Aczone

dapsone

Dosage Form: gel
FULL PRESCRIBING INFORMATION

Indications and Usage for Aczone

Aczone® Gel, 5%, is indicated for the topical treatment of acne vulgaris.

Aczone Dosage and Administration

For topical use only. Not for oral, ophthalmic, or intravaginal use.

After the skin is gently washed and patted dry, apply approximately a pea-sized amount of Aczone® Gel, 5%, in a thin layer to the acne affected areas twice daily. Rub in Aczone® Gel, 5%, gently and completely. Aczone® Gel, 5%, is gritty with visible drug substance particles. Wash hands after application of Aczone® Gel, 5%.

If there is no improvement after 12 weeks, treatment with Aczone® Gel, 5%, should be reassessed.

Dosage Forms and Strengths

Aczone® (dapsone) Gel, 5%, is supplied in the following size tubes:

• Professional Sample: 3 gram laminate tube


• Commercially: 30 and 60 gram laminate tubes

Contraindications

None.

Warnings and Precautions

Hematological Effects

Oral dapsone treatment has produced dose-related hemolysis and hemolytic anemia. Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are more prone to hemolysis with the use of certain drugs. G6PD deficiency is most prevalent in populations of African, South Asian, Middle Eastern and Mediterranean ancestry.

There was no evidence of clinically relevant hemolysis or anemia in patients treated with Aczone® Gel, 5%, including patients who were G6PD deficient. Some subjects with G6PD deficiency using Aczone® Gel developed laboratory changes suggestive of mild hemolysis.

If signs and symptoms suggestive of hemolytic anemia occur, Aczone® Gel, 5% should be discontinued. Aczone® Gel, 5% should not be used in patients who are taking oral dapsone or antimalarial medications because of the potential for hemolytic reactions. Combination of Aczone® Gel, 5%, with trimethoprim/sulfamethoxazole (TMP/SMX) may increase the likelihood of hemolysis in patients with G6PD deficiency.

Peripheral Neuropathy

Peripheral neuropathy (motor loss and muscle weakness) has been reported with oral dapsone treatment. No events of peripheral neuropathy were observed in clinical trials with topical Aczone® Gel, 5% treatment.

Skin

Skin reactions (toxic epidermal necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions, bullous and exfoliative dermatitis, erythema nodosum, and urticaria) have been reported with oral dapsone treatment. These types of skin reactions were not observed in clinical trials with topical Aczone® Gel, 5% treatment.

Adverse Reactions

Clinical Studies Experience

Because clinical trials are conducted under prescribed 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 practice.

Serious adverse reactions reported in patients treated with Aczone® Gel, 5%, during clinical trials included but were not limited to the following:

• Nervous system/Psychiatric – Suicide attempt, tonic clonic movements.


• Gastrointestinal – Abdominal pain, severe vomiting, pancreatitis.


• Other – Severe pharyngitis

In the clinical trials, a total of 12 out of 4032 patients were reported to have depression (3 of 1660 treated with vehicle and 9 of 2372 treated with Aczone® Gel, 5%). Psychosis was reported in 2 of 2372 patients treated with Aczone® Gel, 5%, and in 0 of 1660 patients treated with vehicle.

Combined contact sensitization/irritation studies with Aczone® Gel, 5%, in 253 healthy subjects resulted in at least 3 subjects with moderate erythema. Aczone® Gel, 5%, did not induce phototoxicity or photoallergy in human dermal safety studies.

Aczone® Gel, 5%, was evaluated for 12 weeks in four controlled studies for local cutaneous events in 1819 patients. The most common events reported from these studies include oiliness/peeling, dryness, and erythema. These data are shown by severity in Table 1 below.

Table 1 – Application Site Adverse Reactions by Maximum Severity

	Aczone® (N=1819)			Vehicle (N=1660)
Application Site Event	Mild	Moderate	Severe	Mild	Moderate	Severe
Erythema	9%	5%	<1%	9%	6%	<1%
Dryness	14%	3%	<1%	14%	4%	<1%
Oiliness/Peeling	13%	6%	<1%	15%	6%	<1%

The adverse reactions occurring in at least 1% of patients in either arm in the four vehicle controlled studies are presented in Table 2.

Table 2 – Adverse Reactions Occurring in at least 1% of Patients

NOS = Not otherwise specified
	Aczone® N=1819	Vehicle N=1660
Application Site Reaction NOS	18%	20%
Application Site Dryness	16%	17%
Application Site Erythema	13%	14%
Application Site Burning	1%	2%
Application Site Pruritus	1%	1%
Pyrexia	1%	1%
Nasopharyngitis	5%	6%
Upper Respiratory Tract Inf. NOS	3%	3%
Sinusitis NOS	2%	1%
Influenza	1%	1%
Pharyngitis	2%	2%
Cough	2%	2%
Joint Sprain	1%	1%
Headache NOS	4%	4%

One patient treated with Aczone® Gel in the clinical trials had facial swelling which led to discontinuation of medication.

In addition, 486 patients were evaluated in a 12 month safety study. The adverse event profile in this study was consistent with that observed in the vehicle-controlled studies.

Experience with Oral Use of Dapsone

Although not observed in the clinical trials with Aczone® Gel (topical dapsone) serious adverse reactions have been reported with oral use of dapsone, including agranulocytosis, hemolytic anemia, peripheral neuropathy (motor loss and muscle weakness), and skin reactions (toxic epidermal necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions, bullous and exfoliative dermatitis, erythema nodosum, and urticaria).

Drug Interactions

Trimethoprim-Sulfomethoxazole

A drug-drug interaction study evaluated the effect of the use of Aczone® Gel, 5%, in combination with double strength (160 mg/800 mg) trimethoprim-sulfamethoxazole (TMP/SMX). During co-administration, systemic levels of TMP and SMX were essentially unchanged. However, levels of dapsone and its metabolites increased in the presence of TMP/SMX. Systemic exposure (AUC0-12) of dapsone and N-acetyl-dapsone (NAD) were increased by about 40% and 20% respectively in presence of TMP/SMX. Notably, systemic exposure (AUC0-12) of dapsone hydroxylamine (DHA) was more than doubled in the presence of TMP/SMX. Exposure from the proposed topical dose is about 1% of that from the 100 mg oral dose, even when co-administered with TMP/SMX.

