Evoclin

clindamycin phosphate

Dosage Form: aerosol, foam
FULL PRESCRIBING INFORMATION

Indications and Usage for Evoclin

Evoclin Foam is indicated for topical application in the treatment of acne vulgaris in patients 12 years and older.

Evoclin Dosage and Administration

Evoclin Foam is for topical use only, and not for oral, ophthalmic, or intravaginal use.

Apply Evoclin Foam once daily to affected areas after the skin is washed with mild soap and allowed to fully dry. Use enough to cover the entire affected area.

The contents of Evoclin Foam are flammable; avoid fire, flame and/or smoking during and immediately following application.

Dosage Forms and Strengths

White to off-white thermolabile foam. Each gram of Evoclin Foam contains, as dispensed, 12 mg (1.2%) of clindamycin phosphate, equivalent to 10 mg (1%) of clindamycin.

Contraindications

Evoclin Foam is contraindicated in individuals with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis.

Warnings and Precautions

Colitis

Systemic absorption of clindamycin has been demonstrated following topical use of this product. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. If significant diarrhea occurs, Evoclin Foam should be discontinued. [See Adverse Reactions (6.2).]

Severe colitis has occurred following oral or parenteral administration of clindamycin with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death.

Studies indicate a toxin(s) produced by Clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.

Irritation

Evoclin Foam can cause irritation.

Avoid contact of Evoclin Foam with eyes. If contact occurs, rinse eyes thoroughly with water.

Evoclin Foam should be prescribed with caution in atopic individuals.

Adverse Reactions

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.

A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with Evoclin Foam.

The incidence of adverse reactions occurring in ≥1% of the subjects in clinical trials comparing Evoclin Foam, and its vehicle is presented in Table 1.

Table 1: Adverse Reactions Occurring in ≥1% of Subjects

Adverse Reactions	Number (%) of Subjects
	Evoclin Foam	Vehicle Foam
	N = 439	N = 154
Headache	12 (3%)	1 (1%)
Application site burning	27 (6%)	14 (9%)
Application site pruritus	5 (1%)	5 (3%)
Application site dryness	4 (1%)	5 (3%)
Application site reaction, not otherwise specified	3 (1%)	4 (3%)

In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to Evoclin Foam.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Evoclin Foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, and pain of skin. Because these reactions are 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.

Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin. Orally and parenterally administered clindamycin have been associated with severe colitis, which may end fatally.

Drug Interactions

Erythromycin

Evoclin Foam should not be used in combination with topical or oral erythromycin-containing products due to possible antagonism to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known.

Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Evoclin Foam should be used with caution in patients receiving such agents.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women treated with Evoclin Foam. Evoclin Foam should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus.

Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher, and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from Evoclin Foam based on a mg/m2 comparison.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk following use of Evoclin Foam. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

If used during lactation and Evoclin Foam is applied to the chest, care should be taken to avoid accidental ingestion by the infant.

Pediatric Use

Safety and effectiveness of Evoclin Foam in children under the age of 12 have not been studied.

Geriatric Use

The clinical study with Evoclin Foam did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects.

Evoclin Description

Evoclin (clindamycin phosphate) Foam contains clindamycin (1%) as clindamycin phosphate.

Clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic, lincomycin.

The chemical name for clindamycin phosphate is methyl 7 - chloro - 6,7,8 - trideoxy - 6 - (1 - methyl - trans - 4 - propyl - L - 2 - pyrrolidinecarboxamido) - 1 - thio - L - threo - α - D - galacto - octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:

Molecular Formula: C18H34ClN2O8PS                                     Molecular Weight: 504.97 g/mol

Evoclin Foam contains clindamycin (1%) as clindamycin phosphate, at a concentration equivalent to 10 mg clindamycin per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.

Evoclin - Clinical Pharmacology

Mechanism of Action

Mechanism of action in acne vulgaris is unknown. [See Microbiology (12.4)]

Pharmacodynamics

Pharmacodynamics of Evoclin Foam is unknown.

Pharmacokinetics

In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of Evoclin Foam once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean Cmax and AUC(0-12) were 23% and 9% lower, respectively, for Evoclin Foam than for the clindamycin gel, 1%.

Following multiple applications of Evoclin Foam, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.

Microbiology

No microbiology studies were conducted in the clinical trials with this product.

Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes (P. acnes), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with Evoclin Foam. P. acnes resistance to clindamycin has been documented.

Inducible Clindamycin Resistance

The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing.

Cross Resistance

Resistance to clindamycin is often associated with resistance to erythromycin.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenicity of a 1.2% clindamycin phosphate gel similar to Evoclin Foam was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of Evoclin Foam, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals.

A 1.2% clindamycin phosphate gel similar to Evoclin Foam caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight.

Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.

Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.

Clinical Studies

In one multicenter, randomized, double-blind, vehicle-controlled clinical trial, subjects with mild to moderate acne vulgaris used Evoclin Foam or the vehicle Foam once daily for twelve weeks. Treatment response, defined as the proportion of subjects clear or almost clear, based on the Investigator Static Global Assessment (ISGA), and the mean percent reductions in lesion counts at the end of treatment in this study are shown in Table 2.

