COCAINE Drug Interactions: What You Need to Know

INTERACTIONS 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 cocaine hydrochloride. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required. ( 5.3 , 7.2 ) Disulfiram: Disulfiram treatment increases plasma cocaine exposure. Avoid using cocaine hydrochloride in patients taking disulfiram. ( 7.3 ) CNS stimulants: Concomitant administration may result in nervousness, irritability, or possibly convulsions. ( 7.1 ) Cholinesterase inhibitors: Concomitant administration may increase the risk of cocaine toxicity. ( 7.4 ) Sympathomimetics, postganglionic blocking agents, and tricyclic antidepressants: Concomitant administration may increase the risk of cardiovascular adverse reactions. ( 7.5 , 7.6 ) Monoamine-oxidase inhibitors: Concomitant administration may potentiate the effects and toxicity of monoamine-oxidase inhibitors. ( 7.7 )

7.1 Central Nervous System Stimulants Concurrent use of other central nervous system stimulants with cocaine may result in excessive stimulation, leading to nervousness, irritability, or possibly convulsions, or cardiac arrhythmias.

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 cocaine hydrochloride during nasal and sinus surgery. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required.

7.3 Disulfiram Published literature reported that disulfiram treatment increased plasma cocaine exposure (AUC and C max ), by several folds after acute intranasal cocaine administration. Another literature reported that co-administration of disulfiram increased AUC of plasma cocaine by several folds after intravenous cocaine administration <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Avoid using cocaine hydrochloride in patients taking disulfiram. Consider using other local anesthesia.

7.4 Cholinesterase Inhibitors Cocaine has been described in literature to be primarily metabolized and inactivated by non-enzymatic ester hydrolysis and hepatic carboxylesterase, and also by plasma cholinesterase, hepatic carboxylesterase, and CYP3A4. The pharmacokinetics of cocaine hydrochloride 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, glucocorticoids, antimyasthenics (neostigmine), cyclophosphamide, and possibly thiotepa. 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 cocaine hydrochloride. Because cocaine is metabolized by multiple enzymes, the effect of reduced plasma cholinesterase activity on cocaine exposure may be limited. No dosage adjustment of cocaine hydrochloride is needed in patients with reduced plasma cholinesterase. Monitor patients with reduced plasma cholinesterase activity for adverse reactions such as clinically-relevant increases in heart rate or blood pressure.

7.5 Postganglionic Blocking Agents Agents such as reserpine potentiate cocaine-induced sympathetic stimulation; concurrent use may increase the risk of hypertension and cardiac arrhythmias that may be life-threatening.

7.6 Tricyclic Antidepressants Tricyclic antidepressants may increase the activity of the sympathetic nervous system, which may also be increased by administration of cocaine hydrochloride.

7.7 Monoamine-Oxidase Inhibitors Cocaine hydrochloride may potentiate the effects and toxicity of MAO inhibitors.

COCAINE HYDROCHLORIDE nasal solution 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 COCAINE HYDROCHLORIDE nasal solution. ( 4 )

AND PRECAUTIONS Cocaine hydrochloride is for TOPICAL USE ONLY. NOT FOR INJECTION OR OPHTHALMIC USE. ( 5 ) Seizures: Cocaine hydrochloride may lower the convulsive threshold. Monitor patients for development of seizures.

Blood

Pressure and Heart Rate Increases: Monitor vital signs, including heart rate and rhythm, in patients after receiving cocaine hydrochloride. Avoid use of cocaine hydrochloride in patients with a recent or active history of myocardial infarction, coronary artery disease, congestive heart failure, irregular heart rhythm, abnormal ECG, uncontrolled hypertension, or thyrotoxicosis.

5.1 Potential for Abuse and Dependence Central nervous system (CNS) stimulants, including cocaine hydrochloride, have a high potential for abuse and dependence <span class="opacity-50 text-xs">[see Drug Abuse and Dependence ( 9.2 , 9.3 )]</span> .

5.2 Seizures It has been reported in the literature that cocaine hydrochloride may lower the convulsive threshold. The risk may be higher in patients with a history of seizures or in patients with prior electroencephalogram (EEG) abnormalities without seizures, but has been reported in patients with no prior history or EEG evidence of seizures. Monitor patients for development of seizures.

5.3 Blood Pressure and Heart Rate Increases As reported in the literature, cocaine hydrochloride causes an increase in observed blood pressure and heart rate. In the Phase 3 clinical studies with cocaine hydrochloride, increases in blood pressure and heart rate were observed following pledget removal. Monitor for changes in vital signs, including heart rate and rhythm, after administration of cocaine hydrochloride. Avoid use of cocaine hydrochloride in patients with a history of myocardial infarction, coronary artery disease, congestive heart failure, irregular heart rhythm, abnormal ECG, or uncontrolled hypertension. Avoid use of additional vasoconstrictor agents such as epinephrine or phenylephrine with cocaine hydrochloride. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required. Although not reported in the cocaine hydrochloride clinical trials, myocardial infarction has been reported in the literature, and can occur when the drug has been used as recommended <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span> .

5.4 Toxicology Screening The time after cocaine administration for which cocaine and its metabolites can be detected in plasma and urine depends on the sensitivity of the utilized assay method. The cocaine hydrochloride and its metabolites in cocaine hydrochloride may be detected in plasma for up to one week after administration. Cocaine hydrochloride and its metabolites may be detected in urine toxicology screening for longer than one week after administration.

5.5 Known Hypersensitivity or Idiosyncrasy to the Sympathomimetic Amines Cocaine hydrochloride is contraindicated in patients with a known history of hypersensitivity to cocaine or to the components of the nasal solution. Cocaine is a sympathetic neuronal catecholamine reuptake inhibitor, which may potentiate the actions of concomitantly administered sympathomimetic amines.

5.6 Ophthalmic Use Cocaine hydrochloride is NOT FOR OPHTHALMIC USE. Cocaine can cause sloughing of the corneal epithelium and should not be used in the eyes. Pitting and ulceration of the cornea has been reported in the literature.