Topical Benzoyl Peroxide

Topical application of Aczone® Gel followed by benzoyl peroxide in subjects with acne vulgaris resulted in a temporary local yellow or orange discoloration of the skin and facial hair (reported by 7 out of 95 subjects in a clinical study) with resolution in 4 to 57 days.

Drug Interactions with Oral Dapsone

Certain concomitant medications (such as rifampin, anticonvulsants, St. John's wort) may increase the formation of dapsone hydroxylamine, a metabolite of dapsone associated with hemolysis. With oral dapsone treatment, folic acid antagonists such as pyrimethamine have been noted to possibly increase the likelihood of hematologic reactions.

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects: Pregnancy Category C

There are no adequate and well controlled studies in pregnant women. Dapsone has been shown to have an embryocidal effect in rats and rabbits when administered orally in doses of 75 mg/kg/day and 150 mg/kg/day (approximately 800 and 500 times the systemic exposure observed in human females as a result of use of the maximum recommended topical dose, based on AUC comparisons), respectively. These effects were probably secondary to maternal toxicity. Aczone® Gel, 5%, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Although systemic absorption of dapsone following topical application of Aczone® Gel, 5%, is minimal relative to oral dapsone administration, it is known that dapsone is excreted in human milk. Because of the potential for oral dapsone to cause adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue Aczone® Gel, 5%, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and efficacy was evaluated in 1169 children aged 12-17 years old treated with Aczone® Gel, 5%, in the clinical studies. The adverse event rate for Aczone® Gel, 5%, was similar to the vehicle control group. Safety and efficacy was not studied in pediatric patients less than 12 years of age, therefore Aczone® Gel, 5%, is not recommended for use in this age group.

Geriatric Use

Clinical studies of Aczone® Gel, 5%, did not include sufficient number of patients aged 65 and over to determine whether they respond differently from younger patients.

G6PD Deficiency

Aczone® Gel, 5% and vehicle were evaluated in a randomized, double-blind, cross-over design clinical study of 64 patients with G6PD deficiency and acne vulgaris. Subjects were Black (88%), Asian (6%), Hispanic (2%) or of other racial origin (5%). Blood samples were taken at Baseline, Week 2, and Week 12 during both vehicle and Aczone® Gel, 5% treatment periods. There were 56 out of 64 subjects who had a Week 2 blood draw and applied at least 50% of treatment applications. Table 3 contains results from testing of relevant hematology parameters for these two treatment periods. Aczone® Gel was associated with a 0.32 g/dL drop in hemoglobin after two weeks of treatment, but hemoglobin levels generally returned to baseline levels at Week 12.

Table 3 – Mean Hemoglobin, Bilirubin, and Reticulocyte Levels in Acne Subjects with G6PD Deficiency in Aczone®/Vehicle Cross-Over Study

		Aczone®		Vehicle
		N	Mean	N	Mean
Hemoglobin (g/dL)	Pre-treatment	53	13.44	56	13.36
	2 weeks	53	13.12	55	13.34
	12 weeks	50	13.42	50	13.37
Bilirubin (mg/dL)	Pre-treatment	54	0.58	56	0.55
	2 weeks	53	0.65	55	0.56
	12 weeks	50	0.61	50	0.62
Reticulocytes (%)	Pre-treatment	53	1.30	55	1.34
	2 weeks	53	1.51	55	1.34
	12 weeks	50	1.48	50	1.41

There were no changes from baseline in haptoglobin or lactate dehydrogenase during Aczone® or vehicle treatment at either the 2-week or 12-week time point.

The proportion of subjects who experienced decreases in hemoglobin ≥1 g/dL was similar between Aczone® Gel, 5% and vehicle treatment (8 of 58 subjects had such decreases during Aczone® treatment compared to 7 of 56 subjects during vehicle treatment among subjects with at least one on-treatment hemoglobin assessment). Subgroups based on gender, race, or G6PD enzyme activity did not display any differences in laboratory results from the overall study group. There was no evidence of clinically significant hemolytic anemia in this study. Some of these subjects developed laboratory changes suggestive of mild hemolysis.

Overdosage

Aczone® Gel, 5%, is not for oral use. If oral ingestion occurs, medical advice should be sought.

Aczone Description

Aczone® Gel, 5%, contains dapsone, a sulfone, in an aqueous gel base for topical dermatologic use. Aczone® Gel, 5% is a gritty translucent material with visible drug substance particles. Chemically, dapsone has an empirical formula of C12H12N2O2S. It is a white, odorless crystalline powder that has a molecular weight of 248. Dapsone's chemical name is 4,4'-diaminodiphenylsulfone and its structural formula is:

Each gram of Aczone® Gel, 5%, contains 50 mg of dapsone, USP, in a gel of carbomer 980; diethylene glycol monoethyl ether, NF; methylparaben, NF; sodium hydroxide, NF; and purified water, USP.

Aczone - Clinical Pharmacology

Mechanism of Action

The mechanism of action of dapsone gel in treating acne vulgaris is not known.

Pharmacokinetics

An open-label study compared the pharmacokinetics of dapsone after Aczone® Gel, 5%, (110 ± 60 mg/day) was applied twice daily (~BSA 22.5%) for 14 days (n=18) with a single 100 mg dose of oral dapsone administered to a subgroup of patients (n=10) in a crossover design. On Day 14 the mean dapsone AUC0-24 h was 415 ± 224 ng•h/mL for Aczone® Gel, 5%, whereas following a single 100 mg dose of oral dapsone the AUC0-infinity was 52,641 ± 36,223 ng•h/mL. Exposure after the oral dose of 100 mg dapsone was approximately 100 times greater than after the topical Aczone® Gel, 5% dose, twice a day.

In a long-term safety study of Aczone® Gel, 5% treatment, periodic blood samples were collected up to 12 months to determine systemic exposure of dapsone and its metabolites in approximately 500 patients. Based on the measurable dapsone concentrations from 408 patients (M=192, F=216), obtained at month 3, neither gender, nor race appeared to affect the pharmacokinetics of dapsone. Similarly, dapsone exposures were approximately the same between the age groups of 12-15 years (N=155) and those greater than or equal to 16 years (N=253). There was no evidence of increasing systemic exposure to dapsone over the study year in these patients.