Table 2: Efficacy Results at Week 12

* P < 0.05
Efficacy Parameters	Evoclin Foam N=386	Vehicle Foam N=127
Treatment response (ISGA)	31%	18%*
Percent reduction in lesion counts
Inflammatory Lesions	49%	35%*
Noninflammatory Lesions	38%	27%*
Total Lesions	43%	31%*

How Supplied/Storage and Handling

How Supplied

Evoclin Foam containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is white to off-white in color and thermolabile. It is available in the following sizes:

• 100 gram aerosol can - NDC 0145-0061-00


• 50 gram aerosol can - NDC 0145-0061-50

Storage and Handling

Store at controlled room temperature between 68° to 77°F (20° to 25°C).

Flammable. Avoid fire, flame or smoking during and immediately following application.

Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperature above 120°F (49°C).

Keep out of reach of children.

Patient Counseling Information

See FDA-Approved patient labeling (Patient Information).

Instructions for Use

• Patients should be advised to wash their skin with mild soap and allow it to dry before applying Evoclin Foam.


• Patients should use enough Evoclin Foam to cover the face and to apply once daily.


• Patients should dispense Evoclin Foam directly into the cap or onto a cool surface.


• Patients should wash their hands after applying Evoclin Foam.

Skin Irritation

Evoclin Foam may cause irritation such as erythema, scaling, itching, burning, or stinging.

Colitis

In the event a patient treated with Evoclin Foam experiences severe diarrhea or gastrointestinal discomfort, Evoclin Foam should be discontinued and a physician should be contacted.

EVC:2PI

Patient Information

Evoclin (Ev-o-clin)

(clindamycin phosphate) Foam

Important:

For skin use only. Do not use Evoclin Foam in your eyes, mouth or vagina.

Read the Patient Information that comes with Evoclin Foam before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or treatment.

What is Evoclin Foam?

Evoclin Foam is a prescription medicine used on the skin (topical) to treat acne in people 12 years and older.

It is not known if Evoclin Foam is safe and effective in children under 12 years of age.

Who should not use Evoclin Foam?

Do not use Evoclin Foam if you:

• have Crohn’s disease


• have ulcerative colitis


• have had inflammation of the colon (colitis) or severe diarrhea with past antibiotic use

Tell your doctor if you are not sure if you have any of the conditions listed above.

What should I tell my doctor before using Evoclin Foam?

Before you use Evoclin Foam, tell your doctor if you:

• have a history of eczema


• are planning to have surgery. Evoclin Foam may affect how certain medicines work that may be given during surgery.


• have any other medical conditions


• are pregnant or planning to become pregnant. It is not known if Evoclin Foam may harm your unborn baby.


• are breastfeeding or plan to breastfeed. It is not known if Evoclin Foam passes through your breast milk. You and your doctor should decide if you will use Evoclin Foam or breastfeed. If you use Evoclin Foam while breastfeeding and Evoclin Foam is applied on the chest, take care to avoid getting Evoclin Foam into your baby’s mouth.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. Evoclin Foam may affect the way other medicines work and other medicines may affect how Evoclin Foam works.

Especially tell your doctor if you take erythromycin or use products on your skin that contain erythromycin.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I use Evoclin Foam?

• Evoclin Foam is for use on the skin only. Do not get Evoclin Foam in your eyes, mouth or vagina.


• Use Evoclin Foam exactly as your doctor tells you to use it. See the “Instructions for Applying Evoclin Foam” below.


• Apply Evoclin Foam 1 time a day.


• Wash your skin with mild soap and water and dry before applying Evoclin Foam.


• Do not dispense Evoclin Foam directly onto your hands or face, because the foam will begin to melt on contact with warm skin.

Instructions for Applying Evoclin Foam.

• Remove the clear cap from the Evoclin Foam can (See Figure A).

Figure A: Remove clear cap.

• Line up the black circle with the nozzle (See Figure B).

Figure B: Line up the black circle with the nozzle.

• Hold the can upright and firmly press the nozzle to dispense Evoclin Foam (See Figure C).

Figure C: Hold can upright and press nozzle firmly to dispense.

Dispense Evoclin Foam into the clear cap or onto a cool surface (see Figure D).

Figure D: Dispense Evoclin Foam into clear cap.

• Dispense enough Evoclin Foam to cover the affected area (see Figure E).
  
  
  

Figure E: Dispense enough Evoclin Foam to cover affected area.

• If the can seems warm or the foam seems runny, run the can under cold water (See Figure F).

Figure F: If the can seems warm or the foam is runny, run the can under cold water.

• Pick up small amounts of Evoclin Foam with your fingertips and gently rub the foam into the affected area until the foam disappears (See Figure G).

Figure G: Pick up a small amount of Evoclin Foam on your fingertips and gently rub into the affected area until the foam disappears.

• Wash your hands after applying Evoclin.

Throw away any of the unused medicine that you dispensed out of the can.

What should I avoid while using Evoclin Foam?

• Evoclin Foam is flammable. Avoid fire, flames, or smoking during and right after you apply Evoclin Foam to your skin.


• Avoid getting Evoclin Foam in or near your eyes. If you get Evoclin Foam in your eyes, rinse your eyes well with water.

What are possible side effects with Evoclin Foam?

Evoclin Foam can cause serious side effects including:

• Inflammation of the colon (colitis). Clindamycin can cause severe colitis that may lead to death. Stop using Evoclin Foam and call your doctor right away if you have severe watery diarrhea, or bloody diarrhea.

The most common side effects of Evoclin Foam include:

• Skin irritation. Evoclin Foam may cause skin irritation such as burning, itching, or dryness.


