Nu-Seals 75

1. Name Of The Medicinal Product

Nu-Seals 75, Aspirin 75mg Gastro-resistant Tablets, PostMI 75EC, Nu-Seals Cardio 75

2. Qualitative And Quantitative Composition

Acetylsalicylic Acid 75mg

3. Pharmaceutical Form

White, gastro-resistant tablets, coded “75” or “GP”.

4. Clinical Particulars

4.1 Therapeutic Indications

For the secondary prevention of thrombotic cerebrovascular or cardiovascular disease and following by-pass surgery (see below).

Aspirin has an antithrombotic action, mediated through inhibition of platelet activation, which has been shown to be useful in secondary prophylaxis following myocardial infarction and in patients with unstable angina or ischaemic stroke including cerebral transient attacks.

Nu-Seals 75 is indicated when prolonged dosage of aspirin is required. The special coating resists dissolution in gastric juice, but will dissolve readily in the relatively less acid environment of the duodenum. Owing to the delay that the coating imposes on the release of the active ingredient, Nu-Seals 75 is unsuitable for the short-term relief of pain.

4.2 Posology And Method Of Administration

Nu-Seals 75 is for oral administration to adults only.

Patients should seek the advice of a doctor before commencing therapy for the first time.

The usual dosage, for long-term use, is 75-150mg once daily. In some circumstances a higher dose may be appropriate, especially in the short term, and up to 300mg a day may be used on the advice of a doctor.

Antithrombotic action: 150mg at diagnosis and 75mg daily thereafter. Tablets taken at diagnosis should be chewed in order to gain rapid absorption.

The elderly: The risk-benefit ratio of the antithrombotic action of aspirin has not been fully established.

Children:

Do not give to children aged under 16 years, unless specifically indicated (e.g. for Kawasaki's disease). See 'Special warnings and precautions for use'.

4.3 Contraindications

Hypersensitivity to aspirin. Hypoprothrombinaemia, haemophilia and active peptic ulceration or a history of peptic ulceration.

4.4 Special Warnings And Precautions For Use

There is a possible association between aspirin and Reye's syndrome when given to children. Reye's syndrome is a very rare disease, which affects the brain and liver, and can be fatal. For this reason aspirin should not be given to children aged under 16 years unless specifically indicated (e.g. for Kawasaki's disease).

Before commencing long-term aspirin therapy for the management of cerebrovascular or cardiovascular disease patients should consult their doctor who can advise on the relative benefits versus the risks for the individual patient.

Aspirin decreases platelet adhesiveness and increases bleeding time. Haematological and haemorrhagic effects can occur, and may be severe. Patients should report any unusual bleeding symptoms to their physician.

Salicylates should be used with caution in patients with a history of peptic ulceration or coagulation abnormalities. They may also induce gastro-intestinal haemorrhage, occasionally major.

They may also precipitate bronchospasm or induce attacks of asthma in susceptible subjects.

Aspirin should be used with caution in patients with impaired renal or hepatic function (avoid if severe), or in patients who are dehydrated.

Patients with hypertension should be carefully monitored.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Salicylates may enhance the effect of oral hypoglycaemic agents, phenytoin and sodium valproate. They inhibit the uricosuric effect of probenecid and may increase the toxicity of sulphonamides.

Aspirin may potentiate the effect of heparin and increases the risk of bleeding with oral anticoagulants, antiplatelet agents and fibrinolytics.

Plasma salicylate concentrations may be reduced by concurrent use of corticosteroids, and salicylate toxicity may occur following withdrawal of the corticosteroids. The risk of gastrointestinal ulceration and bleeding may be increased when aspirin and corticosteroids are co-administered.

Concurrent use of aspirin and other NSAIDs should be avoided. Use of two or more NSAID preparations increases the risk of serious gastrointestinal haemorrhage.

Concurrent administration of carbonic anhydrase inhibitors such as acetazolamide and salicylates may result in severe acidosis and increased central nervous system toxicity.

In large doses, salicylates may also decrease insulin requirements.

Patients using gastro-resistant aspirin should be advised against ingesting antacids simultaneously to avoid premature drug release.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex-vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

4.6 Pregnancy And Lactation

Pregnancy: Although clinical and epidemiological evidence suggests the safety of aspirin for use in pregnancy, caution should be exercised when considering use in pregnant patients. Aspirin has the ability to alter platelet function and there may be a risk of haemorrhage in infants whose mothers have consumed aspirin during pregnancy. Prolonged pregnancy and labour, with increased bleeding before and after delivery, decreased birth weight and increased rate of stillbirth have been reported with high blood salicylate levels. With high doses there may be premature closure of the ductus arteriosus and possible persistent pulmonary hypertension in the newborn. Analgesic doses of aspirin should be avoided during the last trimester of pregnancy.

Lactation: As aspirin is excreted in breast milk, Nu-Seals should not be taken by patients who are breast-feeding, as there is a risk of Reye's syndrome in the infant. High maternal doses may impair platelet function in the infant.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Gastrointestinal irritation is common in patients taking aspirin preparations, and nausea, vomiting, dyspepsia, gastritis, gastrointestinal erosions and ulceration have been reported. Anaemia may occur following chronic gastrointestinal blood loss or acute haemorrhage.

Aspirin prolongs bleeding time, and bleeding disorders, such as epistaxis, haematuria, purpura, ecchymoses, haemoptysis, gastrointestinal bleeding, haematoma and cerebral haemorrhage have occasionally been reported. Fatalities have occurred.

Hypersensitivity reactions include skin rashes, urticaria, angioedema, asthma, bronchospasm and rarely, anaphylaxis.

Other side effects: urate kidney stones and tinnitus.

4.9 Overdose

Salicylate poisoning is usually associated with plasma concentrations>350 mg/L (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (5.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.

Symptoms

Common features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases.

A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) is usual in adults and children over the age of 4 years. In children aged 4 years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier.

Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiogenic pulmonary oedema.

Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than in children.

Management

Give activated charcoal if an adult presents within one hour of ingestion of more than 250 mg/kg. The plasma salicylate concentration should be measured, although the severity of poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalisation, which is achieved by the administration of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct metabolic acidosis with intravenous 8.4% sodium bicarbonate (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema.

Haemodialysis is the treatment of choice for severe poisoning and should be considered in patients with plasma salicylate concentrations>700 mg/L (5.1 mmol/L), or lower concentrations associated with severe clinical or metabolic features. Patients under 10 years and over 70 have increased risk of salicylate toxicity, and may require dialysis at an earlier stage.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Aspirin has analgesic, antipyretic and anti-inflammatory actions.

