Triaminic Spray

Chlorpheniramine Maleate:

• Uses
• Warnings
• Directions
• Other information
• Inactive ingredients
• Questions? comments?
• Triaminic Spray (Chlorpheniramine Maleate) reviews

Drug Facts

Uses

temporarily relieves these symptoms due to the common cold, hay fever (allergic rhinitis) or other upper respiratory allergies

• runny nose
• sneezing
• itching of the nose or throat
• itchy, watery eyes
• nasal congestion
• reduces swelling of nasal passages

Warnings

Do not exceed recommended dosage.

Do not use this product in a child who is

• now taking a prescription monoamine oxidase inhibitor (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your child's prescription drug contains an MAOI, ask a doctor or pharmacist before giving this product.

Ask a doctor before use if a child has

• a breathing problem such as chronic bronchitis
• glaucoma
• heart disease
• high blood pressure
• thyroid disease
• diabetes mellitus

Ask a doctor before use if a child is taking sedatives or tranquilizers

When using this product

• excitability may occur, especially in children
• may cause drowsiness
• sedatives and tranquilizers may increase drowsiness effect

Stop use and ask a doctor if

• nervousness, dizziness, or sleeplessness occur
• new symptoms occur

Keep out of reach of children. In case of accidental overdose, seek professional help or contact a Poison Control Center immediately.

Directions

Do not exceed recommended dosage.

Other information

Store at 59°-86°F (15°-30°C)

Inactive ingredients

Applesauce Flavor, Citric Acid, FD&C Blue #1, FD&C Yellow #6, Glycerin, Methyl Paraben, Potassium Citrate, Potassium Sorbate, Propyl Paraben, Propylene Glycol, Purified Water, Sucralose

Questions? Comments?

Call 1-800-543-9560

Rev. 05/11

E

NEW

FORMULA

NDC 00485-0096-02

Triaminic Spray (Chlorpheniramine Maleate)

Pediatric Drops

Antihistamine ▪ Nasal Decongestant

Sugar Free ▪ Alcohol Free ▪ Gluten Free

FOR PROFESSIONAL USE ONLY

Each 1 mL for oral administration

contains:

Triaminic Spray (Chlorpheniramine Maleate) Maleate

2 mg

Phenylephrine HCl

5 mg

APPLESAUCE FLAVOR

Tamper evident by foil seal under cap.

Do not use if foil seal is broken or missing.

Manufactured for:

EDWARDS

Pharmaceuticals, Inc.

Ripley, MS 38663

2 fl. oz. (60 mL)

Oxymetazoline Hydrochloride:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Triaminic Spray (Oxymetazoline Hydrochloride) reviews

1 INDICATIONS AND USAGE

Triaminic Spray (Oxymetazoline Hydrochloride) cream is indicated for the topical treatment of persistent facial erythema associated with rosacea in adults.

Triaminic Spray (Oxymetazoline Hydrochloride) is an alpha_1A adrenoceptor agonist indicated for the topical treatment of persistent facial erythema associated with rosacea in adults. (1)

2 DOSAGE AND ADMINISTRATION

For topical use only. Triaminic Spray (Oxymetazoline Hydrochloride) is not for oral, ophthalmic, or intravaginal use.

Prime the Triaminic Spray (Oxymetazoline Hydrochloride) pump before using for the first time. To do so, with the pump in the upright position, repeatedly depress the actuator until cream is dispensed and then pump three times. Discard the cream from priming actuations. It is only necessary to prime the pump before the first dose.

Triaminic Spray (Oxymetazoline Hydrochloride) tubes do not require priming.

Apply a pea-sized amount of Triaminic Spray (Oxymetazoline Hydrochloride) cream, once daily in a thin layer to cover the entire face (forehead, nose, each cheek, and chin) avoiding the eyes and lips. Wash hands immediately after applying Triaminic Spray (Oxymetazoline Hydrochloride) cream.

• Not for oral, ophthalmic, or intravaginal use. (2)
• Prime pump bottle before initial use and discard product from first three pumps. (2)
• Apply a pea-sized amount once daily in a thin layer to cover the entire face (forehead, nose, each cheek, and chin) avoiding the eyes and lips. (2)
• Wash hands after application. (2)

3 DOSAGE FORMS AND STRENGTHS

Triaminic Spray (Oxymetazoline Hydrochloride) (oxymetazoline hydrochloride) cream, 1% is a white to off-white cream. Each gram of cream contains 10 mg (1%) Triaminic Spray (Oxymetazoline Hydrochloride), equivalent to 8.8 mg (0.88%) of oxymetazoline free base.