• Headache.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the side effects of Evoclin Foam. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to Stiefel at 1-888-784-3335 (1-888- STIEFEL).

How should I store Evoclin Foam?

• Store Evoclin Foam at room temperature between 68° to 77°F (20° to 25°C).


• Keep Evoclin Foam away from heat. Never throw the can into a fire, even if the can is empty.


• Do not store Evoclin Foam at temperatures above 120°F (49°C).


• Do not break through (puncture) the Evoclin Foam can.

Keep Evoclin Foam and all medicines out of the reach of children.

General information about the safe and effective use of Evoclin Foam:

Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use Evoclin Foam for a condition for which it was not prescribed. Do not give Evoclin Foam to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about Evoclin Foam. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about Evoclin Foam that is written for health professionals.

What are the ingredients in Evoclin Foam?

Active ingredient: clindamycin phosphate

Inactive ingredients: cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol. The can is pressurized with a hydrocarbon (propane/butane) propellant.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Stiefel Laboratories, Inc.

Research Triangle Park, NC 27709

EVC:2PIL

Evoclin is a registered trademark of Stiefel Laboratories, Inc.

©2010 Stiefel Laboratories, Inc.

December/2010

Principal Display Panel

NDC 0145-0061-50

Evoclin®

(clindamycin phosphate)

Foam, 1%

50 g

Rx only

FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.

Description: Evoclin® (clindamycin phosphate) Foam 1%, contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.

Dosage: Use only as prescribed by your physician. See package insert for full prescribing information.

Warning: FLAMMABLE. AVOID FIRE, FLAME, OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION.

Keep out of reach of children. Avoid contact with eyes.

Contents under pressure. Do not puncture or incinerate container. Do not expose to heat or store at temperatures above 120°F (49°C).

Store at controlled room temperature, 68°-77°F (20°-25°C).

CFC FREE

Manufactured for

Stiefel Laboratories, Inc.

Research Triangle Park, NC 27709

For additional information:

1-888-784-3335 (1-888-STIEFEL)

or visit www.Evoclin.com

111674

©2011 Stiefel Laboratories, Inc.

Evoclin is a registered trademark of Stiefel Laboratories, Inc.

Made in China

10000000090860

Evoclin  clindamycin phosphate  aerosol, foam

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0145-0061 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CLINDAMYCIN PHOSPHATE (CLINDAMYCIN) CLINDAMYCIN PHOSPHATE 10 mg  in 1 g

Inactive Ingredients Ingredient Name Strength CETYL ALCOHOL   ALCOHOL   POLYSORBATE 60   POTASSIUM HYDROXIDE   PROPYLENE GLYCOL   WATER   STEARYL ALCOHOL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0145-0061-00 1 CAN In 1 CARTON contains a CAN 1 100 g In 1 CAN This package is contained within the CARTON (0145-0061-00) 2 0145-0061-61 6 CAN In 1 CARTON contains a CAN (0145-0061-10) 2 0145-0061-10 10 g In 1 CAN This package is contained within the CARTON (0145-0061-61) 3 0145-0061-50 1 CAN In 1 CARTON contains a CAN 3 50 g In 1 CAN This package is contained within the CARTON (0145-0061-50)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA050801	10/05/2009

Labeler - Stiefel Laboratories Inc (808842343)

Revised: 07/2011Stiefel Laboratories Inc

More Evoclin resources

• Evoclin Side Effects (in more detail)
• Evoclin Use in Pregnancy & Breastfeeding
• Evoclin Drug Interactions
• Evoclin Support Group
• 0 Reviews for Evoclin - Add your own review/rating

• Evoclin Foam MedFacts Consumer Leaflet (Wolters Kluwer)


• Evoclin Consumer Overview


• Evoclin Topical Advanced Consumer (Micromedex) - Includes Dosage Information


• Cleocin T Gel MedFacts Consumer Leaflet (Wolters Kluwer)


• Cleocin Vaginal Advanced Consumer (Micromedex) - Includes Dosage Information


• ClindaMax Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Clindesse Consumer Overview


• Clindesse Cream MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Evoclin with other medications

• Acne
• Perioral Dermatitis

Triveen-PRx RNF

Dosage Form: capsule
Triveen™-PRx RNF

Capsules

Rx Only

Triveen-PRx RNF Description

Triveen™-PRx RNF is a prescription prenatal/postnatal multivitamin/mineral softgel capsule with fish oil-based DHA. Triveen™-PRx RNF is supplied as an oblong, maroon softgel capsule with "T558" imprinted on one side.

Each capsule has the following active ingredient:
Folic Acid	1.2 mg

* from approximately 350 mg of Omega-3s derived from approximately 380 mg of purified fish oil.
Each capsule also contains the following ingredients for nutritional supplementation:
Vitamin C (ascorbic acid)	28 mg
Calcium (tribasic calcium phosphate)	160 mg
Iron (ferrous fumarate)	26 mg
Vitamin D3 (cholecalciferol)	400 IU
Vitamin E (d-alpha tocopherol)	30 IU
Vitamin B6 (pyridoxine hydrochloride)	25 mg
DHA (Docosahexaenoic Acid)	300 mg*
Docusate Sodium	55 mg

Inactive Ingredients

Gelatin, Glycerin, Soybean Oil, Purified water, Lecithin, Yellow Beeswax, Natural Creamy Orange Flavor, FD&C Red #40, Titanium Dioxide, Ethyl Vanillin, FD&C Yellow #6, FD&C Blue #1.

