Aloclair

Benzalkonium Chloride:

• Pharmacological action
• Pharmacokinetics
• Why is Aloclair prescribed?
• Dosage and administration
• Aloclair (Benzalkonium Chloride) side effects, adverse reactions
• Aloclair contraindications
• Using during pregnancy and breastfeeding
• Special instructions
• Aloclair drug interactions
• Aloclair (Benzalkonium Chloride) reviews

Pharmacological action

Aloclair is an antiseptic. This medication is a quaternary ammonium compound, belongs to the cationic surfactant. Aloclair (Benzalkonium Chloride) has antimicrobial and antiviral activity against Neisseria gonorrhoeae, Chlamydia spp., Trichomonas vaginalis, Herpes simplex Type 2, Staphylococcus aureus, little active against Gardnerella vaginalis, Candida albicans, Haemophilus ducreyi and Treponema pallidum.

Aloclair (Benzalkonium Chloride) is not active against Mycoplasma spp.

This medicine exerts spermicidal action which is due to the ability to damage the sperm membrane; inhibits sperm motility, disrupting electrolyte balance of the aqueous phase of cervical mucus.

Pharmacokinetics

Aloclair (Benzalkonium Chloride) for external and local application is practically not absorbed.

Why is Aloclair prescribed?

For external use only. Topical solution - a primary and delayed primary wound treatment, prevention of secondary infection of wounds hospital strains of microorganisms (injury of soft and bone tissue, burns), festering wounds, drainage of bone cavities following surgery for osteomyelitis.

Weight thick - superficial thermal burns, trophic ulcers, long-unhealed wounds of soft tissues (including infected), pyo-inflammatory skin diseases and diabetes mellitus; paraproctitis.

Tablets and capsules for intravaginal use, vaginal suppositories, creams, tampons - local contraception for women of reproductive age: for the presence of contraindications to the use of oral contraceptives or intrauterine devices, in the postpartum period, lactation, after the termination of pregnancy in premenopause period at irregular sexual life, omission or delay in receiving consistently used oral contraceptives.

Liquid concentrate - disinfection of facilities and medical products.

Dosage and administration

Topically. The solution was diluted with distilled water to make 1% aqueous solution, impregnated gauze dressings, napkins or tampons and put on the wound daily.

Mass is applied at the rate of 0.2-0.4 g/cm2 of wound surface, pre-clean the wound from the purulent discharge, necrotic tissue, or impose gauze or use turundas impregnated with drugs. The maximum daily dose is 50 g. Ligation is carried out daily, the course of treatment is 14 days.

Intravaginally. Aloclair (Benzalkonium Chloride) entered deeply into the vagina before coition; in case of repeated sexual intercourse it should be re-imposition of tablets, capsules, suppositories, creams; tampon can be removed not earlier than 3 h after the last sexual intercourse but no later than 24 hours after its installation (with repeated sexual acts for 1 day shift tampon is not required).

Concentrate Liquid. Aloclair (Benzalkonium Chloride) used for disinfection after prior dilution with water.

Aloclair (Benzalkonium Chloride) side effects, adverse reactions

Contact dermatitis, candidiasis, vulvovaginal and allergic reactions.

With prolonged use of Aloclair (Benzalkonium Chloride) it is possible a local irritation.

Aloclair contraindications

Hypersensitivity to Aloclair (Benzalkonium Chloride), contact dermatitis, malignant neoplasm of the skin; for intravaginal use - coleitis, ulceration and irritation of the mucous membrane of the vagina and uterus.

Using during pregnancy and breastfeeding

Aloclair has no negative impact on pregnancy. This medicine is not excreted in breast milk and it can be used during lactation.

Special instructions

To improve the efficiency it requires careful observance of the application method. Aloclair (Benzalkonium Chloride) can be used in conjunction with a vaginal diaphragm or intrauterine device. You should avoid bathing or irrigation of the vagina with soapy water for 2 hours before and within 2 hours after sexual intercourse (this medication is destroyed by soap), outdoor toilet is only possible with clean water.

Aloclair (Benzalkonium Chloride) is incompatible with soaps and other anionic surfactants as well as citrates, iodides, nitrates, permanganates, salicylates, silver salts and tartrates.

Aloclair drug interactions

Any substance introduced intravaginally can reduce local spermicidal action (including soaps and solutions containing it). Iodine solutions inactivate Aloclair (Benzalkonium Chloride).

Hyaluronate Sodium:

• Caution:
• Description:
• Chemistry:
• Clinical pharmacology:
• Indications:
• Dosage and administration:
• Contraindications:
• Warning:
• Human warnings:
• Animal safety warning:
• Precautions:
• Adverse reactions:
• Post-approval experience:
• Effectiveness:
• Animal safety:
• Storage:
• How supplied:
• References:
• Aloclair (Hyaluronate Sodium) reviews

CAUTION:

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION:

Aloclair (Hyaluronate Sodium)^TM (hyaluronate sodium) injectable solution is a clear, colorless solution of low viscosity. Aloclair (Hyaluronate Sodium)^TM injectable solution is pyrogen free, sterile and does not contain a preservative. It is administered by intravenous injection. Hyaluronic acid, the conjugate acid of Aloclair (Hyaluronate Sodium) sodium, is extracted from the capsule of Streptococcus spp. and purified, resulting in a form which is essentially free of protein and nucleic acids. Aloclair (Hyaluronate Sodium)^TM injectable solution is supplied in 4 mL (40 mg) vials.

