Cyklx

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Description for Cyklx

CYKLX (articaine ophthalmic solution) 8% contains articaine, an amide local anesthetic. CYKLX is an aseptically prepared, sterile, clear and colorless solution for topical ophthalmic use with a pH range of 4.5- 5.0.

The chemical name of articaine hydrochloride is methyl 4-methyl-3-[2-(propylamino)propionamido]-2-thiophenecarboxylate, monohydrochloride and the molecular formula is C₁₃H₂₀N₂O₃S·HCl. The molecular weight of articaine hydrochloride is 320.84 g/mol, or 283.374 g/mol as articaine (free base). Articaine hydrochloride is represented by the following structural formula:

Each mL of CYKLX contains 80 mg of articaine (equivalent to 90.2 mg articaine hydrochloride) as the active ingredient. Inactive ingredients: boric acid, edetate disodium dihydrate, glacial acetic acid, mannitol, sodium acetate trihydrate, water for injection. CYKLX does not contain an antimicrobial preservative.

ADVERSE REACTIONS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In controlled trials, the most common adverse reaction with CYKLX was instillation site pain reported in 24.5% (70/286) of subjects, compared to 6.9% (14/203) of subjects in the placebo group.

Drug Interactions for Cyklx

No information provided

Warnings for Cyklx

Included as part of the PRECAUTIONS section.

Precautions for Cyklx

For Topical Ophthalmic Use

CYKLX is not for injection or intraocular administration.

Corneal Injury Due to Insensitivity

Patients should not touch the eye for at least 10 to 20 minutes after using CYKLX as accidental injuries can occur due to insensitivity of the eye.

Corneal Opacification

Prolonged use of topical ocular anesthetics may produce permanent corneal opacification and ulceration with accompanying visual loss.

Risk of Contamination

Do not touch the dropper tip to the eye, eyelids, or any other surface as this may contaminate the solution.

For Administration by Healthcare Provider

CYKLX is indicated for administration under the direct supervision of a healthcare provider. CYKLX is not intended for patient self-administration.

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long term studies in animals have not been performed to evaluate carcinogenic potential.

Mutagenesis

Articaine hydrochloride did not show any potential to cause mutagenicity or genetic toxicity in five standard tests, including three in vitro tests (the nonmammalian Ames test, the mammalian Chinese hamster ovary chromosomal aberration test, and a mammalian gene mutation test with articaine HCl) and two in vivo mouse micronucleus tests (one with articaine and epinephrine 1:100,000 and one with articaine HCl alone).

Impairment of Fertility

Subcutaneous administration of articaine and epinephrine (1:100,000) produced no adverse effects on fertility in rats at doses up to 80 mg/kg/day (approximately 80 times the MRHOD based on body surface area).

OVERDOSAGE

Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution.

Contraindications for Cyklx

CYKLX is contraindicated in patients with known hypersensitivity to any component of this preparation.

Clinical Pharmacology for Cyklx

Mechanism of Action

Articaine hydrochloride is an amide local anesthetic. Local anesthetics block the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of the affected nerve fibers.

Pharmacokinetics

Following ocular administration of CYKLX (2 drops), the geometric mean (geometric CV%) maximum plasma concentration (C_max) is 5.4 ng/mL and total systemic exposure (AUC) is 5.1 ng*hr/mL.

Absorption

Articaine median (min, max) time to maximum plasma concentration (T_max) is 0.25 hour (0.25 – 1.03 hour)

Distribution

Approximately 60 to 80% of articaine HCl is bound to human serum albumin and γglobulins at 37°C in vitro.

Elimination

Articaine estimated elimination half-life is 1.5 hours with an apparent clearance of 872 L/hr.

Metabolism
Articaine HCl is metabolized by plasma carboxyesterase to its primary metabolite, articainic acid, which is inactive. In vitro studies show that the human liver microsome P450 isoenzyme system metabolizes approximately 5% to 10% of available articaine with nearly quantitative conversion to articainic acid.

Excretion
Articaine is excreted primarily through urine with 53-57% of the administered dose eliminated in the first 24 hours following submucosal administration. Articainic acid is the primary metabolite in urine. A minor metabolite, articainic acid glucuronide, is also excreted in urine.

PATIENT COUNSELING INFORMATION

Eye Care Precaution

Do not touch the dropper tip to the eye, eyelids, or to any other surface as this may contaminate the product.

Advise patients to avoid touching the eye for at least 10 to 20 minutes after using CYKLX as accidental injuries can occur due to insensitivity of the eye.