INDICATIONS

Triveen™-PRx RNF is indicated for the supplemental requirements of patients with nutritional deficiencies or are in need of nutritional supplementation.

Contraindications

Triveen™-PRx RNF capsules is contraindicated in patients with a known hypersensitivity to any of the ingredients, including fish or fish oil. Do not take this product if you are presently taking mineral oil, unless directed by a doctor.

Warnings

Daily ingestion of more than 3 g per day of omega-3 fatty acids (ALA, EPA, and DHA) from fish oils may have potential antithrombotic activities, or effects, and may increase bleeding times. Administration of omega-3 fatty acids – including DHA, should be avoided in patients with inherited or acquired bleeding diatheses, including those taking anticoagulants.

WARNING

Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

This product contains soybean oil and fish oil.

CAUTION

Exercise caution to ensure that the prescribed dosage of DHA does not exceed 1 gram (1000 mg) per day.

Precautions

General

Folic acid, when administered as a single agent in doses above 0.1 mg daily, may obscure the detection of B12 deficiency (specifically, the administration of folic acid may reverse the hematological manifestations of B12 deficiency, including pernicious anemia, while not addressing the neurological manifestations). Reduced folates may be less likely than folic acid to mask vitamin B12 deficiency. Folate therapy alone is inadequate for the treatment of B12 deficiency.

PATIENT INFORMATION

Triveen™-PRx RNF is a prescription vitamin for use only under the direction and supervision of a licensed physician.

INTERACTIONS

Pyridoxine hydrochloride should not be given to patients receiving the drug levodopa, because the action of levodopa is antagonized by pyridoxine hydrochloride. However, pyridoxine hydrochloride may be used concurrently in patients receiving a preparation containing both carbidopa and levodopa.

Drugs which may interact with folate include:

• Antiepileptic drugs (AED): The AED class including, but not limited to, phenytoin, carbamazepine, primidone, valproic acid, phenobarbital and lamotrigine have been shown to impair folate absorption and increase the metabolism of circulating folate. Additionally, concurrent use of folic acid has been associated with enhanced phenytoin metabolism, lowering the level of this AED in the blood and allowing breakthrough seizures to occur.


• Capecitabine: Folinic acid (5-formyltetrahydrofolate) may increase the toxicity of Capecitabine.


• Cholestyramine: Reduces folic acid absorption and reduces serum folate levels.


• Colestipol: Reduces folic acid absorption and reduces serum folate levels.


• Cycloserine: Reduces folic acid absorption and reduces serum folate levels.


• Dihydrofolate Reductase Inhibitors (DHFRI): DHFRIs block the conversion of folic acid to its active forms, and lower plasma and red blood cell folate levels. DHFRIs include aminopterin, methotrexate, pyrimethamine, triamterene, and trimethoprim.


• Fluoxetine: Fluoxetine exerts a noncompetitive inhibition of the 5-methyltetrahydrofolate active transport in the intestine.


• Isotretinoin: Reduced folate levels have occurred in some patients taking isotretinoin.


• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): NSAIDs have been shown to inhibit some folate dependent enzymes in laboratory experiments. NSAIDs include ibuprofen, naproxen, indomethacin and sulindac.


• Oral Contraceptives: Serum folate levels may be depressed by oral contraceptive therapy.


• Methylprednisolone: Reduced serum folate levels have been noted after treatment with methylprednisolone.


• Pancreatic Enzymes: Reduced folate levels have occurred in some patients taking pancreatic extracts.


• Pentamidine: Reduced folate levels have been seen with prolonged intravenous pentamidine.


• Smoking and Alcohol: Reduced serum folate levels have been noted.


• Sulfasalazine: Inhibits the absorption and metabolism of folic acid.


• Metformin treatment in patients with type 2 diabetes decreases serum folate.


• Warfarin can produce significant impairment in folate status after a 6-month therapy.

Adverse Reactions

Allergic sensitization has been reported following both oral and parenteral administration of folic acid, as well as possibly the use of other forms of folates – including reduced folates. Paresthesia, somnolence, nausea and headaches have been reported with pyridoxine hydrochloride.

Triveen-PRx RNF Dosage and Administration

Before, during and/or after pregnancy, one softgel capsule daily or as directed by a physician.

How is Triveen-PRx RNF Supplied

Bottles of 30 softgel capsules.

NDC 13811-558-30

Bottles of 60 softgel capsules.

NDC 13811-558-60

STORAGE

Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [See USP controlled room temperature].

Call your doctor about side effects. You may report by calling 888 9 TRIGEN (888-987-4436).

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

Rx Only

All prescriptions using this product shall be pursuant to state statutes as applicable. This is not an Orange Book product. There are no implied or explicit claims on therapeutic equivalence.

Manufactured for:

TRIGEN Laboratories, Inc.

