Cocaine Hydrochloride Nasal
FDA Drug Information • Also known as: Cocaine Hydrochloride Nasal, Numbrino
- Brand Names
- Cocaine Hydrochloride Nasal, Numbrino
- Route
- TOPICAL
- Dosage Form
- SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: ABUSE AND DEPENDENCE CNS stimulants, including cocaine hydrochloride, have a high potential for abuse and dependence. ( 5.1 ) WARNING: ABUSE AND DEPENDENCE See full prescribing information for complete boxed warning. CNS stimulants, including cocaine hydrochloride, have a high potential for abuse and dependence. ( 5.1 )
Description
11 DESCRIPTION NUMBRINO TM (cocaine hydrochloride) nasal solution is a clear, blue-green, aqueous solution, available in 4% strength. Each 1 mL contains cocaine hydrochloride 40 mg, equivalent to 35.7 mg of cocaine free base; 4% as 160 mg/4 mL or 400 mg/10 mL. Cocaine, (1R,2R,3S,5S) methyl 3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate hydrochloride, is a synthetic tropane alkaloid ester, local anesthetic, which occurs as colorless to white crystals or white crystalline powder. The structural formula for cocaine hydrochloride is as follows: Formula C 17 H 21 NO 4 HCl Molecular weight 339.81 NUMBRINO also contains the following inactive ingredients: purified water, citric acid (anhydrous), sodium benzoate, D&C Yellow No. 10, and FD&C Green No. 3. Structural Formula
What Is Cocaine Hydrochloride Nasal Used For?
1 INDICATIONS AND USAGE NUMBRINO (cocaine hydrochloride) nasal solution is indicated for the induction of local anesthesia of the mucous membranes when performing diagnostic procedures and surgeries on or through the nasal cavities in adults. NUMBRINO (cocaine hydrochloride) nasal solution is an ester local anesthetic indicated for the introduction of local anesthesia of the mucous membranes for diagnostic procedures and surgeries on or through the nasal cavities of adults. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For intranasal use only. ( 2.1 ) Do not apply to damaged nasal mucosa. ( 2.1 ) NUMBRINO should not be substituted for other nasal cocaine products unless determined by FDA to be substitutable. ( 2.1 ) The recommended dose of NUMBRINO ranges from 40 mg to 160 mg, depending on the nasal surface area to be anesthetized and the procedure to be performed. ( 2.2 ) NUMBRINO should be administered by means of cotton or rayon applicator pledgets applied to the nasal mucosa. ( 2 ) One pledget will absorb one mL of NUMBRINO nasal solution. ( 2.2 ) Preparation and Application: Draw up 4 mL NUMBRINO 4% nasal solution into a syringe calibrated in mL. Apply 2 mL NUMBRINO nasal solution to the top of four stacked pledgets. Turn the stacked pledgets over and apply 2 mL NUMBRINO nasal solution to the other side. ( 2.3 ) NUMBRINO nasal solution should be evenly distributed on all pledgets. ( 2.3 ) Following soaking, place a maximum of two pledgets in each nasal cavity. ( 2.3 ) Leave pledgets in place for up to 20 minutes. ( 2.3 ) Pledgets should be removed immediately upon any sign or symptom of an adverse event. ( 2.2 ) 2.1 Important Dosage and Administration Instructions NUMBRINO (cocaine hydrochloride) is for intranasal use only. Do not apply NUMBRINO to damaged nasal mucosa. Unless the FDA has determined that these products can be substituted, do not substitute NUMBRINO for other intranasal cocaine products because this may result in different local and/or systemic exposures. 2.2 Dosing Recommendations The recommended dose of NUMBRINO ranges from 40 mg to 160 mg, depending on the nasal mucosal area to be anesthetized and the procedure to be performed. Each pledget absorbs one mL of NUMBRINO nasal solution. A maximum of two soaked cotton or rayon pledgets may be placed in each nasal cavity, for a total dose of 160 mg for NUMBRINO nasal solution 4%. The total dose for any one procedure or surgery should not exceed 3 mg/kg cocaine hydrochloride. The recommended size of the cotton or rayon pledgets for use with NUMBRINO measure ½ inch x 3 inch (sold separately). 2.3 Preparation and Administration of NUMBRINO via Pledgets Draw up 4 mL NUMBRINO into a syringe calibrated in mL. 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. NUMBRINO should be evenly distributed on all pledgets. Following NUMBRINO application to pledgets, place One (1) or two (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.