Prilocaine hydrochloride shares the toxic potentials of local anesthetics, and the usual precautions of local anesthetic therapy should be observed.
A metabolite of prilocaine hydrochloride, probably an N-hydroxy metabolite of o-toluidine, may produce methemoglobin concentrations up to 15% and cyanosis, particularly when 600 mg or more of prilocaine hydrochloride is administered in adults. Other clinical symptoms of methemoglobinemia (namely, tachycardia, fatigue, headache, lightheadedness, and dizziness) may occur with higher doses. If the recommended dose of prilocaine hydrochloride has not been exceeded, symptoms of hypoxia are probably related to improper ventilation and should be treated with oxygen. If hypoxia persists following alveolar ventilation with oxygen, then methylene blue therapy should be instituted. IV infusion of methylene blue as a 1% solution in a dose of 1-2 mg/kg given over a 5-minute period will usually correct methemoglobinemia. In patients with anemia or cardiac failure in whom available oxygen is already at a minimum, the disadvantage of further hypoxia caused by the production of methemoglobinemia by prilocaine should be kept in mind.
Some commercially available formulations of prilocaine hydrochloride contain sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.
Prilocaine is contraindicated in patients with known hypersensitivity to local anesthetics of the amide type and in those with congenital or idiopathic methemoglobinemia.
There is limited experience with the use of prilocaine hydrochloride in children younger than 10 years of age. Animal studies to determine the carcinogenic and mutagenic potential of prilocaine have not been performed to date; however, long-term studies in rats and mice receiving 150-800 and 150-4800 mg/kg, respectively, of o-toluidine, a metabolite of prilocaine (corresponding to about 50-267 and 50-1600 times the usual human dose of prilocaine respectively) have shown the metabolite to be carcinogenic. Studies have not been performed to date to determine whether prilocaine has an effect on fertility.
Serious adverse effects (e.g., seizures, coma, irregular heart beat, respiratory depression) have been reported following topical application of local anesthetics to the skin. These events have occurred following application of extemporaneously prepared topical preparations containing high concentrations of anesthetics for cosmetic procedures and following use for indications approved by the US Food and Drug Administration (FDA).
Life-threatening adverse effects (e.g., irregular heart beat, seizures, breathing difficulties, coma, death) may occur when topical anesthetics are applied to a large area of skin, when the area of application is covered with an occlusive dressing, if a large amount of topical anesthetic is applied, if the anesthetic is applied to irritated or broken skin, or if the skin temperature increases (from exercise or use of a heating pad). When applied in such a manner, the amount of anesthetic that is absorbed systemically is unpredictable and the plasma concentrations achieved may be high enough to cause life-threatening adverse effects. Use of lidocaine gel has been investigated to reduce discomfort during mammography. During the study, the topical anesthetic was spread over a wide area of the chest and covered with an occlusive dressing. Whether such use could result in serious reactions has not been determined. Patients should speak with their clinician if they are considering using a topical anesthetic before obtaining a mammogram.
When a topical anesthetic is needed for a procedure, use of a preparation approved by the FDA has been recommended. A preparation containing the lowest concentration of anesthetic likely to be effective should be used; a small amount of topical anesthetic should be applied to the affected area for the shortest period necessary for the desired effect. The patient should apply the topical preparation as directed by a clinician, and should not apply the topical preparation to broken or irritated skin.