Cocaine is a local anesthetic of the ester type available in a topical solution for application on the mucous membranes of the oral, laryngeal, and nasal cavities. Cocaine may be abused and lead to physical dependence. Despite being an excellent local anesthetic, the risk of abuse and the intense local vasoconstriction it produces prevent cocaine from being more widely used clinically.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
Topical Solution
-Administer topically to mucous membranes of the laryngeal, nasal, and oral cavities.
-Apply as a spray, by instillation into a cavity, or by using cotton applicators or packs.
-Do not apply topical solutions to the eye. Do not administer parenterally.
Topical Nasal Solution (Goprelto)
-For intranasal use only. Do not apply to damaged nasal mucosa.
-Pour 4 mL (160 mg) of solution into a small container. Soak 4 cottonoid pledgets until the solution is fully absorbed.
-Place 2 soaked pledgets in each nasal cavity against the septum.
-Leave pledgets in place for up to 20 minutes before continuing with the procedure.
Topical Nasal Solution (Numbrino)
-For intranasal use only. Do not apply to damaged nasal mucosa.
-Stack 4 pledgets and apply 2 mL (80 mg) of solution to the top of the stacked pledgets. Turn the stacked pledgets over and apply 2 mL of solution to the other side. Ensure even distribution on all pledgets.
-Place 1 or 2 pledgets in each nasal cavity, for a maximum of 2 pledgets used per nostril.
-Leave pledgets in place for up to 20 minutes before continuing with the procedure.
Ophthalmic Administration
NOTE: Cocaine is not FDA-approved for ophthalmic administration.
-Extemporaneously prepared solutions have been applied topically to the eye. Because of its corneal and systemic toxicity, cocaine should only be applied to the eye by clinicians familiar with the risks associated with ophthalmic application of the drug and only for short periods of time.
During a phase 3 clinical trial of cocaine 4% and 8% topical nasal solutions, increases in blood pressure and heart rate were observed for 60 minutes or longer after pledge removal (n = 275). In another phase 3 study in which patients received a single application of 4% (n = 259) or 10% (n = 259) cocaine nasal solution or placebo (n = 128), the following adverse cardiac and vascular reactions were observed up to 7 days after dosing: hypertension (78%, 85%, and 66%, with 4%, 10%, and placebo solutions, respectively), tachycardia (5%, 11%, 1%), bradycardia (3%, 0.4%, 4%), and sinus tachycardia (2%, 4%, 0%). Individual patient response to cocaine varies widely, and toxic symptoms may occur idiosyncratically at low doses. Initial adverse cardiovascular effects (i.e., early stimulation) of cocaine include hypertension, premature ventricular contractions (PVCs), generalized vasoconstriction, and sinus tachycardia or ventricular tachycardia. Low doses can cause sinus bradycardia due to prolonged central vagal stimulation, but after moderate doses, the heart rate is increased by cocaine's central and peripheral effects on the sympathetic nervous system. Cardiac toxicities associated with advanced stimulation include cardiac arrhythmias, such as ventricular tachycardia and ventricular fibrillation, myocardial ischemia, myocardial infarction, and congestive heart failure. Late depressive cardiovascular effects include cardiac arrest and circulatory collapse. Cocaine nasal solution was associated with concentration-dependent QTc prolongation in a randomized, positive- and placebo-controlled, 4-period crossover study in 32 healthy subjects; however, the QTc prolongation observed was not clinically relevant. Based on the concentration-QTc relationship, the mean placebo corrected changes from the baseline QTcF (90% 2-sided upper confidence interval) were 4.7 milliseconds (6.2 milliseconds) and 15.4 milliseconds (20.1 milliseconds) at peak concentrations of 143 ng/mL (corresponds to 4% single dose, 160 mg) and 434 ng/mL (corresponds to 10% single dose, 400 mg), respectively. The estimates of the QTcF interval are confounded by increased heart rates. The mean placebo corrected changes from baseline heart rate (90% 2-sided upper confidence interval) were 12 (14) beats per minute and 20 (22) beats per minute for the 4% and 10% doses, respectively. In a phase 3 study in which patients received a single application of 4% (n = 259) or 10% (n = 259) cocaine nasal solution or placebo (n = 128), QRS prolongation occurred in 2%, 3%, and 2% of patients who received 4%, 10%, and placebo solutions, respectively. QT prolongation occurred in 3%, 4%, and 2% of patients who received 4%, 10%, and placebo solutions, respectively.
During a clinical trial of cocaine 4% and 8% topical nasal solution, epistaxis occurred in 1% of patients who received 4% solution (n = 278) and 1% who received 8% solution (n = 275). Individual patient response to cocaine varies widely, and toxic symptoms may occur idiosyncratically at low doses. Long-term or repeated intranasal use of cocaine can result in rebound hyperemia (nasal congestion) and chronic rhinitis, including sneezing or sniffling, which may lead to chronic sinusitis and increased risk of upper respiratory infection. With repeated or prolonged intranasal use, ischemic damage to the mucosa may occur and may lead to atrophy of the nasal mucosa, necrosis of septal tissue, ulcerative lesions of the nasal septum, and nasal septum perforation. Nasal bone osteomyelitis, fibrous tumor of the nasal cavity, oronasal fistula, and nasal destructive granuloma may also occur. Necrosis and osteomyelitis of the sinuses and the hard and soft palate have been reported.
