Nazene Z

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
• Nazene Z (Oxymetazoline Hydrochloride) reviews

1 INDICATIONS AND USAGE

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

Nazene Z (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. Nazene Z (Oxymetazoline Hydrochloride) is not for oral, ophthalmic, or intravaginal use.

Prime the Nazene Z (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.

Nazene Z (Oxymetazoline Hydrochloride) tubes do not require priming.

Apply a pea-sized amount of Nazene Z (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 Nazene Z (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

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

Cream, 1%. Each gram of cream contains 10 mg (1%) Nazene Z (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. Nazene Z (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

Nazene Z 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

Nazene Z (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 Nazene Z (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 Nazene Z (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 Nazene Z (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 Nazene Z 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 Nazene Z (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 Nazene Z (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 Nazene Z (Oxymetazoline Hydrochloride).

Data

Human Data

No adequate and well-controlled trials of Nazene Z (Oxymetazoline Hydrochloride) have been conducted in pregnant women. Across all clinical trials of Nazene Z (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 Nazene Z (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 Nazene Z (Oxymetazoline Hydrochloride) during the period of organogenesis. Nazene Z (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). Nazene Z (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, Nazene Z (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). Nazene Z (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 Nazene Z (Oxymetazoline Hydrochloride) and any potential adverse effects on the breastfed child from Nazene Z (Oxymetazoline Hydrochloride) or from the underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness of Nazene Z 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 Nazene Z (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 Nazene Z (Oxymetazoline Hydrochloride) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

10 OVERDOSAGE

Nazene Z (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 Nazene Z (Oxymetazoline Hydrochloride) out of reach of children.

11 DESCRIPTION

Nazene Z (Oxymetazoline Hydrochloride) (oxymetazoline hydrochloride) cream 1% contains Nazene Z (Oxymetazoline Hydrochloride), an alpha_1A adrenoceptor agonist. Nazene Z (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 Nazene Z (Oxymetazoline Hydrochloride) (oxymetazoline hydrochloride) cream contains 10 mg (1%) Nazene Z (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 Nazene Z has not been studied.

12.3 Pharmacokinetics

Absorption

The pharmacokinetics of oxymetazoline was evaluated following topical administration of Nazene Z (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 Nazene Z (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

Nazene Z (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 Nazene Z (Oxymetazoline Hydrochloride) for 6 months.

Nazene Z (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 Nazene Z (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 Nazene Z (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 Nazene Z (Oxymetazoline Hydrochloride) (3 times the MRHD on an AUC comparison basis).

14 CLINICAL STUDIES

Nazene Z (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 Nazene Z (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

Nazene Z (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:

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

Nazene Z (Oxymetazoline Hydrochloride) (roe' fayd)

(oxymetazoline hydrochloride)

cream

Tube

Read and follow the steps below so that you use your tube of Nazene Z (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

Nazene Z (Oxymetazoline Hydrochloride) (roe' fayd)

(oxymetazoline hydrochloride) cream

Pump

Read and follow the steps below so that you use your Nazene Z (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

Nazene Z (Oxymetazoline Hydrochloride)

(oxymetazoline hydrochloride) cream, 1%*

*Each gram of Nazene Z (Oxymetazoline Hydrochloride) cream contains 10 mg

of Nazene Z (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

Principal Display Panel

Zinc Sulfate:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Nazene Z (Zinc Sulfate) reviews

INDICATIONS AND USAGE

Nazene Z (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Nazene Z (Zinc Sulfate) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Nazene Z (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and Nazene Z (Zinc Sulfate) doses because these elements are primarily eliminated in the urine.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

General

Do not use unless the solution is clear and the seal is intact.

Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Nazene Z (Zinc Sulfate) from a bolus injection. Administration of Nazene Z (Zinc Sulfate) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Nazene Z (Zinc Sulfate) are suggested as a guideline for subsequent Nazene Z (Zinc Sulfate) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Nazene Z 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nazene Z (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

Pregnancy Category C. Animal reproduction studies have not been conducted with Nazene Z chloride. It is also not known whether Nazene Z (Zinc Sulfate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Nazene Z (Zinc Sulfate) chloride should be given to a pregnant woman only if clearly needed.

Geriatric Use

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Nazene Z (Zinc Sulfate) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Nazene Z (Zinc Sulfate) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending Nazene Z (Zinc Sulfate) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg Nazene Z (Zinc Sulfate) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of Nazene Z (Zinc Sulfate) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Nazene Z (Zinc Sulfate) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against Nazene Z (Zinc Sulfate) toxicity.

DOSAGE AND ADMINISTRATION

Nazene Z (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Nazene Z (Zinc Sulfate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Nazene Z (Zinc Sulfate).

For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.

HOW SUPPLIED

Nazene Z (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004

© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

Nazene Z (Zinc Sulfate)

1 mg/mL

Nazene Z (Zinc Sulfate) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA