Olopatadine is an ophthalmic and nasal selective antihistamine (H1-blocker) with mast cell stabilizing effects. The ophthalmic products are marketed for the prevention of ocular pruritus due to allergic conjunctivitis. The ophthalmic solution is available over-the-counter in strengths of 0.1%, 0.2%, and 0.7%. The nasal spray is available by prescription and is used for the relief of the symptoms of seasonal allergic rhinitis. The rhinitis guidelines strongly recommend intranasal antihistamines, such as olopatadine, as an initial treatment option for seasonal allergic rhinitis and as a first-line monotherapy option for patients with nonallergic rhinitis. They also recommend intranasal antihistamines as a first-line option for patients with intermittent allergic rhinitis. Intranasal antihistamines have a more rapid onset of action than intranasal corticosteroids and oral antihistamines do, are more effective than oral antihistamines in the control of nasal congestion, and provide a favorable safety profile.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Inhalation Administration
Intranasal Inhalation Administration
-To ensure the correct amount of medication is delivered, the unit must be primed before the initial use. Pointed away from the body, pump the activator 5 times or until a fine mist appears. If the unit has not been used for 7 days, re-prime by pumping twice or until a fine mist appears.
-Instruct the patient on the proper use of olopatadine nasal spray. Avoid spraying in the eyes.
-After administration, wipe the tip of the spray bottle with a clean tissue. Replace the cap.
-Discard after 240 sprays (enough for 30 days at the recommended dosage) have been used even though the bottle is not completely empty. The correct amount of medication cannot be assured after 240 sprays have been used.
-To avoid the spread of infection, do not use the sprayer for more than 1 person.
Ophthalmic Administration
-For topical application to the eye only.
-Take care to avoid contamination. Wash hands before and after use. Do not touch the tip of the dropper to the eye, fingertips, or other surface. Do not share ophthalmic drops between patients.
-Remove contact lenses before instilling drops. Instruct patients to wait at least ten minutes before reinserting contact lenses.
-If using other ophthalmic products, wait at least 5 to 15 minutes between each product.
-Remove cap. Hold bottle upside down between thumb and index finger.
-Tilt the head back slightly and pull the lower eyelid down with the index finger of the opposite hand to create a pocket between the eye and the lower eyelid.
-With the bottle positioned above the eye, gently squeeze the side of the bottle to dispense 1 drop.
-Keep head tilted backwards and close eyes for 2 to 3 minutes while gently pressing index finger on the inside corner of the eye.
In clinical trials, headache was one of the most commonly reported adverse reactions for both the ophthalmic solution (7% of subjects in 0.1% solution; and less than 5% in 0.2% solution) and the nasal spray (4.4% of subjects). Somnolence (drowsiness) (0.9% with nasal spray), fatigue (0.9% with nasal spray), and/or asthenia (less than 5% with ophthalmic solutions) have been reported infrequently. Advise patients to avoid driving or other hazardous tasks after olopatadine nasal administration until they are familiar with how this medication affects them.
Three placebo-controlled (vehicle nasal spray) long-term, 12-month trials have been conducted to evaluate an association between treatment with olopatadine nasal spray and nasal septum perforation. In the first trial, nasal septum perforations were reported in 1 patient who received olopatadine containing povidone and 2 patients who received the vehicle spray containing povidone. In the second trial of povidone-free olopatadine nasal spray, there were no reports of nasal septum perforation. In the third trial, 1 patient exposed to the 3.7 pH vehicle nasal spray (containing no povidone) reported a nasal septum perforation.
Dysgeusia (i.e., bitter taste) is a frequent adverse reaction reported with olopatadine nasal spray occurring in 12.8% of adults and children 12 years of age and older and 1% of children 6 to 11 years of age. Dysgeusia has also been reported with the ophthalmic solutions in 2 to 5% of patients.
Ocular adverse reactions associated with olopatadine ophthalmic solution include ocular irritation (burning or stinging), foreign body sensation, hyperemia, keratitis, blepharedema, ocular pruritus, blurred vision, conjunctivitis, and xerophthalmia. These reactions were reported in less than 5% of the patients. Abnormal sensation in the eye was reported by patients receiving olopatadine 0.7% ophthalmic solution.
Epistaxis was reported in 3.2% of patients in a 2-week olopatadine nasal spray trial, 25% of patients in a 12-month nasal spray trial, and 5.7% of patients in a safety trial of children 2 to 5 years old. Nasal ulceration occurred in 10% of patients treated with olopatadine nasal spray in one 12-month trial and resulted in therapy discontinuation in 0.4% of patients. The manufacturer recommends conducting a nasal examination prior to initiating and periodically during olopatadine nasal spray therapy to ensure that patients are free of nasal disease other than allergic rhinitis. Consider alternate therapy if nasal ulcerations develop. Other local effects associated with the use of olopatadine nasal spray include pharyngolaryngeal pain (2.2%), post-nasal drip (1.5%), rash (unspecified) (1.3%), rhinorrhea (4.5%), wheezing (3%), xerostomia (0.9%), nasopharyngitis (0.9%), and throat irritation (0.9%). Cold syndrome and pharyngitis were reported in approximately 10% of patients receiving olopatadine ophthalmic solution. Cough was reported in 1.4% and less than 5% of patients administered olopatadine nasal spray and ophthalmic solutions, respectively. Adverse effects reported in less than 5% of patients with the use of the ophthalmic solutions include rhinitis and sinusitis. Additionally, hyposmia and anosmia have been reported during the post approval use of the nasal spray.
