Version May 2024
CNS stimulants, including cocaine hydrochloride, have a high potential for abuse and dependence.
Note: C-topical (cocaine 4% topical solution) has been discontinued in the United States for >1 year.
Anesthesia:
Intranasal:
Goprelto: Insert 2 cocaine solution soaked cottonoid pledgets (each pledget provides cocaine hydrochloride 40 mg) in each nasal cavity against septum; may leave on septum for up to 20 minutes; remove pledgets and continue with procedure. Maximum dose: 160 mg (4 pledgets) or 3 mg/kg of cocaine hydrochloride per procedure/surgery.
Numbrino: Insert 1 or 2 cocaine solution-soaked pledgets (each pledget provides cocaine hydrochloride 40 mg; recommended dose ranges from 40 to 160 mg depending on the nasal mucosal area and the procedure) in each nasal cavity; may leave in nasal cavity for up to 20 minutes; remove pledgets and continue with procedure. Maximum dose: 160 mg (4 pledgets) or 3 mg/kg of cocaine hydrochloride per procedure/surgery.
Topical (generic solution): Dosage depends on the area to be anesthetized, tissue vascularity, technique of anesthesia, and individual patient tolerance; the lowest dose necessary to produce adequate anesthesia should be used; concentrations of 1% to 10% may be used, with 4% being the most frequently used concentration (maximum total dose: 3 mg/kg or 200 mg) (Liao 1999; McGee 2010). Lasts for 30 minutes or longer depending on concentration and vascularity of anesthetized tissue. Use reduced dosages for children, elderly, or debilitated patients.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to severe impairment: No dosage adjustment may be necessary; however, use of a conservative initial dose should be considered with close monitoring for adverse effects.
Mild to severe impairment: Increased exposure was observed in patients with hepatic impairment in a pharmacokinetic study (Goprelto manufacturer's labeling); no dosage adjustment is necessary, although use with caution and with close monitoring for adverse effects is advised. The manufacturer's labeling for Goprelto also recommends not administering a second dose within 24 hours in patients with hepatic impairment. The manufacturer's labeling for Numbrino recommends avoiding use in patients with hepatic impairment (has not been studied).
Refer to adult dosing; use with caution.
(For additional information see "Topical cocaine: Pediatric drug information")
Note: C-topical (cocaine 4% topical solution) has been discontinued in the United States for >1 year. Approved ages for pediatric patients may vary among products; consult product-specific labeling.
Topical anesthetic: Note: Concentrations of 1% to 4% are used; use lowest effective dose; consider reduced dosages in children and debilitated patients; dose depends on patient tolerance, anesthetic technique, vascularity of tissue, and area to be anesthetized. Solutions >4% are not recommended due to increased risk and severity of systemic toxicities.
Maximum total dose:
Children: Topical: 1 to 2 mg/kg/dose (Liao 1999; McGee 2010).
Adolescents: Topical: 2 to 3 mg/kg or 200 mg, whichever is lower (Liao 1999; McGee 2010).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Use of the topical solution may produce systemic reactions from excessive and rapid absorption.
>10%: Cardiovascular: Hypertension (78%)
1% to 10%:
Cardiovascular: Prolonged QT interval on ECG (3%), sinus tachycardia (2%), tachycardia (5%)
Nervous system: Headache (3%)
Respiratory: Epistaxis (1%)
Frequency not defined:
Cardiovascular: Acute myocardial infarction (Lenders 2013; Makaryus 2006), increased blood pressure, increased heart rate
Nervous system: Drug abuse, drug dependence, nervousness, tonic clonic epilepsy
Neuromuscular & skeletal: Tremor
Ophthalmic: Corneal changes (epithelium sloughing), corneal ulcer
Postmarketing: Anxiety, atrial arrhythmia, ischemic heart disease, ventricular arrhythmia (Lenders 2013)
Hypersensitivity to cocaine, other ester-based anesthetics, or any component of the formulation
Concerns related to adverse effects:
• Seizures: Cocaine may lower seizure threshold. Risk may be higher in patients with a history of seizures or in patients with EEG abnormalities; monitor for seizure development.
