Olopatadine

Class: Antiallergic Agents
- Histamine H1-receptor Antagonists
- Mast-cell Stabilizers
ATC Class: S01GX09
VA Class: OP900
Chemical Name: 11-[(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride
Molecular Formula: C₂₁H₂₃NO₃•HCl
CAS Number: 140462-76-6
Brands: Pataday, Patanase, Patanol

Relatively selective histamine H1-receptor antagonist and mast-cell stabilizer.

Uses for Olopatadine

Allergic Conjunctivitis

Used ophthalmically for symptomatic management of ocular itching associated with allergic conjunctivitis.

Seasonal Allergic Rhinitis

Used intranasally to provide symptomatic relief of seasonal allergic rhinitis (e.g., hay fever).

Provides symptomatic relief of nasal congestion, rhinorrhea, nasal itching, and sneezing.

Olopatadine Dosage and Administration

Administration

Administer intranasally or topically to the eye.

Intranasal Administration

Administer intranasally twice daily, using a metered-dose nasal spray pump. Avoid spraying into the eyes.

Before initial use, prime the pump by releasing 5 sprays or until a fine mist appears. If nasal spray has not been used for >7 days, reprime the pump by releasing 2 sprays.

To actuate the pump, hold the bottle in one hand; with forefinger and middle finger on the shoulders of the pump unit and the thumb on the bottom of the bottle, press down on the shoulders of the pump to produce a fine mist.

Prior to administration, gently blow the nose to clear nasal passages. To administer, close one nostril; then, with head tipped down (chin toward chest), insert nasal applicator ¼ to ½ inch into the other nostril, hold bottle vertically upright, and aim spray tip toward the cheek side of the nose (away from the center of the nose). While gently breathing in through the nose, press firmly and quickly on the pump to release the spray. Breathe out through the mouth.

Do not tip head back or blow the nose immediately after dosing; tipping head back may produce a bitter taste in the mouth.

Repeat procedure for the other nostril. Alternate nostrils between each actuation.

Following administration, wipe nasal applicator with a clean tissue and replace the blue plastic cap.

If nasal applicator becomes clogged, do not attempt to clean by inserting a sharp object. Instead, remove nasal applicator by gently pulling it upward; once removed, wash (while pointing nasal applicator downward) by running warm tap water for about one minute. Shake the applicator to remove any water and place the applicator back on the bottle. Prime by spraying 2 times or until a fine mist appears.

Discard after 240 sprays.

Ophthalmic Administration

Apply topically to the eye as an ophthalmic solution. Not for injection or oral use.

If more than one topical ophthalmic drug is used, administer the drugs at least 5 minutes apart.

Avoid contamination of the solution container.

Dosage

Available as olopatadine hydrochloride; dosage expressed in terms of olopatadine.

Nasal spray delivers about 665 mcg of olopatadine hydrochloride (equivalent to 600 mcg of olopatadine) per metered spray and about 240 metered sprays per 30.5-g bottle.

Pediatric Patients

Allergic Conjunctivitis

Ophthalmic

0.1% ophthalmic solution: In children ≥3 years of age, 1 drop in the affected eye(s) twice daily (at an interval of 6–8 hours).

0.2% ophthalmic solution: In children ≥2 years of age, 1 drop in the affected eye(s) once daily.

Once symptomatic improvement is established, continue therapy for as long as necessary to sustain improvement.

Seasonal Allergic Rhinitis

Intranasal

Children 6–11 years of age: 1 spray (600 mcg) in each nostril twice daily.

Children ≥12 years of age: 2 sprays (1200 mcg) in each nostril twice daily.

Adults

Allergic Conjunctivitis

Ophthalmic

0.1% ophthalmic solution: 1 drop in the affected eye(s) twice daily (at an interval of 6–8 hours).

0.2% ophthalmic solution: 1 drop in the affected eye(s) once daily.

Once symptomatic improvement is established, continue therapy for as long as necessary to sustain improvement.

Seasonal Allergic Rhinitis

Intranasal

2 sprays (1200 mcg) in each nostril twice daily.

Special Populations

Hepatic Impairment

Nasal spray: Dosage adjustment not necessary.

Hepatic Impairment

Nasal spray: Dosage adjustment not necessary.

Geriatric Patients

Nasal spray: Select dosage with caution. (See Geriatric Use under Cautions.)

Cautions for Olopatadine

Contraindications

• Ophthalmic solution: Known hypersensitivity to olopatadine or any ingredient in the formulation.

  Nasal spray: Manufacturer states none known.

Warnings/Precautions

Proper Handling to Avoid Contamination of Ophthalmic Solution

To avoid contamination of the dropper tip and solution, do not to touch the eye, eyelids, or surrounding areas with the dropper tip. Close container tightly when not in use.

Contact Lenses

Ophthalmic solution not indicated for contact lens-related ocular irritation. Do not wear contact lenses if eyes are red.

Remove soft contact lenses prior to administration of each ophthalmic dose, since benzalkonium chloride preservative may be absorbed by soft contact lenses; lenses may be reinserted after ≥10 minutes following administration.

Nasal Effects

Epistaxis, nasal ulcerations, and nasal septal perforations reported with nasal spray. Perform nasal examination prior to initiating intranasal olopatadine therapy to ensure absence of nasal diseases (other than allergic rhinitis). Perform nasal examinations periodically for signs of adverse effects on the nasal mucosa. If nasal ulcerations occur, consider discontinuing nasal spray.