Sayreville, NJ 08872

www.trigenlab.com

Rev. 08/11

PRINCIPAL DISPLAY PANEL - 30 Capsule Bottle Label

NDC 13811-558-30

Rx Only

Triveen™-PRx

RNF

Capsules

30 CAPSULES

TRIGEN

LABORATORIES

TRIVEEN-PRX  RNF folic acid, ascorbic acid, tribasic calcium phosphate, iron, cholecalciferol, alpha-tocopherol, pyridoxine hydrochloride, doconexent, and docusate sodium  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 13811-558 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Folic Acid (Folic Acid) Folic Acid 1.2 mg Ascorbic Acid (Ascorbic Acid) Ascorbic Acid 28 mg Tribasic Calcium Phosphate (Calcium Cation) Tribasic Calcium Phosphate 160 mg Iron (Iron) Iron 26 mg Cholecalciferol (Cholecalciferol) Cholecalciferol 400 [iU] Alpha-Tocopherol (Alpha-Tocopherol) Alpha-Tocopherol 30 [iU] Pyridoxine Hydrochloride (Pyridoxine) Pyridoxine Hydrochloride 25 mg Doconexent (Doconexent) Doconexent 300 mg Docusate Sodium (Docusate) Docusate Sodium 55 mg

Inactive Ingredients Ingredient Name Strength Gelatin   Glycerin   Soybean Oil   Water   Yellow Wax   FD&C Red No. 40   Titanium Dioxide   Ethyl Vanillin   FD&C Yellow No. 6   FD&C Blue No. 1

Product Characteristics Color RED (maroon) Score no score Shape CAPSULE (oblong) Size 25mm Flavor ORANGE (Creamy Orange) Imprint Code T558 Contains

Packaging # NDC Package Description Multilevel Packaging 1 13811-558-30 30 CAPSULE In 1 BOTTLE None 2 13811-558-60 60 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Unapproved drug other		05/15/2010

Labeler - TRIGEN Laboratories, Inc. (830479668)

Revised: 09/2011TRIGEN Laboratories, Inc.

Naproxen EC Tablets 500mg

1. Name Of The Medicinal Product

NAPROXEN EC TABLETS 500mg

2. Qualitative And Quantitative Composition

Each tablet contains: 500mg Naproxen.

3. Pharmaceutical Form

Gastro-resistant tablets.

White, oval, biconvex, deep concave, enteric-coated tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

Naproxen is indicated for the treatment of:

1) Rheumatoid arthritis.

2) Osteoarthritis (degenerative arthritis).

3) Ankylosing spondylitis.

4) Juvenile rheumatoid arthritis.

5) Acute gout.

6) Acute musculoskeletal disorders.

7) Dysmenorrhoea.

4.2 Posology And Method Of Administration

Posology

Adults:

Rheumatoid arthritis, osteoarthritis and ankylosing spondylitis: 500mg-1g daily in two doses at twelve hourly intervals, or alternatively, if 1g daily is needed this can be administered as two 500mg doses or as a single dose. The size of the morning and evening doses can be adjusted on the basis of the predominant symptoms (ie night time pain or morning stiffness)

Acute gout: Initially 750mg followed by 250mg every 8 hours until the attack has passed.

Acute musculoskeletal disorders and dysmenorrhoea: Initially 500mg followed by 250mg every 6-8 hours as necessary to a maximum of 1250mg daily after the first day.

Children over 5 years: For juvenile rhematoid arthritis 10mg/kg a day taken in two doses every 12 hours.

Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy. Studies indicate that although total plasma concentration of naproxen is unchanged, unbound plasma fraction of naproxen is increased in the elderly. The implication of this finding for naproxen dosing is unknown. As with other drugs used in the elderly it is prudent to use the lowest effective dose.

Dosage should be reduced in the elderly where there is an impairment of renal function. (See other special warnings and precautions).

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

Method of Administration

For oral administration. Tablets should be swallowed whole and not broken or crushed. To be taken preferably with or after food.

4.3 Contraindications

Patients with active gastrointestinal bleeding or peptic ulceration, known hypersensitivity to naproxen, naproxen sodium or any other ingredient in the formulation. Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.

Severe heart failure, hepatic failure and renal failure (see section 4.4).

During the last trimester of pregnancy (see section 4.6)

History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

4.4 Special Warnings And Precautions For Use

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI cardiovascular risks below).

Cardiovascular and cerebrovascular effects

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Although data suggest that the use of naproxen (1000mg daily) may be associated with a lower risk, some risk cannot be excluded.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with naproxen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Gastrointestinal bleeding, ulceration and perforation:

GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

The risk of GI bleeding, ulceration or perforation is higher

- with increasing NSAID doses,

- in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3)

- and in the elderly

- when used with alcohol

- in smoking

These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).

Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving naproxen the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).

Cardiovascular, Renal and Hepatic Impairment:

The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3).

Impaired renal function: Naproxen should be used with great caution where there is impairment of renal function as it is eliminated to a large extent (95%) via glomerular filtration; the monitoring of serum creatinine and/or creatinine clearance should be conducted in these patients. Naproxen is not recommended in patients having baseline creatinine clearance less than 20ml/minute.

Certain patients, specifically those whose renal blood flow is compromised, because of extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive heart failure, and pre-existing renal disease, should have renal function assessed before and during naproxen therapy. Some elderly patients in whom impaired renal function may be expected, as well as patients using diuretics, may also fall within this category. A reduction in daily dosage should be considered to avoid the possibility of excessive accumulation of naproxen metabolites in these patients.

Impaired liver function: Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. The implication of this finding for naproxen dosing is unknown but it is prudent to use the lowest effective dose. The product should be used with caution in patients with a history of, or in those with impaired liver function.

Elderly:

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2)

Respiratory disorders:

Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8).

Dermatological:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Naproxen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Impaired female fertilty:

The use of Naproxen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Naproxen should be considered.