Disease-related concerns:
• Cardiovascular disease: May increase blood pressure and heart rate for ≥60 minutes after topical administration; avoid use in patients with a history of uncontrolled hypertension, irregular heart rhythm, abnormal ECG, myocardial infarction, coronary artery disease, or congestive heart failure.
• Cocaine abuse: Use with caution in patients with a history of cocaine abuse.
Special populations:
• Acutely ill patients: Use with caution in acutely ill; reduce dose consistent with age and physical status.
• Debilitated patients: Use with caution in debilitated patients; reduce dose consistent with age and physical status.
• Older adult: Use with caution in the elderly; reduce dose consistent with age and physical status.
• Pediatric: Use with caution in children; reduce dose consistent with age and physical status. Note: Not all products are indicated for use in children; refer to the manufacturer's labeling.
• Pseudocholinesterase deficiency: The pharmacokinetics of topical cocaine have not been evaluated in patients with reduced cholinesterase activity. However, patients with reduced plasma cholinesterase activity (eg, genetic abnormalities of plasma cholinesterase, malignant tumors, severe liver or kidney disease, decompensated heart disease, infection, burns, anemia peptic ulcer, myxedema or pregnancy) may have reduced clearance and increased exposure to cocaine after topical administration; monitor closely for adverse effects (eg, headache, epistaxis, tachycardia, hypertension).
• Surgical patients: Consider anesthesia safe in a cocaine-abusing patient when obvious signs of intoxication are not exhibited (eg, tachycardia, hypertension, hyperthermia, ECG changes including QRS and QTc interval prolongation >500 msec) (Hill 2006).
Other warnings/precautions:
• Appropriate use: For topical use only. Limit to office and surgical procedures only. Not for ophthalmic use; causes sloughing of the corneal epithelium and pitting and ulceration of the cornea also has been reported. Use caution in patients with severely traumatized mucosa and sepsis in the region of the proposed application.
• Toxicology screening: Following administration, cocaine may be detected in plasma (≤1 week) and in urine (>1 week; includes cocaine and active metabolites).
• Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.
Note: C-topical (cocaine 4% topical solution) has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, External, as hydrochloride:
C-Topical: 4% (4 mL [DSC], 10 mL [DSC]) [contains quinoline yellow (d&c yellow #10), sodium benzoate]
Solution, Nasal, as hydrochloride [strength expressed as base]:
Goprelto: 4% [40 mg/mL] (4 mL) [contains quinoline yellow (d&c yellow #10), sodium benzoate]
Numbrino: 4% [40 mg/mL] (4 mL [DSC], 10 mL [DSC]) [contains quinoline yellow (d&c yellow #10), sodium benzoate]
Generic: 4% [40 mg/mL] (4 mL, 10 mL [DSC])
Yes
Solution (Cocaine HCl Nasal)
40 mg/mL (per mL): $66.15 - $107.70
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
C-II
Intranasal (Goprelto, Numbrino): For intranasal use only; place in the nasal cavity against the septum. Remove prior to procedure. Do not apply to damaged nasal mucosa. Do not substitute for other intranasal cocaine products.
Topical (generic solution): Use only on mucous membranes of the oral, laryngeal, and nasal cavities. Do not use on extensive areas of broken skin. May apply with cotton applicators, as a spray, or instill directly into mucous cavity.
Topical: Use only on mucous membranes of the oral, laryngeal, and nasal cavities; do not use on extensive areas of broken skin; do not apply commercially available products to the eye
Anesthesia:
Generic topical solution: Topical anesthesia for mucous membranes of the oral, laryngeal, or nasal cavities.
Goprelto, Numbrino: Topical anesthesia for mucous membranes when performing diagnostic procedures and surgeries on or through nasal cavities in adults.