Cream, 1%. Each gram of cream contains 10 mg (1%) Triaminic Spray (Oxymetazoline Hydrochloride), equivalent to 8.8 mg (0.88%) of oxymetazoline free base. (3)

4 CONTRAINDICATIONS

None.

• None. (4)

5 WARNINGS AND PRECAUTIONS

• Alpha-adrenergic agonists as a class may impact blood pressure. Advise patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension or hypotension to seek medical care if their condition worsens.
• Use with caution in patients with cerebral or coronary insufficiency, Raynaud's phenomenon, thromboangiitis obliterans, scleroderma, or Sjögren's syndrome and advise patients to seek medical care if signs and symptoms of potentiation of vascular insufficiency develop. (5.2)
• Advise patients to seek immediate medical care if signs and symptoms of acute narrow-angle glaucoma develop. (5.3)

5.1 Potential Impacts on Cardiovascular Disease

Alpha-adrenergic agonists may impact blood pressure. Triaminic Spray (Oxymetazoline Hydrochloride) should be used with caution in patients with severe or unstable or uncontrolled cardiovascular disease, orthostatic hypotension, and uncontrolled hypertension or hypotension. Advise patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension/hypotension to seek immediate medical care if their condition worsens.

5.2 Potentiation of Vascular Insufficiency

Triaminic Spray should be used with caution in patients with cerebral or coronary insufficiency, Raynaud's phenomenon, thromboangiitis obliterans, scleroderma, or Sjögren's syndrome. Advise patients to seek immediate medical care if signs and symptoms of potentiation of vascular insufficiency develop.

5.3 Risk of Angle Closure Glaucoma

Triaminic Spray (Oxymetazoline Hydrochloride) may increase the risk of angle closure glaucoma in patients with narrow-angle glaucoma. Advise patients to seek immediate medical care if signs and symptoms of acute angle closure glaucoma develop.

6 ADVERSE REACTIONS

Most common adverse reactions are application site dermatitis, worsening inflammatory lesions of rosacea, application site pruritis, application site erythema, and application site pain. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-433-8871 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Studies Experience

Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 489 subjects with persistent facial erythema associated with rosacea were treated with Triaminic Spray (Oxymetazoline Hydrochloride) once daily for 4 weeks in 3 controlled clinical trials. An additional 440 subjects with persistent facial erythema associated with rosacea were also treated with Triaminic Spray (Oxymetazoline Hydrochloride) once daily for up to one year in a long-term (open-label) clinical trial. Adverse reactions that occurred in at least 1% of subjects treated with Triaminic Spray (Oxymetazoline Hydrochloride) through 4 weeks of treatment are presented in Table 1 below.

In the long-term (open-label) clinical trial, the rates of adverse reactions over a one-year treatment period were as follows: worsening inflammatory lesions of rosacea (3%), application site dermatitis (3%), application site pruritis (2%), application site pain (2%), and application site erythema (2%). Subjects with persistent erythema along with inflammatory lesions were allowed to use additional therapy for the inflammatory lesions of rosacea.

7 DRUG INTERACTIONS

7.1 Anti-hypertensives/Cardiac Glycosides

Alpha-adrenergic agonists, as a class, may impact blood pressure. Caution in using drugs such as beta-blockers, anti-hypertensives and/or cardiac glycosides is advised.

Caution should also be exercised in patients receiving alpha₁ adrenergic receptor antagonists such as in the treatment of cardiovascular disease, benign prostatic hypertrophy, or Raynaud's disease.

7.2 Monoamine Oxidase Inhibitors

Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on Triaminic Spray use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. A literature article describing intranasal decongestant use in pregnant women identified a potential association between second-trimester exposure to oxymetazoline (with no decongestant exposure in the first trimester) and renal collecting system anomalies . In animal reproduction studies, there were no adverse developmental effects observed after oral administration of Triaminic Spray (Oxymetazoline Hydrochloride) in pregnant rats and rabbits at systemic exposures up to 3 times and 73 times, respectively, the exposure associated with the maximum recommended human dose (MRHD) . The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Following repeated use of Triaminic Spray (Oxymetazoline Hydrochloride) solution nasal spray for the treatment of nasal congestion at a dose 5 times higher than recommended, one case of fetal distress was reported in a 41-week pregnant patient. The fetal distress resolved hours later, prior to the delivery of the healthy infant. The anticipated exposures for the case are 8- to18-fold higher than plasma exposures after topical administration of Triaminic Spray (Oxymetazoline Hydrochloride).