It also has antithrombotic action which is mediated through inhibition of platelet activation.

Nu-Seals 75 tablets have a gastro-resistant coat sandwiched between a sealing coat and a top coat. The gastro-resistant coat is intended to resist gastric fluid whilst allowing disintegration in the intestinal fluid.

Owing to the delay that the coating imposes on the release of the active ingredient, Nu-Seals 75 is unsuitable for the short-term relief of pain.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 hours before or within 30 minutes after immediate release aspirin (81mg), a decreased effect of aspirin on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

5.2 Pharmacokinetic Properties

In a bioequivalence study comparing the pharmacokinetics of the 300mg product with 4 x 75mg presentation in human volunteers, measures such as terminal phase half-life, area-under-the curve and peak plasma concentrations were recorded on days 1 and 4. On day 1 salicylate reached a peak plasma concentration of between 10.34 and 31.57 mcg/ml and between 11.76 and 27.47mcg/ml for the 300mg and 75mg tablets respectively. Time to peak concentration ranged from 4 to 8 hours and from 3 to 6 hours respectively. AUC ranged from 54.0 to 131.2 and from 64.3 to 137.6 h.mcg/ml respectively. The terminal phase half-life ranged from 1.33 to 2.63 hours and from 1.47 to 2.59 hours respectively. On day 4 C_max varied from 15.01 to 48.97 mcg/ml for the 300mg tablet and from 11.26 to 60.21 mcg/ml for 4 x 75mg tablets. T_max ranged from 4 to 8 hours and from 3 to 8 hours, whilst AUC ranged from 89.8 to 297.4 h.mcg/ml and from 61.5 to 293.4 h.mcg/ml respectively.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber in addition to that summarised in other sections of the Summary of Product Characteristics.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Maize Starch

Hypromellose

Talc

Methacrylic acid – ethyl acrylate (1:1) copolymer dispersion 30 per cent

Polyethylene Glycol 3350

Propylene Glycol

Benzyl Alcohol

Emulsion silicone

Edible Printing Ink - containing either: E124 Red and Shellac or: E172 Black, Shellac and E322 Lecithin

6.2 Incompatibilities

None known.

6.3 Shelf Life

2 years.

6.4 Special Precautions For Storage

Do not store above 25°C. Keep containers tightly closed.

6.5 Nature And Contents Of Container

Blisters comprising of UPVC on one side and aluminium foil on the other containing 14, 28, 56 or 84 tablets. HDPE bottles with screw caps containing 500 tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Alliance Pharmaceuticals Ltd

Avonbridge House

Bath Road

Chippenham

Wiltshire

SN15 2BB

8. Marketing Authorisation Number(S)

PL 16853/0062

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 21 April 1994

Date of last renewal of authorisation: 12 May 2006

10. Date Of Revision Of The Text

10^th August 2010

Zovirax Ointment

acyclovir

Dosage Form: ointment
ZOVIRAX®

(acyclovir)

Ointment 5%

Zovirax Ointment Description

ZOVIRAX is the brand name for acyclovir, a synthetic nucleoside analogue active against herpes viruses. Zovirax Ointment 5% is a formulation for topical administration. Each gram of Zovirax Ointment 5% contains 50 mg of acyclovir in a polyethylene glycol (PEG) base.

Acyclovir is a white, crystalline powder with the molecular formula C8H11N5O3 and a molecular weight of 225. The maximum solubility in water at 37°C is 2.5 mg/mL. The pka’s of acyclovir are 2.27 and 9.25.

The chemical name of acyclovir is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one; it has the following structural formula:

VIROLOGY

Mechanism of Antiviral Action:

Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV).

The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral TK.

Antiviral Activities:

The quantitative relationship between the in vitro susceptibility of herpes viruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized. Sensitivity testing results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (IC50), vary greatly depending upon a number of factors. Using plaque-reduction assays, the IC50 against herpes simplex virus isolates ranges from 0.02 to 13.5 mcg/mL for HSV-1 and from 0.01 to 9.9 mcg/mL for HSV-2. The IC50 for acyclovir against most laboratory strains and clinical isolates of VZV ranges from 0.12 to 10.8 mcg/mL. Acyclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean IC50 of 1.35 mcg/mL.

Drug Resistance:

Resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of HSV and VZV with reduced susceptibility to acyclovir have been recovered from immunocompromised patients, especially with advanced HIV infection. While most of the acyclovir-resistant mutants isolated thus far from immunocompromised patients have been found to be TK-deficient mutants, other mutants involving the viral TK gene (TK partial and TK altered) and DNA polymerase have been isolated. TK-negative mutants may cause severe disease in infants and immunocompromised adults. The possibility of viral resistance to acyclovir should be considered in patients who show poor clinical response during therapy.

Zovirax Ointment - Clinical Pharmacology

Two clinical pharmacology studies were performed with Zovirax Ointment 5% in immunocompromised adults at risk of developing mucocutaneous Herpes simplex virus infections or with localized varicella-zoster infections. These studies were designed to evaluate the dermal tolerance, systemic toxicity, and percutaneous absorption of acyclovir.

In 1 of these studies, which included 16 inpatients, the complete ointment or its vehicle were randomly administered in a dose of 1-cm strips (25 mg acyclovir) 4 times a day for 7 days to an intact skin surface area of 4.5 square inches. No local intolerance, systemic toxicity, or contact dermatitis were observed. In addition, no drug was detected in blood and urine by radioimmunoassay (sensitivity, 0.01 mcg/mL).

The other study included 11 patients with localized varicella-zoster infections. In this uncontrolled study, acyclovir was detected in the blood of 9 patients and in the urine of all patients tested. Acyclovir levels in plasma ranged from <0.01 to 0.28 mcg/mL in 8 patients with normal renal function, and from <0.01 to 0.78 mcg/mL in 1 patient with impaired renal function. Acyclovir excreted in the urine ranged from <0.02% to 9.4% of the daily dose. Therefore, systemic absorption of acyclovir after topical application is minimal.

Clinical Trials

In clinical trials of initial genital herpes infections, Zovirax Ointment 5% has shown a decrease in healing time and, in some cases, a decrease in duration of viral shedding and duration of pain. In studies in immunocompromised patients mainly with herpes labialis, there was a decrease in duration of viral shedding and a slight decrease in duration of pain.

In studies of recurrent genital herpes and of herpes labialis in nonimmunocompromised patients, there was no evidence of clinical benefit; there was some decrease in duration of viral shedding.

Indications and Usage for Zovirax Ointment

ZOVIRAX (acyclovir) Ointment 5% is indicated in the management of initial genital herpes and in limited non-life-threatening mucocutaneous Herpes simplex virus infections in immunocompromised patients.