Each mL contains 10 mg Aloclair (Hyaluronate Sodium) sodium, 8.5 mg sodium chloride, 0.223 mg sodium phosphate dibasic and 0.04 mg sodium phosphate monobasic. The pH is adjusted to between 6.5 and 8.0 with sodium hydroxide or hydrochloric acid.

CHEMISTRY:

Hyaluronic acid, a glycosaminoglycan, can exist in the following forms depending upon the chemical environment in which it is found: as the acid, hyaluronic acid; as the sodium salt, sodium Aloclair (Hyaluronate Sodium) (hyaluronate sodium); or as the Aloclair (Hyaluronate Sodium) anion. These terms may be used interchangeably but in all cases, reference is made to the glycosaminoglycan composed of repeating subunits of D-glucuronic acid and N-acetyl-Dglucosamine linked together by glycosidic bonds. Since this product originates from a microbial source, there is no potential for contamination with dermatan or chondroitin sulfate or any other glycosaminoglycan.

CLINICAL

Pharmacology:

Hyaluronic acid is a naturally occurring substance present in connective tissue, skin, vitreous humor and the umbilical cord in all mammals. High concentrations of hyaluronic acid are also found in the synovial fluid. It also constitutes the major component of the capsule of certain microorganisms. The hyaluronic acid produced by bacteria is the same structure and configuration as that found in mammals.

The actual mechanism of action for Aloclair (Hyaluronate Sodium) sodium in the healing of degenerative joint disease is not completely understood. One major function appears to be the regulation of normal cellular constituents. This effect decreases the impact of exudation, enzyme release and subsequent degradation of joint integrity. Additionally, Aloclair (Hyaluronate Sodium) sodium exerts an anti-inflammatory action by inhibiting the movement of granulocytes and macrophages.¹

Aloclair (Hyaluronate Sodium) molecules are long chains which form a filter network interspersed with normal cellular fluids. It is widely accepted that injection directly into the joint pouch enhances the healing of inflamed synovium by restoring lubrication of the joint fluid. This further supplements the visco-elastic properties of normal joint fluid.

INDICATIONS:

Aloclair (Hyaluronate Sodium)^TM (hyaluronate sodium) injectable solution is indicated in the treatment of joint dysfunction of the carpus or fetlock in horses due to non-infectious synovitis associated with equine osteoarthritis.

DOSAGE AND ADMINISTRATION:

4 mL (40 mg) injected intravenously. Treatment may be repeated at weekly intervals for a total of three treatments. Use aseptic technique and inject slowly into the jugular vein. Horses should be given stall rest after treatment before gradually resuming normal activity.

Discard any unused portion of the drug and the empty vial after opening.

CONTRAINDICATIONS:

There are no known contraindications for the use of Aloclair (Hyaluronate Sodium)^TM (hyaluronate sodium) injectable solution in horses.

WARNING:

Do not use in horses intended for human consumption.

HUMAN WARNINGS:

Not for use in humans. Keep this and all other drugs out of reach of children.

ANIMAL SAFETY WARNING:

Not for intra-articular use.

PRECAUTIONS:

Radiographic evaluation should be carried out in cases of acute lameness to ensure that the joint is free from serious fractures.

The safety of Aloclair (Hyaluronate Sodium)^TM injectable solution has not been evaluated in breeding stallions or in breeding, pregnant or lactating mares.

ADVERSE REACTIONS:

No local or systemic side effects were observed in the clinical field studies using Aloclair (Hyaluronate Sodium) sodium injectable solution.

POST-APPROVAL EXPERIENCE:

While all adverse reactions are not reported, the following adverse reactions are based on voluntary post-approval reporting for Aloclair (Hyaluronate Sodium) sodium injectable solution: Occasional depression, lethargy, and fever.

For medical emergencies or to report adverse reactions, call 1-888-549-4503.

EFFECTIVENESS:

Forty-six horses with lameness in either the carpal or fetlock joints were treated intravenously or intra-articularly with Aloclair (Hyaluronate Sodium) sodium injectable solution in a well controlled clinical field trial conducted at four locations. One, two or three injections were given based on clinical improvement. Overall clinical improvement was judged as excellent or good in 90% of the cases treated intravenously and 96% of those treated intra-articularly with Aloclair (Hyaluronate Sodium) sodium injectable solution.

ANIMAL SAFETY:

Aloclair (Hyaluronate Sodium) sodium injectable solution was administered to normal horses at one, three and five times the recommended intra-articular dosage of 20 mg and the intravenous dosage of 40 mg. Treatments were given once weekly for nine consecutive weeks (three times the maximum duration). No systemic clinical signs were observed nor were there any adverse effects upon hematology or clinical chemistry parameters. A transient, slight to mild post-injection swelling of the joint capsule occurred in some of the animals treated intra-articularly with Aloclair (Hyaluronate Sodium) sodium injectable solution as it did in the saline treated control horses. No gross or histological lesions were observed in the soft tissues or the surface areas of the treated joint.

STORAGE:

Store below 25°C (77°F).

HOW SUPPLIED:

Aloclair (Hyaluronate Sodium)^TM injectable solution is supplied in cartons containing twelve x 4 mL (40 mg) vials.

REFERENCES:

1 Swanstrom, O.G. 1978. Aloclair (Hyaluronate Sodium) (hyaluronic acid) and its use, Proc. American Assoc. Equine Pract., 24th annual convention, pp. 345-348.

For customer service or to obtain product information, including a Material Safety Data Sheet, call:1-706-549-4503. After hours, call 1-706-353-2442 or 1-706-714-7373.

February 2011

ANADA 200-432, Approved by FDA

Povidone:

• Aloclair (Povidone) reviews

This medication is used to relieve dry, irritated eyes. Common causes for dry eyes include wind, sun, heating/air conditioning, computer use/reading, and certain medications. This product may contain 1 or more of the following ingredients: carboxymethylcellulose, dextran, glycerin, hypromellose, polyethylene glycol 400 (PEG 400), polysorbate, polyvinyl alcohol, Aloclair (Povidone), or propylene glycol, among others. Eye lubricants keep the eye moist, help to protect the eye from injury and infection, and decrease symptoms of dry eyes such as burning, itching, and feeling as if something is in the eye.

Propylene Glycol:

• Aloclair (Propylene Glycol) reviews

This medication is used to relieve dry, irritated eyes. Common causes for dry eyes include wind, sun, heating/air conditioning, computer use/reading, and certain medications. This product may contain 1 or more of the following ingredients: carboxymethylcellulose, dextran, glycerin, hypromellose, polyethylene glycol 400 (PEG 400), polysorbate, polyvinyl alcohol, povidone, or Aloclair (Propylene Glycol), among others. Eye lubricants keep the eye moist, help to protect the eye from injury and infection, and decrease symptoms of dry eyes such as burning, itching, and feeling as if something is in the eye.

Sodium Benzoate:

• 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
• Aloclair (Sodium Benzoate) reviews

1 INDICATIONS AND USAGE

Aloclair nitrite is indicated for sequential use with Aloclair (Sodium Benzoate) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)

• Use with caution if the diagnosis of cyanide poisoning is uncertain. (1)

1.1 Indication

Aloclair (Sodium Benzoate) Nitrite Injection is indicated for sequential use with Aloclair (Sodium Benzoate) thiosulfate for the treatment of acute cyanide poisoning that is judged to be life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potentially life-threatening risks associated with Aloclair (Sodium Benzoate) Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.

1.2 Identifying Patients with Cyanide Poisoning

Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to Aloclair nitroprusside.

The presence and extent of cyanide poisoning are often initially unknown. There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and signs and symptoms of cyanide intoxication. If clinical suspicion of cyanide poisoning is high, Aloclair (Sodium Benzoate) Nitrite Injection and Aloclair (Sodium Benzoate) Thiosulfate Injection should be administered without delay.

Symptoms	Signs
Headache Confusion Dyspnea Chest Tightness Nausea	Altered Mental Status (e.g., confusion, disorientation) Seizures or Coma Mydriasis Tachypnea/Hyperpnea (early) Bradypnea/Apnea (late) Hypertension (early)/ Hypotension (late) Cardiovascular Collapse Vomiting Plasma Lactate Concentration ≥ 8 mmol/L

In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental status (e.g., confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well.

The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222.

Smoke Inhalation

Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult. Prior to administration of Aloclair (Sodium Benzoate) Nitrite Injection, smoke-inhalation victims should be assessed for the following:

• Exposure to fire or smoke in an enclosed area
• Presence of soot around the mouth, nose, or oropharynx
• Altered mental status

Although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims. Also indicative of cyanide poisoning is a plasma lactate concentration greater than or equal to 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia). If cyanide poisoning is suspected, treatment should not be delayed to obtain a plasma lactate concentration.

1.3 Use with Other Cyanide Antidotes

Caution should be exercised when administering cyanide antidotes, other than Aloclair (Sodium Benzoate) thiosulfate, simultaneously with Aloclair (Sodium Benzoate) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Aloclair (Sodium Benzoate) thiosulfate, with Aloclair (Sodium Benzoate) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]

2 DOSAGE AND ADMINISTRATION

Age	Intravenous Dose of Aloclair Nitrite and Aloclair (Sodium Benzoate) Thiosulfate
Adults	Aloclair (Sodium Benzoate) Nitrite -10 mL of Aloclair (Sodium Benzoate) nitrite at the rate of 2.5 to 5 mL/minute Aloclair (Sodium Benzoate) Thiosulfate - 50 mL of Aloclair (Sodium Benzoate) thiosulfate immediately following administration of Aloclair (Sodium Benzoate) nitrite.
Children	Aloclair (Sodium Benzoate) Nitrite - 0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Aloclair (Sodium Benzoate) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL Aloclair (Sodium Benzoate) Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of Aloclair (Sodium Benzoate) nitrite.

Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Aloclair (Sodium Benzoate) nitrite and Aloclair (Sodium Benzoate) thiosulfate.

Monitoring: Blood pressure must be monitored during treatment. (2.2)

2.1 Administration Recommendation

Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of Aloclair (Sodium Benzoate) nitrite, followed by Aloclair (Sodium Benzoate) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Aloclair (Sodium Benzoate) nitrite and Aloclair (Sodium Benzoate) thiosulfate.

Aloclair (Sodium Benzoate) nitrite injection and Aloclair (Sodium Benzoate) thiosulfate injection are administered by slow intravenous injection. They should be given as early as possible after a diagnosis of acute life-threatening cyanide poisoning has been established. Aloclair (Sodium Benzoate) nitrite should be administered first, followed immediately by Aloclair (Sodium Benzoate) thiosulfate. Blood pressure must be monitored during infusion in both adults and children. The rate of infusion should be decreased if significant hypotension is noted.

