cocaine (Rx)

>10%

Hypertension (78%)

1-10%

Tachycardia (5%)

Headache (3%)

Bradycardia (3%)

Sinus tachycardia (2%)

QT prolonged (3%)

QRS prolonged (2%)

Epistaxis (1%)

Postmarketing Reports

Nervous system disorders: Headache, seizure

Cardiac disorders: Hypertension, tachycardia, atrial and ventricular arrhythmias, myocardial ischemia and infarction

Psychiatric disorders: Anxiety

Contraindications

Hypersensitivity to cocaine, other ester-type local anesthetics, or other product ingredients

Cautions

CNS stimulants, including cocaine hydrochloride, have a high potential for abuse and dependence

May lower convulsive threshold; risk may be higher in patients with history of seizures or with prior EEG abnormalities without seizures, but has been reported in patients with no prior history or EEG evidence of seizures; monitor for development of seizures

Increases blood pressure and heart rate; monitor for changes in vital signs, including heart rate and rhythm; avoid with history of MI, CAD, CHF, arrhythmia, abnormal ECG, or uncontrolled hypertension

Not for ophthalmic use; can cause sloughing of the corneal epithelium; pitting and ulceration of the cornea reported

Toxicology screening

• The time after cocaine administration for which cocaine and its metabolites can be detected in plasma and urine depends on the sensitivity of the utilized assay method
• Plasma: May be detected for up to 1 week after administration
• Urine: May be detected >1 week after administration

Drug interaction overview

• Avoid use of additional vasoconstrictor agents (eg, epinephrine, phenylephrine); if unavoidable, prolonged vital sign and ECG monitoring may be required
• Cocaine is a sympathetic neuronal catecholamine reuptake inhibitor, which may potentiate the actions of concomitantly administered sympathomimetic amines
• Concurrent use of other CNS stimulants may result in excessive stimulation, leading to nervousness, irritability, or possibly convulsions, or cardiac arrhythmias
• Disulfiram treatment increases plasma cocaine exposure (AUC and Cmax), by several folds after acute intranasal or IV cocaine administration; avoid use in patients taking disulfiram
• Postganglionic blocking agents (eg, reserpine) potentiate cocaine-induced sympathetic stimulation; concurrent use may increase the risk of hypertension and cardiac arrhythmias that may be life-threatening
• Tricyclic antidepressants may increase activity of the sympathetic nervous system, which may also be increased by cocaine administration
• MAO inhibitor effects and toxicity may be potentiated by cocaine

• Cholinesterase inhibitors

  • Cocaine is primarily metabolized and inactivated by nonenzymatic ester hydrolysis and hepatic carboxylesterase, and also by plasma cholinesterase, hepatic carboxylesterase, and CYP3A4
  • Plasma cholinesterase activity may be decreased by chronic administration of certain monoamine oxidase inhibitors, oral contraceptives, glucocorticoids, antimyasthenics (neostigmine), cyclophosphamide, and possibly thiotepa
  • May also be diminished by administration of irreversible plasma cholinesterase inhibitors (eg, echothiophate, organophosphate insecticides, and certain antineoplastic agents)
  • Patients with reduced plasma cholinesterase (pseudocholinesterase) activity may have reduced clearance and increased exposure of plasma cocaine
  • Because cocaine is metabolized by multiple enzymes, the effect of reduced plasma cholinesterase activity on cocaine exposure may be limited; no dosage adjustment of is needed in patients with reduced plasma cholinesterase
  • Monitor patients with reduced plasma cholinesterase activity for adverse reactions (eg, increased heart rate or blood pressure)

Pregnancy

Data are not available on the use of cocaine for mucosal anesthesia in pregnant women to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Adverse maternal and fetal/neonatal outcomes have been seen in women with chronic cocaine abuse during pregnancy including congenital malformations, prematurity, miscarriage, premature rupture of membranes, and gestational hypertension

Cocaine crosses the placenta by simple diffusion and accumulates in the fetus after repeated use

Applicability of findings from these studies of chronic abuse in pregnancy to a single topical exposure is limited

Fertility

• Published animal studies suggest that cocaine can alter female reproductive hormone levels, disrupt the estrous cycle, and reduce ovulation at doses ~1-2 times the human reference dose based on BSA

Lactation

Because of the potential for serious adverse reactions in breastfed infants, advise a lactating woman that breastfeeding is not recommended during treatment with and to pump and discard breastmilk for 48 hr after use

Based on case reports in published literature, cocaine is present in human milk at widely varying concentrations

Based on its pharmacochemical characteristics, high concentrations of cocaine are expected in breast milk with systemic exposure

The applicability of these findings to a single topical exposure with limited systemic absorption is unclear

No studies have evaluated cocaine concentrations in milk after topical administration

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Local ester-type anesthetic; prevents conduction in nerve fibers by reversibly blocking voltage-gated sodium channels and preventing the transient rise in sodium conductance necessary for generation of an action potential

Absorption

Significant absorption from mucosa

160-mg nasal mucosa dose over 20 min

• Estimated systemic absorption: 23.44%
• Peak plasma time: 30 min
• Peak plasma concentration: 142.68 ng/mL (mean); 142.7 ng/mL (median)

Distribution

Protein Bound: 84-92%

Vd: 2 L/kg

Metbolism

Metabolized by hydrolysis to benzoylecgonine (major, but inactive metabolite) by hepatic carboxylesterase-1

Also metabolized by hydrolysis to ecgonine methyl ester (major, but inactive metabolite) by plasma butyrylcholinesterase and hepatic carboxylesterase-2

N-demethylated by CYP3A4 to produce norcocaine (active metabolite); total systemic exposure of norcocaine is <1% that observed with cocaine

Elimination

Half-life: 1.5 hr

Excreted almost exclusively in urine as metabolites

<5% eliminated unchanged in urine

Intranasal preparation

Numbrino or Goprelto

• Draw up 4 mL into a syringe calibrated in mL
• Recommended size of the cotton or rayon pledgets for use measure 0.5 x 3 inches (sold separately)
• Each pledget absorbs 1 mL (40 mg) of nasal solution
• Stack four pledgets and apply 2 mL of solution to the top of the stacked pledgets; turn the stacked pledgets over and apply 2 mL of solution to the other side
• Evenly distribute solution 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, remove pledgets and continue with the procedure
• Discard pledgets, and dispose of any unused pledgets and remaining solution in accordance with institutional procedures for CII products
• Pledgets should be removed immediately upon any sign or symptom of an adverse event

Intranasal application

Use product specific for intranasal use only

Do not apply to damaged nasal mucosa

Unless the FDA has determined that these products can be substituted, do not substitute for other intranasal cocaine products because this may result in different local and/or systemic exposures

Mucous membrane application

Administer using cotton applicators or packs, instilled into a cavity, or as a spray

Apply only on mucous membranes of mouth, laryngeal, or nasal cavities

Storage

All formulations

• Store at 20-25ºC (68-77ºF) with excursions permitted to 15-30ºC (59-86ºF)
• Avoid freezing
• Keep out of reach of children