Contraindications

Zovirax Ointment 5% is contraindicated in patients who develop hypersensitivity to the components of the formulation.

Warnings

Zovirax Ointment 5% is intended for cutaneous use only and should not be used in the eye.

Precautions

General:

The recommended dosage, frequency of applications, and length of treatment should not be exceeded (see DOSAGE AND ADMINISTRATION). There are no data to support the use of Zovirax Ointment 5% to prevent transmission of infection to other persons or prevent recurrent infections when applied in the absence of signs and symptoms. Zovirax Ointment 5% should not be used for the prevention of recurrent HSV infections. Although clinically significant viral resistance associated with the use of Zovirax Ointment 5% has not been observed, this possibility exists.

Drug Interactions:

Clinical experience has identified no interactions resulting from topical or systemic administration of other drugs concomitantly with Zovirax Ointment 5%.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Systemic exposure following topical administration of acyclovir is minimal. Dermal carcinogenicity studies were not conducted. Results from the studies of carcinogenesis, mutagenesis, and fertility are not included in the full prescribing information for Zovirax Ointment 5% due to the minimal exposures of acyclovir that result from dermal application. Information on these studies is available in the full prescribing information for ZOVIRAX Capsules, Tablets, and Suspension and ZOVIRAX for Injection.

Pregnancy:

Teratogenic Effects:

Pregnancy Category B. Acyclovir was not teratogenic in the mouse, rabbit, or rat at exposures greatly in excess of human exposure. There are no adequate and well-controlled studies of systemic acyclovir in pregnant women. A prospective epidemiologic registry of acyclovir use during pregnancy was established in 1984 and completed in April 1999. There were 749 pregnancies followed in women exposed to systemic acyclovir during the first trimester of pregnancy resulting in 756 outcomes. The occurrence rate of birth defects approximates that found in the general population. However, the small size of the registry is insufficient to evaluate the risk for less common defects or to permit reliable or definitive conclusions regarding the safety of acyclovir in pregnant women and their developing fetuses. Systemic acyclovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers:

It is not known whether topically applied acyclovir is excreted in breast milk. Systemic exposure following topical administration is minimal. After oral administration of ZOVIRAX, acyclovir concentrations have been documented in breast milk in 2 women and ranged from 0.6 to 4.1 times the corresponding plasma levels. These concentrations would potentially expose the nursing infant to a dose of acyclovir up to 0.3 mg/kg per day. Nursing mothers who have active herpetic lesions near or on the breast should avoid nursing.

Geriatric Use:

Clinical studies of Zovirax Ointment did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Systemic absorption of acyclovir after topical administration is minimal (see CLINICAL PHARMACOLOGY).

Pediatric Use:

Safety and effectiveness in pediatric patients have not been established.

Adverse Reactions

In the controlled clinical trials, mild pain (including transient burning and stinging) was reported by about 30% of patients in both the active and placebo arms; treatment was discontinued in 2 of these patients. Local pruritus occurred in 4% of these patients. In all studies, there was no significant difference between the drug and placebo group in the rate or type of reported adverse reactions nor were there any differences in abnormal clinical laboratory findings.

Observed During Clinical Practice:

Based on clinical practice experience in patients treated with Zovirax Ointment in the US, spontaneously reported adverse events are uncommon. Data are insufficient to support an estimate of their incidence or to establish causation. These events may also occur as part of the underlying disease process. Voluntary reports of adverse events that have been received since market introduction include:

General: Edema and/or pain at the application site.

Skin: Pruritus, rash.

Overdosage

Overdosage by topical application of Zovirax Ointment 5% is unlikely because of limited transcutaneous absorption (see CLINICAL PHARMACOLOGY).

Zovirax Ointment Dosage and Administration

Apply sufficient quantity to adequately cover all lesions every 3 hours, 6 times per day for 7 days. The dose size per application will vary depending upon the total lesion area but should approximate a one-half inch ribbon of ointment per 4 square inches of surface area. A finger cot or rubber glove should be used when applying ZOVIRAX to prevent autoinoculation of other body sites and transmission of infection to other persons. Therapy should be initiated as early as possible following onset of signs and symptoms.

How is Zovirax Ointment Supplied

Each gram of Zovirax Ointment 5% contains 50 mg acyclovir in a polyethylene glycol base. It is supplied as follows:

15-g tubes (NDC 64455-993-94)

30-g tubes (NDC 64455-993-95)

Store at 15° to 25°C (59° to 77°F) in a dry place.

Manufactured by

GlaxoSmithKline

Research Triangle Park, NC 27709

for

BTA Pharmaceuticals, Inc. (subsidiary of Biovail Corporation)

Bridgewater, NJ 08807

©2010, GlaxoSmithKline. All rights reserved.

September 2010        ZVO:3PI

Principal Display Panel

NDC 64455-993-94

ZOVIRAX®

(ACYCLOVIR)

OINTMENT 5%

Rx only

15 g

Each gram contains acyclovir 50 mg in a polyethylene glycol base.

Store at 15o to 25oC (59o to 77oF) in a dry place.

USUAL DOSAGE: Apply 6 times a day (every 3 hours) for 7 days. See prescribing information for dosage information.

SEE CRIMP FOR LOT NO. AND EXPIRATION DATE.

FILLED BY WEIGHT, NOT BY VOLUME.

Manufactured by

GlaxoSmithKline

Research Triangle Park, NC 27709

for BTA Pharmaceuticals, Inc. (subsidiary of Biovail Corporation)

Bridgewater, NJ 08807

Made in India

Rev. 8/09 A071969

ZOVIRAX  acyclovir  ointment

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 64455-993 Route of Administration TOPICAL DEA Schedule

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

Inactive Ingredients Ingredient Name Strength POLYETHYLENE GLYCOL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 64455-993-94 15 g In 1 TUBE None 2 64455-993-20 0.9 g In 1 PACKET None 3 64455-993-95 30 g In 1 TUBE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA018604	10/29/2004

Labeler - BTA PHARMACEUTICALS INC (830950668)

Revised: 02/2011BTA PHARMACEUTICALS INC

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Spectazole

econazole nitrate

Dosage Form: cream

631-11-331-1

For Topical Use Only

DESCRIPTION:

Spectazole Cream contains the antifungal agent, econazole nitrate 1%, in a water-miscible base consisting of pegoxol 7 stearate, peglicol 5 oleate, mineral oil, benzoic acid, butylated hydroxyanisole, and purified water. The white to off-white soft cream is for topical use only.