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following treatment-emergent adverse events are discussed in more detailed in other sections of the labeling: Increases in Blood Pressure and Heart Rate [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (> 1%) occurring in patients treated with NUMBRINO were hypertension, tachycardia, and sinus tachycardia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Omnivium Pharmaceuticals LLC at 1-888-807-1048 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. NUMBRINO nasal solution has been evaluated in one Phase 1 study, one QT study and two Phase 3 studies, which included 702 adult subjects who received a single application of NUMBRINO nasal solution 4%, NUMBRINO nasal solution 10%, or placebo. The randomized, double-blind, placebo controlled Phase 3 studies were conducted in adult patients undergoing diagnostic procedures and surgeries on or through the mucous membranes of the nasal cavities, of which 316 received NUMBRINO nasal solution 4%, 318 received NUMBRINO nasal solution 10%, and 168 received placebo. Safety was evaluated for up to 7 days after dosing. In a Phase 3 study, patients received a mean dose of 126 mg (80 to 160 mg, N=259) of cocaine hydrochloride using NUMBRINO nasal solution 4% and a mean dose of 319 mg (200 to 400 mg, N=259) of cocaine hydrochloride using NUMBRINO nasal solution 10% as a single application. The most common adverse reactions reported with NUMBRINO 4% are included in Table 1 (preexisting nasal conditions are not included). There were two patients treated with NUMBRINO nasal solution 4% who withdrew due to an adverse reaction. One patient developed anxiety and systolic hypertension and one patient developed intermittent paroxysmal tachycardia. Both patients developed symptoms within 10 minutes of nasal pledget application. Three patients treated with NUMBRINO nasal solution 10% required premature removal of pledgets due to nausea and diastolic hypertension; mild intermittent paroxysmal hypertension and paroxysmal tachycardia; and vasovagal syncope with bradycardia. Table 1. Common Adverse Reactions with NUMBRINO in > 1% of Treated Patients MedDRA System Organ Class and Preferred Term NUMBRINO, 4% (N=259) n, % NUMBRINO, 10% (N=259) n, % Placebo (N=128) n, % Vascular Disorders 203 (78) 224 (87) 86 (67) Hypertension 201 (78) 220 (85) 85 (66) Cardiac Disorders 31 (12) 47 (18) 10 (8) Tachycardia 12 (5) 28 (11) 1 (1) Bradycardia 8 (3) 1 (0.4) 5 (4) Sinus tachycardia 6 (2) 9 (4) 0 Investigations 13 (5) 30 (12) 8 (6) QRS prolonged 4 (2) 8 (3) 3 (2) QT interval prolonged 7 (3) 10 (4) 3 (2) 6.2 Postmarketing Experience The following adverse reactions have been identified during use of Cocaine Hydrochloride Nasal Solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Nervous system disorders: Headache, Seizure Cardiac disorders: Hypertension, tachycardia, atrial and ventricular arrhythmias, myocardial ischemia and infarction Psychiatric disorders: Anxiety
Drug Interactions
7 DRUG INTERACTIONS Epinephrine, Phenylephrine: There have been reports of myocardial ischemia, myocardial infarction, and ventricular arrhythmias with concomitant use during nasal surgery. Avoid use of additional vasoconstrictor agents with NUMBRINO. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required. ( 5.3 , 7.2 ) Disulfiram: Disulfiram treatment increases plasma cocaine exposure. Avoid using NUMBRINO in patients taking disulfiram. ( 7.3 ) CNS stimulants: Concomitant administration may result in nervousness, irritability, or possibly convulsions. ( 7.1 ) Cholinesterase inhibitors: Concomitant administration may increase the risk of cocaine toxicity. ( 7.4 ) Sympathomimetics, postganglionic blocking agents, and tricyclic antidepressants: Concomitant administration may increase the risk of cardiovascular adverse reactions. ( 7.5 , 7.6 ) Monoamine-oxidase inhibitors: Concomitant administration may potentiate the effects and toxicity of monoamine-oxidase inhibitors. ( 7.7 ) 7.1 Central Nervous System Stimulants Concurrent use of other central nervous system stimulants with cocaine may result in excessive stimulation, leading to nervousness, irritability, or possibly convulsions, or cardiac arrhythmias. 7.2 Epinephrine, Phenylephrine There are reports in the published literature of myocardial ischemia, myocardial infarction, and ventricular arrhythmias after concomitant administration of topical intranasal cocaine with epinephrine and phenylephrine during nasal and sinus surgery. Avoid use of additional vasoconstrictor agents such as epinephrine and phenylephrine with NUMBRINO during nasal and sinus surgery. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required. 