Anaphylactic (anaphylactoid) reactions:

Hypersensitivity reactions may occur in susceptible individuals. Anaphylactic (anaphylactoid) reactions may occur both in patients with and without a history of hypersensitivity or exposure to aspirin, other non-steroidal anti-inflammatory drugs or naproxen-containing products. They may also occur in individuals with a history of angioedema, bronchospastic reactivity (eg asthma), rhinitis and nasal polyps.

Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.

Naproxen, in common with other NSAIDs, decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined. Patients who have coagulation disorders, or who are receiving drug therapy that interferes with haemostasis, should be carefully observed if they are taking naproxen. Patients on full anticoagulant therapy (eg heparin or warfarin) may be at an increased risk of bleeding if given naproxen concurrently. Therefore, the benefits should be weighed against these risks.

Mild peripheral oedema has been observed in a few patients. Although sodium retention has not been reported in metabolic studies, patients with questionable or compromised cardiac function may be at a greater risk when taking Naproxen.

This product contains potassium sorbate. Caution should be used in treating patients on a low potassium diet. High blood levels of potassium can cause stomach upset and diarrhoea.

Sporadic abnormalities in laboratory tests (eg liver function tests) have occurred in patients on Naproxen therapy, but no definite trends indicating toxicity were seen in any test.

Steroids: If steroid dosage is reduced or eliminated during therapy, the steroid dosage should be reduced slowly and the patients must be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

Ocular effects: Studies have not shown changes in the eye attributable to naproxen administration. In rare cases, adverse ocular disorders including papillitis, retrobulbar optic neuritis and papilledema, have been reported in users of NSAIDs including naproxen, although a cause-and-effect relationship cannot be established; accordingly, patients who develop visual disturbances during treatment with naproxen-containing products should have an ophtalmological examination.

Combination with other NSAIDs: The combination of naproxen-containing products and others NSAIDs is not recommended, because of the cummulative risks of inducing serious NSAID-related adverse events.

Patients who have coagulation disorders or who are receiving drug therapy that affects haemostasis should be carefully observed when given naproxen (see section 4.5).

The use of Naproxen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

The antipyretic and anti-inflammatory activities of naproxen may reduce fever and inflammation, thereby diminishing their utility as diagnostic signs.

Interference in tests:

Naproxen therapy should be temporarily withdrawn 48 hours before adrenal function tests are performed as it may artifactually interfere with some tests for 17-ketogenic steroids. Similarly, naproxen may interfere with some assays of urinary 5-hydroxyindoleacetic acid.

Sporadic abnormalities in laboratory tests (e.g. liver function test) have occurred in patients on naproxen therapy, but no definite trend was seen in any test indicating toxicity.

Contains Lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

• Naproxen is highly protein-bound hence patients receiving hydantoins, anticoagulants or a highly protein-bound sulphonamide should be closely monitored for signs of overdosage of these drugs. No interactions have been observed in clinical studies with naproxen and sulphonylureas, but caution is nevertheless advised since interaction has been seen with other non-steroidal agents of this class.

• NSAIDs, including naproxen, have been reported to increase steady state plasma lithium levels by inhibition of renal lithium clearance. Decreased elimination of lithium. It is recommended that these levels are monitored whenever initiating, adjusting or discontinuing naproxen.

• Anti-hypertensives: Reduced anti-hypertensive effect. Concomitant administration of naproxen with beta blockers such as propranolol may reduce their antihypertensive effect and may increase the risk of renal impairment associated with the use of ACE inhibitors or angiotensin II receptor antagonists.

• Probenecid given concurrently increases naproxen plasma levels and extends its half-life considerably.

• Decreased elimination of methotrexate. Caution is advised when methotrexate is administered concurrently, due to the possible enhancement of its toxicity as naproxen, like other NSAIDs, has been reported to reduce tubular secretion of methotrexate in an animal model.

• The natriuretic effect of frusemide has been reported to be inhibited by some drugs of this class. Naproxen therapy should be temporarily withdrawn 48 hours before adrenal function tests are performed as it may artifactually interfere with some tests for 17-ketogenic steroids. Similarly, naproxen may interfere with some assays of urinary 5-hydroxyindoleacetic acid.

• NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides.

• As with all NSAIDs, caution is advised when ciclosporin is co-administered because of the increased risk of nephrotoxicity.

• NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.

• As with all NSAIDs, caution should be taken when co-administering with corticosteroids because of the increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

• Patients taking quinolones may have an increased risk of developing convulsions.

• Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.4).

• Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

• Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4).

• Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

• Anti-platelet agents and selective serotonin reuptake inhibitors (SSRls): Increased risk of gastrointestinal bleeding (see section 4.4).

• Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

• Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haem arthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

• Bisphosphonates: concomitant use of bisphosphonates and NSAIDs may increase the risk of gastric mucosal damage.

• Colestyramine: colestyramine delays the absorption of naproxen. Naproxen should be taken at least one hour before or four to six hours after colestyramine.

4.6 Pregnancy And Lactation

Pregnancy:

Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (see section 4.3). NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.

Lactation:

In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

See section 4.4 Special warnings and precautions for use, regarding female fertility.