Data

Human Data

No adequate and well-controlled trials of Triaminic Spray (Oxymetazoline Hydrochloride) have been conducted in pregnant women. Across all clinical trials of Triaminic Spray (Oxymetazoline Hydrochloride), two pregnancies were reported. One pregnancy resulted in the delivery of a healthy child. One pregnancy resulted in a spontaneous abortion, which was considered to be unrelated to the trial medication. A literature article summarizing the results of exploratory analyses of intranasal decongestant use during pregnancy identified a potential association between second-trimester exposure to Triaminic Spray (Oxymetazoline Hydrochloride) solution (with no decongestant exposure in the first trimester) and renal collecting system anomalies.

Animal Data

Effects on embryo-fetal development were evaluated in rats and rabbits following oral administration of Triaminic Spray (Oxymetazoline Hydrochloride) during the period of organogenesis. Triaminic Spray (Oxymetazoline Hydrochloride) did not cause adverse effects to the fetus at oral doses up to 0.2 mg/kg/day in pregnant rats during the period of organogeneisis (3 times the MRHD on an AUC comparison basis). Triaminic Spray (Oxymetazoline Hydrochloride) did not cause adverse effects to the fetus at oral doses up to 1 mg/kg/day in pregnant rabbits during the period of organogeneisis (73 times the MRHD on an AUC comparison basis). Maternal toxicity, such as decreased maternal body weight, was produced at the high dose of 1 mg/kg/day in pregnant rabbits and was associated with findings of delayed skeletal ossification.

In a rat perinatal and postnatal development study, Triaminic Spray (Oxymetazoline Hydrochloride) was orally administered to pregnant rats once daily from gestation day 6 through lactation day 20. Maternal toxicity was produced at the high dose of 0.2 mg/kg/day (3 times the MRHD on an AUC comparison basis) in pregnant rats and was associated with an increase in pup mortality and reduced pup body weights. Delayed sexual maturation was noted at 0.1 and 0.2 mg/kg/day (2 times the MRHD and 3 times the MRHD on an AUC comparison basis, respectively). Triaminic Spray (Oxymetazoline Hydrochloride) did not have any adverse effects on fetal development at a dose of 0.05 mg/kg/day (one-half of the MRHD on an AUC comparison basis).

8.2 Lactation

No clinical data are available to assess the effects of oxymetazoline on the quantity or rate of breastmilk production, or to establish the level of oxymetazoline present in human breastmilk post-dose. Oxymetazoline was detected in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Triaminic Spray (Oxymetazoline Hydrochloride) and any potential adverse effects on the breastfed child from Triaminic Spray (Oxymetazoline Hydrochloride) or from the underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness of Triaminic Spray have not been established in pediatric patients below the age of 18 years.

8.5 Geriatric Use

One hundred and ninety-three subjects aged 65 years and older received treatment with Triaminic Spray (Oxymetazoline Hydrochloride) (n = 135) or vehicle (n = 58) in clinical trials. No overall differences in safety or effectiveness were observed between subjects≥ 65 years of age and younger subjects, based on available data. Clinical studies of Triaminic Spray (Oxymetazoline Hydrochloride) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

10 OVERDOSAGE

Triaminic Spray (Oxymetazoline Hydrochloride) is not for oral use. If oral ingestion occurs, seek medical advice. Monitor patient closely and administer appropriate supportive measures as necessary. Accidental ingestion of topical solutions (nasal sprays) containing imidazoline derivatives (e.g., oxymetazoline) in children has resulted in serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma. Keep Triaminic Spray (Oxymetazoline Hydrochloride) out of reach of children.