During a clinical trial of cocaine 4% and 8% topical nasal solution, headache occurred in 3% of patients who received 4% solution (n = 278) and 2% who received 8% (n = 275). Severe headache occurred in 2 patients who received 4% solution. Anxiety occurred in 1% of patients who received 8% solution. Individual patient response to cocaine varies widely, and toxic symptoms may occur idiosyncratically at low doses. CNS toxicity is extremely common with cocaine use, and, initially, patients present with symptoms of CNS stimulation such as agitation, anxiety, apprehension, confusion, dizziness, emotional lability, a feeling of well-being or euphoria (or sometimes dysphoria), excitement, exophthalmos, formication (especially during withdrawal), hallucinations (may be auditory, gustatory, olfactory, tactile, or visual), urinary incontinence, fecal incontinence, irritability, lightheadedness, mydriasis, nervousness, preconvulsive movements, pressured speech, psychosis, restlessness, and/or generalized tics or twitching of small muscles, and headache (such as vascular headaches of withdrawal). Sudden onset of headache may indicate cerebral aneurysm rupture. CNS effects seen with advanced stimulation include delirium, malignant encephalopathy, hyperreflexia, intracranial bleeding, psychosis, seizures, and status epilepticus. Seizures may be life-threatening. In the general population, IV dosing or smoking crack cocaine is more likely to precipitate seizures, while intranasal use is more likely to cause seizures in patients with pre-existing seizure disorders. First-time use of cocaine can result in seizure, with single generalized motor seizures being most common, but multiple seizures and status epilepticus can occur immediately or within 2 hours of ingestion (coinciding with peak blood concentrations). Ischemic stroke has been associated with all forms of cocaine use. Late depressive effects include hyporeflexia, muscle paralysis, mydriasis, and death. Long-term use can result in agnosia, ageusia, dystonic reaction, tardive dyskinesia, chorea, and akathisia.
Individual patient response to cocaine varies widely, and toxic symptoms may occur idiosyncratically at low doses. Respiratory adverse reactions to cocaine include tachypnea, pulmonary edema, Cheyne-Stokes respiration, respiratory depression, apnea, and respiratory arrest. Pulmonary hypertension is associated with long-term use. Bronchoconstriction may occur, leading to worse or even fatal asthma exacerbations in asthmatic patients. Alveolar or pulmonary hemorrhage has been reported. Patients with acute pulmonary syndromes have presented with crack lung following inhalation of freebase cocaine, during which dyspnea, hypoxemia, diffuse alveolar infiltrates, and respiratory failure may occur.
Individual patient response to cocaine varies widely, and toxic symptoms may occur idiosyncratically at low doses. Cocaine causes hyperthermia, rigors (tremor), and diaphoresis by increasing muscular activity in the presence of vasoconstriction. Acute renal failure (unspecified) or renal infarction have been observed. Rhabdomyolysis can occur with myoglobinuria causing renal tubular obstruction.
Individual patient response to cocaine varies widely, and toxic symptoms may occur idiosyncratically at low doses. Gastrointestinal adverse reactions to cocaine include bowel ischemia and perforation, abdominal pain, nausea, and vomiting.
Application of cocaine topical solution to the eye has caused ocular irritation and sloughing of the corneal epithelium with clouding, pitting, and occasionally ulceration of the cornea.
Cocaine may cause a transient erythrocytosis, increasing blood viscosity while maintaining tissue oxygenation during vasoconstriction. Ten to 30 minutes following cocaine administration hemoglobin, hematocrit, and red blood cell counts have been found to increase compared to baseline, with no change in white blood cell counts. There may also be an increase in von Willebrand factor within 30 to 240 minutes following cocaine administration.
Chronic use of cocaine may lead to tolerance, dependence, and drug addiction. Tolerance refers to the diminishing effect of a drug after repeated administration at a given dosage, or the need for increasing doses to produce the desired effect. Many of the responses to cocaine exhibit tolerance. Cocaine does not produce physical dependence, since the drug does not have receptors on neurons that regulate peripheral physical functions like heart rate, bowel function, or blood pressure. However, psychological dependence, or the compulsive use of a drug to experience emotion, motivation, or behavior, does occur. A cocaine withdrawal syndrome is not observed with all patients and is more likely to include depressed mood, drug cravings, and other behavioral effects rather than physical symptoms on abrupt discontinuation of the drug.
Cocaine readily crosses the placenta and has been associated with premature labor, spontaneous fetal abortion, and a multitude of adverse effects on the fetus and infant. Cocaine causes placental vasoconstriction decreasing the blood flow to the fetus and may cause an increase in uterine contractility. Use of cocaine during pregnancy is associated with shorter gestation, premature delivery, spontaneous abortion, abruptio placentae, and fetal death. Infants who were exposed to cocaine in utero have exhibited depression of interactive behavior and a poor organizational response to environmental stimuli. Infants whose mothers used cocaine regularly during pregnancy are likely to be born having a birth weight and head circumference below the tenth percentile for their gestational age. Other fetal effects noted following maternal cocaine use include growth retardation, fetal distress, cerebrovascular accidents, and congenital anomalies. While the presence of a true neonatal abstinence syndrome has been debated (because cocaine dose not have effects on neurons that regulate physical functions), abnormal mild behavioral symptoms (e.g., irritability, muscular rigidity, tremulousness, increased startle response) are prevalent after birth in cocaine-exposed neonates, and GI symptoms (e.g., vomiting) have occurred.
Published animal studies suggest cocaine may pose a reproductive risk potentially leading to infertility by altering female reproductive hormone concentrations, disrupting the estrous cycle, and reducing ovulation at doses less than the human reference dose (HRD) of 58 mg (estimated amount absorbed from the 160 mg cocaine-soaked pledgets of cocaine topical nasal solution). Acute parenteral administration of cocaine to female rats increased luteinizing hormone and progesterone by approximately 2-fold at 0.3 to 2.5 times the HRD. Suppression of estrous/menstrual cycle and ovulation was observed in rats at 0.8 times the HRD and in monkeys at 0.3 times the human daily dose.
Cocaine may be detected in plasma for up to 1 week after topical application. Cocaine and its metabolites may be detected in urine toxicology screening for more than 1 week after application.
Cocaine is contraindicated in patients with known hypersensitivity to the drug, other ester-based anesthetics, or any other component of the product. Cautious use of cocaine may be warranted for patients with para-aminobenzoic acid, PABA hypersensitivity. Cocaine is an ester-bonded agent, and most literature reports of allergic reactions with local anesthetics have been to ester-bonded agents, which are derivatives of PABA. Cross-reactivity, as demonstrated by patch testing, does occur among members of the ester class.
Do not apply cocaine nasal solution (Goprelto) to damaged nasal mucosa or nasal trauma. Cocaine topical solutions should be used with extreme caution in patients with traumatized mucosa or infection in the region of intended application. Topical solutions of cocaine intended for use in anesthetizing the mucous membranes of the oral, laryngeal, and nasal cavities are NOT intended for systemic parenteral administration or ophthalmic administration.
