Olopatadine (ophthalmic)

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# Overview
Olopatadine (ophthalmic) is a antihistamine and H1 receptor antagonist that is FDA approved for the treatment of ocular itching associated with allergic conjunctivitis.   Common adverse reactions include blurred vision, burning sensation in eye and dry eye.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- PAZEO is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

### Dosing Information
- The recommended dosage of PAZEO is to instill one drop in each affected eye once a day.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Olopatadine (ophthalmic) in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Olopatadine (ophthalmic) in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Olopatadine (ophthalmic) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Olopatadine (ophthalmic) in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Olopatadine (ophthalmic) in pediatric patients.

# Contraindications
There is limited information regarding Olopatadine (ophthalmic) Contraindications in the drug label.

# Warnings
- As with any eye drop, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle to prevent contaminating the tip and solution. Keep bottle tightly closed when not in use.
- Patients should not wear a contact lens if their eye is red. The preservative in PAZEO solution, 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 five minutes after instilling PAZEO before they insert their contact lenses.

# Adverse Reactions

## Clinical Trials Experience
- Because clinical trials are conducted under widely 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.
- In a randomized, double-masked, vehicle-controlled trial, patients at risk for developing allergic conjunctivitis received one drop of either PAZEO (N=330) or vehicle (N=169) in both eyes for 6 weeks.  The mean age of the population was 32 years (range 2 to 74 years).  Thirty-five percent were male.  Fifty-three percent had brown iris color and 23% had blue iris color.  The most commonly reported adverse reactions occurred in 2-5% of patients treated with either PAZEO or vehicle. These events were blurred vision, dry eye, superficial punctate keratitis, dysgeusia and abnormal sensation in eye.

## Postmarketing Experience
There is limited information regarding Olopatadine (ophthalmic) Postmarketing Experience in the drug label.

# Drug Interactions
There is limited information regarding Olopatadine (ophthalmic) Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA):
- There are no adequate or well-controlled studies with PAZEO in pregnant women. Olopatadine caused maternal toxicity and embryofetal toxicity in rats at levels 1,080 to 14,400 times the maximum recommended human ophthalmic dose (MRHOD).  There was no toxicity in rat offspring at exposures estimated to be 45 to 150 times that at MRHOD.  Olopatadine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- In a rabbit embryofetal study, rabbits treated orally at 400 mg/kg/day during organogenesis showed a decrease in live fetuses. This dose is 14,400 times the MRHOD, on a mg/m2 basis.
- An oral dose of 600 mg/kg/day olopatadine (10,800 times the MRHOD) was shown to be maternally toxic in rats, producing death and reduced maternal body weight gain.  When administered to rats throughout organogenesis, olopatadine produced cleft palate at 60 mg/kg/day (1080 times the MRHOD) and decreased embryofetal viability and reduced fetal weight in rats at 600 mg/kg/day. When administered to rats during late gestation and throughout the lactation period, olopatadine produced decreased neonatal survival at 60 mg/kg/day and reduced body weight gain in offspring at 4 mg/kg/day.  A dose of 2 mg/kg/day olopatadine produced no toxicity in rat offspring.  An oral dose of 1 mg/kg olopatadine in rats resulted in a range of systemic plasma area under the curve (AUC) levels that were 45 to 150 times higher than the observed human exposure  following administration of the recommended human ophthalmic dose.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Olopatadine (ophthalmic) in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Olopatadine (ophthalmic) during labor and delivery.

### Nursing Mothers
- Olopatadine has been identified in the milk of nursing rats following oral administration. Oral administration of olopatadine doses at or above 4 mg/kg/day throughout the lactation period produced decreased body weight gain in rat offspring; a dose of 2 mg/kg/day olopatadine produced no toxicity.  An oral dose of 1 mg/kg olopatadine in rats resulted in a range of systemic plasma area under the curve (AUC) levels that were 45 to 150 times higher than the observed human exposure  following administration of the recommended human ophthalmic dose. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when PAZEO is administered to a nursing mother.

### Pediatric Use
- The safety and effectiveness of PAZEO have been established in pediatric patients two years of age and older.  Use of PAZEO in these pediatric patients is supported by evidence from adequate and well-controlled studies of PAZEO in adults and an adequate and well controlled study evaluating the safety of PAZEO in pediatric and adult patients.

### Geriatic Use
- No overall differences in safety and effectiveness have been observed between elderly and younger patients.

### Gender
There is no FDA guidance on the use of Olopatadine (ophthalmic) with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Olopatadine (ophthalmic) with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Olopatadine (ophthalmic) in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Olopatadine (ophthalmic) in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Olopatadine (ophthalmic) in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Olopatadine (ophthalmic) in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Ophthalmic

### Monitoring
There is limited information regarding Olopatadine (ophthalmic) Monitoring in the drug label.

# IV Compatibility
There is limited information regarding the compatibility of Olopatadine (ophthalmic) and IV administrations.

# Overdosage
There is limited information regarding Olopatadine (ophthalmic) overdosage.  If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

# Pharmacology

## Mechanism of Action
- Olopatadine is a mast cell stabilizer and a histamine H1 antagonist. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated.