Microbiology

In Vivo Activity: No microbiology or immunology studies were conducted during dapsone gel clinical trials.

Drug Resistance: No dapsone resistance studies were conducted during dapsone gel clinical trials. Because no microbiology studies were done, there are no data available as to whether dapsone treatment may have resulted in decreased susceptibility of Propionibacterium acnes, an organism associated with acne, to other antimicrobials that may be used to treat acne. Therapeutic resistance to dapsone has been reported for Mycobacterium leprae, when patients have been treated with oral dapsone.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Dapsone was not mutagenic in a bacterial reverse mutation assay (Ames test) using S. typhimurium and E. coli, with and without metabolic activation and was negative in a micronucleus assay conducted in mice. Dapsone increased both numerical and structural aberrations in a chromosome aberration assay conducted with Chinese hamster ovary (CHO) cells.

Dapsone was not carcinogenic to rats when orally administered to females for 92 weeks or males for 100 weeks at dose levels up to 15 mg/kg/day (approximately 160 times the systemic exposure observed in human males and 300 times the systemic exposure observed in human females as a result of use of the maximum recommended topical dose, based on AUC comparisons).

No evidence of potential to induce carcinogenicity was obtained in a dermal study in which dapsone gel was topically applied to Tg.AC transgenic mice for approximately 26 weeks. Dapsone concentrations of 3%, 5%, and 10% were evaluated; 3% material was judged to be the maximum tolerated dosage.

Aczone® Gel, 5%, did not increase the rate of formation of ultra violet light-induced skin tumors when topically applied to hairless mice in a 12-month photocarcinogenicity study.

The effects of dapsone on fertility and general reproduction performance were assessed in male and female rats following oral (gavage) dosing. Dapsone reduced sperm motility at dosages of 3 mg/kg/day or greater (approximately 17 times the systemic exposure observed in human males as a result of use of the maximum recommended topical dose, based on AUC comparisons). The mean numbers of embryo implantations and viable embryos were significantly reduced in untreated females mated with males that had been dosed at 12 mg/kg/day or greater (approximately 70 times the systemic exposure observed in human males as a result of use of the maximum recommended topical dose, based on AUC comparisons), presumably due to reduced numbers or effectiveness of sperm, indicating impairment of fertility. Dapsone had no effect on male fertility at dosages of 2 mg/kg/day or less (approximately 13 times the systemic exposure observed in human males as a result of use of the maximum recommended topical dose, based on AUC comparisons). When administered to female rats at a dosage of 75 mg/kg/day (approximately 800 times the systemic exposure observed in human females as a result of use of the maximum recommended topical dose, based on AUC comparisons) for 15 days prior to mating and for 17 days thereafter, dapsone reduced the mean number of implantations, increased the mean early resorption rate, and reduced the mean litter size. These effects were probably secondary to maternal toxicity.

Dapsone was assessed for effects on perinatal/postnatal pup development and postnatal maternal behavior and function in a study in which dapsone was orally administered to female rats daily beginning on the seventh day of gestation and continuing until the twenty-seventh day postpartum. Maternal toxicity (decreased body weight and food consumption) and developmental effects (increase in stillborn pups and decreased pup weight) were seen at a dapsone dose of 30 mg/kg/day (approximately 500 times the systemic exposure observed in human females as a result of use of the maximum recommended topical dose, based on AUC comparisons). No effects were observed on the viability, physical development, behavior, learning ability, or reproductive function of surviving pups.

Clinical Studies

Two randomized, double-blind, vehicle-controlled, clinical studies were conducted to evaluate Aczone® Gel, 5%, for the treatment of patients with acne vulgaris (N=1475 and 1525). The studies were designed to enroll patients 12 years of age and older with 20 to 50 inflammatory and 20 to 100 non-inflammatory lesions at baseline. In these studies patients applied either Aczone® Gel, 5%, or vehicle control twice daily for up to 12 weeks. Efficacy was evaluated in terms of success on the Global Acne Assessment Score (no or minimal acne) and in the percent reduction in inflammatory, non-inflammatory, and total lesions.

The Global Acne Assessment Score was a 5-point scale as follows:

0 None: no evidence of facial acne vulgaris

1 Minimal: few non-inflammatory lesions (comedones) are present; a few inflammatory lesions (papules/pustules) may be present

2 Mild: several to many non-inflammatory lesions (comedones) are present; a few inflammatory lesions (papules/pustules) are present

3 Moderate: many non-inflammatory (comedones) and inflammatory lesions (papules/pustules) are present; no nodulo-cystic lesions are allowed

4 Severe: significant degree of inflammatory disease; papules/pustules are a predominant feature; a few nodulo-cystic lesions may be present; comedones may be present.

The success rates on the Global Acne Assessment Score (no or minimal acne) at Week 12 are presented in Table 4.

Table 4 - Success (No or Minimal Acne) on the Global Acne Assessment Score at Week 12

*Analysis excludes subjects classified with minimal acne at baseline
	Study 1*		Study 2*
	Aczone® N=699	Vehicle N=687	Aczone® N=729	Vehicle N=738
Subjects with No or Minimal Acne	291 (42%)	223 (32%)	253 (35%)	206 (28%)

Table 5 presents the mean percent reduction in inflammatory, non-inflammatory, and total lesions from baseline to Week 12.

Table 5 - Percent Reduction in Lesions from Baseline to Week 12

	Study 1		Study 2
	Aczone® N=745	Vehicle N=740	Aczone® N=761	Vehicle N=764
Inflammatory	46%	42%	48%	40%
Non-Inflammatory	31%	24%	30%	21%
Total	38%	32%	37%	29%

The clinical studies enrolled about equal proportions of male and female subjects. Female patients tended to have greater percent reductions in lesions and greater success on the Global Acne Assessment Score than males. The breakdown by race in the clinical studies was about 73% Caucasian, 14% Black, 9% Hispanic, and 2% Asian. Efficacy results were similar across the racial subgroups.

