Patanol

Patanol

olopatadine

Manufacturer:

Novartis Healthcare

Distributor:

Mundipharma
Full Prescribing Info
Contents
Olopatadine HCl.
Description
Each mL of OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution contains: Active: 1.11 mg Olopatadine Hydrochloride equivalent to 1 mg Olopatadine.
Preservative: Benzalkonium Chloride 100 mcg.
OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution is a colorless to pale yellow sterile ophthalmic solution containing olopatadine, a relatively selective H1-receptor antagonist and inhibitor of histamine release from the mast cell for topical administration to the eyes. Olopatadine hydrochloride is a white, crystalline, water-soluble powder with a molecular weight of 373.88.
Chemical Name: 11-[(Z)-3-(Dimethylamino)propylidene]-6-11-dihydrodibenz[b,e] oxepin-2-acetic acid hydrochloride.
Excipients/Inactive Ingredients: Disodium Phosphate Dodecahydrate; Sodium Chloride; Hydrochloric Acid and/or Sodium Hydroxide and Purified Water.
Action
Pharmacotherapeutic group: decongestants and antiallergics; other antiallergics. ATC code: S01X09.
Pharmacology: Pharmacodynamics: Olopatadine is a potent selective antiallergic/antihistaminic agent that exerts its effects through multiple distinct mechanisms of actions. It antagonizes histamine (the primary mediator of allergic response in humans) and prevents histamine induced inflammatory cytokine production by human conjunctival OLOPATADINE HCl epithelial cells. Data from in vitro studies suggest that it may act on human conjunctival mast cells to inhibit the release of pro-inflammatory mediators. In patients with patent nasolacrimal ducts, topical ocular administration of OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution was suggested to reduce the nasal signs and symptoms that frequently accompany seasonal allergic conjunctivitis. It does not produce a clinically significant change in pupil diameter.
Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H1-antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction. Olopatadine is devoid of effects on alpha-adrenergic, dopamine, muscarinic type 1 and 2, and serotonin receptors.
Following topical ocular administration in man, olopatadine was shown to have low systemic exposure. Two studies in normal volunteers (totaling 24 subjects) dosed bilaterally with olopatadine 0.15% ophthalmic solution once every 12 hours for 2 weeks demonstrated plasma concentrations to be generally below the quantitation limit of the assay (<0.5 ng/mL). Samples in which olopatadine was quantifiable were typically found within 2 hours of dosing and ranged from 0.5 to 1.3 ng/mL. The half-life in plasma was approximately 3 hours, and elimination was predominantly through renal excretion. Approximately 60-70% of the dose was recovered in the urine as parent drug. Two metabolites, the mono-desmethyl and the N-oxide, were detected at low concentrations in the urine.
Results from conjunctival antigen challenge studies demonstrated that OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution when subjects were challenged with antigen both initially and up to 8 hours after dosing, was significantly more effective than its vehicle in preventing ocular itching associated with allergic conjunctivitis.
Pharmacokinetics: Biotransformation/Metabolism: Studies have not been conducted to investigate the metabolism of olopatadine in ocular tissues since toxicology and clinical studies have shown it to be safe and effective. The major metabolites of Olopatadine following oral administration in humans are N-desmethyl olopatadine (M1) and olopatadine N-oxide (M3). N-desmethyl olopatadine (M1) is almost exclusively demethylated by the cytochrome P-450 isozyme 3A4 (CYP3A4). Olopatadine was not an inhibitor of cytochrome P-450 isozymes and therefore drug-drug interactions due to metabolic interactions were not expected.
In the humans after topical ocular administration, N-desmethyl metabolite of olopatadine (M1) was not quantifiable (≤0.050 ng/mL) in plasma sample in all subjects.
Excretion/Elimination: Studies have not been conducted to investigate the excretion of olopatadine in the urine or feces after topical ocular instillation. In rats after 14C oral administration, olopatadine was rapidly eliminated from the body primarily by urinary excretion and biotransformation (metabolism). In humans, urinary excretion of unchanged drug was the major route of elimination.
Linearity/Non-Linearity: In a single dose study, olopatadine showed a dose proportional increasing in exposure (Cmax and AUC) in ocular tissues after topical ocular instillation.
Indications/Uses
OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution is indicated for the temporary prevention of itching of the eye due to allergic conjunctivitis.
Dosage/Direction for Use
The recommended dose is one to two drops in each affected eye two times per day at an interval of 6 to 8 hours.
For topical ocular use only. Not for injection or oral use.
After bottle cap is removed, if tamper evident snap collar is loose, remove before using the product.
To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip. Keep the bottle tightly closed when not in use.
In case of concomitant therapy with other topical ocular medicines, an interval of 5 minutes should be allowed between successive applications. Eye ointments should be administered last.
Patients should be advised not to wear a contact lens if their eye is red.
Special Populations: OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution has not been studied in patients with renal or hepatic disease. However, no dosage adjustment is expected to be necessary in hepatic or renal impairment.
Overdosage
Due to the characteristics of this preparation, no toxic effects are to be expected with an ocular overdose of this product, nor in the event of accidental ingestion of the contents of one bottle.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Warnings
For topical use only. Not for injection. Patients should be instructed not to instill OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution while wearing contact lenses.
OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution contains benzalkonium chloride which may cause eye irritation and is known to discolor soft contact lenses. Avoid contact with soft contact lenses. Patients must be instructed to remove contact lenses prior to application of OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution and wait at least 15 minutes before reinsertion.
Special Precautions
Information for Patients: To prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use.
Effects on ability to drive and use machines: Olopatadine is a non-sedating anti-histamine. Temporary blurred vision after drop use, or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs after instillation, the patient must wait until the vision clears before driving or using machinery.
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 40 μl drop size, these doses were 78,125 and 31,250 times higher than the maximum recommended ocular human dose (MROHD). 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 to male and female rats at oral doses of 62,500 times MROHD level resulted in a slight decrease in the fertility index and reduced implantation rate; no effects on reproductive function were observed at doses of 7,800 times the maximum recommended ocular human use level.
Studies have not been performed to evaluate the effect of topical ocular administration of olopatadine on human fertility. Effects in non-clinical fertility studies in male and female animals were observed only at dosages considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. Olopatadine can be used by women of childbearing potential.
Use in Pregnancy: Pregnancy Category C. Olopatadine was found not to be teratogenic in rats and rabbits. However, rats treated at 600 mg/kg/day, 93,750 times the MROHD and rabbits treated at 400 mg/kg /day, or 62,500 times the MROHD, during organogenesis showed a decrease in live fetuses. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the embryo or fetus. There are no or limited amount of data from the use of ophthalmic olopatadine in pregnant women. Studies in animals with olopatadine have shown reproductive toxicity following systemic administration. Effects in non-clinical reproduction and developmental toxicity studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. Before prescribing olopatadine to a pregnant woman, a physician should weigh the benefit of administration to the woman to the risk of the fetus.
Use in Lactation: Olopatadine has been identified in the milk of nursing rats following oral administration. 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 OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution is administered to a nursing mother.
Studies in animals have shown that olopatadine is excreted in breast milk following oral administration. However, it is unknown whether olopatadine/metabolites are excreted in human milk following topical ocular administration.
Patients should be informed that antihistamines may affect the milk production of a nursing mother. Before prescribing olopatadine to a nursing mother, a physician should weigh the benefit of administration to the mother to the risk of the breastfeeding child.
Use in Children: Safety and effectiveness in pediatric patients below the age of 3 years have not been established.
Use In Pregnancy & Lactation
Use in Pregnancy: Pregnancy Category C. Olopatadine was found not to be teratogenic in rats and rabbits. However, rats treated at 600 mg/kg/day, 93,750 times the MROHD and rabbits treated at 400 mg/kg /day, or 62,500 times the MROHD, during organogenesis showed a decrease in live fetuses. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the embryo or fetus. There are no or limited amount of data from the use of ophthalmic olopatadine in pregnant women. Studies in animals with olopatadine have shown reproductive toxicity following systemic administration. Effects in non-clinical reproduction and developmental toxicity studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. Before prescribing olopatadine to a pregnant woman, a physician should weigh the benefit of administration to the woman to the risk of the fetus.
Use in Lactation: Olopatadine has been identified in the milk of nursing rats following oral administration. 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 OLOPATADINE HCl (PATANOL) 1 mg/mL (0.1%) Sterile Ophthalmic Solution is administered to a nursing mother.
Studies in animals have shown that olopatadine is excreted in breast milk following oral administration. However, it is unknown whether olopatadine/metabolites are excreted in human milk following topical ocular administration.
Patients should be informed that antihistamines may affect the milk production of a nursing mother. Before prescribing olopatadine to a nursing mother, a physician should weigh the benefit of administration to the mother to the risk of the breastfeeding child.
Adverse Reactions
Headaches were reported at an incidence of 7%. The following additional ocular and non-ocular adverse reactions were reported at an incidence of less than 5%.
Ocular: Burning or stinging, dry eye, foreign body sensation, hyperemia, keratitis, lid edema, and pruritus.
Non-ocular: Asthenia, cold syndrome, pharyngitis, rhinitis, sinusitis, and taste perversion.
The following adverse reactions have been reported during clinical studies with OLOPATADINE HCl (PATANOL) Sterile Ophthalmic Solution 0.1% and are classified according to the subsequent convention: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). Within each frequency-grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 1.)

Click on icon to see table/diagram/image

The following additional nonocular adverse reactions were reported at an incidence of less than 5%: Asthenia, cold syndrome, pharyngitis, and sinusitis.
Additional adverse reactions identified from post-marketing surveillance include the following. Frequencies cannot be estimated from the available data. Within each System Organ Class, adverse reactions are presented in order of decreasing seriousness. (See Table 2.)

Click on icon to see table/diagram/image
Drug Interactions
No clinically relevant interactions have been described.
Storage
Store at temperatures not exceeding 25°C.
ATC Classification
S01GX09 - olopatadine ; Belongs to the class of other ophthalmologic antiallergics.
Presentation/Packing
Eye drops 0.1% x 5 mL.
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