## Structure
- PAZEO is a sterile ophthalmic solution containing olopatadine, which is a mast cell stabilizer, for topical administration to the eyes. Olopatadine hydrochloride is a white, crystalline, watersoluble powder with a molecular weight of 373.88 and a molecular formula of C21H23NO3HCl.
- The chemical structure is presented below:

## Pharmacodynamics
There is limited information regarding Olopatadine (ophthalmic) Pharmacodynamics in the drug label.

## Pharmacokinetics
- In healthy subjects, topical ocular dosing of 1 drop of PAZEO once daily for 7 days into both eyes  resulted in mean  SD (range) steady state plasma olopatadine Cmax and AUC0-12  of 1.6  0.9 ng/mL (0.6 to 4.5 ng/mL) and 9.7  4.4 ng*h/mL (3.7 to 21.2 ng*h/mL), respectively.  The olopatadine Cmax and AUC0-12 after the first dose were similar to those measured on day 7 in these subjects, suggesting that there was no systemic accumulation of olopatadine after repeated topical ocular dosing with PAZEO.  The median (range) time to achieve peak olopatadine concentrations (Tmax) was 2.0 hours (0.25 to 4 hours). The mean  SD (range) elimination halflife of olopatadine was 3.4  1.2 hours (2 to 8 hours). N-oxide olopatadine (M3) was detected during the first 4 hours after bilateral topical ocular dosing of PAZEO in approximately half of the subjects and in less than 10% of the total plasma samples collected, at concentrations not exceeding 0.121 ng/mL on day 1 and 0.174 ng/mL on day 7. None of the plasma samples from these subjects had mono-desmethyl olopatadine (M1) concentrations that were above the lower limit of quantitation (0.05 ng/mL) of the PK assay.

## Nonclinical Toxicology

### Carcinogenesis & Mutagenesis & Impairment Of Fertility
- Olopatadine administered orally was not carcinogenic in mice and rats in doses up to 500 mg/kg/day and 200 mg/kg/day, respectively.  Based on a 35 L drop size and a 60 kg person, these doses are approximately 4,500 and 3,600 times the MRHOD, on a mg/m2 basis.
- No mutagenic potential was observed when olopatadine was tested in an in vitro bacterial reverse mutation (Ames) test, an in vitro mammalian chromosome aberration assay or an in vivo mouse micronucleus test.
- Olopatadine administered at an oral dose of 400 mg/kg/day (approximately 7,200 times the MRHOD) produced toxicity in male and female rats, and resulted in a decrease in the fertility index and reduced implantation rate.  No effects on reproductive function were observed at 50 mg/kg/day (approximately 900 times the MRHOD).

# Clinical Studies
- The efficacy of PAZEO was established in two randomized, double-masked, placebo-controlled, conjunctival allergen challenge (CAC) clinical studies in patients with a history of allergic conjunctivitis (Studies 1 and 2).
- In Study 1, patients were randomized to receive one of the following study treatments:  PAZEO, PATADAY, or vehicle ophthalmic solutions.  In Study 2, patients were randomized to receive one of the following study treatments:  PAZEO, PATADAY, PATANOL, or vehicle ophthalmic solutions.
- Patients were evaluated with an ocular itching severity score ranging from 0 (no itching) to 4 (incapacitating itch) at several time points after CAC administration.  Table 1 displays the mean ocular itching severity scores after ocular administration of a specific antigen using the CAC model in Studies 1 and 2, respectively.  A one unit difference compared to vehicle is considered a clinically meaningful change in the ocular itching severity score.
- PAZEO demonstrated statistically significantly improved relief of ocular itching compared to vehicle at 30-34 minutes, 16 hours, and 24 hours after study treatment.   PAZEO demonstrated statistically significantly improved relief of ocular itching compared to PATADAY at 24 hours after study treatment, but not at 30-34 minutes after study treatment.

# How Supplied
PAZEO (olopatadine hydrochloride ophthalmic solution) 0.7% is supplied in a white, oval, low density polyethylene DROP-TAINER*dispenser with a natural low density polyethylene dispensing plug and a white polypropylene cap. Tamper evidence is provided with a shrink band around the closure and neck area of the package.  PAZEO is supplied in a 4 mL bottle that contains 2.5 mL of olopatadine hydrochloride ophthalmic solution :
NDC 0065-4273-25

## Storage
- Storage: Store at 2C to 25C (36F to 77F).
- Keep bottle tightly closed when not in use.

# Images

## Drug Images

## Package and Label Display Panel
NDC 0065-4273-25
Pazeo- 
(olopatadine hydrochloride ophthalmic solution) 0.7%
2.5 mL
STERILE
Alcon 
a Novartis company

# Patient Counseling Information
- Advise patients to not touch dropper tip to eyelids or surrounding areas, as this may contaminate the dropper tip and ophthalmic solution.
- Advise patients not to wear contact lenses if their eyes are red. Advise patients that PAZEO should not be used to treat contact lensrelated irritation. Advise patients to remove contact lenses prior to instillation of PAZEO. The preservative in PAZEO solution, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted 5 minutes following administration of PAZEO.
Patents: 8,791,154
ALCON
ALCON LABORATORIES, INC.
Fort Worth, Texas76134 USA 
 2015 Novartis.
is a Trademark of Novartis

# Precautions with Alcohol
Alcohol-Olopatadine (ophthalmic) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- Pataday
- Pazeo

# Look-Alike Drug Names
There is limited information regarding Olopatadine (ophthalmic) Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price