olopatadine intranasal/mometasone, intranasal (Rx)

1-10%

Dysgeusia (3%)

Epistaxis (1%)

Nasal discomfort (1%)

Contraindications

Hypersensitivity to any ingredients of nasal spray

Cautions

May cause somnolence; avoid operating heavy machinery or engaging in tasks that require mental alertness and coordination; caution patients against engaging in hazardous occupations requiring complete mental alertness and motor coordination (eg, operating machinery, driving a motor vehicle) after administration

Avoid concurrent use with alcohol or other central nervous system (CNS) depressants; additional reductions in alertness and additional impairment of CNS performance may occur

Glaucoma and/or cataracts may develop; closely monitor patients with vision changes or history of increased intraocular pressure, glaucoma, and/or cataracts

Hypersensitivity reactions, including wheezing, have occurred after nasal administration of mometasone; discontinue therapy if such reactions occur

Nasal corticosteroids may cause reduction in growth velocity when administered to pediatric patients; routinely monitor growth of pediatric patients; safety and efficacy not established in pediatric patients aged <12 years; not indicated for use in this population

Hypercorticism and adrenal suppression may occur when nasal corticosteroids are misused by taking higher-than-recommended dosages or in patients at risk for such effects

Local nasal adverse reactions

• Epistaxis, nasal ulceration, and nasal septal perforation reported
• Periodically monitor for signs of adverse effects on nasal mucosa
• Corticosteroids may impair wound healing; avoid use in patients who have experienced recent nasal septal ulcers, nasal surgery, or nasal trauma until resolved
• Localized Candida infections of the nose and pharynx have occurred from mometasone intranasal; if infection occurs, discontinue therapy, and treat appropriately; examine periodically for evidence of Candida infection if use is over several months or longer

Immunosuppression and risk of infections

• Immunosuppressive drugs (eg, corticosteroids) may increase susceptibility to infection
• Chickenpox and measles may be more serious or even fatal in susceptible children or adults using corticosteroids
• Risk of developing an infection based on therapy (ie, dose, duration, route), underlying disease, and/or prior corticosteroid use is unknown
• If exposed to chickenpox, prophylaxis with varicella zoster immune globulin may be indicated; if exposed to measles, prophylaxis with pooled IM immunoglobulin may be indicated; if chickenpox develops, consider treating with antiviral agents
• Use with caution in active or quiescent tuberculous infections of the respiratory tract, untreated local or systemic fungal or bacterial infections, systemic viral or parasitic infections, or ocular herpes simplex

Drug interaction overview

• CNS depressants

  • Avoid coadministration
  • Alcohol and other CNS depressants may potentiate somnolence and CNS depression

• Strong CYP3A4 inhibitors

  • Use with caution
  • Strong CYP3A4 inhibitors may inhibit metabolism of, and increase mometasone furoate plasma concentration, and potentially increase risk for adverse reactions

Pregnancy

Data are unavailable on use in pregnant females to evaluate for drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

Animal data

• Olopatadine: Oral administration of olopatadine to pregnant rats and rabbits caused a decrease in number of live fetuses at maternal doses 120x and 1600x the maximum recommended human daily intranasal dose (MRHDID) on a mg/m² basis, respectively
• Mometasone: Administration of mometasone to pregnant rats and rabbits caused increased fetal malformations and decreased fetal survival and growth at doses that produced exposures 1-16x the MRHDID on a mcg/m² or AUC basis

Lactation

Data are unavailable on presence of drug in human milk, effects on breastfed children, or on milk production

Other corticosteroids are excreted in human milk

Olopatadine has been identified in milk of nursing rats following oral administration; unknown whether topical nasal administration could result in sufficient systemic absorption to produce detectable quantities in human breast milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Olopatadine: Antihistamine (H1 antagonist); inhibits release of histamine from mast cells

Mometasone: Corticosteroid with potent anti-inflammatory properties; elicits effects on various cells, including mast cells and eosinophils; also elicits effects on inflammatory mediators (eg, histamine, eicosanoids, leukotrienes, cytokines)

Absorption

Peak plasma time: 1 hr

Peak plasma concentration

• Olopatadine: 19.8 ng/mL
• Mometasone: 9.92 pg/mL

AUC

• Olopatadine: 88.77 ng·hr/mL
• Mometasone: 58.4 pg·hr/mL

Distribution

Protein bound

• Olopatadine: 55% (binds primarily to serum albumin)
• Mometasone: 98-99%

Metabolism

Olopatadine

• Not extensively metabolized
• Metabolites: Olopatadine N-oxide and N-desmethyl olopatadine; at least 6 minor metabolites circulate in human plasma

Mometasone

• Metabolized by CYP3A4
• Metabolites: No major metabolites detectable in plasma; 6ß-hydroxy-mometasone furoate (minor metabolite)

Elimination

Half-life

• Olopatadine: 9 hr
• Mometasone: 18 hr

Excretion

• Olopatadine: 70% (urine [86% unchanged]); 17% (feces)
• Any absorbed drug is excreted as metabolites mostly via the bile, and to a limited extent, into the urine

Intranasal Preparation

Priming

• Shake bottle gently before each use
• Prime bottle before initial use by releasing 6 sprays
• Reprime bottle if unused for >14 days by spraying 2 sprays or until fine mist appears

Intranasal Administration

Gently blow nose to clear nostrils

Administer by intranasal route only

Hold 1 nostril closed with finger and insert spray pump tip into other nostril, pointing it slightly toward outside of nose, away from nasal septum

Avoid spraying into eyes or mouth

Do not blow nose for at least 15 minutes after administration

Storage

Store upright with dust cap on at room temperature (20-25ºC [68-77ºF]; excursions permitted at 15-30ºC [59-86ºF])

Do not freeze or refrigerate