Chemically, econazole nitrate is 1-[2-{(4-chloro-phenyl) methoxy}-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole mononitrate. Its structure is as follows:

CLINICAL PHARMACOLOGY:

After topical application to the skin of normal subjects, systemic absorption of econazole nitrate is extremely low. Although most of the applied drug remains on the skin surface, drug concentrations were found in the stratum corneum which, by far, exceeded the minimum inhibitory concentration for dermatophytes. Inhibitory concentrations were achieved in the epidermis and as deep as the middle region of the dermis. Less than 1% of the applied dose was recovered in the urine and feces.

Microbiology: Econazole nitrate has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Dermatophytes		Yeasts
Epidermophyton floccosum	Trichophyton mentagrophytes	Candida albicans
Microsporum audouini	Trichophyton rubrum	Malassezia furfur
Microsporum canis	Trichophyton tonsurans
Microsporum gypseum

Econazole nitrate exhibits broad-spectrum antifungal activity against the following organisms in vitro, but the clinical significance of these data is unknown.

Dermatophytes	Yeasts
Trichophyton verrucosum	Candida guillermondii
	Candida parapsilosis
	Candida tropicalis

INDICATIONS AND USAGE:

Spectazole Cream is indicated for topical application in the treatment of tinea pedis, tinea cruris, and tinea corporis caused by Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Microsporum canis, Microsporum audouini, Microsporum gypseum, and Epidermophyton floccosum, in the treatment of cutaneous candidiasis, and in the treatment of tinea versicolor.

CONTRAINDICATIONS:

Spectazole Cream is contraindicated in individuals who have shown hypersensitivity to any of its ingredients.

WARNINGS:

Spectazole is not for ophthalmic use.

PRECAUTIONS:

General: If a reaction suggesting sensitivity or chemical irritation should occur, use of the medication should be discontinued.

For external use only. Avoid introduction of Spectazole Cream into the eyes.

Carcinogenicity Studies: Long-term animal studies to determine carcinogenic potential have not been performed.

Fertility (Reproduction): Oral administration of econazole nitrate in rats has been reported to produce prolonged gestation. Intravaginal administration in humans has not shown prolonged gestation or other adverse reproductive effects attributable to econazole nitrate therapy.

Pregnancy: Pregnancy Category C. Econazole nitrate has not been shown to be teratogenic when administered orally to mice, rabbits or rats. Fetotoxic or embryotoxic effects were observed in Segment I oral studies with rats receiving 10 to 40 times the human dermal dose. Similar effects were observed in Segment II or Segment III studies with mice, rabbits and/or rats receiving oral doses 80 or 40 times the human dermal dose.

Econazole nitrate should be used in the first trimester of pregnancy only when the physician considers it essential to the welfare of the patient. The drug should be used during the second and third trimesters of pregnancy only if clearly needed.

Nursing Mothers: It is not known whether econazole nitrate is excreted in human milk. Following oral administration of econazole nitrate to lactating rats, econazole and/or metabolites were excreted in milk and were found in nursing pups. Also, in lactating rats receiving large oral doses (40 or 80 times the human dermal dose), there was a reduction in post partum viability of pups and survival to weaning; however, at these high doses, maternal toxicity was present and may have been a contributing factor. Caution should be exercised when econazole nitrate is administered to a nursing woman.

ADVERSE REACTIONS:

During clinical trials, approximately 3% of patients treated with econazole nitrate 1% cream reported side effects thought possibly to be due to the drug, consisting mainly of burning, itching, stinging, and erythema. One case of pruritic rash has also been reported.

OVERDOSE:

Overdosage of econazole nitrate in humans has not been reported to date. In mice, rats, guinea pigs and dogs, the oral LD 50 values were found to be 462, 668, 272, and >160 mg/kg, respectively.

DOSAGE AND ADMINISTRATION:

Sufficient Spectazole Cream should be applied to cover affected areas once daily in patients with tinea pedis, tinea cruris, tinea corporis, and tinea versicolor, and twice daily (morning and evening) in patients with cutaneous candidiasis.

Early relief of symptoms is experienced by the majority of patients and clinical improvement may be seen fairly soon after treatment is begun; however, candidal infections and tinea cruris and corporis should be treated for two weeks and tinea pedis for one month in order to reduce the possibility of recurrence. If a patient shows no clinical improvement after the treatment period, the diagnosis should be redetermined. Patients with tinea versicolor usually exhibit clinical and mycological clearing after two weeks of treatment.

HOW SUPPLIED:

Spectazole (econazole nitrate 1%) Cream is supplied in tubes of 15 grams (NDC 0062-5460-02), 30 grams (NDC 0062-5460-01), and 85 grams (NDC 0062-5460-03).

Store Spectazole Cream below 86°F.

Ortho Dermatological, Division of

Ortho-McNeil Pharmaceutical, Inc.

Skillman, New Jersey 08558

© OMP 2001

Printed in U.S.A

Rev January 2001

631-11-331-1

Spectazole  econazole nitrate  cream

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0062-5460 Route of Administration TOPICAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Econazole nitrate (Econazole) Active 10 MILLIGRAM  In 1 GRAM Pegoxol 7 stearate Inactive   Peglicol 5 oleate Inactive   Mineral oil Inactive   Benzoic acid Inactive   Butylated hydroxyanisole Inactive   Water Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0062-5460-02 15 g (GRAM) In 1 TUBE None 2 0062-5460-01 30 g (GRAM) In 1 TUBE None 3 0062-5460-03 85 g (GRAM) In 1 TUBE None

Revised: 03/2007Ortho Dermatological, Division of Ortho-McNeil Pharmaceutical, Inc.

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Nasop Suspension

Pronunciation: fen-il-EF-rin
Generic Name: Phenylephrine Tannate
Brand Name: Examples include Nasop and Ricobid-D

Nasop Suspension is used for:

Relieving congestion due to colds, flu, hay fever, and other allergies. It may also be used for other conditions as determined by your doctor.

Nasop Suspension is a decongestant. It works by shrinking swollen and congested nasal tissues by constricting blood vessels. This results in relief of congestion (stuffy feeling) and improved breathing through the nose.