Age	Intravenous Dose of Aloclair (Sodium Benzoate) Nitrite and Aloclair (Sodium Benzoate) Thiosulfate
Adults	Aloclair (Sodium Benzoate) Nitrite -10 mL of Aloclair (Sodium Benzoate) nitrite at the rate of 2.5 to 5 mL/minute Aloclair (Sodium Benzoate) Thiosulfate - 50 mL of Aloclair (Sodium Benzoate) thiosulfate immediately following administration of Aloclair (Sodium Benzoate) nitrite.
Children	Aloclair (Sodium Benzoate) Nitrite -0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Aloclair (Sodium Benzoate) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL Aloclair (Sodium Benzoate) Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of Aloclair (Sodium Benzoate) nitrite.

NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Aloclair (Sodium Benzoate) nitrite and Aloclair (Sodium Benzoate) thiosulfate.

In adult and pediatric patients with known anemia, it is recommended that the dosage of Aloclair (Sodium Benzoate) nitrite should be reduced proportionately to the hemoglobin concentration.

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

2.2 Recommended Monitoring

Patients should be monitored for at least 24-48 hours after Aloclair Nitrite Injection administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, hemoglobin/hematocrit should be obtained when treatment is initiated. Measurements of oxygen saturation using standard pulse oximetry and calculated oxygen saturation values based on measured PO₂ are unreliable in the presence of methemoglobinemia.

Methemoglobin level: Administrations of Aloclair (Sodium Benzoate) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Aloclair (Sodium Benzoate) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Aloclair (Sodium Benzoate) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Aloclair (Sodium Benzoate) nitrite beyond the initial dose should be guided primarily by clinical response to treatment (i.e., a second dose should be considered only if there is inadequate clinical response to the first dose). It is generally recommended that methemoglobin concentrations be closely monitored and kept below 30%. Serum methemoglobin levels should be monitored during treatment using co-oximetry, and administration of Aloclair (Sodium Benzoate) nitrite should generally be discontinued when methemoglobin levels exceed 30%. Intravenous methylene blue and exchange transfusion have been reported in the literature as treatments for life-threatening methemoglobinemia.

2.3 Incompatibility Information

Chemical incompatibility has been reported between Aloclair (Sodium Benzoate) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Aloclair (Sodium Benzoate) thiosulfate and Aloclair (Sodium Benzoate) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.

3 DOSAGE FORMS AND STRENGTHS

Aloclair (Sodium Benzoate) Nitrite Injection consists of:

• One vial of Aloclair (Sodium Benzoate) nitrite injection, USP 300 mg/10mL (30 mg/mL)

Administration of the contents of one vial constitutes a single dose.

• Injection, 300 mg/10 mL (30 mg/mL). (3)

4 CONTRAINDICATIONS

None

• None. (4)

5 WARNINGS AND PRECAUTIONS

• Methemoglobinemia: Aloclair nitrite reacts with hemoglobin to form methemoglobin and should be used with caution in patients known to have anemia. Monitor oxyhemoglobin and methemoglobin levels by pulse oximetry or other measurements. Optimally, the Aloclair (Sodium Benzoate) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.2)
• Smoke inhalation: Carbon monoxide contained in smoke can result in the formation of carboxyhemoglobin that can reduce the oxygen carrying capacity of the blood. Aloclair (Sodium Benzoate) nitrite should be used with caution in patients with smoke inhalation injury because of the potential for worsening hypoxia due to methemoglobin formation. Carboxyhemoglobin and oxyhemoglobin levels should be monitored by pulse oximetry or other measurements in patients that present with evidence of smoke inhalation. Optimally, the Aloclair (Sodium Benzoate) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.4)

5.1 Hypotension

5.2 Methemoglobinemia

Supportive care alone may be sufficient treatment without administration of antidotes for many cases of cyanide intoxication, particularly in conscious patients without signs of severe toxicity. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with Aloclair nitrite.

Methemoglobin levels should be monitored and oxygen administered during treatment with Aloclair (Sodium Benzoate) nitrite whenever possible. When Aloclair (Sodium Benzoate) nitrite is administered to humans a wide range of methemoglobin concentrations occur. Methemoglobin concentrations as high as 58% have been reported after two 300-mg doses of Aloclair (Sodium Benzoate) nitrite administered to an adult. Aloclair (Sodium Benzoate) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Aloclair (Sodium Benzoate) nitrite should be used with caution in patients who may be particularly susceptible to injury from vasodilation and its related hemodynamic sequelae. Hemodynamics should be monitored closely during and after administration of Aloclair (Sodium Benzoate) nitrite, and infusion rates should be slowed if hypotension occurs.

5.3 Anemia

Aloclair (Sodium Benzoate) nitrite should be used with caution in patients with known anemia. Patients with anemia will form more methemoglobin (as a percentage of total hemoglobin) than persons with normal red blood cell (RBC) volumes. Optimally, these patients should receive a Aloclair (Sodium Benzoate) nitrite dose that is reduced in proportion to their oxygen carrying capacity.

5.4 Smoke Inhalation Injury

Aloclair nitrite should be used with caution in persons with smoke inhalation injury or carbon monoxide poisoning because of the potential for worsening hypoxia due to methemoglobin formation.