How Supplied/Storage and Handling

Aczone® (dapsone) Gel, 5%, is supplied in the following size tubes:

Professional Sample

5% NDC 0023-3670-03

3 gram laminate tube

Commercially Available as:

5% NDC 0023-3670-30

30 gram laminate tube


5% NDC 0023-3670-60

60 gram laminate tube

KEEP OUT OF THE REACH OF CHILDREN LESS THAN 12 YEARS OLD.

Storage conditions:

Store at controlled room temperature, 20 - 25° C (68 - 76° F), excursions permitted to 15 - 30º C (59 - 86º F). Protect from freezing.

Patient Counseling Information

See FDA Approved-Patient Labeling (17.2)

Information for Patients

1. Patients should use Aczone® Gel, 5%, as directed by the physician. Aczone® Gel, 5%, is for external topical use only. Aczone® Gel, 5%, is not for oral, ophthalmic or intravaginal use.


2. Patients should not use this medication for any disorder other than that for which it was prescribed.


3. Patients should report any signs of adverse reactions to their physician.


4. Protect Aczone® Gel, 5%, from freezing.


5. See Patient Labeling for additional information on safety, efficacy, general use, and storage of Aczone® Gel, 5%.

FDA-Approved Patient Labeling

Aczone® (dapsone) Gel 5%

Read this important information before you start using Aczone® (AK-zôn) Gel and each time you refill your prescription. There may be new information that you need to know. This summary is not meant to take the place of your doctor's advice. If you have any questions or want more information about Aczone® Gel, ask your doctor or pharmacist.

What is Aczone® Gel?

Aczone® Gel is a prescription medicine used on your skin (topical) to treat acne in people 12 years and older.

Aczone® Gel has not been studied in children under 12 years of age.

Who should not use Aczone® Gel?

Do not use Aczone® Gel if you are allergic to any of the ingredients in Aczone® Gel or if you are younger than 12 years of age.

Active ingredient: dapsone.

Inactive ingredients: Carbomer 980, diethylene glycol monoethyl ether (DGME), methylparaben, sodium hydroxide, and purified water.

What should I tell my doctor before using Aczone® Gel?

Tell your doctor about all of your medical conditions, including if you:

• are pregnant or planning to become pregnant. It is not known if Aczone® Gel may harm your unborn baby. You and your doctor will need to decide if Aczone® is right for you.


• are breastfeeding. Aczone® Gel passes into your milk and may harm your baby. You should choose either to use Aczone® Gel, or breastfeed, but not both. Talk to your doctor about the best way to feed your baby while using Aczone® Gel.


• have glucose-6-phosphate dehydrogenase deficiency.

Tell your doctor about all the medicines you are taking including prescription and nonprescription medicines, vitamins and herbal supplements. Especially, tell your doctor if you are using any other medicines applied to the skin, such as acne medicines with benzoyl peroxide.

How do I use Aczone® Gel?

• Use Aczone® Gel exactly as prescribed by your doctor. Aczone® Gel is usually used on your affected skin twice a day, once in the morning and once in the evening.


• Wash the areas of your skin where you will apply Aczone® Gel. Gently pat your skin dry with a clean towel.


• Apply a thin layer of Aczone® Gel to the areas of your skin that have acne. A pea-sized amount of Aczone® Gel will usually be enough.


• Rub the medicine in gently and completely


• Make sure to put the cap back on the Aczone® Gel tube. Close it tightly.


• Wash your hands after applying Aczone® Gel.


• Keep Aczone® Gel away from your mouth and eyes. Do not swallow Aczone® Gel. If you swallow Aczone® Gel, call your doctor or poison control center right away.


• If your acne does not get better after using Aczone® Gel for 12 weeks, talk to your doctor about other treatments for acne.

What are the possible side effects of Aczone® Gel?

Like all medicines, Aczone® Gel can cause some side effects. The most common side effects of Aczone® Gel are dryness, redness, oiliness and peeling of the skin being treated.

When the active ingredient of Aczone® Gel (called dapsone) is taken orally as a pill, it has been related to the abnormal breakdown of red blood cells (hemolytic anemia). If you have glucose-6-phoshate dehydrogenase deficiency, you may have a greater risk for lowering your hemoglobin level. However, using Aczone® Gel on the skin is not expected to put enough dapsone in the blood to cause clinical symptoms of hemolytic anemia. You are advised to be alert for signs and symptoms suggestive of this type of anemia (sudden onset of: back pain, breathlessness, tiredness/weakness with daily activities, dark-brown urine, high fever and yellow or pale skin). If you experience these signs and symptoms, stop use and call your doctor immediately.

Use of benzoyl peroxide together with Aczone® Gel at the same time may cause your skin to temporarily turn yellow or orange at the site of application.

This is not a complete list of all the possible side effects. Call your doctor if you have any side effects that do not go away or bother you. If you have any questions, ask your doctor or pharmacist.

How should I store Aczone® Gel?

Store Aczone® Gel at room temperature 68 to 76ºF. Do not freeze Aczone® Gel.

Keep Aczone® Gel out of the reach of children less than 12 years of age.

Where can I find more information about Aczone® Gel?

If you have any questions or want more information about Aczone® Gel, ask your doctor or pharmacist. Your doctor or pharmacist can also give you a copy of the Aczone® Gel Package Insert written for health professionals. Ask them to explain anything you do not understand.

You may call 1-800-433-8871 or visit www.allergan.com to obtain more information about Aczone® Gel.

Aczone® (dapsone) Gel, 5%

Manufactured for: Allergan, Inc., Irvine, CA 92612, U.S.A.

Manufactured by: TOLMAR Inc., Fort Collins, CO 80526, U.S.A.

© 2009 Allergan, Inc., Irvine, CA 92612, U.S.A.

® marks owned by Allergan, Inc.