Cocaine is readily absorbed from mucous membranes and can cause severe adverse effects, the drug should be used with caution, and careful attention should be given to dosage and administrative technique. Avoid unintended ocular exposure or accidental exposure to the mucus membranes. Resuscitative drugs and equipment for the treatment of severe adverse reactions should be readily available any time cocaine is used.
Avoid use of cocaine in patients with a history of uncontrolled hypertension, unstable angina, myocardial infarction, coronary artery disease, congestive heart failure, cardiac arrhythmias, or abnormal ECG. Use caution in patients with cardiac disease. Increases in blood pressure and heart rate have been observed more than 1 hour after exposure.
Cocaine is not recommended for use in young children because of variable absorption rates. If cocaine is used, a reduced dosage is recommended. Care should be taken during topical administration to avoid unintended exposure to mucus membranes in children, infants, and neonates that might result in significant absorption and an increased risk of side effects in children.
Cocaine is a strong CNS stimulant and is therefore subject to substance abuse and psychological dependence (i.e., drug addiction) or criminal diversion. Repeated topical application of cocaine can result in psychological dependance and tolerance; this drug is often abused by parenteral or intranasal administration or by inhalation (smoking). Drug addiction is characterized by compulsive use, use for non-medical purposes, and continued use despite harm or risk for harm. Patients with a previous history of substance abuse may be at increased risk of relapse if treated with cocaine.
Use cocaine with caution in patietns with a history of seizures a seizure disorder. Cocaine may lower the seizure threshold. The risk for seizures may be increased with patients with and without prior EEG abnormalities.
Cocaine is partially metabolized by hepatic enzymes. Monitor patients with hepatic disease for adverse reactions such as headache, epistaxis, and clinically relevant increases in heart rate or blood pressure after cocaine administration. Do not administer a second dose of cocaine nasal solution to patients with hepatic impairment within 24 hours of the first dose. Avoid use of Numbrino nasal solution in patients with hepatic impairment. Sufficient data are not available to guide dosing in these subjects.
Follow a conservative approach for dose initiation in patients with renal disease, including renal impairment or renal failure. Monitor patients with renal impairment for adverse reactions such as clinically relevant increases in heart rate or blood pressure.
Monitor patients with reduced cholinesterase activity for adverse reactions such as headache, epistaxis, and clinically relevant increases in heart rate or blood pressure after cocaine administration. Plasma cholinesterase activity may be decreased by chronic administration of certain medications, including irreversible plasma cholinesterase inhibitors. Patients with pseudocholinesterase deficiency may have reduced clearance and increased exposure of plasma cocaine after administration. Since cocaine is metabolized by multiple enzymes, the effect of reduced plasma cholinesterase exposure may be limited.
Use caution when determining the dose of cocaine for geriatric patients, considering the patient's age and physical status. Hypertension was observed in all geriatric patients (n = 13) who received cocaine nasal solution during clinical trials.
There are no available data on the use of topical cocaine solution from human pregnancies to inform a drug-associated risk of adverse developmental outcomes. Vertebral and rib anomalies were observed in the offspring of pregnant rabbits who were given cocaine 16 mg/kg subcutaneously (8 times the adult human AUC exposure following administration of pledgets containing 160 mg of cocaine) on gestation days 7 through 20. Maternal toxicity was also observed. No adverse effects occurred in offspring when pregnant rabbits were given cocaine 8 mg/kg (1.5 times the adult human AUC exposure following administration of pledgets containing 160 mg of cocaine) on gestation days 7 through 20. An increased incidence of pup mortality between postnatal days 0 to 4 and decreased pup body weights between postnatal days 1 to 21 were observed when pregnant rats were given cocaine 20 mg/kg (47 times the adult human AUC exposure following administration of pledgets containing 160 mg of cocaine) on gestation day 6 through lactation day 20. Maternal toxicity was not observed. No adverse effects on pre- or post-natal development occurred when pregnant rats were given cocaine 6 mg/kg (7 times the adult human AUC exposure following administration of pledgets containing 160 mg of cocaine) on gestation day 6 through lactation day 20. High exposure to cocaine during animal studies (approximately 17 to 32 times the adult human AUC following cocaine 160 mg pledget administration) resulted in adverse effects in offspring, including exencephaly, cerebral hemorrhage, hydrocephalus, immaturely developed cerebral ventricles, limb abnormalities, incomplete bone ossification, hydronephrosis, cryptorchidism, dilated or cystic ureters, cleft lip, and cleft palate. Developmental delays and altered spontaneous exploratory behavior were observed in rat pups born to mothers treated with cocaine 6 mg/kg intravenously (1.5 times a human reference dose [HRD] of 37.5 mg via 4% solution). Reduced fetal body and brain weights and alterations in fetal central neurotransmitter concentrations were noted after treatment of pregnant mice with cocaine 20 mg/kg (2.6 times the HRD) from gestation days 8 to 12 or 12 to 18. Chronic cocaine use or abuse can lead to major toxicity in the mother, fetus, and neonate. Cocaine causes placental vasoconstriction, decreasing the blood flow to the fetus, and may cause an increase in uterine contractility. Women who use cocaine during pregnancy are at significant risk for shorter gestation, premature delivery, spontaneous abortion, abruptio placentae, and fetal death. Intrauterine growth restriction and low birth weight (less than 2,500 g) are frequent adverse fetal consequences of in utero cocaine exposure. Congenital malformations, such as limb abnormalities, may occur. Maternal illicit use of cocaine during pregnancy has been epidemiologically associated with developmental delay in cocaine-exposed infants. Neonates exposed to cocaine in utero may experience withdrawal symptoms. The applicability of pregnancy outcome data for cocaine from studies of chronic abuse to a single topical exposure is limited.
Cocaine is excreted in breast milk at varying concentrations, and higher concentrations are expected in breast milk than maternal blood with systemic exposure. Breast-feeding immediately after topical administration of cocaine may have adverse effects on nursing infants. It is estimated that infant plasma concentrations that are approximately one-half the anticipated maximum maternal plasma concentrations may occur with administration of a clinical dose of 160 mg of cocaine topical nasal solution. Previous American Association of Pediatrics (AAP) recommendations considered cocaine to be contraindicated during breast-feeding. The metabolite, benzoylecgonine, can be detected in breast milk for up to 36 hours after the mother's last dose of cocaine. Infants exposed to cocaine through breast milk may develop symptoms of cocaine toxicity (i.e., irritability, tremulousness, increased startle response). Because of the potential for serious adverse effects in the nursing infant, discontinue breast-feeding during cocaine use. Pump and discard breast milk for 48 hours after topical cocaine exposure.