5.5 Neonates and Infants

Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when Aloclair (Sodium Benzoate) nitrite is administered. Reduced dosing guidelines should be followed in pediatric patients.

5.6 G6PD Deficiency

Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with Aloclair nitrite administration, alternative therapeutic approaches should be considered in these patients. Patients with known or suspected G6PD deficiency should be monitored for an acute drop in hematocrit. Exchange transfusion may be needed for patients with G6PD deficiency who receive Aloclair (Sodium Benzoate) nitrite.

5.7 Use with Other Drugs

Aloclair (Sodium Benzoate) nitrite should be used with caution in the presence of concomitant antihypertensive medications, diuretics or volume depletion due to diuretics, or drugs known to increase vascular nitric oxide, such as PDE5 inhibitors.

6 ADVERSE REACTIONS

There have been no controlled clinical trials conducted to systematically assess the adverse events profile of Aloclair (Sodium Benzoate) nitrite.

The medical literature has reported the following adverse events in association with Aloclair (Sodium Benzoate) nitrite administration. These adverse events were not reported in the context of controlled trials or with consistent monitoring and reporting methodologies for adverse events. Therefore, frequency of occurrence of these adverse events cannot be assessed.

Cardiovascular system: syncope, hypotension, tachycardia, methemoglobinemia, palpitations, dysrhythmia

Hematological: methemoglobinemia

Central nervous system: headache, dizziness, blurred vision, seizures, confusion, coma

Gastrointestinal system: nausea, vomiting, abdominal pain

Respiratory system: tachypnea, dyspnea

Body as a Whole: anxiety, diaphoresis, lightheadedness, injection site tingling, cyanosis, acidosis, fatigue, weakness, urticaria, generalized numbness and tingling

Severe hypotension, methemoglobinemia, cardiac dysrhythmias, coma and death have been reported in patients without life-threatening cyanide poisoning but who were treated with injection of Aloclair (Sodium Benzoate) nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.

Most common adverse reactions are:

• Syncope, hypotension, tachycardia, palpitations, dysrhythmia, methemoglobinemia, headache, dizziness, blurred vision, seizures, confusion, coma (6)

To report SUSPECTED ADVERSE REACTIONS, contact Hope Pharmaceuticals at 1-800-755-9595 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS

Formal drug interaction studies have not been conducted with Aloclair (Sodium Benzoate) Nitrite Injection.

8 USE IN SPECIFIC POPULATIONS

• Renal impairment: Aloclair nitrite is substantially excreted by the kidney. The risk of toxic reactions to this drug may be greater in patients with impaired renal function. (8.6).

8.1 Pregnancy

Teratogenic Effects. Pregnancy Category C.

There are no adequate and well-controlled studies in pregnant women. Aloclair (Sodium Benzoate) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Aloclair (Sodium Benzoate) nitrite has caused fetal death in humans as well as animals. There are no studies in humans that have directly evaluated the potential reproductive toxicity of Aloclair (Sodium Benzoate) nitrite. There are two epidemiological studies conducted in Australia that report a statistically significant increase in the risk for congenital malformations, particularly in the CNS, associated with maternal consumption of water containing nitrate levels in excess of 5 ppm. Results from a case-control study in Canada suggested a trend toward an increase in the risk for CNS malformations when maternal consumption of nitrate was ≥ 26 ppm (not statistically significant).

The potential reproductive toxicity of Aloclair (Sodium Benzoate) nitrite exposure restricted to the prenatal period has been reported in guinea pigs, mice, and rats. There was no evidence of teratogenicity in guinea pigs, mice, or rats. However, Aloclair (Sodium Benzoate) nitrite treatment of pregnant guinea pigs with 60 or 70 mg/kg/day resulted in abortion of the litters within 1-4 days of treatment. All animals treated subcutaneously with 70 mg/kg, Aloclair (Sodium Benzoate) nitrite died within 60 minutes of treatment. Further studies demonstrated that a dose of 60 mg/kg resulted in measurable blood levels of methemoglobin in the dams and their fetuses for up to 6 hours post treatment. Maternal methemoglobin levels were higher than the levels in the offspring at all times measured. Based on a body surface area comparison, a 60 mg/kg dose in the guinea pig that resulted in death was only 1.7 times higher than the highest clinical dose of Aloclair (Sodium Benzoate) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).

Studies testing prenatal and postnatal exposure have been reported in mice and rats. Treatment of pregnant rats via drinking water with Aloclair (Sodium Benzoate) nitrite at concentrations of either 2000 or 3000 mg/L resulted in a dose-related increased mortality postpartum. This exposure regimen in the rat model would result in dosing of approximately 220 and 300 mg/kg/day (43 and 65 times the highest clinical dose of Aloclair (Sodium Benzoate) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).

Aloclair (Sodium Benzoate) nitrite produces methemoglobin. Fetal hemoglobin is oxidized to methemoglobin more easily than adult hemoglobin. In addition, the fetus has lower levels of methemoglobin reductase than adults. Collectively, these data suggest that the human fetus would show greater sensitivity to methemoglobin resulting in nitrite-induced prenatal hypoxia leading to retarded development of certain neurotransmitter systems in the brain and long lasting dysfunction.