U.S. Patents 5,863,560; 6,060,085; and 6,620,435

72062US11A

44426 Rev 1 2/09

Principal Display Panel – 60g Tube Label

NDC 0023-3670-60

Aczone®

(dapsone) gel, 5%

FOR TOPICAL USE ONLY

ALLERGAN®

Rx only

60 g

Principal Display Panel – 60 g Carton

NDC 0023-3670-60

Aczone®

(dapsone) gel, 5%

FOR TOPICAL USE ONLY

ALLERGAN®

Rx only

60 g

Aczone  dapsone  gel

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0023-3670 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength dapsone (dapsone) dapsone 50 mg  in 1 g

Inactive Ingredients Ingredient Name Strength CARBOMER HOMOPOLYMER TYPE C   diethylene glycol monoethyl ether   methylparaben   sodium hydroxide   water

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0023-3670-03 15 TUBE In 1 CARTON contains a TUBE 1 3 g In 1 TUBE This package is contained within the CARTON (0023-3670-03) 2 0023-3670-30 1 TUBE In 1 CARTON contains a TUBE 2 30 g In 1 TUBE This package is contained within the CARTON (0023-3670-30) 3 0023-3670-60 1 TUBE In 1 CARTON contains a TUBE 3 60 g In 1 TUBE This package is contained within the CARTON (0023-3670-60)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA021794	06/24/2009

Labeler - Allergan, Inc. (144796497)

Establishment
Name	Address	ID/FEI	Operations
Tolmar, Inc.		791156578	MANUFACTURE

Revised: 03/2009Allergan, Inc.

More Aczone resources

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

• Aczone topical Monograph (AHFS DI)


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


• Aczone Gel MedFacts Consumer Leaflet (Wolters Kluwer)


• Aczone Consumer Overview

Compare Aczone with other medications

• Acne

Levocarnitine

Pronunciation: lee-voe-KAR-ni-teen
Generic Name: Levocarnitine
Brand Name: Carnitor

Levocarnitine is used for:

Treating low levels of levocarnitine in the body and treating patients with metabolism problems that may cause low levels of levocarnitine. It may also be used for other conditions as determined by your doctor.

Levocarnitine is an amino acid derivative. It works by replacing levocarnitine in the body when your body does not produce enough.

Do NOT use Levocarnitine if:

• you are allergic to any ingredient in Levocarnitine

Contact your doctor or health care provider right away if any of these apply to you.

Before using Levocarnitine:

Some medical conditions may interact with Levocarnitine. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have kidney problems or seizures

Some MEDICINES MAY INTERACT with Levocarnitine. However, no specific interactions with Levocarnitine are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Levocarnitine may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Levocarnitine:

Use Levocarnitine as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Levocarnitine during or after meals unless otherwise directed by your doctor.


• Take your dose of Levocarnitine slowly and space your doses evenly throughout the day.


• If you miss a dose of Levocarnitine, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Levocarnitine.

Important safety information:

• Do not use products containing D,L-carnitine (vitamin BT), which are available without a prescription and in health food stores, without first checking with your doctor.


• LAB TESTS, including blood chemistry and blood carnitine levels, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Levocarnitine during pregnancy. It is unknown whether Levocarnitine is excreted in breast milk. If you are or will be breast-feeding while you are using Levocarnitine, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Levocarnitine:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Bad taste in mouth; diarrhea; mild muscle weakness; nausea; stomach cramps; unpleasant body odor; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); seizures.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Levocarnitine side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include severe diarrhea.

Proper storage of Levocarnitine:

Store Levocarnitine at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not freeze. Do not store in the bathroom. Keep Levocarnitine out of the reach of children and away from pets.

General information:

• If you have any questions about Levocarnitine, please talk with your doctor, pharmacist, or other health care provider.


• Levocarnitine is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Levocarnitine. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Levocarnitine resources

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

• Levocarnitine Monograph (AHFS DI)


• levocarnitine Oral, Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Levocarnitine with other medications

• Carnitine Deficiency
• Peripheral Neuropathy

Benylin Children’s Blackcurrant Flavour Cough Syrup

1. Name Of The Medicinal Product

Glycerin and Blackcurrant Soothing Cough Syrup or Glycerin and Blackcurrant Linctus or Benylin Dry Coughs Blackcurrant or CalCough Children's Soothing Syrup or Benylin Children's Blackcurrant Flavour Cough Syrup

2. Qualitative And Quantitative Composition

Active Ingredient	Quantity per 5ml
Glycerin Ph. Eur.	0.75ml
Liquid sugar	1.93ml
(Equivalent to sucrose B.P.	1.7g)

3. Pharmaceutical Form

Liquid

4. Clinical Particulars

4.1 Therapeutic Indications

For the relief of irritating, tickling dry coughs and sore throats.

4.2 Posology And Method Of Administration

Adults, elderly and children over 5 years: 10ml

Children 1 - 5 years: 5ml

The dose may be repeated three or four times a day.

Children under one year: Not to be given to children under 1 year.

For oral administration.

4.3 Contraindications

Hypersensitivity or intolerance to any of the ingredients.

4.4 Special Warnings And Precautions For Use

Diabetics should take note of the carbohydrate content of this product.

Do not give to children under one year.

Keep all medicines out of the reach of children.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically significant interactions known.

4.6 Pregnancy And Lactation

The safety of this medicine during pregnancy and lactation has not been established, but is not considered to constitute a hazard during these periods.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

No adverse effects would be anticipated.

4.9 Overdose

Overdosage would not be expected to cause any problems and treatment would be merely symptomatic and supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Glycerin and sucrose have demulcent properties and will soothe irritated sore throats and possibly block sensory cough receptors within the respiratory tract.

5.2 Pharmacokinetic Properties

Glycerin is readily absorbed from the gastrointestinal tract and undergoes extensive metabolism principally in the liver. It may be used in the synthesis of lipids, and is metabolised to glucose or glycogen or oxidised to carbon dioxide and water. It may also be excreted in the urine unchanged.

Sucrose is hydrolysed in the small intestine by the enzyme sucrase to glucose and fructose which are then absorbed.

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Citric acid monohydrate gran

Sodium benzoate

Anthocyanin

Blackcurrant Flavour 1740.7107 IFF

Blackcurrant Juice 1740.1436 IFF

Liquid Glucose BPC 1963

Purified Water

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

None stated.

6.5 Nature And Contents Of Container

125ml, 150ml or 200ml white flint glass, or amber glass bottle with an aluminium roll-on pilfer-proof cap with a flowed in liner, or a triseal (LDPE/EPE/LDPE) liner.

Alternative caps: A wadless polypropylene tamper evident cap, or a child resistant polypropylene cap with a LDPE liner.

