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Adverse reactions may be due to high plasma levels as a result of excessive and rapid absorption of the drug. Reactions are systemic in nature and involve the central nervous system and/or the cardiovascular system. A small number of reactions may result from hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.

CNS reactions are excitatory and/or depressant, and may be characterized by nervousness, restlessness and excitement. Tremors and eventually clonictonic convulsions may result. Emesis may occur. Central stimulation is followed by depression, with death resulting from respiratory failure.

Small doses of cocaine (cocaine hydrochloride topical solution) slow the heart rate, but after moderate doses, the rate is increased due to central sympathetic stimulation.

Cocaine (cocaine hydrochloride topical solution) is pyrogenic, augmenting heat production in stimulating muscular activity and causing vasoconstriction which decreases heat loss. Cocaine (cocaine hydrochloride topical solution) is known to interfere with the uptake of norepinephrine by adrenergic nerve terminals, producing sensitization to catecholamines, causing vasoconstriction and mydriasis.

Cocaine (cocaine hydrochloride topical solution) causes sloughing of the corneal epithelium, causing clouding, pitting, and occasionally ulceration of the cornea. The drug is not meant for ophthalmic use.