In clinical trials, urinary tract infection was reported in 1.2% of adults and children 12 years of age and older that received olopatadine nasal spray. In a 2-week trial of children 6 to 11 years of age, upper respiratory tract infection was reported in 2.6% of patients, and fever was reported in 1.3% of patients receiving olopatadine nasal spray. Influenza was reported in 0.9% of adolescent patients 12 years and older. Flu syndrome and infection were reported in less than 5% of patients with the use of 0.2% olopatadine ophthalmic solution.
Depression and worsening of depression have been reported among patients using olopatadine nasal spray and nasal spray vehicle in a 12-month safety trial. Of the studied patients, 9 of 445 patients (2%) using olopatadine nasal spray reported depression symptoms; 3 patients were hospitalized. Five of the 445 patients (1.1%) using the nasal spray vehicle reported the same, and none were hospitalized. Two of the 3 hospitalized olopatadine-using patients had a pre-existing history of depression.
Sixty-six children 2 to 5 years of age were given olopatadine nasal spray (1 spray per nostril twice daily) to assess safety in this population. The most common adverse event reported was diarrhea, which occurred in 9.1% of patients. Diarrhea was reported in less than 1% of older children ages 6 to 11 years. Nausea was reported in less than 5% of patients with the use of olopatadine ophthalmic solution.
Back pain was reported in less than 5% of patients with the use of 0.2% olopatadine ophthalmic solution.
Olopatadine ophthalmic solution is formulated with the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Users of soft contact lenses should not administer olopatadine while wearing the lenses. Contact lenses may be inserted 10 minutes after instilling the drug. Do not use olopatadine to treat contact lens related ocular irritation. Avoid spraying olopatadine nasal spray in the eyes.
No overall differences in safety or effectiveness have been observed between the geriatric patients and younger patients receiving olopatadine ophthalmic solution (Patanol, Pataday) or olopatadine nasal spray; however, clinical studies have not included sufficient numbers of patients older than 65 years of age to determine whether they respond differently than younger patients.
Somnolence has been reported in patients using olopatadine nasal spray. Caution should be used when driving or operating machinery or participating in any activities requiring mental alertness.
Safe and effective use of ophthalmic olopatadine and intranasal olopatadine has not been established in neonates, infants, or children younger than 2 years and 6 years, respectively.
Patients using olopatadine nasal spray have reported epistaxis, nasal ulceration, and nasal perforation. Examine nasal mucosa prior to initiating and periodically during olopatadine nasal spray therapy to ensure patients are free of pre-existing or drug-induced nasal trauma or nasal septal perforation. Consider stopping treatment if the drug recipient develops nasal ulcerations.
Depression and worsening of depression have been reported among patients using olopatadine nasal spray and nasal spray vehicle in a 12-month safety trial. Of an undisclosed number of studied patients, 9 using olopatadine nasal spray reported depression symptoms and 3 patients were hospitalized. Five patients using the nasal spray vehicle reported the same and none were hospitalized. Two of the 3 hospitalized olopatadine-using patients had a pre-existing history of depression. The likelihood of a drug-event relationship has not been released. Screen and monitor patients accordingly.
No adequate and well-controlled studies have been conducted to evaluate the use of olopatadine during human pregnancy; however, published data from postmarketing use of antihistamines with similar mechanisms of action to olopatadine have not identified a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. In animal studies, a decrease in the number of live fetuses was observed in rabbits and rats at oral olopatadine doses approximately 88- and 100-times the maximum recommended human dose (MRHD) or 1,460- and 110-times the maximum recommended human daily intranasal dose (MRHDID), respectively. Additionally, maternal and fetal toxicities were observed in rats at drug concentrations 1,080- to 14,400-times the maximum recommended human ophthalmic dose (MRHOD) or 110- to 1,100-times the MRHDID. The use of olopatadine in pregnant women is only justified if the benefits outweigh the possible risks to the fetus.
Olopatadine may be taken during breast-feeding. There are no data on the presence of olopatadine in human milk, the effects on a breastfed infant, or the effects on milk production. Also, it is not known whether intranasal or topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk; however, it is unlikely that nursing infants would be exposed to clinically significant amounts via breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
For the treatment of the signs and symptoms of allergic conjunctivitis, including ocular pruritus:
Ophthalmic dosage (0.1% ophthalmic solution):
Adults: 1 drop in the affected eye(s) twice daily at an interval of 6 to 8 hours.
Children and Adolescents 2 to 17 years: 1 drop in the affected eye(s) twice daily at an interval of 6 to 8 hours.