A double ended measuring spoon of 2.5ml and 5.0ml capacity may optionally be provided with the product.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

The Boots Company PLC

1 Thane Road West

Nottingham NG2 3AA

Trading as: BCM

8. Marketing Authorisation Number(S)

PL 00014/0307

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of First Authorisation: 14 March 1984

Date of Last Renewal: 25 July 2000

10. Date Of Revision Of The Text

April 2010

Actidose-Aqua

Generic Name: charcoal (CHAR coal)

Brand Names: Actidose-Aqua, Activated Charcoal, Charcoal Plus DS, EZChar, Insta-Char, Liqui-Char, Optimum Charcoal

What is Actidose-Aqua (charcoal)?

Charcoal is used to treat stomach pain caused by excess gas, diarrhea, or indigestion.

Charcoal also is used to relieve itching related to kidney dialysis treatment and to treat poisoning or drug overdose.

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

What is the most important information I should know about Actidose-Aqua (charcoal)?

You should not use this medication if you have ever had an allergic reaction to charcoal.

Before taking this medication, tell your doctor if you are allergic to any drugs, or if you have liver or kidney disease, or any type of serious illness.

In a poisoning or overdose situation, it may not be possible before you are treated to tell your caregivers about any health conditions you have or if you are pregnant or breast-feeding. However, make sure any doctor caring for you afterward knows that you have received this medication.

If you are taking charcoal at home to treat diarrhea, stop taking it and call your doctor if your diarrhea lasts longer than 2 days or you also have a fever. Do not take charcoal with any other medicine. Take your dose of charcoal at least 2 hours before or 1 hour after a dose of any other medicine. Charcoal binds to other drugs and can make them less effective, which could become dangerous.

What should I discuss with my healthcare provider before taking Actidose-Aqua (charcoal)?

You should not use this medication if you have ever had an allergic reaction to charcoal.

If possible, before you receive charcoal, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  liver disease;

  
  


• 
  

  kidney disease; or

  
  


• 
  

  any type of serious illness.

  
  

If you have any of these conditions, you may need a dose adjustment or special tests to safely take this medication.

It is not known whether charcoal is harmful to an unborn baby. Before you take charcoal, tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether charcoal passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

In a poisoning or overdose situation, it may not be possible to tell your caregivers that you are pregnant or breast-feeding before you are treated with charcoal. However, make sure any doctor caring for your pregnancy or your baby knows that you have received the medication.

Do not give this medication to a child younger than 1 year old without the advice of a doctor.

How should I take Actidose-Aqua (charcoal)?

Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Take this medicine with a full glass (8 ounces) of water. Do not crush, break, or chew a charcoal tablet or capsule. Swallow the pill whole.

Charcoal is usually taken after meals or at the first sign of stomach discomfort.

Stop taking charcoal and call your doctor if your diarrhea lasts longer than 2 days or you also have a fever.

Store charcoal at room temperature away from moisture and heat.

What happens if I miss a dose?

Since charcoal is often taken only 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. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of charcoal is not likely to cause life-threatening symptoms.

What should I avoid while taking Actidose-Aqua (charcoal)?

Do not take charcoal with any other medicine. Take your dose of charcoal at least 2 hours before or 1 hour after a dose of any other medicine. Charcoal binds to other drugs and can make them less effective, which could become dangerous.

Actidose-Aqua (charcoal) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

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 Actidose-Aqua (charcoal)?

There may be other drugs that can interact with charcoal. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Actidose-Aqua resources

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

• Actidose-Aqua Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• Charcoal Natural MedFacts for Professionals (Wolters Kluwer)


• Charcoal MedFacts Consumer Leaflet (Wolters Kluwer)


• Charcoal, Activated Monograph (AHFS DI)

Compare Actidose-Aqua with other medications

• Gas
• Gastrointestinal Decontamination

Where can I get more information?

• Your pharmacist can provide more information about charcoal.

See also: Actidose-Aqua side effects (in more detail)

Prevacid SoluTab

Generic Name: lansoprazole (Oral route)

lan-SOE-pra-zole

Commonly used brand name(s)

In the U.S.

• Prevacid


• Prevacid SoluTab

Available Dosage Forms:

• Tablet Disintegrating, Delayed Release


• Capsule, Delayed Release


• Packet

Therapeutic Class: Gastric Acid Secretion Inhibitor

Pharmacologic Class: Proton Pump Inhibitor

Uses For Prevacid SoluTab

Lansoprazole is used to treat certain conditions where there is too much acid in the stomach. It is used to treat duodenal and gastric ulcers, erosive esophagitis, and gastroesophageal reflux disease (GERD). GERD is a condition where the acid in the stomach washes back up into the esophagus. Sometimes lansoprazole is used in combination with antibiotics (e.g., amoxicillin, clarithromycin) to treat ulcers associated with an infection caused by H. pylori bacteria.

Lansoprazole is also used to treat Zollinger-Ellison syndrome (ZES), which is a condition where the stomach produces too much acid.

Lansoprazole is a proton pump inhibitor (PPI). It works by decreasing the amount of acid produced by the stomach.

This medicine is available both over-the-counter (OTC) and with your doctor's prescription.

Before Using Prevacid SoluTab

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of lansoprazole to treat GERD and erosive esophagitis in children 1 to 17 years of age. Safety and efficacy have not been established for children younger than 1 year of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of lansoprazole in the elderly.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Rilpivirine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atazanavir


• Citalopram


• Dasatinib


• Delavirdine


• Erlotinib


• Mycophenolate Mofetil


• Nelfinavir


• Nilotinib

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol


• Aluminum Carbonate, Basic


• Aluminum Hydroxide


• Aluminum Phosphate


• Calcium Carbonate


• Cranberry


• Dicumarol


• Dihydroxyaluminum Aminoacetate


• Dihydroxyaluminum Sodium Carbonate


• Magaldrate


• Magnesium Carbonate


• Magnesium Hydroxide


• Magnesium Oxide


• Magnesium Trisilicate


• Phenprocoumon


• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Hypomagnesemia (low magnesium in the blood), history of or


• Osteoporosis (bone problem) or


• Seizures, history of—Use with caution. May make these conditions worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Phenylketonuria (PKU)—The orally disintegrating tablet contains phenylalanine, which can make this condition worse.

Proper Use of lansoprazole

This section provides information on the proper use of a number of products that contain lansoprazole. It may not be specific to Prevacid SoluTab. Please read with care.