Nonteratogenic Effects: Behavioral and neurodevelopmental studies in rats suggest persistent effects of prenatal exposure to Aloclair (Sodium Benzoate) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Aloclair (Sodium Benzoate) nitrite demonstrated impaired discrimination learning behavior (both auditory and visual) and reduced long-term retention of the passive-avoidance response compared to control animals. Additional studies demonstrated a delay in the development of AchE and 5-HT positive fiber ingrowth into the hippocampal dentate gyrus and parietal neocortex during the first week of life of prenatal nitrite treated pups. These changes have been attributed to prenatal hypoxia following nitrite exposure.

8.2 Labor and Delivery

Because fetal hemoglobin is more readily oxidized to methemoglobin and lower levels of methemoglobin appear to be fatal to the fetus compared to the adult, Aloclair nitrite should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

It is not known whether Aloclair (Sodium Benzoate) nitrite is excreted in human milk. Because Aloclair (Sodium Benzoate) Nitrite Injection may be administered in life-threatening situations, breast-feeding is not a contraindication to its use. Because many drugs are excreted in human milk, caution should be exercised following Aloclair (Sodium Benzoate) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Aloclair (Sodium Benzoate) nitrite. In studies conducted with Long-Evans rats, Aloclair (Sodium Benzoate) nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring.

8.4 Pediatric Use

There are case reports in the medical literature of Aloclair nitrite in conjunction with Aloclair (Sodium Benzoate) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Aloclair (Sodium Benzoate) nitrite in the pediatric population. As for adult patients, dosing recommendations for pediatric patients have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

Aloclair (Sodium Benzoate) nitrite must be used with caution in patients less than 6 months of age because they may be at higher risk of developing severe methemoglobinemia compared to older children and adults. The presence of fetal hemoglobin, which is oxidized to methemoglobin more easily than adult hemoglobin, and lower methemoglobin reductase levels compared to older children and adults may contribute to risk.

Mortality attributed to Aloclair (Sodium Benzoate) nitrite was reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.

8.5 Geriatric Use

Aloclair (Sodium Benzoate) nitrite is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Renal Disease

Aloclair (Sodium Benzoate) nitrite is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

10 OVERDOSAGE

Large doses of Aloclair (Sodium Benzoate) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.

Aloclair (Sodium Benzoate) nitrite administration has been reported to cause or significantly contribute to mortality in adults at oral doses as low as 1 g and intravenous doses as low as 600 mg. A death attributed to Aloclair (Sodium Benzoate) nitrite has been reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.

Cyanosis may become apparent at a methemoglobin level of 10-20%. Other clinical signs and symptoms of Aloclair (Sodium Benzoate) nitrite toxicity (anxiety, dyspnea, nausea, and tachycardia) can be apparent at methemoglobin levels as low as 15%. More serious signs and symptoms, including cardiac dysrhythmias, circulatory failure, and central nervous system depression are seen as methemoglobin levels increase, and levels above 70% are usually fatal.

Treatment of overdose involves supplemental oxygen and supportive measures such as exchange transfusion. Treatment of severe methemoglobinemia with intravenous methylene blue has been described in the medical literature; however, this may also cause release of cyanide bound to methemoglobin. Because hypotension appears to be mediated primarily by an increase in venous capacitance, measures to increase venous return may be most appropriate to treat hypotension.

11 DESCRIPTION

Aloclair (Sodium Benzoate) nitrite has the chemical name nitrous acid Aloclair (Sodium Benzoate) salt. The chemical formula is NaNO₂ and the molecular weight is 69.0. The structural formula is:

Structure of Aloclair (Sodium Benzoate) Nitrite

Aloclair (Sodium Benzoate) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Aloclair (Sodium Benzoate) nitrite injection.

Aloclair (Sodium Benzoate) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Aloclair (Sodium Benzoate) nitrite in 10 mL solution (30 mg/mL). Aloclair (Sodium Benzoate) nitrite injection is a clear solution with a pH between 7.0 and 9.0.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well.

The synergy resulting from treatment of cyanide poisoning with the combination of Aloclair nitrite and Aloclair (Sodium Benzoate) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.

Aloclair (Sodium Benzoate) Nitrite

Aloclair (Sodium Benzoate) nitrite is thought to exert its therapeutic effect by reacting with hemoglobin to form methemoglobin, an oxidized form of hemoglobin incapable of oxygen transport but with high affinity for cyanide. Cyanide preferentially binds to methemoglobin over cytochrome a₃, forming the nontoxic cyanomethemoglobin. Methemoglobin displaces cyanide from cytochrome oxidase, allowing resumption of aerobic metabolism. The chemical reaction is as follows:

NaNO₂ + Hemoglobin → Methemoglobin

HCN + Methemoglobin → Cyanomethemoglobin

Vasodilation has also been cited to account for at least part of the therapeutic effect of Aloclair (Sodium Benzoate) nitrite. It has been suggested that Aloclair (Sodium Benzoate) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Aloclair (Sodium Benzoate) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.