For local anesthesia and/or mucosal anesthesia prior to instrumentation or surgical procedures:
Topical dosage (crystals or flakes):
Adults: 400 mg, or lowest effective dose, topically.
-for anesthesia of accessible mucous membranes of the oral, laryngeal, and nasal cavities:
Topical dosage (solution):
Adults: 4% or 10% topically. Use the lowest effective dose. Max: 200 mg. In general, solutions more than 4% are not recommended due to increased risk of systemic toxicity.
Adolescents and Children: 4% or 10% topically. Use the lowest effective dose. Max: 2 to 3 mg/kg. The use of cocaine solution in young children is not advisable because of variable absorption rates. In general, solutions more than 4% are not recommended due to increased risk of systemic toxicity.
-for anesthesia of the mucous membranes when performing diagnostic procedures and surgeries on or through the nasal cavities:
Nasal dosage (Goprelto nasal solution):
Adults: 80 mg (2 soaked cottonoid pledgets) in each nasal cavity, for a total dose of 160 mg. Max: 3 mg/kg.
Nasal dosage (Numbrino nasal solution):
Adults: 40 to 160 mg intranasally, depending on the nasal mucosal area to be anesthetized and the procedure performed. Max: 80 mg (2 soaked cotton or rayon pledgets) per nasal cavity and total dose of 160 mg or 3 mg/kg.
For the treatment of epistaxis*:
Nasal dosage (4% solution):
Adults: Soak gauze or a cotton pledget in solution and place in the affected nostril(s) for at least 5 minutes.
Maximum Dosage Limits:
-Adults
200 mg total dose topically (generic solution); 160 mg or 3 mg/kg total dose nasally (Goprelto and Numbrino nasal solutions).
-Geriatric
200 mg total dose topically (generic solution); 160 mg or 3 mg/kg total dose nasally (Goprelto and Numbrino nasal solutions).
-Adolescents
3 mg/kg total dose topically (generic solution). Safety and efficacy have not been established for Goprelto and Numbrino nasal solutions.
-Children
3 mg/kg total dose topically (generic solution). Safety and efficacy have not been established for Goprelto and Numbrino nasal solutions.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Avoid use of Numbrino nasal solution in patients with hepatic impairment. Monitor patients with hepatic impairment for adverse reactions such as headache, epistaxis, and clinically relevant increases in heart rate or blood pressure after cocaine administration.
Patients with Renal Impairment Dosing
Follow a conservative approach for dose initiation in patients with renal impairment. Monitor patients with renal impairment for adverse reactions such as clinically relevant increases in heart rate or blood pressure.
*non-FDA-approved indication
Acebutolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Acetaminophen; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Aclidinium; Formoterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Acrivastine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Albuterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Albuterol; Budesonide: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Aliskiren; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Almotriptan: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Alprazolam: (Major) Avoid coadministration of alprazolam and cocaine due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with cocaine, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and cocaine is a weak CYP3A4 inhibitor. Coadministration with another weak CYP3A4 inhibitor, increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
Amiloride: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amiloride; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amitriptyline: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Amlodipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amlodipine; Atorvastatin: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amlodipine; Benazepril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amlodipine; Celecoxib: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amlodipine; Olmesartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amlodipine; Valsartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Amoxapine: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and amoxapine. Concurrent use of cocaine and cyclic antidepressants may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Amphetamine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Amphetamine; Dextroamphetamine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Angiotensin II receptor antagonists: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Angiotensin-converting enzyme inhibitors: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Aprepitant, Fosaprepitant: (Major) Use caution if cocaine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in cocaine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Cocaine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of cocaine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Cocaine is also a weak CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur. Information is not available regarding the use of aprepitant with weak CYP3A4 inhibitors.
Arformoterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Articaine; Epinephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Atazanavir: (Moderate) Caution is warranted when atazanavir is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when atazanavir is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4. (Moderate) Caution is warranted when cobicistat is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4. Cocaine is also an inhibitor of CYP2D6; cobicistat is a CYP2D6 substrates/inhibitors.
Atenolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Atenolol; Chlorthalidone: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Axitinib: (Moderate) Use caution if coadministration of axitinib with cocaine is necessary, due to the risk of increased axitinib-related adverse reactions. Axitinib is a CYP3A4 substrate and cocaine is a weak CYP3A4 inhibitor. Coadministration with a strong CYP3A4/5 inhibitor, ketoconazole, significantly increased the plasma exposure of axitinib in healthy volunteers. The manufacturer of axitinib recommends a dose reduction in patients receiving strong CYP3A4 inhibitors, but recommendations are not available for moderate or weak CYP3A4 inhibitors.
Azilsartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Azilsartan; Chlorthalidone: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Benazepril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Benazepril; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and cocaine may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and cocaine increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents, like cocaine, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Benzphetamine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Beta-adrenergic blockers: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Beta-agonists: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Betaxolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Bisoprolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Brimonidine; Timolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Bromocriptine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, sudden loss of vision, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, pseudoephedrine, amphetamines, and phentermine should be approached with caution.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Brompheniramine; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Brompheniramine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Budesonide; Formoterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Bumetanide: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Bupivacaine; Epinephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as cocaine. This is of particular concern in those with excessive cocaine use (i.e., cocaine addition). Patients should be closely monitored if this combination is necessary.
Bupropion; Naltrexone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as cocaine. This is of particular concern in those with excessive cocaine use (i.e., cocaine addition). Patients should be closely monitored if this combination is necessary.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with drugs that are known to lower seizure threshold such as cocaine.
Calcium-channel blockers: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Candesartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Candesartan; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Captopril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Captopril; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Carbidopa; Levodopa: (Major) Concomitant use of cocaine with levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) can result in an increase in the risk of developing cardiac arrhythmias. Levodopa should be used cautiously in patients who are known users of cocaine. Conversely, electrocardiographic monitoring should be considered when using cocaine in patients receiving levodopa.