Ophthalmic dosage (0.2% or 0.7% ophthalmic solution):
Adults: 1 drop in the affected eye(s) once daily.
Children and Adolescents 2 to 17 years: 1 drop in the affected eye(s) once daily.
For the management of nasal symptoms of seasonal allergies and seasonal allergic rhinitis (e.g., rhinorrhea, sneezing, and nasal pruritus):
Nasal dosage (nasal spray solution):
Adults: 2 sprays (665 mcg/spray) in each nostril twice daily.
Adolescents and Children 2 to 17 years: 2 sprays (665 mcg/spray) in each nostril twice daily.
Children 6 to 11 years: 1 spray (665 mcg/spray) in each nostril twice daily.
Children 2 to 5 years*: 1 spray (665 mcg/spray) in each nostril twice daily has been evaluated in 66 children aged 2 to 5 years for safety; however, efficacy has not been established in this population.
Maximum Dosage Limits:
-Adults
2 drops/day 0.1% ophthalmic solution in each affected eye; 1 drop/day 0.2% or 0.7% ophthalmic solution in each affected eye; 4 nasal sprays/day in each nostril.
-Geriatric
2 drops/day 0.1% ophthalmic solution in each affected eye; 1 drop/day 0.2% or 0.7% ophthalmic solution in each affected eye; 4 nasal sprays/day in each nostril.
-Adolescents
2 drops/day 0.1% ophthalmic solution each affected eye; 1 drop/day 0.2% or 0.7% ophthalmic solution in each affected eye; 4 nasal sprays/day in each nostril.
-Children
12 years: 2 drops/day 0.1% ophthalmic solution each affected eye; 1 drop/day 0.2% or 0.7% ophthalmic solution in each affected eye; 4 nasal sprays/day in each nostril.
6 to 11 years: 2 drops/day 0.1% ophthalmic solution each affected eye; 1 drop/day 0.2% or 0.7% ophthalmic solution in each affected eye; 2 nasal sprays/day in each nostril.
2 to 5 years: 2 drops/day 0.1% ophthalmic solution in each affected eye; 1 drop/day 0.2% or 0.7% ophthalmic solution in each affected eye. Safety and efficacy have not been established for the nasal spray; however, 2 nasal sprays/day in each nostril has been studied.
younger than 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
*non-FDA-approved indication
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Olopatadine exhibits two distinct mechanisms of action. It inhibits histamine release from mast cells and is a relatively selective antagonist of H1-receptors. As a result, olopatadine prevents type 1 immediate hypersensitivity reactions. Topical ocular administration relieves the ocular pruritus associated with allergic conjunctivitis. Intranasal administration relieves symptoms associated with seasonal allergic rhinitis. Olopatadine does not act upon alpha-adrenergic, dopaminergic, type 1 or type 2 muscarinic, or serotonergic receptors.
Olopatadine is administered topically to the eye or intranasally. Olopatadine exhibits moderate protein binding (approximately 55% in human serum) and is mainly bound to serum albumin. Olopatadine is not extensively metabolized. After oral administration, at least 6 minor metabolites are present in human plasma. Excretion is primarily renal with approximately 60 to 70% of a dose recovered in the urine. Of the recovered drug-related material within the first 24 hours, approximately 86% is unchanged olopatadine. The plasma elimination half-life of olopatadine is 8 to 12 hours. Olopatadine exhibits linear pharmacokinetics over a large dose range.
Affected cytochrome (CYP) 450 isoenzymes and drug transporters: None
-Route-Specific Pharmacokinetics
Other Route(s)
Intranasal Route
After twice daily intranasal administration to adults, peak plasma concentrations (Cmax) were reached within 30 to 60 minutes. The mean steady-state Cmax was 16 +/- 8.99 ng/mL. The average absolute bioavailability of intranasal olopatadine is 57%.
Ophthalmic Route
Following topical ocular administration, plasma concentrations of olopatadine were in the range of 0.5 to 1.3 ng/mL within 2 hours of dosing and were undetectable after 2 weeks of dosing in normal volunteers.
-Special Populations
Renal Impairment
The mean Cmax values for olopatadine after single intranasal doses were not different between healthy subjects and patients with mild, moderate, or severe renal impairment. Patients with severe renal impairment (CrCl less than 30 mL/min/1.73m2) had a two-fold higher mean plasma AUC(0 to 12), however, peak steady state concentrations in these patients were approximately 10-fold lower than those concentrations observed after oral doses of 20 mg twice daily, which were safe and well-tolerated. Therefore, the manufacturer concludes that no dosage adjustment is necessary for intranasal administration in patients with renal impairment.
Pediatrics
The pharmacokinetics of olopatadine nasal spray were studied in 42 children 6 to 11 years of age and 66 children 2 to 5 years of age; the children received 1 spray in each nostril twice daily for a minimum of 14 days. The mean Cmax in children 6 to 11 years was 15.4 +/- 7.3 ng/mL, and in children 2 to 5 years, the mean Cmax was 13.4 +/- 4.6 ng/mL.
Geriatric
The effects of age on olopatadine pharmacokinetics has not been adequately studied.