Do NOT use Nasop Suspension if:

• you are allergic to any ingredient in Nasop Suspension


• you are taking furazolidone or have taken a monoamine oxidase (MAO) inhibitor (eg, phenelzine) in the last 14 days

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

Before using Nasop Suspension:

Some medical conditions may interact with Nasop Suspension. 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 heart disease, diabetes, high blood pressure, prostate problems, an overactive thyroid, or a tumor on your adrenal gland

Some MEDICINES MAY INTERACT with Nasop Suspension. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Rauwolfia derivatives (eg, reserpine) or tricyclic antidepressants (eg, amitriptyline) because the effectiveness of Nasop Suspension may be decreased


• Cocaine, furazolidone, methyldopa, MAO inhibitors (eg, phenelzine), oxytocic medicines (eg, oxytocin), rauwolfia derivatives (eg, reserpine), or tricyclic antidepressants (eg, amitriptyline) because the actions and side effects of Nasop Suspension may be increased


• Bromocriptine, COMT inhibitors (eg, entacapone), cocaine, or droxidopa because the actions and side effects of these medicines may be increased


• Guanethidine because its effectiveness may be decreased by Nasop Suspension

This may not be a complete list of all interactions that may occur. Ask your health care provider if Nasop Suspension 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 Nasop Suspension:

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

• Nasop Suspension may be taken with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• Shake well before using.


• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.


• If you miss a dose of Nasop Suspension and are taking it regularly, 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 Nasop Suspension.

Important safety information:

• Nasop Suspension may cause dizziness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Nasop Suspension. Using Nasop Suspension alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Do not take diet or appetite control medicines while you are taking Nasop Suspension.


• If your symptoms do not improve within 7 days or if you develop a high fever, check with your doctor.


• If you have trouble sleeping, ask your pharmacist or doctor about the best time to take Nasop Suspension.


• Diabetes patients - Nasop Suspension may affect your blood sugar. Check blood sugar levels closely and ask your doctor before adjusting the dose of your diabetes medicine.


• Use Nasop Suspension with caution in the ELDERLY because they may be more sensitive to its effects.


• Use Nasop Suspension with extreme caution in CHILDREN younger than 6 years of age. Safety and effectiveness in this age group have not been confirmed.


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

Possible side effects of Nasop Suspension:

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:

Difficulty urinating; dizziness; headache; nausea; nervousness; restlessness; stomach irritation; trouble sleeping.

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).

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: Nasop 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 confusion; excitement; hallucinations; rapid breathing; rapid heartbeat; seizures; unusual nervousness.

Proper storage of Nasop Suspension:

Store Nasop Suspension at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Nasop Suspension out of the reach of children and away from pets.

General information:

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


• Nasop Suspension 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 Nasop Suspension. 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 Nasop resources

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

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• Hypotension
• Nasal Congestion
• Shock
• Supraventricular Tachycardia

Ipratropium Nasal 0.03

Generic Name: ipratropium bromide

Dosage Form: nasal spray
IPRATROPIUM BROMIDE Nasal Solution 0.03%

NASAL SPRAY 21 mcg/spray

Rx only

Prescribing Information

Ipratropium Nasal 0.03 Description

The active ingredient in Ipratropium Bromide Nasal Spray is ipratropium bromide monohydrate. It is an anticholinergic agent chemically described as 8-azoniabicyclo (3.2.1) octane,3-(3-hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(1-methylethyl)-, bromide, monohydrate (endo,syn)-, (±)- :a synthetic quaternary ammonium compound, chemically related to atropine. Its structural formula is:

ipratropium bromide monohydrate C20H30BrNO3 • H2O Mol. Wt. 430.4

Ipratropium bromide is a white to off-white, crystalline substance. It is freely soluble in lower alcohols and water, existing in an ionized state in aqueous solutions, and relatively insoluble in non-polar media.

Ipratropium Bromide Nasal Spray 0.03% is a metered-dose, manual pump spray unit which delivers 21 mcg (70mcL) ipratropium bromide per spray on an anhydrous basis in an isotonic, aqueous solution with pH adjusted to 4.7. It also contains benzalkonium chloride, edetate disodium, sodium chloride, sodium hydroxide, hydrochloric acid, and purified water. Each bottle contains 345 sprays.

Ipratropium Nasal 0.03 - Clinical Pharmacology

Mechanism of Action

Ipratropium bromide is an anticholinergic agent that inhibits vagally-mediated reflexes by antagonizing the action of acetylcholine at the cholinergic receptor. In humans, ipratropium bromide has anti-secretory properties and, when applied locally, inhibits secretions from the serous and seromucous glands lining the nasal mucosa. Ipratropium bromide is a quaternary amine that minimally crosses the nasal and gastrointestinal membrane and the blood-brain barrier, resulting in a reduction of the systemic anticholinergic effects (e.g., neurologic, ophthalmic, cardiovascular, and gastrointestinal effects) that are seen with tertiary anticholinergic amines.

Pharmacokinetics

Absorption

Ipratropium bromide is poorly absorbed into the systemic circulation following oral administration (2 to 3%). Less than 20% of an 84 mcg per nostril dose was absorbed from the nasal mucosa of normal volunteers, induced-cold patients, or perennial rhinitis patients.

Distribution

Ipratropium bromide is minimally bound (0 to 9% in vitro) to plasma albumin and α1-acid glycoprotein. Its blood/plasma concentration ratio was estimated to be about 0.89. Studies in rats have shown that ipratropium bromide does not penetrate the blood-brain barrier.

Metabolism

Ipratropium bromide is partially metabolized to ester hydrolysis products, tropic acid and tropane. These metabolites appear to be inactive based on in vitro receptor affinity studies using rat brain tissue homogenates.

Elimination

After intravenous administration of 2 mg ipratropium bromide to 10 healthy volunteers, the terminal half-life of ipratropium was approximately 1.6 hours. The total body clearance and renal clearance were estimated to be 2,505 and 1,019 ml/min, respectively. The amount of the total dose excreted unchanged in the urine (Ae) within 24 hours was approximately one-half of the administered dose.

Pediatrics

Following administration of 42 mcg of ipratropium bromide per nostril two or three times a day in perennial rhinitis patients 6 to 18 years old, the mean amounts of the total dose excreted unchanged in the urine (8.6 to 11.1%) were higher than those reported in adult volunteers or adult perennial rhinitis patients (3.7 to 5.6%). Plasma ipratropium concentrations were relatively low (ranging from undetectable up to 0.49 ng/ml). No correlation of the amount of the total dose excreted unchanged in the urine (Ae) with age or gender was observed in the pediatric population.

Special Populations

Gender does not appear to influence the absorption or excretion of nasally administered ipratropium bromide. The pharmacokinetics of ipratropium bromide have not been studied in patients with hepatic or renal insufficiency or in the elderly.

Drug-Drug Interaction

No specific pharmacokinetic studies were conducted to evaluate potential drug-drug interactions.

Pharmacodynamics

In two single-dose trials (n=17), doses up to 336 mcg of ipratropium bromide did not significantly affect pupillary diameter, heart rate, or systolic/diastolic blood pressure. Similarly, in patients with induced-colds, Ipratropium Bromide Nasal Spray 0.06% (84 mcg/nostril four times a day), had no significant effects on pupillary diameter, heart rate or systolic/diastolic blood pressure.