Carbidopa; Levodopa; Entacapone: (Major) Concomitant use of cocaine with levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) can result in an increase in the risk of developing cardiac arrhythmias. Levodopa should be used cautiously in patients who are known users of cocaine. Conversely, electrocardiographic monitoring should be considered when using cocaine in patients receiving levodopa.
Cardiac glycosides: (Moderate) Monitor patients closely for cardiac arrhythmias during coadministration of cocaine and cardiac glycosides. Concomitant use of cardiac glycosides with drugs that have sympathomimetic activity, including cocaine, may increase the risk for arrhythmia.
Carteolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Carvedilol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Celecoxib; Tramadol: (Major) Cocaine use has been associated with precipitating seizures. Since tramadol decreases the seizure threshold, an increased risk of seizures may be seen with concomitant use of these two drugs.
Central-acting adrenergic agents: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Cetirizine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Chlorothiazide: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Chlorpheniramine; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Chlorpheniramine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Chlorthalidone: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Cholinesterase inhibitors: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Citalopram: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Clevidipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Clomipramine: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Clonidine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4. Cocaine is also an inhibitor of CYP2D6; cobicistat is a CYP2D6 substrates/inhibitors.
Cobimetinib: (Major) If concurrent use of cobimetinib and cocaine is necessary, use caution and monitor for increased cobimetinib-related adverse effects. Cobimetinib is a CYP3A substrate in vitro, and cocaine is a weak inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7). Simulations showed that predicted steady-state concentrations of cobimetinib at a reduced dose of 20 mg administered concurrently with short-term (less than 14 days) treatment of a moderate CYP3A inhibitor were similar to observed steady-state concentrations of cobimetinib 60 mg alone. The manufacturer of cobimetinib recommends avoiding coadministration with moderate to strong CYP3A inhibitors, and significantly reducing the dose of cobimetinib if coadministration with moderate CYP3A inhibitors cannot be avoided. Guidance is not available regarding concomitant use of cobimetinib with weak CYP3A inhibitors.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Codeine; Phenylephrine; Promethazine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Daratumumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Darunavir: (Moderate) Caution is warranted when darunavir is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4. Cocaine is also an inhibitor of CYP2D6; cobicistat is a CYP2D6 substrates/inhibitors. (Moderate) Caution is warranted when darunavir is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4. Cocaine is also an inhibitor of CYP2D6; cobicistat is a CYP2D6 substrates/inhibitors. (Moderate) Caution is warranted when darunavir is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4.
Desipramine: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Desloratadine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Desvenlafaxine: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as cocaine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Dexbrompheniramine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Dexmethylphenidate: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Dextroamphetamine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Dextromethorphan; Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as cocaine. This is of particular concern in those with excessive cocaine use (i.e., cocaine addition). Patients should be closely monitored if this combination is necessary.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Diazoxide: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Diethylpropion: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Digoxin: (Moderate) Monitor patients closely for cardiac arrhythmias during coadministration of cocaine and cardiac glycosides. Concomitant use of cardiac glycosides with drugs that have sympathomimetic activity, including cocaine, may increase the risk for arrhythmia.
Dihydroergotamine: (Contraindicated) Concomitant use of ergotamine with cocaine is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Diltiazem: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Diphenhydramine; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Disulfiram: (Major) Avoid concomitant use of cocaine and disulfiram. Consider using other local anesthetic agents. Disulfiram increased the Cmax and the AUC of cocaine by 2- to 3-fold and 3- to 6-fold, respectively, in a study of volunteers with cocaine-abuse histories who received intranasal cocaine after disulfiram. Disulfiram increased the heart rate response to cocaine compared to placebo. After administration of 2 mg/kg cocaine intranasally, disulfiram-treated patients also experienced increased diastolic and systolic blood pressures.
Dobutamine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Donepezil: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Donepezil; Memantine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Dopamine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Dorzolamide; Timolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Doxapram: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Doxepin: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Doxorubicin Liposomal: (Major) Cocaine is a potent CYP2D6 inhibitor and a mild inhibitor of CYP3A4; doxorubicin is a major CYP2D6 and CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6 and/or CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Increased side effects of doxorubicin, including myelosuppression and cardiotoxicity, might occur. Avoid coadministration of cocaine and doxorubicin when possible. Local, limited topical use of cocaine in medical procedures is not expected to produce interactions.
Doxorubicin: (Major) Cocaine is a potent CYP2D6 inhibitor and a mild inhibitor of CYP3A4; doxorubicin is a major CYP2D6 and CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6 and/or CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Increased side effects of doxorubicin, including myelosuppression and cardiotoxicity, might occur. Avoid coadministration of cocaine and doxorubicin when possible. Local, limited topical use of cocaine in medical procedures is not expected to produce interactions.
Dronabinol: (Major) Use caution with coadministration of dronabinol and cocaine, and monitor for additive hypertension, tachycardia, and possible cardiotoxicity, as well as an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol can be associated with hemodynamic instability (e.g., occasional hypotension, hypertension, syncope, and tachycardia) which may be enhanced when coadministered with drugs that have similar cardiac effects. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, <= 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm. Additionally, dronabinol is a CYP2C9 and 3A4 substrate; cocaine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Duloxetine: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as cocaine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Efgartigimod Alfa; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with cocaine may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Cocaine is a substrate and mild inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity.
Eletriptan: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Eliglustat: (Major) Coadministration of cocaine and eliglustat may result in increased plasma concentrations of eliglustat and an increased risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Cocaine is a strong inhibitor of CYP2D6 and a weak inhibitor of CYP3A4; eliglustat is a CYP2D6 and CYP3A substrate. FDA-approved labeling states the coadministration of a strong CYP2D6 inhibitor, such as cocaine, and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily in extensive or intermediate CYP2D6 metabolizers (EMs or IMs). In poor metabolizers (PMs), coadministration of weak a CYP3A inhibitor, such as cocaine, and eliglustat is not recommended. In addition, coadministration of eliglustat with both a strong or moderate CYP2D6 inhibitor (e.g., cocaine) and a strong or moderate CYP3A inhibitor is contraindicated in all patients. Although this interaction may be more likely to occur with the illicit systemic use of cocaine, cocaine is well absorbed topically from mucous membranes and, thus, may also pose risk when used as a topical anesthetic.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4. Cocaine is also an inhibitor of CYP2D6; cobicistat is a CYP2D6 substrates/inhibitors. (Moderate) Caution is warranted when elvitegravir; is administered with cocaine as there is a potential for elevated concentrations of elvitegravir. Clinical monitoring for adverse effects is recommended during coadministration. Cocaine is an inhibitor of CYP3A4. Elvitegravir is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with cocaine as there is a potential for elevated concentrations of both drugs. Clinical monitoring for adverse effects is recommended during coadministration. Both drugs are substrates and inhibitors of CYP3A4. Cocaine is also an inhibitor of CYP2D6; cobicistat is a CYP2D6 substrates/inhibitors. (Moderate) Caution is warranted when elvitegravir; is administered with cocaine as there is a potential for elevated concentrations of elvitegravir. Clinical monitoring for adverse effects is recommended during coadministration. Cocaine is an inhibitor of CYP3A4. Elvitegravir is a CYP3A4 substrate.