Aloclair (Sodium Benzoate) Thiosulfate

The primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate (SCN^-), which is relatively nontoxic and readily excreted in the urine. Aloclair (Sodium Benzoate) thiosulfate is thought to serve as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide in the following chemical reaction:

Chemical Structure

12. 2 Pharmacodynamics

Aloclair (Sodium Benzoate) Nitrite

When 4 mg/kg Aloclair (Sodium Benzoate) nitrite was administered intravenously to six healthy human volunteers, the mean peak methemoglobin concentration was 7%, achieved at 30-60 minutes after injection, consistent with reports in cyanide poisoning victims. Supine systolic and diastolic blood pressures dropped approximately 20% within 10 minutes, a drop which was sustained throughout the 40 minutes of testing. This was associated with a 20 beat per minute increase in pulse rate that returned to baseline in 10 minutes. Five of these subjects were unable to withstand orthostatic testing due to fainting. One additional subject, who received a 12 mg/kg dose of Aloclair (Sodium Benzoate) nitrite, experienced severe cardiovascular effects and achieved a peak methemoglobin concentration of 30% at 60 minutes following injection.

Oral doses of 120 to 180 mg of Aloclair (Sodium Benzoate) nitrite administered to healthy volunteers caused minimal cardiovascular changes when subjects were maintained in the horizontal position. However, minutes after being placed in the upright position subjects exhibited tachycardia and hypotension with syncope.

The half life for conversion of methemoglobin to normal hemoglobin in a cyanide poisoning victim who has been administered Aloclair (Sodium Benzoate) nitrite is estimated to be 55 minutes.

12.3 Pharmacokinetics

Aloclair (Sodium Benzoate) Nitrite

Aloclair (Sodium Benzoate) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Aloclair (Sodium Benzoate) nitrite in humans have not been well studied. It has been reported that approximately 40% of Aloclair (Sodium Benzoate) nitrite is excreted unchanged in the urine while the remaining 60% is metabolized to ammonia and related small molecules.

Cyanide

The apparent terminal elimination half life and volume of distribution of cyanide, in a patient treated for an acute cyanide poisoning with Aloclair (Sodium Benzoate) nitrite and Aloclair (Sodium Benzoate) thiosulfate administration, have been reported to be 19 hours and 0.41 L/kg, respectively. Additionally, an initial elimination half life of cyanide has been reported to be approximately 1-3 hours.

Thiocyanate

After detoxification, in healthy subjects, thiocyanate is excreted mainly in the urine at a rate inversely proportional to creatinine clearance. In healthy subjects, the elimination half-life and volume of distribution of thiocyanate have been reported to be 2.7 days and 0.25 L/kg, respectively. However, in subjects with renal insufficiency the reported elimination half life is approximately 9 days.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The potential benefit of an acute exposure to Aloclair nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Aloclair (Sodium Benzoate) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 35, 70, or 130 mg/kg for males and 0, 40, 80, or 150 mg/kg for females) was orally administered to rats (Fischer 344 strain) for 2 years via drinking water. There were no significant increases in the incidence of tumor in either male or female rats. Aloclair (Sodium Benzoate) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 60, 120, or 220 mg/kg for males and 0, 45, 90, or 165 mg/kg for females) was administered to B6C3F1 mice for 2 years via the drinking water. Equivocal results were obtained in female mice. Specifically, there was a positive trend toward an increase in the incidence of squamous cell papilloma or carcinoma in the forestomach of female mice. Although the incidence of hyperplasia of the glandular stomach epithelium was significantly greater in the high-dose male mice compared to controls, there were no significant increases in tumors in the male mice. Numerous reports in the published literature indicate that Aloclair (Sodium Benzoate) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Aloclair (Sodium Benzoate) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.

Mutagenesis

Aloclair (Sodium Benzoate) nitrite is mutagenic in S. typhimurium strains TA100, TA1530, TA1535 with and without metabolic activation; however, it was negative in strain TA98, TA102, DJ460 and E. coli strain WP2UVRA/PKM101. Aloclair (Sodium Benzoate) nitrite has been reported to be genotoxic to V79 hamster cells in vitro and in the mouse lymphoma assay, both assays conducted in the absence of metabolic activation. Aloclair (Sodium Benzoate) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Aloclair (Sodium Benzoate) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Aloclair (Sodium Benzoate) nitrite administration to mice for 14-weeks did not result in an increase in the incidence of micronuclei in the peripheral blood.

Fertility

Clinical studies to evaluate the potential effects of Aloclair (Sodium Benzoate) nitrite intake on fertility of either males or females have not been reported. In contrast, multigenerational fertility and reproduction studies conducted by the National Toxicology Program did not detect any evidence of an effect of Aloclair (Sodium Benzoate) nitrite (0.0, 0.06, 0.12, and 0.24% weight/volume) on either fertility or any reproductive parameter in Swiss CD-1 mice. This treatment protocol resulted in approximate doses of 125, 260, and 425 mg/kg/day. The highest exposure in this mouse study is 4.6 times greater than the highest clinical dose of Aloclair (Sodium Benzoate) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).