Two nasal provocation trials in perennial rhinitis patients (n=44) using ipratropium bromide nasal spray showed a dose dependent increase in inhibition of methacholine induced nasal secretion with an onset of action within 15 minutes (time of first observation).

Controlled clinical trials demonstrated that intranasal fluorocarbon-propelled ipratropium bromide does not alter physiologic nasal functions (e.g., sense of smell, ciliary beat frequency, mucociliary clearance, or the air conditioning capacity of the nose).

Clinical Trials

The clinical trials for Ipratropium Bromide Nasal Spray 0.03% were conducted in patients with nonallergic perennial rhinitis (NAPR) and in patients with allergic perennial rhinitis (APR). APR patients were those who experienced symptoms of nasal hypersecretion and nasal congestion or sneezing when exposed to specific perennial allergens (e.g., dust mites, molds) and were skin test positive to these allergens. NAPR patients were those who experienced symptoms of nasal hypersecretion and nasal congestion or sneezing throughout the year, but were skin test negative to common perennial allergens.

In four controlled, four- and eight-week comparisons of Ipratropium Bromide Nasal Spray 0.03% (42 mcg per nostril, two or three times daily) with its vehicle, in patients with allergic or nonallergic perennial rhinitis, there was a statistically significant decrease in the severity and duration of rhinorrhea in the Ipratropium Bromide group throughout the entire study period. An effect was seen as early as the first day of therapy.

There was no effect of Ipratropium Bromide Nasal Spray 0.03% on degree of nasal congestion, sneezing, or postnasal drip. The response to Ipratropium Bromide Nasal Spray 0.03% did not appear to be affected by the type of perennial rhinitis (NAPR or APR), age, or gender. No controlled clinical trials directly compared the efficacy of BID versus TID treatment.

Indications and Usage for Ipratropium Nasal 0.03

Ipratropium Bromide Nasal Spray 0.03% is indicated for the symptomatic relief of rhinorrhea associated with allergic and nonallergic perennial rhinitis in adults and children age 6 years and older. Ipratropium Bromide Nasal Spray 0.03% does not relieve nasal congestion, sneezing, or postnasal drip associated with allergic or nonallergic perennial rhinitis.

Contraindications

Ipratropium Bromide Nasal Spray 0.03% is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to any of the other ingredients.

Warnings

Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.

Precautions

General

Ipratropium Bromide Nasal Spray 0.03% should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, or bladder neck obstruction, particularly if they are receiving an anticholinergic by another route. Cases of precipitation or worsening of narrow-angle glaucoma and acute eye pain have been reported with direct eye contact of ipratropium bromide administered by oral inhalation.

Information for Patients

Patients should be advised that temporary blurring of vision, precipitation or worsening of narrow-angle glaucoma, or eye pain may result if Ipratropium Bromide Nasal Spray 0.03% comes into direct contact with the eyes. Patients should be instructed to avoid spraying Ipratropium Bromide Nasal Spray 0.03% in or around their eyes. Patients who experience eye pain, blurred vision, excessive nasal dryness, or episodes of nasal bleeding should be instructed to contact their doctor. Patients should be reminded to carefully read and follow the accompanying Patient’s Instructions for Use.

Drug Interactions

No controlled clinical trials were conducted to investigate drug-drug interactions. Ipratropium Bromide Nasal Spray 0.03% is minimally absorbed into the systemic circulation; nonetheless, there is some potential for an additive interaction with other concomitantly administered anticholinergic medications, including Ipratropium Bromide for oral inhalation.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In two-year carcinogenicity studies in rats and mice, ipratropium bromide at oral doses up to 6 mg/kg (approximately 190 and 95 times the maximum recommended daily intranasal dose in adults, respectively, and approximately 110 and 60 times the maximum recommended daily intranasal dose in children, respectively, on a mg/m2 basis) showed no carcinogenic activity. Results of various mutagenicity studies (Ames test, mouse dominant lethal test, mouse micronucleus test, and chromosome aberration of bone marrow in Chinese hamsters) were negative.

Fertility of male or female rats was unaffected by ipratropium bromide at oral doses up to 50 mg/kg (approximately 1,600 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis). At an oral dose of 500 mg/kg (approximately 16,000 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis), ipratropium bromide produced a decrease in the conception rate.

Pregnancy

Teratogenic Effects

Pregnancy Category B

Oral reproduction studies were performed at doses of 10 mg/kg in mice, 1000 mg/kg in rats and 125 mg/kg in rabbits. These doses correspond, in each species respectively, to approximately 160, 32,000, and 8,000 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis. Inhalation reproduction studies were conducted in rats and rabbits at doses of 1.5 and 1.8 mg/kg, respectively, (approximately 50 and 120 times, respectively, the maximum recommended daily intranasal dose in adults on a mg/m2 basis). These studies demonstrated no evidence of teratogenic effects as a result of ipratropium bromide. At oral doses above 90 mg/kg in rats (approximately 2,900 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis) embryotoxicity was observed as increased resorption. This effect is not considered relevant to human use due to the large doses at which it was observed and the difference in route of administration. However, no adequate or well controlled studies have been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, Ipratropium Bromide Nasal Spray 0.03% should be used during pregnancy only if clearly needed.

Nursing Mothers

It is known that some ipratropium bromide is systemically absorbed following nasal administration; however the portion which may be excreted in human milk is unknown. Although lipid-insoluble quaternary bases pass into breast milk, the minimal systemic absorption makes it unlikely that ipratropium bromide would reach the infant in an amount sufficient to cause a clinical effect. However, because many drugs are excreted in human milk, caution should be exercised when Ipratropium Bromide Nasal Spray 0.03% is administered to a nursing woman.

Pediatric Use

The safety of Ipratropium Bromide Nasal Spray 0.03% at a dose of two sprays (42 mcg) per nostril two or three times daily (total dose 168 to 252 mcg/day) has been demonstrated in 77 pediatric patients 6-12 years of age in placebo-controlled, 4-week trials and in 55 pediatric patients in active-controlled, 6 month trials. The effectiveness of Ipratropium Bromide Nasal Spray 0.03% for the treatment of rhinorrhea associated with allergic and nonallergic perennial rhinitis in this pediatric age group is based on an extrapolation of the demonstrated efficacy of Ipratropium Bromide Nasal Spray 0.03% in adults with these conditions and the likelihood that the disease course, pathophysiology, and the drug’s effects are substantially similar to that of the adults. The recommended dose for the pediatric population is based on within and cross-study comparisons of the efficacy of Ipratropium Bromide Nasal Spray 0.03% in adults and pediatric patients and on its safety profile in both adults and pediatric patients. The safety and effectiveness of Ipratropium Bromide Nasal Spray 0.03% in patients under 6 years of age have not been established.