CNS Effects

Somnolence reported with nasal spray. Avoid engaging in activities requiring complete mental alertness and motor coordination (e.g., driving or operating machinery) after administration of nasal spray. Concomitant use of nasal spray with alcohol or other CNS depressants may result in additive CNS depression; therefore, avoid such concomitant use.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats following oral administration.

Ophthalmic solution: Not known whether distributed into human milk following topical application to the eye. Use with caution.

Nasal spray: Use only if potential benefits outweigh risks.

Pediatric Use

0.1% ophthalmic solution: Safety and efficacy not established in children <3 years of age. Appears to be well-tolerated in children 3–16 years of age.

0.2% ophthalmic solution : Safety and efficacy not established in children <2 years of age.

Nasal spray: Safety and efficacy not established in children <6 years of age. In clinical studies, incidence of epistaxis was higher in children 6–11 years of age (5.7%) compared with adolescents or adults (3.2%).

Geriatric Use

Ophthalmic solution: No substantial differences in safety and efficacy relative to younger adults.

Nasal spray: Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. Other clinical experience has not identified differences in responses between geriatric and younger patients. Select dosage with caution because of age-related decreases in hepatic, renal, or cardiac function and potential for concomitant disease and drug therapy.

Common Adverse Effects

0.1% ophthalmic solution: Headache.

0.2% ophthalmic solution: Symptoms similar to cold syndrome, pharyngitis.

Nasal spray: In adults and children ≥12 years of age, bitter taste, headache, epistaxis, pharyngolaryngeal pain, postnasal drip, cough, urinary tract infection. In children 6–11 years of age, epistaxis, headache, upper respiratory tract infection, bitter taste, pyrexia, rash.

Interactions for Olopatadine

No formal drug interaction studies involving ophthalmic solution or nasal spray to date.

Does not inhibit in vitro metabolism of substrates of CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4.

Drugs Affecting or Metabolized by Hepatic Enzymes

Interactions with drugs that inhibit hepatic enzymes (e.g., CYP microsomal enzymes) unlikely because olopatadine is eliminated predominantly by renal excretion.

Potential for olopatadine and its metabolites to act as inducers of CYP isoenzymes not evaluated.

Protein-bound Drugs

Interactions with protein-bound drugs (e.g., possible displacement of other protein-bound drugs) unlikely because olopatadine is modestly protein bound.

Specific Drugs

Olopatadine Pharmacokinetics

Absorption

Bioavailability

Ophthalmic solution: Limited systemic exposure following topical application to the eye; plasma concentrations usually are undetectable.

Nasal solution: Peak plasma concentrations observed between 15 minutes and 2 hours following twice-daily intranasal administration. Average absolute bioavailability in healthy individuals is 57%.

Onset

Ophthalmic solution: Rapid onset; symptomatic relief of itching generally occurs within 30 minutes.

Nasal spray: Onset of action occurs after one day.

Duration

0.1% ophthalmic solution: Long duration (≥8 hours).

Special Populations

Nasal spray: Mean peak plasma concentrations following single intranasal doses not markedly different between healthy individuals and patients with mild, moderate, or severe renal impairment.

Distribution

Extent

Distribution into human ocular tissues and fluids not characterized.

Plasma Protein Binding

Approximately 55% bound (mainly albumin).

Elimination

Metabolism

Not extensively metabolized.

Following oral administration, unchanged olopatadine accounts for 77% of peak plasma total radioactivity, while metabolites (e.g., olopatadine N-oxide, N-desmethyl olopatadine) account for <6%.

Elimination Route

Eliminated principally by renal excretion; about 60–70% of systemically absorbed dose excreted in urine (86% as unchanged olopatadine) , and about 17% excreted in feces.

Half-life

Approximately 3 hours following topical application to the eyes.

8–12 hours following oral administration.

Stability

Storage

Nasal

Solution

4–25°C.

Ophthalmic

Solution

2–25°C.

Actions

• Inhibits type I immediate hypersensitivity reactions in vitro and in vivo.

• Suppresses the release of inflammatory mediators (e.g., histamine, prostaglandin D2, tryptase) in response to antigenic stimulation of human conjunctival mast cells in a dose-dependent manner.

• Decreases chemotaxis and inhibits eosinophil activation.

• Inhibits histamine-stimulated conjunctival vascular permeability response in a concentration-dependent manner.

• Potency is comparable to that of levocabastine and exceeds that of pheniramine or antazoline.

Advice to Patients

• Importance of learning and adhering to proper administration techniques to avoid contamination of the ophthalmic solution container.

• Importance of learning and adhering to proper techniques for priming and administration of nasal spray. Importance of alternating nostrils between each actuation. Importance of avoiding spraying into eyes.

• With ophthalmic solution, importance of removing soft contact lenses prior to administration of each dose. Delay reinsertion for ≥10 minutes after administration if eyes are not red; do not wear contact lenses if eye(s) are red. Not indicated for contact lens-related irritation.

• With ophthalmic solution, importance of administering different topical ophthalmic preparations at least 5 minutes apart.

• With nasal spray, risk of epistaxis and nasal ulcerations.

• With nasal spray, risk of somnolence. Avoid engaging in activities requiring complete mental alertness and motor coordination (e.g., driving or operating machinery) after administration. Avoid concomitant use with alcohol or other CNS depressants.

• Importance of patients informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name