OPTIVAR® (azelastine hydrochloride ophthalmic solution), 0.05% is a sterile ophthalmic solution containing azelastine hydrochloride, a relatively selective H₁ -receptor antagonist for topical administration to the eyes. Azelastine hydrochloride is a white crystalline powder with a molecular weight of 418.37. Azelastine hydrochloride is sparingly soluble in water, methanol and propylene glycol, and slightly soluble in ethanol, octanol, and glycerine. Azelastine hydrochloride is a racemic mixture with a melting point of 225°C. The chemical name for azelastine hydrochloride is (±)-1-(2H)-phthalazinone,4-[(4-chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-, monohydrochloride and is represented by the following chemical structure:

Empirical chemical structure: C₂₂H₂₄ClN₃O•HCl

Each mL of OPTIVAR® contains: Active: 0.5 mg azelastine hydrochloride, equivalent to 0.457mg of azelastine base; Preservative: 0.125 mg benzalkonium chloride; Inactives: disodium edetate dihydrate, hypromellose, sorbitol solution, sodium hydroxide and water for injection. It has a pH of approximately 5.0 to 6.5 and an osmolarity of approximately 271 to 312 mOsmol/L.

Last updated on RxList: 8/5/2008

OPTIVAR® is indicated for the treatment of itching of the eye associated with allergic conjunctivitis.

The recommended dose is one drop instilled into each affected eye twice a day.

OPTIVAR® (azelastine hydrochloride ophthalmic solution), 0.05% is supplied as follows:

OPTIVAR® 6 mL (NDC#0037-7025-60) solution in a translucent 10 mL HDPE container with a LDPE dropper tip and a white HDPE screw cap.

OPTIVAR® 0.2 mL (NDC#0037-7025-01) solution in a translucent 1 mL HDPE single-use container, packaged as 4 single-use containers in a foil pouch in a carton.

Attention

Once OPTIVAR® 0.2 mL unit dose foil pouch is open, unopened containers can be used for one month, not to exceed the expiration date imprinted on the container. After one month they should be discarded. Use only if foil pouch is sealed and single container is intact. Discard each container immediately after use.

Storage

OPTIVAR® 6 mL container: Store UPRIGHT between 2° and 25°C (36° and 77°F).
OPTIVAR® 0.2 mL container: Store at controlled room temperature 20°-25°C (68° -77°F).

OPTIVAR® 6 mL container Manufactured by: Patheon UK Ltd., Swindon, United Kingdom. OPTIVAR® 0.2 mL container Manufactured by: Catalent Pharma Solutions, Woodstock, Illinois, USA. Distributed by: Meda Pharmaceuticals™, Meda Pharmaceuticals Inc., Somerset, New Jersey 08873-4120. OPTIVAR® 6 ml container Made in United Kingdom. OPTIVAR® 0.2 mL Made in United States. Issued 06/2008. FDA revision date: 07/02/08

Last updated on RxList: 8/5/2008

In controlled multiple-dose studies where patients were treated for up to 56 days, the most frequently reported adverse reactions were transient eye burning/stinging (approximately 30%), headaches (approximately 15%) and bitter taste (approximately 10%). The occurrence of these events was generally mild.

The following events were reported in 1-10% of patients: asthma, conjunctivitis, dyspnea, eye pain, fatigue, influenza-like symptoms, pharyngitis, pruritus, rhinitis and temporary blurring. Some of these events were similar to the underlying disease being studied.

No information provided.

Last updated on RxList: 8/5/2008

OPTIVAR® is for ocular use only and not for injection or oral use.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Azelastine hydrochloride administered orally for 24 months was not carcinogenic in rats and mice at doses up to 30 mg/kg/day and 25 mg/kg/day, respectively. Based on a 30 µL drop size, these doses were approximately 25,000 and 21,000 times higher than the maximum recommended ocular human use level of 0.001 mg/kg/day for a 50 kg adult.

Azelastine hydrochloride showed no genotoxic effects in the Ames test, DNA repair test, mouse lymphoma forward mutation assay, mouse micronucleus test, or chromosomal aberration test in rat bone marrow. Reproduction and fertility studies in rats showed no effects on male or female fertility at oral doses of up to 25,000 times the maximum recommended ocular human use level. At 68.6 mg/kg/day (57,000 times the maximum recommended ocular human use level), the duration of the estrous cycle was prolonged and copulatory activity and the number of pregnancies were decreased. The numbers of corpora lutea and implantations were decreased; however, the implantation ratio was not affected.