Adverse Reactions

Adverse reaction information on Ipratropium Bromide Nasal Spray 0.03% in patients with perennial rhinitis was derived from four multicenter, vehicle-controlled clinical trials involving 703 patients (356 patients on Ipratropium Bromide and 347 patients on vehicle), and a one-year, open-label, follow-up trial. In three of the trials, patients received Ipratropium Bromide Nasal Spray 0.03% three times daily, for eight weeks. In the other trial, Ipratropium Bromide Nasal Spray 0.03% was given to patients two times daily for four weeks. Of the 285 patients who entered the open-label, follow-up trial, 232 were treated for 3 months, 200 for 6 months, and 159 up to one year. The majority (>86%) of patients treated for one year were maintained on 42 mcg per nostril, two or three times daily, of Ipratropium Bromide Nasal Spray 0.03%.

The following table shows adverse events, and the frequency that these adverse events led to the discontinuation of treatment, reported for patients who received Ipratropium Bromide Nasal Spray 0.03% at the recommended dose of 42 mcg per nostril, or vehicle two or three times daily for four or eight weeks. Only adverse events reported with an incidence of at least 2.0% in the Ipratropium Bromide group and higher in the Ipratropium Bromide group than in the vehicle group are shown.

% of Patients Reporting Events*

	Ipratropium Bromide Nasal Spray 0.03% (n=356)		Vehicle Control (n=347)
	Incidence%	Discontinued%	Incidence%	Discontinued%
* This table includes adverse events which occurred at an incidence rate of at least 2.0% in the Ipratropium Bromide group and more frequently in the Ipratropium Bromide group than in the vehicle group. † Epistaxis reported by 7.0% of Ipratropium Bromide patients and 2.3% of vehicle patients, blood-tinged mucus by 2.0% of Ipratropium Bromide patients and 2.3% of vehicle patients. ‡ All events are listed by their WHO term; rhinitis has been presented by descriptive terms for clarification. § Nasal irritation includes reports of nasal itching, nasal burning, nasal irritation, and ulcerative rhinitis. ¶ Other nasal symptoms include reports of nasal congestion, increased rhinorrhea, increased rhinitis, posterior nasal drip, sneezing, nasal polyps, and nasal edema.
Headache	9.8	0.6	9.2	0.0
Upper respiratory tract infection	9.8	1.4	7.2	1.4
Epistaxis†	9.0	0.3	4.6	0.3
Rhinitis‡
Nasal dryness	5.1	0.0	0.9	0.3
Nasal irritation§	2.0	0.0	1.7	0.6
Other nasal symptoms¶	3.1	1.1	1.7	0.3
Pharyngitis	8.1	0.3	4.6	0.0
Nausea	2.2	0.3	0.9	0.0

Ipratropium Bromide Nasal Spray 0.03% was well tolerated by most patients. The most frequently reported nasal adverse events were transient episodes of nasal dryness or epistaxis. These adverse events were mild or moderate in nature, none was considered serious, none resulted in hospitalization and most resolved spontaneously or following a dose reduction. Treatment for nasal dryness and epistaxis was required infrequently (2% or less) and consisted of local application of pressure or a moisturizing agent (e.g., petroleum jelly or saline nasal spray). Patient discontinuation for epistaxis or nasal dryness was infrequent in both the controlled (0.3% or less) and one-year, open-label (2% or less) trials. There was no evidence of nasal rebound (i.e., a clinically significant increase in rhinorrhea, posterior nasal drip, sneezing or nasal congestion severity compared to baseline) upon discontinuation of double-blind therapy in these trials.

Adverse events reported by less than 2% of the patients receiving Ipratropium Bromide Nasal Spray 0.03% during the controlled clinical trials or during the open-label follow-up trial, which are potentially related to Ipratropium Bromide’s local effects or systemic anticholinergic effects include: dry mouth/throat, dizziness, ocular irritation, blurred vision, conjunctivitis, hoarseness, cough, and taste perversion.

Additional anticholinergic effects noted with other Ipratropium Bromide dosage forms (Ipratropium Bromide Inhalation Solution, Ipratropium Bromide Inhalation Aerosol, and Ipratropium Bromide Nasal Spray 0.06%) include: precipitation or worsening of narrow angle glaucoma, urinary retention, prostatic disorders, tachycardia, constipation, and bowel obstruction.

There were infrequent reports of skin rash in both the controlled and uncontrolled clinical studies. Allergic-type reactions such as skin rash, angioedema of the throat, tongue, lips and face, generalized urticaria, laryngospasm, and anaphylactic reactions have been reported with Ipratropium Bromide Nasal Spray 0.03% and other ipratropium bromide products.

Overdosage

Acute overdosage by intranasal administration is unlikely since ipratropium bromide is not well absorbed systemically after intranasal or oral administration. Following administration of a 20 mg oral dose (equivalent to ingesting more than four bottles of Ipratropium Bromide Nasal Spray 0.03%) to 10 male volunteers, no change in heart rate or blood pressure was noted. Following a 2 mg intravenous infusion over 15 minutes to the same 10 male volunteers, plasma ipratropium concentrations of 22 to 45 ng/mL were observed (>100 times the concentrations observed following intranasal administration). Following intravenous infusion these 10 volunteers had a mean increase of heart rate of 50 bpm and less than 20 mmHg change in systolic or diastolic blood pressure at the time of peak ipratropium levels.

Oral median lethal doses of ipratropium bromide were greater than 1,000 mg/kg in mice (approximately 16,000 and 9,500 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m2 basis), 1,700 mg/kg in rats (approximately 55,000 and 32,000 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m2 basis), and 400 mg/kg in dogs (approximately 43,000 and 25,000 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m2 basis).

Ipratropium Nasal 0.03 Dosage and Administration

The recommended dose of Ipratropium Bromide Nasal Spray 0.03% is two sprays (42 mcg) per nostril two or three times daily (total dose 168 to 252 mcg/day) for the symptomatic relief of rhinorrhea associated with allergic and nonallergic perennial rhinitis in adults and children age 6 years and older. Optimum dosage varies with the response of the individual patient. Initial pump priming requires seven sprays of the pump. If used regularly as recommended, no further priming is required. If not used for more than 24 hours, the pump will require two sprays, or if not used for more than seven days, the pump will require seven sprays to reprime.