4.7 Effects On Ability To Drive And Use Machines

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

4.8 Undesirable Effects

System Organ Class	Very Common (	Common (	Uncommon (	Rare (	Very Rare (< 1/10,00)	Frequency not known (cannot be estimated from the available data)
Blood and lymphatic system disorders				haemolytic anaemia	granulocyctopenia, thrombocytopenia, agranulocytosis	aplastic anaemia, neutropenia
Immune system disorders				allergic and hyper-sensitivity reactions, anaphylaxis
Endocrine disorders
Metabolism and nutrition disorders				hyperkalaemia
Psychiatric disorders			depression, cognitive dysfunction, insomnia, loss of concentration, abnormal dreams			hallucinations
Nervous system disorders		confusion, dizziness, drowsiness, headache			convulsions, aseptic meningitis*	vertigo, paraesthesia, malaise, exacerbation of Parkinson's disease
Eye disorders		visual disturbances				optic neuritis, papilloedema
Ear and labyrinth disorders		tinnitus		hearing impairment
Cardiac disorders		oedema, cardiac failure	palpitations
Vascular disorders				vasculitis	arterial thrombotic events e.g. myocardial infarction or stroke(see 4.4)	hypertension
Respiratory, thoracic and mediastinal disorders				aggravated asthma, eosinophilic pneumontitis		bronchospasm, dyspnoea, rhinitis, pulmonary oedema
Gastrointestinal disorders	nausea, abdominal pain, constipation	vomiting, diarrhoea, dyspepsia	perforation or GI bleeding (see 4.4), melaena, haematemesis	ulcerative stomatitis	pancreatitis	peptic ulcers, flatulence, exacerbation of colitis and Crohn's disease (see 4.4), gastritis, thirst
Hepatobiliary				fatal hepatitis, jaundice		abnormal liver function, hepatitis
Skin and subcutaneous tissue disorders		rash, pruritis, purpura	urticaria, photo-sensitivity	alopecia, pseudo-porphyria	erythema multiforme, Stevens Johnsons syndrome, toxic epidermal necrosis, epidermolysis bullosa	angio-oedema, epidermal necrosis, exfoliative and bullous dermatoses, lichen planus
Musculoskeletal and connective tissue disorders				myalgia, muscle weakness
Renal and urinary disorders					glomerular nephritis, haematuria, interstitial nephritis, nephritic syndrome, renal papillary necrosis	renal failure, nephropathy, increase in serum creatinine
Reproductive system and breast disorders						impaired female fertility (see 4.4)
General disorders and administration site complications		fatigue				mild peripheral oedema, pyrexia

*especially in patients with existing auto-immune disorders, such as system lupus erythematosus, mixed connective tissue disease, with symptoms such as stiff neck headache, nausea, vomiting, fever and disorientation.

Clinical trial and epidemiological data suggests that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke (see section 4.4)

4.9 Overdose

a) Symptoms

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, occasionally convulsions. In cases of significant poisoning acute renal failure and liver damage are possible.

b) Therapeutic measure

Patients should be treated symptomatically as required.

Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.

Good urine output should be ensured.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam.

Other measures may be indicated by the patient's clinical condition.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Naproxen is a non-steroidal anti-inflammatory agent.

Naproxen reduces the synthesis of prostaglandins primarily by inhibiting the enzyme cyclo-oxygenase. Naproxen has been shown to have anti-inflammatory activity in a number of experimental models. Naproxen inhibits prostaglandin E₂ synthesis in vitro by human rheumatoid synovial microsomes. It also inhibits prostaglandin E₂ production by phytohaemagglutin-stimulated peripheral blood mononuclear cells. At 10^-4 M (23mg.1^-1) naproxen inhibits neutral protease activity derived from human polymorphonuclear leucocytes. Naproxen also inhibits in vitro the activity of cathepsin-β and other hydrolytic enzymes derived from lysosomes. Naproxen is a potent in inhibitor of leucocyte migration and produces effects comparable to those of colchicine.

5.2 Pharmacokinetic Properties

Naproxen is readily absorbed from the gastrointestinal tract. Peak plasma concentrations are attained 2-4 hours after ingestion. Plasma concentrations of naproxen increase proportionally with dose up to about 500mg daily; at higher doses there is an increase in clearance caused by saturation of plasma proteins. At therapeutic concentrations naproxen is more than 99% bound to plasma proteins and has a plasma half-life of about 13 hours. Approximately 95% of a dose is excreted in urine as naproxen and 6-O-desmethylnaproxen and their conjugates. Less than 3% of a dose has been recovered in the faeces. Naproxen crosses the placenta and is excreted in breast milk.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Methacrylic acid-ethylacrylate copolymer (1:1)

Lactose

Magnesium stearate

Maize starch

Crospovidone

Propylene glycol

Sodium hydroxide

Triethyl citrate

Titanium dioxide (E171)

Potassium sorbate (E202)

Sodium citrate (E331)

Xanthan gum (E415)

Hydroxypropyl cellulose (E463)

Purified talc (E553)

Beeswax

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Shelf-life

36 months from the date of manufacture.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

6.4 Special Precautions For Storage

Do not store above 25°C .

Store in the original package.

6.5 Nature And Contents Of Container

PVC/PVdC/Aluminium blister. Pack sizes of 28, 30, 56, 60, 84, 90, 100, 112 tablets.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data

7. Marketing Authorisation Holder

Actavis UK Limited

(Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL/0142/0439

9. Date Of First Authorisation/Renewal Of The Authorisation

31.1.00

Renewed – 18.03.09

10. Date Of Revision Of The Text

07.06.2011

PediaTan

Generic Name: chlorpheniramine (KLOR fen IR a meen)

Brand Names: AHist, Aller-Chlor, Allergy Relief, C.P.M., Chlo-Amine, Chlor-Mal, Chlor-Trimeton, Chlor-Trimeton Allergy SR, Chlorphen, ChlorTan, Ed Chlor-Tan, Ed ChlorPed, PediaTan, TanaHist-PD, Triaminic Allergy, Wal-finate

What is PediaTan (chlorpheniramine)?

Chlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Chlorpheniramine is used to treat sneezing, itching, watery eyes, and runny nose caused by allergies or the common cold.

Chlorpheniramine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about PediaTan (chlorpheniramine)?

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not take chlorpheniramine if you are allergic to it.

Ask a doctor or pharmacist before taking chlorpheniramine if you have glaucoma, a stomach ulcer, severe constipation, kidney disease, urination problems, an enlarged prostate, or a thyroid disorder.

Ask a doctor or pharmacist before using any other cold, cough, or allergy medicine. Chlorpheniramine is contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine.

Chlorpheniramine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine.

What should I discuss with my healthcare provider before taking PediaTan (chlorpheniramine)?

Do not take this medication if you are allergic to chlorpheniramine. Do not use chlorpheniramine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

• 
  

  glaucoma;

  
  


• 
  

  a stomach ulcer;

  
  


• 
  

  severe constipation;

  
  


• 
  

  kidney disease;

  
  


• 
  

  urination problems or an enlarged prostate; or

  
  


• 
  

  a thyroid disorder.

  
  

FDA pregnancy category B. Chlorpheniramine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Chlorpheniramine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Older adults may be more likely to have side effects from this medication.

How should I take PediaTan (chlorpheniramine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cold or allergy medicine is usually taken only for a short time until your symptoms clear up.

Take this medication with a full glass of water. Take chlorpheniramine with food or milk if it upsets your stomach. Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

This medication can cause unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cold or allergy medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include feeling restless or nervous, nausea, vomiting, stomach pain, dizziness, drowsiness, dry mouth, warmth or tingly feeling, or seizure (convulsions).

What should I avoid while taking PediaTan (chlorpheniramine)?

Ask a doctor or pharmacist before using any other cold, cough, or allergy medicine. Chlorpheniramine is contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Chlorpheniramine can decrease perspiration and you may be more prone to heat stroke.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine.

PediaTan (chlorpheniramine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop taking chlorpheniramine and call your doctor at once if you have a serious side effect such as:

• 
  

  urinating less than usual or not at all;

  
  


• 
  

  confusion, extreme drowsiness;

  
  


• 
  

  severe dizziness, anxiety, restless feeling, nervousness; or

  
  


• 
  

  weak or shallow breathing.

  
  

Less serious side effects may include:

• 
  

  mild dizziness, drowsiness;

  
  


• 
  

  blurred vision;

  
  


• 
  

  dry mouth;

  
  


• 
  

  nausea, stomach pain, constipation;

  
  


• 
  

  problems with memory or concentration; or

  
  


• 
  

  feeling restless or excited (especially in children).

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect PediaTan (chlorpheniramine)?

Other cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by chlorpheniramine. Tell your doctor if you regularly use any of these medicines.

Tell your doctor about all other medicines you use, especially:

• 
  

  glycopyrrolate (Robinul);

  
  


• 
  

  mepenzolate (Cantil);

  
  


• 
  

  probenecid (Benemid, Probalan);

  
  


• 
  

  rifampin (Rifadin, Rifater, Rifamate, Rimactane);

  
  


• 
  

  zidovudine (Retrovir, AZT);

  
  


• 
  

  a diuretic (water pill);

  
  


• 
  

  atropine (Atreza, Sal-Tropine), belladonna (Donnatal, and others), benztropine (Cogentin), dimenhydrinate (Dramamine), methscopolamine (Pamine), or scopolamine (Transderm-Scop);

  
  


• 
  

  bladder or urinary medications such as darifenacin (Enablex), flavoxate (Urispas), oxybutynin (Ditropan, Oxytrol), tolterodine (Detrol), or solifenacin (Vesicare);

  
  


• 
  

  bronchodilators such as ipratropium (Atrovent) or tiotropium (Spiriva);

  
  


• 
  

  irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Hyomax), or propantheline (Pro-Banthine); or

  
  


• 
  

  salicylates such as aspirin, Backache Relief Extra Strength, Novasal, Nuprin Backache Caplet, Doan's Pills Extra Strength, Pepto-Bismol, Tricosal, and others;

  
  

This list is not complete and other drugs may interact with chlorpheniramine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More PediaTan resources

• PediaTan Side Effects (in more detail)
• PediaTan Use in Pregnancy & Breastfeeding
• PediaTan Drug Interactions
• PediaTan Support Group
• 0 Reviews for PediaTan - Add your own review/rating

• Ahist MedFacts Consumer Leaflet (Wolters Kluwer)


• Aller-Chlor Syrup MedFacts Consumer Leaflet (Wolters Kluwer)


• Chlorpheniramine Maleate/Tannate, Dexchlorpheniramine Maleate Monograph (AHFS DI)


• Ed ChlorPed Suspension Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Pediox-S Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• QDALL AR Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Compare PediaTan with other medications

• Allergic Reactions
• Cold Symptoms
• Hay Fever
• Urticaria

Where can I get more information?

• Your pharmacist can provide more information about chlorpheniramine.

See also: PediaTan side effects (in more detail)