11 DESCRIPTION

Triaminic Spray (Oxymetazoline Hydrochloride) (oxymetazoline hydrochloride) cream 1% contains Triaminic Spray (Oxymetazoline Hydrochloride), an alpha_1A adrenoceptor agonist. Triaminic Spray (Oxymetazoline Hydrochloride) is a white to off-white cream. It has a chemical name of 3-[(4,5-Dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-phenol hydrochloride and a molecular weight of 296.8. It is freely soluble in water and ethanol and has a partition coefficient of 0.1 in 1-octanol/water. The molecular formula of oxymetazoline HCl is C₁₆H₂₅ClN₂O and its structural formula is:

Each gram of Triaminic Spray (Oxymetazoline Hydrochloride) (oxymetazoline hydrochloride) cream contains 10 mg (1%) Triaminic Spray (Oxymetazoline Hydrochloride), equivalent to 8.8 mg (0.88%) of oxymetazoline free base. The cream contains the following inactive ingredients: sodium citrate dihydrate, citric acid anhydrous, disodium edetate dihydrate, butylated hydroxytoluene, anhydrous lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol 300, PEG-6 stearate, glycol stearate, PEG-32 stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, methylparaben, propylparaben, phenoxyethanol, and purified water.

Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Oxymetazoline is an alpha_1A adrenoceptor agonist. Oxymetazoline acts as a vasoconstrictor.

12.2 Pharmacodynamics

The pharmacodynamics of Triaminic Spray has not been studied.

12.3 Pharmacokinetics

Absorption

The pharmacokinetics of oxymetazoline was evaluated following topical administration of Triaminic Spray (Oxymetazoline Hydrochloride) in a thin layer to cover the entire face in adult subjects with erythema associated with rosacea. The median weight of cream for each dose administration was 0.3 g. Plasma oxymetazoline concentrations were measurable in most of the subjects. Following the first dose application, the mean ± standard deviation (SD) peak concentrations (C_max) and area under the concentration-time curves from time 0 to 24 hours (AUC_0-24hr) were 60.5 ± 53.9 pg/mL and 895 ±798 pg*hr/mL, respectively. Following once daily applications for 28 days, the mean ± SD C_max and AUC_0-24hr were 66.4 ± 67.1 pg/mL and 1050 ± 992 pg*hr/mL, respectively. Following twice daily applications (twice the recommended frequency of application) for 28 days, the mean ± SD C_max and AUC_0-24hr were 68.8 ± 61.1 pg/mL and 1530 ± 922 pg*hr/mL, respectively.

Distribution

An in vitro study demonstrated that oxymetazoline is 56.7% to 57.5% bound to human plasma proteins.

Metabolism

In vitro studies using human liver microsomes showed that oxymetazoline was minimally metabolized, generating mono-oxygenated and dehydrogenated products of oxymetazoline. The percentage of parent drug oxymetazoline remaining was 95.9% after a 120-minute incubation with human liver microsomes.

Excretion

The excretion of oxymetazoline following administration of Triaminic Spray (Oxymetazoline Hydrochloride) has not been characterized in humans.

Drug Interaction

In vitro studies using human liver microsomes demonstrated that oxymetazoline up to the tested concentration of 100 nM had no inhibition on the activities of the cytochrome P450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5. Treatment of cultured human hepatocytes with up to 100 nM oxymetazoline did not induce CYP1A2, CYP2B6, or CYP3A4.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Triaminic Spray (Oxymetazoline Hydrochloride) was not associated with an increased incidence of neoplastic or proliferative changes in transgenic mice given oral doses of 0.5, 1.0, or 2.5 mg/kg/day Triaminic Spray (Oxymetazoline Hydrochloride) for 6 months.

Triaminic Spray (Oxymetazoline Hydrochloride) revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and human lymphocyte chromosomal aberration assay) and one in vivo gentoxicity test (mouse micronucleus assay).

Effects on fertility and early embryonic development were evaluated in rats following oral administration of 0.05, 0.1, or 0.2 mg/kg/day Triaminic Spray (Oxymetazoline Hydrochloride) prior to and during mating and through early pregnancy. Decreased number of corpora lutea and increased post-implantation losses were noted at 0.2 mg/kg/day Triaminic Spray (Oxymetazoline Hydrochloride) (3 times the MRHD on an AUC comparison basis). However, no treatment related effects on fertility or mating parameters were noted at 0.2 mg/kg/day Triaminic Spray (Oxymetazoline Hydrochloride) (3 times the MRHD on an AUC comparison basis).