How is Ipratropium Nasal 0.03 Supplied

Ipratropium Bromide Nasal Spray 0.03% is supplied in a white high density polyethylene (HDPE) bottle fitted with a white and clear metered nasal spray pump, a green safety clip to prevent accidental discharge of the spray, and a clear plastic dust cap. It contains 31.1g of product formulation, 345 sprays, each delivering 21 mcg (70mcL) of ipratropium per spray, or 28 days of therapy at the maximum recommended dose (two sprays per nostril three times a day).

IPRATROPIUM BROMIDE Nasal Solution 0.03% NASAL SPRAY 21 mcg/spray

NDC 0054-0045-44: Bottle of 30 mL (345 metered sprays)

Storage

Store at 20º to 25ºC (68º to 77ºF). [See USP Controlled Room Temperature.] Avoid freezing. Keep out of reach of children. Do not spray in the eyes.

Patients should be reminded to read and follow the accompanying Patient’s Instructions for Use, which should be dispensed with the product.

10001011/04

Revised October 2009

© RLI, 2009

PATIENT'S INSTRUCTIONS FOR USE

IPRATROPIUM BROMIDE Nasal Solution 0.03%

NASAL SPRAY 21 mcg/spray

Ipratropium Bromide Nasal Spray 0.03% is indicated for the symptomatic relief of rhinorrhea (runny nose) associated with allergic and nonallergic perennial rhinitis in adults and children age 6 years and older. Ipratropium Bromide Nasal Spray 0.03% does not relieve nasal congestion, sneezing, or postnasal drip associated with allergic or nonallergic perennial rhinitis. Read complete instructions carefully and use only as directed.

Read complete instructions carefully and use only as directed.

To Use:

Figure 1

1. Remove the clear plastic dust cap and the green safety clip from the nasal spray pump (Figure 1). The safety clip prevents the accidental discharge of the spray in your pocket or purse.

Figure 2

2. The nasal spray pump must be primed before Ipratropium Bromide Nasal Spray 0.03% is used for the first time. To prime the pump, hold the bottle with your thumb at the base and your index and middle fingers on the white shoulder area. Make sure the bottle points upright and away from your eyes. Press your thumb firmly and quickly against the bottle seven times (Figure 2). The pump is now primed and can be used. Your pump should not have to be reprimed unless you have not used the medication for more than 24 hours; repriming the pump will only require two sprays. If you have not used your nasal spray for more than seven days, repriming the pump will require seven sprays.

3.Before using Ipratropium Bromide Nasal Spray 0.03%, blow your nose gently to clear your nostrils if necessary.

Figure 3

4. Close one nostril by gently placing your finger against the side of your nose, tilt your head slightly forward and, keeping the bottle upright, insert the nasal tip into the other nostril (Figure 3). Point the tip toward the back and outer side of the nose.

5. Press firmly and quickly upwards with the thumb at the base while holding the white shoulder portion of the pump between your index and middle fingers. Following each spray, sniff deeply and breathe out through your mouth.

6. After spraying the nostril and removing the unit, tilt your head backwards for a few seconds to let the spray spread over the back of the nose.

7. Repeat steps 4 through 6 in the same nostril.

8. Repeat steps 4 through 7 in the other nostril (i.e., two sprays per nostril).

9. Replace the clear plastic dust cap and safety clip.

10. At some time before the medication is completely used up, you should consult your physician or pharmacist to determine whether a refill is needed. You should not take extra doses or stop using Ipratropium Bromide Nasal Spray 0.03% without consulting your physician.

To Clean:

Figure 4

If the nasal tip becomes clogged, remove the clear plastic dust cap and safety clip. Hold the nasal tip under running, warm tap water (Figure 4) for about a minute. Dry the nasal tip, reprime the nasal spray pump (step 2 above), and replace the plastic dust cap and safety clip.

Caution:

Ipratropium Bromide Nasal Spray 0.03% is intended to relieve your rhinorrhea (runny nose) with regular use. It is therefore important that you use Ipratropium Bromide Nasal Spray 0.03% as prescribed by your physician. For most patients, some improvement in runny nose is usually apparent during the first full day of treatment with Ipratropium Bromide Nasal Spray 0.03%. Some patients may require up to two weeks of treatment to obtain maximum benefit.

Do not spray Ipratropium Bromide Nasal Spray 0.03% in your eyes. Should this occur, immediately flush your eye with cool tap water for several minutes. If you accidentally spray Ipratropium Bromide Nasal Spray 0.03% in your eyes, you may experience a temporary blurring of vision and increased sensitivity to light, which may last a few hours. Should eye pain or blurred vision occur, contact your doctor.

Should you experience excessive nasal dryness or episodes of nasal bleeding contact your doctor.

You should not use this drug if you have glaucoma or difficult urination due to an enlargement of the prostate, unless directed by a physician. Ipratropium Bromide Nasal Spray 0.03% should not be used during pregnancy or breast feeding unless directed by a physician. It is not known whether ipratropium bromide is excreted in human milk; however, many drugs are excreted in human milk.

Storage

Store at 20º to 25ºC (68º to 77ºF). [See USP Controlled Room Temperature.] Avoid freezing. Keep out of reach of children. Do not spray in the eyes.

10001011/04

Revised October 2009

© RLI, 2009

Package Label - IPRATROPIUM BROMIDE Nasal Solution 0.03% NASAL SPRAY 21 mcg/spray

NDC 0054-0045-44: Bottle of 30 mL (345 metered sprays)

Rx Only

Roxane Laboratories, Inc.

IPRATROPIUM BROMIDE  ipratropium bromide  spray

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0054-0045 Route of Administration NASAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength IPRATROPIUM BROMIDE (IPRATROPIUM) IPRATROPIUM BROMIDE 21 ug

Inactive Ingredients Ingredient Name Strength HYDROXYETHYL CELLULOSE (140 CPS AT 5%)   BENZALKONIUM CHLORIDE   EDETATE CALCIUM DISODIUM   HYDROCHLORIC ACID   WATER   SODIUM CHLORIDE   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0054-0045-44 1 BOTTLE In 1 CARTON contains a BOTTLE, SPRAY 1 345 SPRAY In 1 BOTTLE, SPRAY This package is contained within the CARTON (0054-0045-44)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA076664	11/05/2003

Labeler - Roxane Laboratories, Inc (833490464)

Registrant - Roxane Laboratories, Inc (833490464)

Establishment
Name	Address	ID/FEI	Operations
Boehringer Ingelheim Roxane Inc		058839929	MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Boehringer Ingelheim GmbH & Co, K,G,		551147440	API MANUFACTURE

Revised: 06/2010Roxane Laboratories, Inc

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