cocaine hydrochloride nasal 40 mg/mL Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Esters of benzoic acid class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 2968PHW8QP
A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
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UNII 35SW5USQ3G
A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
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UNII 3P3ONR6O1S
A synthetic green dye approved by the FDA for use in medicines and foods. It serves as a colorant to make the pill or liquid visually distinctive and help with product identification.
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UNII OJ245FE5EU
Sodium benzoate is a salt derived from benzoic acid, a preservative. It's added to medicines to prevent growth of bacteria, fungi, and other microorganisms that could spoil the product.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
5 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $28.71 | $114.85 / 4 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Goprelto 40 mg/mL 70839-0359-04 | LXO | 1 bottle | — | — | FDA listed | — |
| Cocaine Hydrochloride 40 mg/mL 70839-0362-04 | LXO | 1 bottle | — | — | FDA listed | — |
| Numbrino 40 mg/mL 81665-0300-02 | OMNIVIUM | 1 bottle | — | — | FDA listed | — |
| cocaine hydrochloride nasal 40 mg/mLthis 81665-0301-02 | OMNIVIUM | 1 bottle | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 10973811 ↗ | Method of use | U-3680 | Feb 7, 2037 |
| US 10894012 ↗ | Method of use | U-3014 | Feb 7, 2037 |
| US 10857095 ↗ | Method of use | U-3014 | Feb 7, 2037 |
| US 10420760 ↗ | Method of use | U-2478 | Feb 7, 2037 |
| US 10413505 ↗ | Method of use | U-3014 | Feb 7, 2037 |
| US 10149843 ↗ | Method of use | U-2478 | Feb 7, 2037 |
| US 10149843 ↗ | Method of use | U-2479 | Feb 7, 2037 |
| US 10016407 ↗ | Method of use | U-2225 | Feb 7, 2037 |
| US 10016407 ↗ | Method of use | U-2226 | Feb 7, 2037 |
| US 10016407 ↗ | Method of use | U-2329 | Feb 7, 2037 |
| US 9867815 ↗ | Method of use | U-2225 | Feb 7, 2037 |
| US 9867815 ↗ | Method of use | U-2329 | Feb 7, 2037 |
| US 9867815 ↗ | Method of use | U-2227 | Feb 7, 2037 |
| US 9867815 ↗ | Method of use | U-2226 | Feb 7, 2037 |
| US 10933060 ↗ | Method of use | U-2478 | Feb 7, 2037 |
| US 10933060 ↗ | Method of use | U-3014 | Feb 7, 2037 |
| US 11040032 ↗ | Drug product | — | Feb 7, 2037 |
| US 10231961 ↗ | Drug product | — | Feb 7, 2037 |
Is there a generic version of COCAINE HCL 4% NASAL SOLUTION?
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🗺️ Medicaid utilization & spend
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 81665-0301-02 You're viewing this | 1 BOTTLE, GLASS in 1 CARTON (81665-301-02) / 4 mL in 1 BOTTLE, GLASS | 2023-10-15 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
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 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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. Cocaine hydrochloride nasal solution is an ester local anesthetic 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. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For intranasal use only. ( 2.1 ) Do not apply to damaged nasal mucosa. ( 2.1 ) Cocaine hydrochloride should not be substituted for other nasal cocaine products unless determined by FDA to be substitutable.
( 2.1 ) The recommended dose of cocaine hydrochloride ranges from 40 mg to 160 mg, depending on the nasal surface area to be anesthetized and the procedure to be performed. ( 2.2 ) Cocaine hydrochloride should be administered by means of cotton or rayon applicator pledgets applied to the nasal mucosa. ( 2 ) One pledget will absorb one mL of cocaine hydrochloride nasal solution.
( 2.2 ) Preparation and Application: Draw up 4 mL cocaine hydrochloride 4% nasal solution into a syringe calibrated in mL. Apply 2 mL cocaine hydrochloride nasal solution to the top of four stacked pledgets. Turn the stacked pledgets over and apply 2 mL cocaine hydrochloride nasal solution to the other side.
( 2.3 ) Cocaine hydrochloride 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 )
2.1Important Dosage and Administration Instructions Cocaine hydrochloride is for intranasal use only. Do not apply cocaine hydrochloride to damaged nasal mucosa. Unless the FDA has determined that these products can be substituted, do not substitute cocaine hydrochloride for other intranasal cocaine products because this may result in different local and/or systemic exposures.
2.2Dosing Recommendations The recommended dose of cocaine hydrochloride 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 cocaine hydrochloride 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 cocaine hydrochloride 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 cocaine hydrochloride measure ½ inch x 3 inch (sold separately).