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cannabinoid-Containing Products: Cocaine (Topical) may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Disulfiram: May increase the serum concentration of Cocaine (Topical). Risk X: Avoid combination
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Iobenguane Radiopharmaceutical Products: Cocaine (Topical) may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer cocaine until at least 7 days after each iobenguane dose. Risk X: Avoid combination
Ioflupane I 123: Cocaine (Topical) may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination
Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy
Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider therapy modification
Methemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: Cocaine (Topical) may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Reserpine: Cocaine (Topical) may enhance the adverse/toxic effect of Reserpine. Risk C: Monitor therapy
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Sympathomimetics: Cocaine (Topical) may enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: Cocaine (Topical) may enhance the adverse/toxic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Illicit cocaine use has been found to decrease sperm concentration and possibly sperm motility, leading to subfertility (Bracken 1990).
Cocaine crosses the placenta; repeated use leads to accumulation in the fetus.
Following maternal abuse of nonmedical products, cocaine rapidly crosses the placenta in concentrations equal to those in the mother. Adverse events occur in the fetus (eg, congenital malformations, preterm birth, low birthweight, small for gestational age infants), infant (neonatal abstinence syndrome), and mother (eg, preterm labor, placental abruption) (Fajemirokun-Odudeyi 2004; Gouin 2011). Prenatal exposure following illicit maternal use may also influence neurodevelopment. However, pregnancy outcomes following illicit cocaine exposure are also confounded by other factors (eg, social circumstances, polysubstance abuse) (Buckingham-Howes 2013; Lambert 2012).
Outcome data specific to medical use of cocaine following topical anesthesia in pregnant patients has not been located. However, due to the potential for adverse events, including decreased uterine blood flow or maternal cardiotoxicity (eg, in the presence of preeclampsia), other agents may be preferred (Arendt 2011; Harper 2006; Mokriski 1988).
Cocaine is present in breast milk.
Following maternal use of illicit intranasal cocaine, irritability, hypertension, tachypnea, tachycardia, and tremors were reported in a breastfed infant; cocaine was measurable in the infant serum and urine (Chasnoff 1987). Convulsions, diarrhea, and vomiting have also been reported in breastfed infants following maternal abuse.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer following prescribed use as a local anesthetic; breast milk should be expressed and discarded for 48 hours after nasal application.
Because the amount of cocaine present in breast milk will be highly variable following illicit use, breastfeeding should be interrupted until the mother can be evaluated (Cressman 2012; Reece-Stremtan 2015; Sarkar 2005).
Vital signs
Ester local anesthetic blocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction; interferes with the uptake of norepinephrine by adrenergic nerve terminals producing vasoconstriction
Following topical administration to mucosa:
Onset of action: ~1 minute.
Peak effect: ~5 minutes.
Duration (dose dependent): ≥30 minutes.
Absorption: Mucous membranes: Variable: ~23% to 35% when applied intranasally with pledget (Liao 1999; Numbrino prescribing information).
Distribution: Vd: 3,877 ± 1,266 L.
Protein binding: 84% to 92%, primarily to alpha-1 acid glycoprotein (AAG) and albumin.
Metabolism: Primarily metabolized and inactivated by nonenzymatic ester hydrolysis and hepatic carboxylesterase 1 to benzoylecgonine (inactive), and by plasma cholinesterase and hepatic carboxylesterase 2 to ecgonine methyl ester (inactive). Also undergoes hepatic CYP3A4 mediated N-demethylation to norcocaine (active).
Half-life elimination: 1 to 1.7 hours.
Excretion: Primarily urine (<5% to 10% as unchanged drug and metabolites).
Altered kidney function: AUC and Cmax were increased and clearance was decreased in patients with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2).
Hepatic function impairment: AUC increased from 79.2 ng.h/mL to 225 ng.h/mL and clearance decreased from 1,735 L/h to 629 L/h in normal and Child-Pugh class B patients, respectively. AUC increased from 79.2 ng.h/mL to 142 ng.h/mL and clearance decreased from 1,735 L/h to 959 L/h in normal and Child-Pugh class C patients, respectively.
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