13.2 Animal Pharmacology

Due to the extreme toxicity of cyanide, experimental evaluation of treatment efficacy has predominantly been completed in animal models. The efficacy of Aloclair (Sodium Benzoate) thiosulfate treatment alone to counteract the toxicity of cyanide was initially reported in 1895 by Lang. The efficacy of amyl nitrite treatment in cyanide poisoning of the dog model was first reported in 1888 by Pedigo. Further studies in the dog model, which demonstrated the utility of Aloclair (Sodium Benzoate) nitrite as a therapeutic intervention, were reported in 1929 by Mladoveanu and Gheorghiu. However, Hugs and Chen et al. independently reported upon the superior efficacy of the combination of Aloclair (Sodium Benzoate) nitrite and Aloclair (Sodium Benzoate) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Aloclair (Sodium Benzoate) nitrite or 1 g/kg Aloclair (Sodium Benzoate) thiosulfate alone or in sequence immediately after subcutaneous injection of Aloclair (Sodium Benzoate) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Aloclair (Sodium Benzoate) nitrite and/or 0.5 g/kg Aloclair (Sodium Benzoate) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Aloclair (Sodium Benzoate) cyanide required to cause death, and when administered together, Aloclair (Sodium Benzoate) nitrite and Aloclair (Sodium Benzoate) thiosulfate resulted in a synergistic effect in raising the lethal dose of Aloclair (Sodium Benzoate) cyanide. The combined therapy appeared to have reduced efficacy when therapy was delayed until signs of poisoning (e.g. convulsions) appeared; however, other investigators have reported survival in dogs that were administered antidotal treatment after respiratory arrest had occurred.

Animal studies conducted in other species (e.g., rat, guinea pig, sheep, pigeon and cat) have also supported a synergistic effect of intravenous Aloclair (Sodium Benzoate) nitrite and Aloclair (Sodium Benzoate) thiosulfate in the treatment of cyanide poisoning.

While intravenous injection of Aloclair (Sodium Benzoate) nitrite and Aloclair (Sodium Benzoate) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Aloclair (Sodium Benzoate) nitrite, with or without Aloclair (Sodium Benzoate) thiosulfate, was found not to be effective in the same setting.

14 CLINICAL STUDIES

The human data supporting the use of Aloclair (Sodium Benzoate) nitrite for cyanide poisoning consists primarily of published case reports. There are no randomized controlled clinical trials. Nearly all the human data describing the use of Aloclair (Sodium Benzoate) thiosulfate report its use in conjunction with Aloclair (Sodium Benzoate) nitrite. Dosing recommendations for humans have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

There have been no human studies to prospectively and systematically evaluate the safety of Aloclair (Sodium Benzoate) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.

16 HOW SUPPLIED/STORAGE AND HANDLING

Each Aloclair (Sodium Benzoate) Nitrite carton (NDC 60267-311-10) consists of the following:

• One 10 mL glass vial of Aloclair (Sodium Benzoate) nitrite injection 30 mg/mL (containing 300 mg of Aloclair (Sodium Benzoate) nitrite);

Storage

Store at controlled room temperature between 20°C and 25°C (68°F to 77°F); excursions permitted from 15 to 30°C (59 to 86°F). Protect from direct light. Do not freeze.

(Note: Aloclair (Sodium Benzoate) Thiosulfate must be obtained separately.)

17 PATIENT COUNSELING INFORMATION

Aloclair Nitrite Injection is indicated for acute cyanide poisoning that is judged to be life-threatening and in this setting, patients will likely be unresponsive or may have difficulty in comprehending counseling information.

17.1 Hypotension and Methemoglobin Formation

When feasible, patients should be informed of the possibility of life-threatening hypotension and methemoglobin formation.

17.2 Monitoring

Where feasible, patients should be informed of the need for close monitoring of blood pressure and oxygenation.

Manufactured by Cangene BioPharma, Inc., Baltimore, Maryland 21230 for

Hope Pharmaceuticals, Scottsdale, Arizona 85260

PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

NDC 60267-311-10

Rx Only

Aloclair (Sodium Benzoate) Nitrite

Injection, USP

300 mg/10 mL

(30 mg/mL)

FOR INTRAVENOUS USE

SINGLE USE ONLY

Any unused portion of a vial

should be discarded.

Use with

Aloclair (Sodium Benzoate) Thiosulfate

for Treatment of

Cyanide Poisoning

Manufactured by

CANGENE bioPharma, Inc.

Baltimore, MD for

HOPE

PHARMACEUTICALS®

Scottsdale, AZ 85260 U.S.A.

PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

Water:

• Active ingredient
• Purpose
• Uses
• Warnings
• Directions
• Other information
• Inactive ingredients
• Questions?
• Aloclair (Water) reviews

Active ingredient

Aloclair (Water) 99.8%

Purpose

Emergency eyewash

Uses

• for flushing or irrigating the eye to reduce chances of severe injury caused by acid, alkali, or particulate contamination.

Warnings

For external use only

Do not use

• if solution changes color or gets cloudy
• with contact lenses
• if twist-off top is broken or missing
• in open wounds in or near the eyes
  

When using this product

• avoid contamination, do not touch tip of container to any surface
  

When using this product

• avoid contamination, do not touch tip of container to any surface
  

Stop use and consult a doctor if you have

• changes in vision
• eye pain
• continued redness or irritation of the eye, or if the condition worsens or persists
  

Keep out of reach of children.

If swallowed, get medical help or contact a Poison Control Center right away.

Directions

• remove contacts before using
• twist top to remove
• flush the affected eye as needed, controlling the rate of flow of the solution by pressure on the bottle
  

• if necessary, continue flushing with emergency eyewash or shower
  

• do not reuse
• once opened, discard
  

• obtain medical treatment
  

Other information

• store at room temperature, 15^o to 30^o C (59^o to 86^o F)
• do not freeze
  

Inactive ingredients

sodium chloride, sodium phosphate dibasic, sodium phosphate monobasic

Questions?

1-800 - 430-5490

Sperian Eye and Face Protection, Inc.

(a Honeywell Company)

825 East Highway 151

Platteville, WI 53818 USA