2.3Preparation and Administration of Cocaine Hydrochloride via Pledgets Draw up 4 mL cocaine hydrochloride 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.
Cocaine hydrochloride should be evenly distributed on all pledgets. Following cocaine hydrochloride 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.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Cocaine Hydrochloride nasal solution is a clear, blue-green solution provided in a concentration of 4% (40 mg/mL). The 4% nasal solution is provided in both a single-use 4 mL (160 mg/4 mL) and multiple-use 10 mL (400 mg/10 mL) bottles. Each 1 mL of the 4% solution contains 40 mg of cocaine hydrochloride, equivalent to 35.7 mg of cocaine free base as aqueous solution, for topical nasal administration.
Nasal solution: 4% nasal solution (40 mg/ mL; available in both 4mL and 10mL bottles) ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Cocaine hydrochloride 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 cocaine hydrochloride. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Cocaine hydrochloride is for TOPICAL USE ONLY. NOT FOR INJECTION OR OPHTHALMIC USE. ( 5 ) Seizures: Cocaine hydrochloride may lower the convulsive threshold.
Monitor patients for development of seizures. Blood Pressure and Heart Rate Increases: Monitor vital signs, including heart rate and rhythm, in patients after receiving cocaine hydrochloride. Avoid use of cocaine hydrochloride in patients with a recent or active history of myocardial infarction, coronary artery disease, congestive heart failure, irregular heart rhythm, abnormal ECG, uncontrolled hypertension, or thyrotoxicosis.
5.1Potential for Abuse and Dependence Central nervous system (CNS) stimulants, including cocaine hydrochloride, have a high potential for abuse and dependence [see Drug Abuse and Dependence ( 9.2 , 9.3 )] .
5.2Seizures It has been reported in the literature that cocaine hydrochloride may lower the convulsive threshold. The risk may be higher in patients with a history of seizures or in patients with prior electroencephalogram (EEG) abnormalities without seizures, but has been reported in patients with no prior history or EEG evidence of seizures. Monitor patients for development of seizures.
5.3Blood Pressure and Heart Rate Increases As reported in the literature, cocaine hydrochloride causes an increase in observed blood pressure and heart rate. In the Phase 3 clinical studies with cocaine hydrochloride, increases in blood pressure and heart rate were observed following pledget removal. Monitor for changes in vital signs, including heart rate and rhythm, after administration of cocaine hydrochloride.
Avoid use of cocaine hydrochloride in patients with a history of myocardial infarction, coronary artery disease, congestive heart failure, irregular heart rhythm, abnormal ECG, or uncontrolled hypertension. Avoid use of additional vasoconstrictor agents such as epinephrine or phenylephrine with cocaine hydrochloride. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required.
Although not reported in the cocaine hydrochloride clinical trials, myocardial infarction has been reported in the literature, and can occur when the drug has been used as recommended [see Adverse Reactions ( 6 )] .
5.4Toxicology Screening The time after cocaine administration for which cocaine and its metabolites can be detected in plasma and urine depends on the sensitivity of the utilized assay method. The cocaine hydrochloride and its metabolites in cocaine hydrochloride may be detected in plasma for up to one week after administration. Cocaine hydrochloride and its metabolites may be detected in urine toxicology screening for longer than one week after administration.
5.5Known Hypersensitivity or Idiosyncrasy to the Sympathomimetic Amines Cocaine hydrochloride is contraindicated in patients with a known history of hypersensitivity to cocaine or to the components of the nasal solution. Cocaine is a sympathetic neuronal catecholamine reuptake inhibitor, which may potentiate the actions of concomitantly administered sympathomimetic amines.
5.6Ophthalmic Use Cocaine hydrochloride is NOT FOR OPHTHALMIC USE. Cocaine can cause sloughing of the corneal epithelium and should not be used in the eyes. Pitting and ulceration of the cornea has been reported in the literature.
🤒 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 cocaine hydrochloride 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.
6.1Clinical 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. Cocaine hydrochloride 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 cocaine hydrochloride nasal solution 4%, cocaine hydrochloride 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 cocaine hydrochloride nasal solution 4%, 318 received cocaine hydrochloride 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 cocaine hydrochloride nasal solution 4% and a mean dose of 319 mg (200 to 400 mg, N=259) of cocaine hydrochloride using cocaine hydrochloride nasal solution 10% as a single application.
The most common adverse reactions reported with cocaine hydrochloride 4% are included in Table 1 (preexisting nasal conditions are not included). There were two patients treated with cocaine hydrochloride 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 cocaine hydrochloride 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 Cocaine Hydrochloride in > 1% of Treated Patients MedDRA System Organ Class and Preferred Term Cocaine Hydrochloride, 4% (N=259) n, % Cocaine Hydrochloride, 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)
6.2Postmarketing 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 cocaine hydrochloride. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required.
