Cocaine: uses, dosing, side effects & brands

The most common adverse reactions (>0.5%) occurring in patients treated with GOPRELTO (cocaine hydrochloride) nasal solution 4% were headache and epistaxis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact LXO US., INC. at 1-844-800-8007 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial 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. GOPRELTO has been evaluated in four Phase 1 studies and one Phase 3 study, which included 647 adult subjects who received a single topical intranasal 160 mg dose (four pledgets), of GOPRELTO. The randomized, double-blind, controlled Phase 3 study was conducted in adult patients undergoing diagnostic procedures and surgeries on or through the mucous membranes of the nasal cavities, of which 278 received GOPRELTO (4% solution), 275 received cocaine hydrochloride solution 8%, and 95 received placebo. Safety was evaluated for up to 7 days after dosing. The most commonly reported adverse reactions (>1 patient) to occur in the Phase 3 study with GOPRELTO (4% solution) were headache and epistaxis. Two adverse reactions of headache were severe (Table 1). No premature discontinuations due to an adverse event,…

GOPRELTO is contraindicated in patients with a known history of hypersensitivity to cocaine hydrochloride, other ester-based anesthetics, or any other component of the product. Known hypersensitivity to cocaine hydrochloride, other ester-based anesthetics, or any other component of GOPRELTO. ( 4 )

Disulfiram : Increases plasma cocaine exposure. Avoid using GOPRELTO in patients taking disulfiram. ( 7 ) • Epinephrine, Phenylephrine : There have been reports of myocardial ischemia, myocardial infarction, and ventricular arrhythmias with concomitant use during nasal surgery. Avoid use of additional vasoconstrictor agents with GOPRELTO. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required. ( 5.3 , 7 ) 7.1 Disulfiram Published literature reported that disulfiram treatment increased plasma cocaine exposure, including both AUC and C max , by several fold after acute intranasal cocaine administration. Other literature reported that co-administration of disulfiram increased AUC of plasma cocaine by several fold after intravenous cocaine administration [see Clinical Pharmacology ( 12.3 )]. Avoid using GOPRELTO in patients taking disulfiram. Consider using other local anesthetic agents. 7.2 Epinephrine, Phenylephrine There are reports in the published literature of myocardial ischemia, myocardial infarction, and ventricular arrhythmias after concomitant administration of topical intranasal cocaine with epinephrine and phenylephrine during nasal and sinus surgery. Avoid use of additional vasoconstrictor agents such as epinephrine and phenylephrine with GOPRELTO during nasal and sinus surgery. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required [see Warnings and Precautions ( 5.3 ) ]. 7.3 Inhibitors of plasma cholinesterase (pseudocholinesterase) Cocaine has been described in literature to be primarily metabolized and inactivated by nonenzymatic ester hydrolysis and hepatic carboxylesterase, and also by plasma cholinesterase, hepatic carboxylesterase, and CYP3A4 [see Clinical Pharmacology ( 12.3 )]. The pharmacokinetics of GOPRELTO in patients with reduced plasma cholinesterase activity has not been studied. Plasma cholinesterase activity may be decreased by chronic administration of certain monoamine oxidase inhibitors, oral contraceptives, or glucocorticoids. It may also be diminished by administration of irreversible plasma cholinesterase inhibitors such as echothiophate, organophosphate insecticides, and certain antineoplastic agents. Patients with reduced plasma cholinesterase (pseudocholinesterase) activity may have reduced clearance and increased exposure of plasma cocaine after administration of GOPRELTO. Since cocaine is metabolized by multiple enzymes, the effect of reduced plasma cholinesterase activity on cocaine exposure may be limited. No dosage adjustment of GOPRELTO is needed in patients with reduced plasma cholinesterase. Monitor patients with reduced plasma cholinesterase activity for adverse reactions such as headache, epistaxis, and clinically-relevant increases in heart rate or blood pressure.