NEOLAP OPHTHALMIC SOLUTION USP 0.2 %W/V

Indications

• Acute seasonal allergic conjunctivitis
• Perennial allergic conjunctivitis

Dosage

Children: Children aged 4 to 17 years: Apply 4 times a day. Consult product literature for specific dosing recommendations.

Adults: Apply twice daily for a maximum of 4 months, as per product literature.

Mechanism of action

Olopatadine acts as a selective antagonist at the histamine H1 receptors, preventing histamine from binding and activating the receptor. This inhibition blocks downstream signaling pathways that lead to inflammation, including the release of cytokines and other mediators from mast cells. Additionally, olopatadine stabilizes mast cells, preventing the immunologically-stimulated release of histamine and other pro-inflammatory substances, thereby mitigating the effects of allergic responses.

Pharmacodynamics

The drug effectively reduces inflammatory reactions mediated by histamine and other pro-inflammatory factors. By blocking histamine receptor activation and stabilizing mast cells, olopatadine mitigates symptoms associated with allergic conjunctivitis, such as ocular itching and tearing. It has demonstrated rapid onset of action, with effects observable within 5 minutes that can last up to 24 hours. As a non-sedating antihistamine, it provides relief without causing significant drowsiness.

Pharmacokinetics

Olopatadine is administered topically as eye drops, leading to localized effects with minimal systemic absorption. It exhibits a relatively rapid onset of action and a prolonged duration, allowing for twice-daily dosing. The pharmacokinetic profile indicates effective concentrations are achieved quickly, contributing to its rapid symptom relief. The drug's metabolism and elimination details are not specified, but its localized application suggests limited systemic exposure.

Adverse effects

• Eye discomfort
• Dry eye
• Headache
• Nausea
• Dizziness
• Corneal deposits
• Allergic dermatitis
• Vision disorders
• Malaise
• Palpitations
• Hypertension
• Myiasis
• Hyperhidrosis
• Facial swelling

Precautions

• Avoid sunlight exposure
• Discontinue use if evidence of corneal epithelial breakdown is present
• May mask symptoms of infection

Pregnancy

Olopatadine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when using olopatadine during breastfeeding, as it is not known if it is excreted in human milk.

Storage

Store at room temperature, away from light and moisture. Once opened, use within the time specified in the product literature.

Formulations

• {'formulation': 'Olopatadine hydrochloride', 'concentration': '1 mg/ml', 'form': 'Eye drops', 'volume': '5 ml'}
• {'formulation': 'Olopatadine hydrochloride', 'concentration': '1 mg/ml', 'form': 'Eye drops', 'volume': '10 ml'}

Mechanism of action

Histamine is a biogenic vasoactive amine that binds to its receptors, which are G-protein coupled receptors. Signaling through the histamine H1 receptor is thought to primarily promote the activation of inflammatory reactions, such as allergy, asthma, and autoimmune diseases. H1 receptor signaling activates the intracellular transcription factors, such as IP3, PLC, PKC, DAG, and intracellular calcium ions, which all work to activate further downstream cascades. Activated downstream cascades lead to the production of cytokines, the release of mast cell inflammatory mediators, synthesis of prostacyclins, activation of platelet factor, as well as the synthesis of nitric oxide, arachidonic acid, and thromboxane, which all contribute to inflammatory reactions. Olopatadine is an anti-allergic molecule that works via several mechanisms. As a mast cell stabilizer, it stabilizes rodent basophils and human conjunctival mast cells and inhibits the immunologically-stimulated release of histamine. Olopatadine acts as an antagonist at the histamine H1 receptors with high selectivity, which is explained by a unique receptor binding pocket that consists of the aspartate residue in the third transmembrane helix and other sites in the H1 receptor. Upon binding, olopatadine blocks the H1 receptor signaling pathway, inhibiting the release of inflammatory mediators, such as tryptase, prostaglandin D2, TNF-alpha, as well as pro-inflammatory cytokines. It also decreases chemotaxis and inhibits eosinophil activation. _In vitro_, olopatadine was shown to inhibit epithelial cell intercellular adhesion molecule-1 (ICAM-1), which promotes the recruitment of migrating pro-inflammatory mediators.

Pharmacodynamics

Inflammatory reactions in response to various stimuli are mediated by endogenous mediators and other pro-inflammatory factors. Histamine receptor activation and mast cell degranulation are primary mechanisms that cause inflammatory reactions such as ocular itching, hyperemia, chemosis, eyelid swelling, and tearing of seasonal allergic conjunctivitis. Olopatadine is an anti-allergenic molecule and mast cell stabilizer that inhibits the _in vivo_ type 1 immediate hypersensitivity reaction. By blocking the effects of histamine, olopatadine works to reduce the symptoms of allergies and inflammation at various sites of administration, including the eyes and nose. It has shown to exert antihistaminic effects in isolated tissues, animal models, and humans. Olopatadine also demonstrated dose-dependent inhibition of immunologically-stimulated release of histamine from rat basophilic leukemia cells and human conjunctival mast cells _in vitro_. Olopatadine has a relatively rapid onset of action and prolonged duration, where it was shown to mediate anti-histaminic effects at 5 minutes to 24 hours post-administration. While olopatadine is a non-sedating antihistamine agent, there have been reports of somnolence in some patients taking nasal olopatadine during clinical trials. Temporary blurred vision or other visual disturbances were observed following ophthalmic administration. Olopatadine has negligible effects on alpha-adrenergic, dopamine, muscarinic type 1 and 2, and serotonin receptors. In clinical trials, there was no evidence of any effect of olopatadine on QT prolongation was observed following intranasal administration.