be discontinued. Fluids should 
be administered to promote urinary excretion. Treatment
 with sodium bicarbonate (oral or intravenous) 
should be instituted as appropriate. Patients
 should be cautioned against the use of oral aspirin 
and other salicylate containing medications, such 
as sports injury creams, to avoid additional excessive
 exposure to salicylic acid. Where needed, aspirin 
should be replaced by an alternative non-steroidal
anti-inflammatory agent that is not salicylate based. 
Due to potential risk of developing Reye’s syndrome, 
salicylate products should not be used in children
 and teenagers with varicella or influenza, unless
 directed by a physician.

For external use only. Avoid contact with eyes and other mucous
membranes.

The following interactions are from a published
review and include reports concerning both oral and
topical salicylate administration. The relationship of
these interactions to the use of Salicylic Acid 6%
Cream is not known.


I. Due to the competition of salicylate with other
drugs for binding to serum albumin the following
drug interactions may occur:


DRUG DESCRIPTION OF INTERACTION


Sulfonylureas Hypoglycemia potentiated.


Methotrexate Decreases tubular reabsorption; clinical toxicity from methotrexate can result.


Oral Anticoagulants Increased bleeding.

II. Drugs changing salicylate levels by altering renal
tubular reabsorption:


DRUG DESCRIPTION OF INTERACTION


Corticosteroids Decreases plasma salicylate level; tapering doses of steroids may promote salicylism.


Acidifying Agents Increases plasmasalicylate level.


Alkalizing Agents Decreased plasma salicylate levels.

III. Drugs with complicated interactions with
salicylates:


DRUG DESCRIPTION OF INTERACTION


Heparin Salicylate decreases platelet adhesiveness and interferes with hemostasis in heparin-treated patients.


Pyrazinamide Inhibits pyrazinamideinduced hyperuricemia.


Uricosuric Agents Effect of probenemide, sulfinpyrazone and phenylbutazone inhibited.

The following alterations of laboratory tests have
been reported during salicylate therapy:


LABORATORY TESTS EFFECT OF SALICYLATES


Thyroid Function Decreased PBI; increased T3 uptake.


Urinary Sugar False negative with glucose oxidase; false positive with Clinitest with high-dose salicylate therapy (2-5g q.d.).


5-Hydroxyindole acetic acid False negative with fluorometric test.

Acetone, False positive FeCl3 in Gerhardt reaction; red color persists with boiling.
ketone bodies


17-OH corticosteroids False reduced values with >4.8g q.d. salicylate.



Vanilmandelic acid False reduced values.


Uric acid May increase or decrease depending on dose.


Prothrombin Decreased levels; slightly increased prothrombin time.

Category C – Salicylic acid has been shown to be 
teratogenic in rats and monkeys. It is difficult to extrapolate from
 oral doses of acetylsalicylic acid used in these studies to topical 
administration as the oral dose to monkeys may represent six 
times the maximal daily human dose of salicylic acid when
 applied topically over a large body surface. There are no adequate
 and well-controlled studies in pregnant women. Salicylic Acid 6%
(w/w) Shampoo should be used during pregnancy only if the 
potential benefit justifies the potential risk to the fetus.

Salicylic acid has been shown to be
teratogenic in rats and monkeys. It is difficult to extrapolate from
oral doses of acetylsalicylic acid used in these studies to topical
administration as the oral dose to monkeys may represent six
times the maximal daily human dose of salicylic acid when
applied topically over a large body surface. There are no adequate
and well-controlled studies in pregnant women. Salicylic Acid 6%
(w/w) Shampoo should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.

No data are available 
concerning potential carcinogenic or reproductive
 effects of Salicylic Acid 6% Cream. Salicylic acid has 
been shown to lack mutagenic potential in the Ames
 Salmonella test

Excessive erythema and scaling conceivably could
 result from use on open skin lesions.


See Warnings.

The preferable method of use is to apply 6% Salicylic 
Acid Cream thoroughly to the affected area and to 
cover the treated area at night after washing and
 before retiring. Preferably, the skin should be
 hydrated for at least five minutes prior to application.
The medication is washed off in the morning and if 
excessive drying and/or irritation is observed, a bland
 cream or lotion may be applied. Once clearing is 
apparent, the occasional use of Salicylic Acid 6%
 Cream will usually maintain the remission. In those 
areas where occlusion is difficult or impossible,
 application may be made more frequently; hydration
by wet packs or baths prior to application apparently
 enhances the effect. (See WARNINGS.) Unless hands
 are being treated, hands should be rinsed thoroughly 
after application. Excessive repeated application of 
Salicylic Acid 6% Cream will not necessarily increase
 its therapeutic benefit, but could result in increased 
local intolerance and systemic adverse effects such
 as salicylism.

Salicylic Acid 6% Cream Kit includes a 454 g 
(16 oz.) jar with Salicylic Acid 6% Cream (NDC 
42546-270-16) as well as a complimentary 12 fl. oz.
PruDrate Hydrating Cleanser.
 Store at controlled room temperature 20°-25°C
 (68°-77°F). Do not freeze.

NDC 42546-270-01

Rx Only

Salicylic Acid 6% Cream Kit

Dispense as a complete kit

For topical use only

Kit includes:

- 1 jar of salicylic acid 6% cream. Net Wt. 454g (16 oz)

- 1 bottle PruDrate Hydrating Cleanser. 12 fl. oz.

- Package insert

PruGen, Inc. Pharmaceuticals