Pregnancy

Teratogenic Effects: Pregnancy Category C. Azelastine hydrochloride has been shown to be embryotoxic, fetotoxic, and teratogenic (external and skeletal abnormalities) in mice at an oral dose of 68.6 mg/kg/day (57,000 times the recommended ocular human use level). At an oral dose of 30 mg/kg/day (25,000 times the recommended ocular human use level), delayed ossification (undeveloped metacarpus) and the incidence of 14 th rib were increased in rats. At 68.6 mg/kg/day (57,000 times the maximum recommended ocular human use level) azelastine hydrochloride caused resorption and fetotoxic effects in rats. The relevance to humans of these skeletal findings noted at only high drug exposure levels is unknown.

There are no adequate and well-controlled studies in pregnant women. OPTIVAR® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether azelastine hydrochloride is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when OPTIVAR® is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 3 have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.

Last updated on RxList: 8/5/2008

No information provided.

OPTIVAR® is contraindicated in persons with known or suspected hypersensitivity to any of its components.

Last updated on RxList: 8/5/2008

Azelastine hydrochloride is a relatively selective histamine H₁ antagonist and an inhibitor of the release of histamine and other mediators from cells (e.g. mast cells) involved in the allergic response. Based on in-vitro studies using human cell lines, inhibition of other mediators involved in allergic reactions (e.g. leukotrienes and PAF) has been demonstrated with azelastine hydrochloride. Decreased chemotaxis and activation of eosinophils has also been demonstrated.

Pharmacokinetics and Metabolism

Absorption of azelastine following ocular administration was relatively low. A study in symptomatic patients receiving one drop of OPTIVAR® in each eye two to four times a day (0.06 to 0.12 mg azelastine hydrochloride) demonstrated plasma concentrations of azelastine hydrochloride to generally be between 0.02 and 0.25 ng/mL after 56 days of treatment. Three of nineteen patients had quantifiable amounts of N-desmethylazelastine that ranged from 0.25-0.87 ng/mL at Day 56.

Based on intravenous and oral administration, the elimination half-life, steady-state volume of distribution and plasma clearance were 22 hours, 14.5 L/kg and 0.5 L/h/kg, respectively. Approximately 75% of an oral dose of radiolabeled azelastine hydrochloride was excreted in the feces with less than 10% as unchanged azelastine. Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system. In-vitro studies in human plasma indicate that the plasma protein binding of azelastine and N-desmethylazelastine are approximately 88% and 97%, respectively.

Clinical Trials

In a conjunctival antigen challenge study, OPTIVAR® was more effective than its vehicle in preventing itching associated with allergic conjunctivitis. OPTIVAR® had a rapid (within 3 minutes) onset of effect and a duration of effect of approximately 8 hours for the prevention of itching.

In environmental studies, adult and pediatric patients with seasonal allergic conjunctivitis were treated with OPTIVAR® for two to eight weeks. In these studies, OPTIVAR® was more effective than its vehicle in relieving itching associated with allergic conjunctivitis.

Last updated on RxList: 8/5/2008

To prevent contaminating the dropper tip and solution, care should be taken not to touch any surface, the eyelids, or surrounding areas with the dropper tip of the bottle or single-use container. Keep bottle tightly closed when not in use. Discard single-use container immediately after use. This product is sterile when packaged.

Patients should be advised not to wear a contact lens if their eye is red. OPTIVAR® should not be used to treat contact lens related irritation. The preservative in OPTIVAR® , benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling OPTIVAR® before they insert their contact lenses.

Last updated on RxList: 8/5/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

AZELASTINE DROPS - OPHTHALMIC

(azz-ELL-ust-een)

COMMON BRAND NAME(S): Optivar

USES: Azelastine is used to treat itching eyes caused by allergies (allergic conjunctivitis). This medication is an antihistamine. It works by blocking certain natural substances (such as histamines) responsible for allergic symptoms.

Do not use this medication to treat redness and irritation due to wearing contact lenses.

HOW TO USE: To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

Remove contact lenses before using this medication because it contains a preservative that can be absorbed by them. Wait at least 10 minutes after using this medication before putting the lenses back in. Do not wear contact lenses if your eyes are red.

Use this medication usually twice a day or as directed by your doctor. Tilt your head back, look upward and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed.

Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e.g., drops or ointments), wait at least 5 minutes before applying other medications. Use eye drops before eye ointments to allow the eye drops to enter the eye.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: This medication may temporarily sting or burn your eyes for a minute or two when applied. Temporary blurred vision, headache, or a bitter taste in your mouth may also occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: trouble breathing, eye pain.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using azelastine, tell your doctor or pharmacist if you are allergic to it; or to preservatives (e.g., benzalkonium chloride); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history.

Use caution engaging in activities requiring clear vision such as driving or using machinery because your vision may be temporarily blurred or unstable after applying this drug. Limit alcoholic beverages.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Do not share this medication with others.

Consult your doctor for additional ways to minimize and relieve your symptoms (e.g., avoiding irritants that trigger allergies, using cold compresses and lubricating eye drops).

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store upright and tightly closed between 36-77 degrees F (2-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.