7.3 Disulfiram Published literature reported that disulfiram treatment increased plasma cocaine exposure (AUC and C max ), by several folds after acute intranasal cocaine administration. Another literature reported that co-administration of disulfiram increased AUC of plasma cocaine by several folds after intravenous cocaine administration [see Clinical Pharmacology ( 12.3 )] . Avoid using NUMBRINO in patients taking disulfiram. Consider using other local anesthesia. 7.4 Cholinesterase Inhibitors Cocaine has been described in literature to be primarily metabolized and inactivated by non-enzymatic ester hydrolysis and hepatic carboxylesterase, and also by plasma cholinesterase, hepatic carboxylesterase, and CYP3A4. The pharmacokinetics of NUMBRINO in patients with reduced plasma cholinesterase activity has not been studied. Plasma cholinesterase activity may be decreased by chronic administration of certain monoamine oxidase inhibitors, oral contraceptives, glucocorticoids, antimyasthenics (neostigmine), cyclophosphamide, and possibly thiotepa. It may also be diminished by administration of irreversible plasma cholinesterase inhibitors such as echothiophate, organophosphate insecticides, and certain antineoplastic...
Contraindications
4 CONTRAINDICATIONS NUMBRINO is contraindicated in: patients with a known history of hypersensitivity to cocaine hydrochloride, other ester-based local anesthetics, or any other component of the nasal solution [see Warnings and Precautions ( 5.5 )] . Hypersensitivity to cocaine, or any component of NUMBRINO. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on the use of NUMBRINO 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 ( see Data ) . In published animal reproduction studies, cocaine administered to pregnant females during the gestational period produced hydronephrosis (0.5 times the human reference dose (HRD) of 37.5 mg via the 4% solution), developmental delays in the offspring (1.5 times the HRD), cerebral hemorrhage and fetal edema (2.0 times the HRD), reduced fetal body weights and brain weights (2.6 times the HRD), and reduced fetal survival (3.7 times the HRD). Single dose administration of cocaine intravenously during organogenesis in mice produced cryptochidism, anophthalmia, exencephaly, and delayed ossification at 7.8 times the HRD. In rats, a single dose of cocaine administered by intraperitoneal injection produced edematous fetuses, hemorrhages and limb defects at 12.9 times the HRD ( see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data There are no available data on the use of intranasal cocaine hydrochloride solution in pregnant women to inform a drug-associated risk for major congenital malformations or miscarriage. There are published data describing adverse developmental outcomes in women with chronic cocaine abuse during pregnancy. The published case-control and observational studies examining the effect of in utero cocaine exposure on fetal growth parameters, after controlling for confounding variables,...
Overdosage
10 OVERDOSAGE No cases of overdose with NUMBRINO were reported in clinical trials. Reported blood pressure and heart rate increases were greater with NUMBRINO nasal solution 10% than with NUMBRINO nasal solution 4%. In the case of an overdose, consult with a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice for treatment of overdosage. Individual patient response to cocaine varies widely. Toxic symptoms may occur idiosyncratically at low doses. Manifestations of cocaine overdose associated with illicit use of cocaine reported in literature and based on reports in FDA’s Adverse Events Reporting System (AERS) database include death, cardio-respiratory arrest, cardiac arrest, respiratory arrest, tachycardia, myocardial infarction, agitation, aggression, restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central nervous system stimulation. Other reactions include arrhythmias, hypertension or hypotension, circulatory collapse, nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma. Because cocaine is significantly distributed to tissues and rapidly metabolized, dialysis and hemoperfusion are not effective. Acidification of the urine does not significantly enhance cocaine elimination.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied NUMBRINO TM (cocaine hydrochloride) nasal solution is a clear, blue-green solution available as follows: 4% (40 mg/ mL) Nasal Solution NDC 81665-300-02: 4mL Single-use Bottles NDC 81665-300-03: 10mL Multi-use Bottles 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F) with excursions permitted between 15° and 30°C (59° and 86° F) [see USP Controlled Room Temperature].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.