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If you are using this medicine without a prescription, follow the instructions on the medicine label.

Take this medicine before a meal and for the full time of treatment, even if you begin to feel better after a few days.

If you are taking this medicine to treat an ulcer that is associated with an H. pylori infection, take it together with the antibiotics (e.g., amoxicillin, clarithromycin) at the same time of day.

To use the capsule:

• Swallow the capsule whole. Do not break, crush, or chew it.


• If the capsule cannot be swallowed, open it and sprinkle the contents on one tablespoonful of applesauce, Ensure® pudding, cottage cheese, yogurt, or strained pears. Swallow the mixture right away. Do not chew or crush the granules.


• The contents of the capsule can also be mixed with 2 ounces (1/4 cup or 60 mL) of apple juice, orange juice, or tomato juice. After mixing, drink and swallow the mixture right away. Do not chew or crush the granules. Refill the cup 2 more times with juice and drink the liquid to make sure all of the medicine is taken.

To use the capsule with a nasogastric (NG) tube:

• Open the capsule and mix the contents with 40 mL of apple juice. Do not use any other liquids.


• Inject or pour the mixture into the nasogastric tube.


• Flush the tube with more apple juice to rinse all of the medicine from the tube into the stomach.

To use the orally disintegrating tablet:

• Make sure your hands are dry before you handle the tablet.


• Do not crush, chew, break, or cut the tablet.


• Place the tablet on the tongue, with or without water, and allow it to dissolve into particles. Swallow the particles right away.

To use the orally disintegrating tablet with an oral syringe:

• Make sure your hands are dry before you handle the tablet.


• Do not crush, break, or cut the tablet.


• For the 15 mg tablet: Place it in the oral syringe and add 4 mL of water.


• For the 30 mg tablet: Place it in the oral syringe and add 10 mL of water.


• Shake the syringe gently until the tablet dissolves and is mixed well.


• Give the mixture within 15 minutes.


• Refill the syringe with 2 mL (15 mg tablet) or 5 mL (30 mg tablet) of water and shake it gently. Give the mixture to make sure all of the medicine is taken.

To use the orally disintegrating tablet with a nasogastric (NG) tube:

• Make sure your hands are dry before you handle the tablet.


• Do not crush, break, or cut the tablet.


• For the 15 mg tablet: Place it in the syringe and add 4 mL of water.


• For the 30 mg tablet: Place it in the syringe and add 10 mL of water.


• Shake the syringe gently until the tablet dissolves and is mixed well.


• Inject or pour the mixture into the nasogastric tube within 15 minutes.


• Refill the syringe with 5 mL of water and shake it gently. Flush the tube with the water to rinse all of the medicine from the tube into the stomach.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (capsules or orally disintegrating tablets):
  
  • To treat duodenal ulcers:
    
    • Adults—15 milligrams (mg) once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • To treat duodenal ulcers with H. pylori infection:
    
    • Adults—30 milligrams (mg) before meals 2 or 3 times a day. The dose is usually taken together with amoxicillin or clarithromycin plus amoxicillin. Your doctor may adjust your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • To treat erosive esophagitis:
    
    • Adults—15 to 30 milligrams (mg) once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Teenagers and children 12 years of age—30 mg once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children 1 to 11 years of age and weighing over 30 kg—30 mg once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children 1 to 11 years of age and weighing 30 kg or less—15 mg once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children younger than 1 year of age—Use and dose must be determined by your doctor.
    
    
  
  
  • To treat gastric ulcers:
    
    • Adults—15 to 30 milligrams (mg) once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • To treat gastroesophageal reflux disease (GERD):
    
    • Adults, teenagers, and children 12 years of age—15 milligrams (mg) once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children 1 to 11 years of age and weighing over 30 kg—30 mg once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children 1 to 11 years of age and weighing 30 kg or less—15 mg once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children younger than 1 year of age—Use and dose must be determined by your doctor.
    
    
  
  
  • To treat Zollinger-Ellison syndrome (ZES):
    
    • Adults—60 milligrams (mg) once a day before a meal. Your doctor may adjust your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Prevacid SoluTab

It is important that your doctor check the progress of you or your child at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects. If your or your child's condition does not improve, or if it becomes worse, discuss this with your doctor.

Lansoprazole may increase your risk of having fractures of the hip, wrist, and spine. This is more likely if you have osteoporosis, if you are 50 years of age and older, if you receive high doses of this medicine, or use it for one year or more.

This medicine may cause hypomagnesemia (low magnesium in the blood). This is more likely to occur if you are taking this medicine for more than one year, or if you are taking this medicine together with digoxin (Lanoxin®) or certain diuretics or "water pills". Stop using this medicine and check with your doctor right away if you have convulsions (seizures); fast, racing, or uneven heartbeat; muscle spasms (tetany); tremors; or unusual tiredness or weakness.

Do not stop taking this medicine without first checking with your doctor, or unless told to do so by your doctor.

Before you have any medical tests, tell the medical doctor in charge that you or your child are taking this medicine. The results of some tests may be affected by this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Prevacid SoluTab Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Diarrhea


• skin rash or itching

Less common

• Abdominal or stomach pain


• increased or decreased appetite


• joint pain


• nausea


• vomiting

Rare

• Anxiety


• cold or flu-like symptoms


• constipation


• increased cough


• mental depression


• muscle pain


• rectal bleeding


• unusual bleeding or bruising

Incidence not known

• Abdominal or stomach tenderness


• back, leg, or stomach pains


• bleeding gums


• blistering, peeling, or loosening of the skin


• bloating


• bloody, black, or tarry stools


• change in mental status


• chest pain


• chills


• clay colored stools


• constipation


• cough or hoarseness


• dark or bloody urine


• difficulty with swallowing


• drowsiness


• fast heartbeat


• fever


• general body swelling


• high fever


• hives


• indigestion


• loss of appetite


• lower back or side pain


• mood or mental changes


• muscle spasms (tetany) or twitching seizures


• nosebleeds


• painful or difficult urination


• pains in the stomach, side, or abdomen, possibly radiating to the back


• pale skin


• pinpoint red spots on the skin


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• red, irritated eyes


• red skin lesions, often with a purple center


• seizures


• shortness of breath


• sore throat


• sores, ulcers, or white spots on the lips or in the mouth


• swelling of the feet or lower legs


• swollen or painful glands


• tightness in the chest


• trembling


• unusual tiredness or weakness


• wheezing


• yellowing of the eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Dizziness