Enalapril, Enalaprilat: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Enalapril; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Ephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Ephedrine; Guaifenesin: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Epinephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Eplerenone: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Epoprostenol: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Eprosartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Eprosartan; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Ergotamine: (Contraindicated) Concomitant use of ergotamine with cocaine is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Ergotamine; Caffeine: (Contraindicated) Concomitant use of ergotamine with cocaine is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Escitalopram: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Esmolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Ethacrynic Acid: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Felodipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Fenfluramine: (Major) Do not exceed a maximum dose of fenfluramine 20 mg per day if coadministered with cocaine; for patients also receiving stiripentol plus clobazam, do not exceed a maximum dose of fenfluramine 17 mg per day. Concomitant use may increase fenfluramine plasma concentrations and the risk of adverse reactions. Fenfluramine is a CYP2D6 substrate and cocaine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased fenfluramine overall exposure by 81% and decreased norfenfluramine overall exposure by 13%.
Fenoldopam: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Fexofenadine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Fluoxetine: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Fluticasone; Salmeterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Fluticasone; Vilanterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Fluvoxamine: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Formoterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Formoterol; Mometasone: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Fosinopril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Frovatriptan: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Furosemide: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Galantamine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Glycopyrrolate; Formoterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Guaifenesin; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Guaifenesin; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Guanfacine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Hydralazine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Hydralazine; Isosorbide Dinitrate, ISDN: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Hydrochlorothiazide, HCTZ; Moexipril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Theoretically, concurrent use of methylene blue and cocaine may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and cocaine increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents, like cocaine, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cocaine, a CYP3A substrate, as cocaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloprost: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Imipramine: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Indacaterol; Glycopyrrolate: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Iobenguane I 123: (Major) Discontinue medications that decrease norepinephrine uptake, such as cocaine, for at least 5 biological half-lives prior to iobenguane I 123 administration. Consider medication tapering or additional supportive therapy as appropriate to minimize the risk for precipitating cocaine withdrawal symptoms. Medications that decrease the uptake of norepinephrine can cause false negative imaging results. Increasing the dose of iobenguane I 123 will not overcome any potential uptake limiting effect of this medication.
Iodixanol: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Ioflupane I 123: (Major) Allow at least 2 days to elapse before performing dopamine transporter (DAT) imaging with radiolabeled ioflupane in patients who used cocaine or have received cocaine anesthesia. Cocaine binds the dopamine transporter. Acute cocaine ingestion may interfere with striatal tracer binding and increase the risk for a false-positive scan. Chronic cocaine use may have a more complex effect on dopamine transporter expression which may impact imaging interpretation.
Iohexol: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Iomeprol: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Iopamidol: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Iopromide: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Ioversol: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Ipratropium; Albuterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Irbesartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Irbesartan; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with cocaine may result in increased serum concentrations of both drugs. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of the hepatic isoenzyme CYP3A4; cocaine is a substrate and inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Isoflurane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including cocaine. The combination may also result in an increased risk of QT prolongation.
Isoproterenol: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Isosorbide Dinitrate, ISDN: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Isosorbide Mononitrate: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Isradipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Labetalol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as cocaine. Concomitant use of cocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with cocaine systemically as concurrent use may increase lemborexant exposure and the risk of adverse effects. The relatively low plasma concentrations of cocaine resulting from topical or nasal solutions are not expected to raise significant drug-drug interaction concerns. Recreational use of cocaine, however, should be avoided by the patient. Lemborexant is a CYP3A4 substrate; cocaine is reported to be a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Levalbuterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Levamlodipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Levobunolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Levodopa: (Major) Concomitant use of cocaine with levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) can result in an increase in the risk of developing cardiac arrhythmias. Levodopa should be used cautiously in patients who are known users of cocaine. Conversely, electrocardiographic monitoring should be considered when using cocaine in patients receiving levodopa.
Levomilnacipran: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as cocaine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Levothyroxine: (Moderate) The concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
Levothyroxine; Liothyronine (Porcine): (Moderate) The concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
Levothyroxine; Liothyronine (Synthetic): (Moderate) The concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
Lidocaine; Epinephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Linezolid: (Major) Linezolid is an antibiotic which is a reversible, non-selective inhibitor of MAO. Administration of an indirect-acting sympathomimetic, like cocaine, to patients receiving a MAOI may invoke a hypertensive reaction. In general, traditional MAO inhibitors should be discontinued for 10 days prior to elective surgery with general anesthetics or spinal anesthesia if possible.
Liothyronine: (Moderate) The concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
Lisdexamfetamine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Lisinopril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Lisinopril; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Loop diuretics: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Lopinavir; Ritonavir: (Moderate) Concurrent use of cocaine with ritonavir may result in elevated plasma concentrations of cocaine and ritonavir. Cocaine is a substrate/inhibitor of CYP3A4 and an inhibitor of CYP2D6; ritonavir is a substrate/inhibitor of both these enzymes. While single uses of topical cocaine for local anethesia would not be expected to have clinically significant interactions, users of systemic cocaine could experience adverse events.