14 CLINICAL STUDIES

Triaminic Spray (Oxymetazoline Hydrochloride) was evaluated for the treatment of persistent erythema associated with rosacea in two identical, randomized, double-blind, vehicle-controlled, parallel-group clinical trials. The trials enrolled 885 subjects aged 18 years and older. Overall, 90% of subjects were Caucasian and 79% were female. Subjects applied either Triaminic Spray (Oxymetazoline Hydrochloride) or vehicle once daily for 29 days.

Disease severity was graded by the clinician using a 5-point clinician erythema assessment (CEA) scale and by the subject on a similar 5-point subject self-assessment (SSA) scale, on which subjects scored either “moderate” or “severe” on both scales.

CEA and SSA were measured over a 12-hour period at equally-spaced timepoints (hours 3, 6, 9, and 12) post-dose on Days 1, 15, and 29. The primary efficacy endpoint was defined as the proportion of subjects with at least a 2-grade reduction in erythema (improvement) from baseline (pre-dose on Day 1) on both the CEA and SSA measured at hours 3, 6, 9, and 12 on Day 29. The results from both trials on the composite endpoint for Day 29 are presented in Table 2.

^*Composite success is defined as the proportion of subjects achieving at least a 2-grade improvement on both CEA and SSA.

16 HOW SUPPLIED/STORAGE AND HANDLING

Triaminic Spray (Oxymetazoline Hydrochloride) (oxymetazoline hydrochloride) cream, 1%, is a white to off-white cream. The product is available in a laminated tube and an airless pump polypropylene bottle in the following packaging configurations, each with a child-resistant closure:

NDC 0023-5300-30 30 gram tube

NDC 0023-5300-60 60 gram tube

NDC 0023-5300-35 30 gram pump

NDC 0023-5300-65 60 gram pump

Storage: Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30ºC (59°F-86ºF).

17 PATIENT COUNSELING INFORMATION

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Important Administration Instructions

Advise patients of the following:

• Triaminic Spray (Oxymetazoline Hydrochloride) is for topical use only.
• Triaminic Spray (Oxymetazoline Hydrochloride) pumps require priming before initial use and discard product from the first three pumps.
• Do not to apply Triaminic Spray (Oxymetazoline Hydrochloride) to irritated skin or open wounds.
• Avoid contact with the eyes and lips.
• Wash hands immediately after application.
• Keep Triaminic Spray (Oxymetazoline Hydrochloride) out of reach of children.

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

by DPT Laboratories, Ltd, San Antonio, TX 78215

© 2017 Allergan. All rights reserved.

Irvine, CA 92612

All trademarks are the property of their respective owners.

Patented. See www.allergan.com/patents

Made in the U.S.A.

73141US10

Logo

73141US10

INSTRUCTIONS FOR USE

Triaminic Spray (Oxymetazoline Hydrochloride) (roe' fayd)

(oxymetazoline hydrochloride)

cream

Tube

Read and follow the steps below so that you use your tube of Triaminic Spray (Oxymetazoline Hydrochloride) cream correctly:

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

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

by DPT Laboratories, Ltd, San Antonio, TX 78215

© 2017 Allergan. All rights reserved. Irvine, CA 92612, U.S.A.

All trademarks are the property of their respective owners.

Patented. See www.allergan.com/patents. Made in the U.S.A.

Approved: 01/2017

73141US10

Figure Figure Figure Figure

INSTRUCTIONS FOR USE

Triaminic Spray (Oxymetazoline Hydrochloride) (roe' fayd)

(oxymetazoline hydrochloride) cream

Pump

Read and follow the steps below so that you use your Triaminic Spray (Oxymetazoline Hydrochloride) cream pump correctly:

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

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

by DPT Laboratories, Ltd, San Antonio, TX 78215

© 2017 Allergan. All rights reserved. Irvine, CA 92612, U.S.A.

All trademarks are the property of their respective owners.

Patented. See www.allergan.com/patents. Made in the U.S.A.

Approved: 01/2017

73141US10

Figure Figure Figure Figure Figure

NDC 0023-5300-30

Triaminic Spray (Oxymetazoline Hydrochloride)

(oxymetazoline hydrochloride) cream, 1%*

*Each gram of Triaminic Spray (Oxymetazoline Hydrochloride) cream contains 10 mg

of Triaminic Spray (Oxymetazoline Hydrochloride), equivalent to

8.8 mg of oxymetazoline free base

For Topical Use Only

Keep Out of Reach of Children

Allergan

Rx only

30 g

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