• headache

Less common

• Bleeding, blistering, burning, coldness, or discoloration of the skin


• mild nausea

Rare

• Acid or sour stomach


• bad, unusual or unpleasant (after) taste


• belching


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• change in taste


• feeling faint, dizzy, or lightheaded


• feeling of heat or warmth


• flushing or redness of the skin, especially on the face and neck


• heartburn


• indigestion


• mild diarrhea


• mild headache


• mild vomiting


• stomach discomfort, upset, or pain


• sweating

Incidence not known

• Decrease in passing urine (dribbling)


• decrease in the frequency of urination


• decrease in urine volume


• difficulty with speaking

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Prevacid SoluTab side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Prevacid SoluTab resources

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

• Prevacid SoluTab Orally Disintegrating Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Lansoprazole Professional Patient Advice (Wolters Kluwer)


• Lansoprazole Prescribing Information (FDA)


• Lansoprazole MedFacts Consumer Leaflet (Wolters Kluwer)


• Lansoprazole Monograph (AHFS DI)


• Prevacid Prescribing Information (FDA)


• Prevacid Delayed-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Prevacid Consumer Overview

Compare Prevacid SoluTab with other medications

• Aspiration Pneumonia
• Barrett's Esophagus
• Duodenal Ulcer
• Duodenal Ulcer Prophylaxis
• Erosive Esophagitis
• GERD
• Helicobacter Pylori Infection
• Multiple Endocrine Adenomas
• NSAID-Induced Gastric Ulcer
• NSAID-Induced Ulcer Prophylaxis
• Stomach Ulcer
• Systemic Mastocytosis
• Zollinger-Ellison Syndrome

Naproxen Tablets 250mg

1. Name Of The Medicinal Product

NAPROXEN TABLETS BP 250mg

2. Qualitative And Quantitative Composition

Each tablet contains 250mg Naproxen PhEur.

3. Pharmaceutical Form

Yellow uncoated tablets.

Yellow, circular, flat bevelled-edge uncoated tablets impressed “C” and the identifying letters “NC” on either side of a central division line on one face.

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) Acute gout.

5) Acute musculoskeletal disorders such as cervical spondylitis, lumbosacral pain, direct trauma, strains and sprains, fibrositis and tenosynovitis.

4.2 Posology And Method Of Administration

Adults:

Rheumatoid arthritis, osteoarthritis and ankylosing spondylitis: 500mg-1g daily in two doses at twelve hour intervals, or alternatively, as a single administration of two tablets, morning or evening.

A loading dose of 750mg-1g daily for the acute phase is recommended in the following cases:

a) Patients reporting severe night time pain and/or morning stiffness.

b) Patients commencing naproxen therapy following a switch from a high dose of another antirheumatic compound.

c) Osteoarthritis where pain is the predominant symptom.

For patients requiring 750mg or 1g daily, the size of the morning and evening doses may be adjusted on the basis of the predominant symptoms eg night time pain or morning stiffness.

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

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

Children under 16 years: Not recommended.

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.

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

Route of administration

For oral administration preferably with or after food.

4.3 Contraindications

Patients with active peptic ulceration or a history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding); known hypersensitivity to naproxen, naproxen sodium or any other ingredient in the formulation. 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. Patients with severe hepatic, renal and cardiac failure (see section 4.4), severe heart failure, a history of upper gastrointestinal bleeding or perforation related to previous NSAID therapy. During the third trimester of pregnancy (see section 4.6).

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).

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).

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 ot 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)

- 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 the elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment. 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).

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.

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).

Naproxen should be used with great caution where there is impairment of renal function; the monitoring of serum creatinine and/or creatinine clearance should be conducted in these.

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.

Mild peripheral oedema has been observed in a few patients receiving naproxen. Although sodium retention has not been reported in metabolic studies, it is possible that patients with questionable or compromised function may be at a greater risk when taking naproxen.

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.

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).

Impaired female fertility

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 fertility, withdrawal of naproxen should be considered.

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

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.

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

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).

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.

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).

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

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 ophthalmological examination.

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 beern observed in clinical studies with naproxen or sulphonylureas, but caution is nevertheless advised since interaction has been seen with other non-steroidal agents of this class.

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).

Naproxen reduces the effects of diuretics, also diuretics can increase the risk of nephrotoxicity of NSAIDs.

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels of cardiac glycosides.

There is an increased risk of nephrotoxicity with ciclosporin or tacrolimus.

If mifepristone is taken NSAIDs should not be used for 8-12 days after mifepristone administration as the NSAIDs can reduce the effect of the mifepristone.

There is an increased risk of gastrointestinal ulceration or bleeding with corticosteroids.

The effects or anti-coagulants, such as warfarin, may be enhanced by NSAIDs (see section 4.4.).

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

Animal data indicates that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Therefore, Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

NSAIDs, including naproxen, have been reported to increase steady state plasma lithium levels, 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 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.

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. Decreased elimination of methotrexate.

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 trimestersof 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 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 hypersensitivity 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, photosensitivity	alopecia, pseudoporphyria	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

Symptoms: 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.

Treatment: 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

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Also contains: lactose, magnesium stearate, maize starch, polyvidone, E172, E463.

6.2 Incompatibilities

None known.

6.3 Shelf Life

Shelf-life

Three years 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

Store below 25°C in a dry place. Protect from light.

6.5 Nature And Contents Of Container

The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers with polyfoam wad or polyethylene ullage filler and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps and polyfoam wad or cotton wool.

The product may also be supplied in blister packs in cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-6g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 20s, 28s, 30s, 50s, 56s, 60s, 84s, 90s, 100s, 112s, 120s, 168s, 180s, 250s.

Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.

Maximum size of bulk packs: 50,000.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data

7. Marketing Authorisation Holder

Name or style and permanent address of registered place of business of the holder of the Marketing Authorisation:

Actavis UK Limited

(Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL 0142/0277

9. Date Of First Authorisation/Renewal Of The Authorisation

16.05.90

10. Date Of Revision Of The Text

07.06.2011