Loratadine; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Losartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Losartan; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Maprotiline: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and maprotiline. Concurrent use of cocaine and cyclic antidepressants may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Mecamylamine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Metaproterenol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Methamphetamine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Theoretically, concurrent use of methylene blue and cocaine may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and cocaine increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents, like cocaine, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Methyldopa: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Methylene Blue: (Moderate) Theoretically, concurrent use of methylene blue and cocaine may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and cocaine increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents, like cocaine, with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Methylergonovine: (Contraindicated) Ergot alkaloids should not be administered with vasoconstrictors such as cocaine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Ergoloid mesylates preparations are not expected to interact with sympathomimetics because this compound does not possess the vasoconstrictor properties of other ergot alkaoloids.
Methylphenidate: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Metolazone: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Metoprolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Midodrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Milnacipran: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as cocaine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Minocycline: (Moderate) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
Minoxidil: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Mirtazapine: (Major) Although unlikely to occur with use of mirtazapine alone, there have been rare case reports of serotonin syndrome with the drug. It is likely that the activation of 5-HT1A receptors by mirtazapine, combined with coadministration of other medications that increase serotonin release, such as cocaine, could result in serotonin syndrome.
Moexipril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Monoamine oxidase inhibitors: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Nabilone: (Major) Concurrent use of nabilone with sympathomimetics like amphetamine or cocaine may result in additive hypertension, tachycardia, and possibly cardiotoxicity.
Nadolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Nanoparticle Albumin-Bound Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 if coadministration with cocaine is necessary. The dose of sirolimus may also need to be reduced with coadministration of cocaine. Monitor sirolimus serum concentrations as appropriate and watch for sirolimus-related adverse reactions with coadministration of cocaine. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; cocaine is a weak CYP3A inhibitor.
Naproxen; Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Naratriptan: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Nebivolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Nebivolol; Valsartan: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Nefazodone: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as nefazodone, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Symptoms may include mental status changes, diaphoresis, tremor, myoclonus, hyperreflexia or fever.
Neostigmine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Neostigmine; Glycopyrrolate: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Nicardipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
NIFEdipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Nimodipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent use of cocaine with ritonavir may result in elevated plasma concentrations of cocaine and ritonavir. Cocaine is a substrate/inhibitor of CYP3A4 and an inhibitor of CYP2D6; ritonavir is a substrate/inhibitor of both these enzymes. While single uses of topical cocaine for local anethesia would not be expected to have clinically significant interactions, users of systemic cocaine could experience adverse events.
Nisoldipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Nitrates: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Nitroglycerin: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Nitroprusside: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold, such as cocaine, should be carefully evaluated when considering intrathecal radiopaque contrast agentsl. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
Norepinephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Nortriptyline: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Olanzapine; Fluoxetine: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cocaine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cocaine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cocaine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and cocaine is a strong CYP2D6 inhibitor.
Olmesartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Olmesartan; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Olodaterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Paroxetine: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Perindopril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Perindopril; Amlodipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Perphenazine; Amitriptyline: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Pertuzumab; Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Phendimetrazine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Phenelzine: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Phenoxybenzamine: (Major) Phenoxybenzamine would likely antagonize the sympathomimetic effects of cocaine.
Phentermine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Phentermine; Topiramate: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Physostigmine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Pindolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Potassium-sparing diuretics: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Prilocaine; Epinephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Procarbazine: (Major) Patients taking procarbazine should not be given local anesthetics containing sympathomimetic vasoconstrictors; coadministration may invoke a severe hypertensive reaction. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
Promethazine; Phenylephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Propranolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Protriptyline: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Pseudoephedrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Pseudoephedrine; Triprolidine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Pyridostigmine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Quinapril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Racepinephrine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Ramipril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsades de pointes and should be used cautiously in combination with other drugs that also prolong the QT interval, including local anesthetics.
Ritonavir: (Moderate) Concurrent use of cocaine with ritonavir may result in elevated plasma concentrations of cocaine and ritonavir. Cocaine is a substrate/inhibitor of CYP3A4 and an inhibitor of CYP2D6; ritonavir is a substrate/inhibitor of both these enzymes. While single uses of topical cocaine for local anethesia would not be expected to have clinically significant interactions, users of systemic cocaine could experience adverse events.
Rituximab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Rivastigmine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Rizatriptan: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Sacubitril; Valsartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Salmeterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Selective serotonin reuptake inhibitors: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Serdexmethylphenidate; Dexmethylphenidate: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Serotonin norepinephrine reuptake inhibitors: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as cocaine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Serotonin-Receptor Agonists: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Sertraline: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Sevoflurane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including cocaine. The combination may also result in an increased risk of QT prolongation.
Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 if coadministration with cocaine is necessary. The dose of sirolimus may also need to be reduced with coadministration of cocaine. Monitor sirolimus serum concentrations as appropriate and watch for sirolimus-related adverse reactions with coadministration of cocaine. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; cocaine is a weak CYP3A inhibitor.
Sodium Oxybate: (Major) Sodium oxybate has the potential to induce seizures; it has been speculated that this effect may be mediated through the action of sodium oxybate at GABA receptors. Although convulsant effects occur primarily at high dosages, sodium oxybate should be used cautiously with drugs that are known to lower seizure threshold such as cocaine.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with cocaine. Cocaine may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Cocaine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with cocaine. Cocaine may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Cocaine is a weak CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as cocaine. Caution is recommended since this combination has not been evaluated. In addition, the noradrenergic effects of cocaine may increase the likelihood of an elevated blood pressure and heart rate, both of which have been associated with solriamfetol administration.
Spironolactone: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
St. John's Wort, Hypericum perforatum: (Major) St. John's wort, Hypericum Perforatum may reduce the neuronal uptake of monoamines and should be used cautiously with drugs with sympathomimetic-like actions, like cocaine.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Sumatriptan: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Sumatriptan; Naproxen: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Sympathomimetics: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
Tamoxifen: (Major) Monitor for decreased efficacy of tamoxifen if the patient uses cocaine. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Cocaine is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Tedizolid: (Moderate) Caution is warranted with the concurrent use of tedizolid and cocaine. Sympathomimetics, especially indirect-acting sympathomimetics like cocaine, are not generally recommended for use in patients receiving non-selective traditional MAO inhibitors. Tedizolid is an antibiotic which is a weak reversible, non-selective inhibitor of MAO. Administration of an indirect-acting sympathomimetic (e.g., those that cause release of norepinephrine) to patients receiving a MAOI may invoke a hypertensive reaction. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid, which is structurally similar to tedizolid, and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including cocaine.
Telmisartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Telmisartan; Amlodipine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Telmisartan; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Terbutaline: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Thiazide diuretics: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Thyroid hormones: (Moderate) The concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
Timolol: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Tiotropium; Olodaterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Torsemide: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Tramadol: (Major) Cocaine use has been associated with precipitating seizures. Since tramadol decreases the seizure threshold, an increased risk of seizures may be seen with concomitant use of these two drugs.
Tramadol; Acetaminophen: (Major) Cocaine use has been associated with precipitating seizures. Since tramadol decreases the seizure threshold, an increased risk of seizures may be seen with concomitant use of these two drugs.
Trandolapril: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Trandolapril; Verapamil: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Tranylcypromine: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Treprostinil: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Triamterene: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Triamterene; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with cocaine and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and cocaine is a weak CYP3A inhibitor.
Tricyclic antidepressants: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Trimipramine: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and tricyclic antidepressants (TCAs). Concurrent use of cocaine and TCAs may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with cocaine. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; cocaine is a weak CYP3A4 inhibitor.
Umeclidinium; Vilanterol: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Valsartan: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Valsartan; Hydrochlorothiazide, HCTZ: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Vasodilators: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Venlafaxine: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties such as cocaine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Verapamil: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as cocaine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored closely for toxicity.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and cocaine. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with cocaine, a mild CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Vortioxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vortioxetine with other drugs that have serotonergic properties such as cocaine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, vortioxetine and concurrent serotonergic agents should be discontinued.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with cocaine is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Cocaine is a weak CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Ziprasidone: (Moderate) Ziprasidone should be used cautiously with drugs that are known to lower seizure threshold such as cocaine. Also, ziprasidone has a risk for QT prolongation, and cocaine, if absorbed systemically, can sensitize the myocardium.
Zolmitriptan: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
Cocaine decreases nerve permeability to sodium. This stabilizes the nerve membrane, increasing the threshold of electrical excitability and inhibiting depolarization, and results in the failure to propagate an action potential and initiate or conduct nerve impulses. Direct nerve membrane penetration is necessary for effective anesthesia, which is achieved by applying cocaine directly to the area to be anesthetized. Unlike other local anesthetics, cocaine also affects the nervous system by potentiating catecholamines. Centrally, the actions of cocaine are presumed to include stimulation of presynaptic release of norepinephrine combined with inhibition of presynaptic reuptake of norepinephrine, dopamine, and serotonin. Peripherally, cocaine stimulates the presynaptic release of norepinephrine and inhibits neuronal reuptake of both norepinephrine and epinephrine. Norepinephrine acts on alpha-adrenergic receptors in blood vessels to produce vasoconstriction, which facilitates examination and surgery by reducing congestion, swelling, and bleeding at the site of application. The drug not only lessens sensitivity to pain and touch but, when applied to the nose or mouth, diminishes the acuity of taste and smell.
Cocaine is administered topically to mucosal surfaces. Cocaine is well absorbed from the mucous membranes. Plasma protein binding is 84% to 92%, binding primarily to alpha-1-acid glycoprotein and albumin. Cocaine rapidly crosses the blood-brain barrier. The apparent volume of distribution is 3,877 +/- 1,266 L after intranasal administration. Cocaine is rapidly and extensively metabolized to 3 principle metabolites, ecgonine methyl ester, norcocaine, and benzoylecgonine. Ecgonine methyl ester (EME) is produced by hydrolysis of cocaine through serum cholinesterases, plasma pseudocholinesterases, and hepatic enzymes; N-demethylation in the liver by CYP3A4 forms norcocaine; benzoylecgonine (BE) is formed by hydrolysis, both nonenzymatic and enzymatic, in the liver, plasma, and other tissues. Norcocaine is pharmacologically active, while EME and BE are inactive. Cocaine is excreted by the kidneys with less than 10% of the dose excreted unchanged in the urine. Urinary recoveries of cocaine, BE, and EME as a percentage of dose are approximately 0.1%, 2%, and 1%, respectively. The apparent clearance of cocaine after intranasal administration is 3,096 +/- 1,276 L/hour. The elimination half-life is approximately 1 to 1.7 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2D6
A minor route of elimination is N-demethylation through CYP3A4. Cocaine is a strong inhibitor of CYP2D6 and a weak inhibitor of CYP3A4.
-Route-Specific Pharmacokinetics
Topical Route
After intranasal application of 2, 40 mg pledgets of cocaine nasal solution applied to each nasal cavity (160 mg total dose) for 20 minutes, the mean (SD) cocaine Cmax was 43.2 (1.73) ng/mL in 74 healthy adults. The median (range) Tmax was 0.42 (0.25 to 1.75) hours after application. The estimated mean systemic absorption of cocaine was 23.44% of the topically applied dose after pledget administration of a single 160 mg total dose over 20 minutes in healthy adult subjects. Mean and median Cmax values were 142.68 ng/mL and 142.7 ng/mL, respectively. Median Tmax was 30 minutes. The onset of action of cocaine for topical anesthesia typically occurs within 1 minute of application. Maximum effects are seen within 5 minutes and the duration of action ranges from 30 to 60 minutes.
-Special Populations
Hepatic Impairment
Hepatic impairment (Child-Pugh Class B and C) had a minimal effect on cocaine Cmax. In moderately impaired subjects (Child-Pugh Class B) AUC increased more than 2-fold compared to subjects with normal hepatic function (79.2 ng x hour/mL to 225 ng x hour/mL), and clearance was reduced by more than half (1,735 L/hour to 629 L/hour). In severely impaired subjects (Child-Pugh Class C), AUC increased 80% compared to normal subjects (79.5 ng x hour/mL to 142 ng x hour/mL), and clearance was reduced by half (1,735 L/hour to 959 L/hour).
Renal Impairment
Mean AUC and Cmax were slightly higher, and clearance was slightly lower, in subjects with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2) compared to those with normal renal function.
Geriatric
Age had no impact on the pharmacokinetics of cocaine.
Gender Differences
The Cmax and AUC of topical cocaine was slightly greater in females than in males. Tmax and half-life are similar in males and females.
Obesity
Weight had no impact on the pharmacokinetics of cocaine.