( 5.3 , 7.2 ) Disulfiram: Disulfiram treatment increases plasma cocaine exposure. Avoid using cocaine hydrochloride in patients taking disulfiram. ( 7.3 ) CNS stimulants: Concomitant administration may result in nervousness, irritability, or possibly convulsions.
( 7.1 ) Cholinesterase inhibitors: Concomitant administration may increase the risk of cocaine toxicity. ( 7.4 ) Sympathomimetics, postganglionic blocking agents, and tricyclic antidepressants: Concomitant administration may increase the risk of cardiovascular adverse reactions. ( 7.5 , 7.6 ) Monoamine-oxidase inhibitors: Concomitant administration may potentiate the effects and toxicity of monoamine-oxidase inhibitors.
( 7.7 )
7.1Central 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.
7.2Epinephrine, Phenylephrine There are reports in the published literature of myocardial ischemia, myocardial infarction, and ventricular arrhythmias after concomitant administration of topical intranasal cocaine with epinephrine and phenylephrine during nasal and sinus surgery. Avoid use of additional vasoconstrictor agents such as epinephrine and phenylephrine with cocaine hydrochloride during nasal and sinus surgery. If concomitant use is unavoidable, prolonged vital sign and ECG monitoring may be required.
7.3Disulfiram 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 cocaine hydrochloride in patients taking disulfiram.
Consider using other local anesthesia.
7.4Cholinesterase Inhibitors Cocaine has been described in literature to be primarily metabolized and inactivated by non-enzymatic ester hydrolysis and hepatic carboxylesterase, and also by plasma cholinesterase, hepatic carboxylesterase, and CYP3A4. The pharmacokinetics of cocaine hydrochloride in patients with reduced plasma cholinesterase activity has not been studied. Plasma cholinesterase activity may be decreased by chronic administration of certain monoamine oxidase inhibitors, oral contraceptives, glucocorticoids, antimyasthenics (neostigmine), cyclophosphamide, and possibly thiotepa.
It may also be diminished by administration of irreversible plasma cholinesterase inhibitors such as echothiophate, organophosphate insecticides, and certain antineoplastic agents. Patients with reduced plasma cholinesterase (pseudocholinesterase) activity may have reduced clearance and increased exposure of plasma cocaine after administration of cocaine hydrochloride. Because cocaine is metabolized by multiple enzymes, the effect of reduced plasma cholinesterase activity on cocaine exposure may be limited.
No dosage adjustment of cocaine hydrochloride is needed in patients with reduced plasma cholinesterase. Monitor patients with reduced plasma cholinesterase activity for adverse reactions such as clinically-relevant increases in heart rate or blood pressure.
7.5Postganglionic Blocking Agents Agents such as reserpine potentiate cocaine-induced sympathetic stimulation; concurrent use may increase the risk of hypertension and cardiac arrhythmias that may be life-threatening.
7.6Tricyclic Antidepressants Tricyclic antidepressants may increase the activity of the sympathetic nervous system, whi…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation : Breastfeeding not recommended during treatment, but a lactating woman can pump and discard breast milk for 48 hours after treatment. ( 8.2 ) Geriatric Patients : May be more susceptible to cardiovascular adverse events. ( 8.5 ) Hepatic impairment : It is not recommended to dose cocaine hydrochloride in patients with hepatic impairment.
( 8.6 ) Renal impairment : Monitor for adverse reactions such as headache, epistaxis, and clinically-relevant increases in heart rate or blood pressure. ( 8.7 ) Pseudocholinesterase deficiency . ( 8.8 )
8.1Pregnancy Risk Summary There are no available data on the use of cocaine hydrochloride 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, found exposure was associated with reduced fetal growth compared with non-drug-abuse populations. Published data from a large number of studies of women with chronic cocaine abuse during pregnancy are inconsistent in their findings with regard to congenital malformations, prematurity, miscarriage, premature rupture of membranes and gestational hypertension.
The applicability of the findings from these studies of chronic abuse in pregnancy to a single topical exposure is limited. Animal Data Formal animal reproduction and development studies have not been conducted with intranasal cocaine hydrochloride. However, reproduction and development studies with cocaine have been reported in the published literature.
Exposure margins below are based on body surface area comparison to the human reference dose (HRD) of 37.5 mg (estimated amount absorbed from the 160 mg (4%) cocaine-soaked pledgets). Hydronephrosis was noted in embryos from pregnant rats treated wtih cocaine 2.1 mg/kg (0.5 times the HRD) and higher from Gestation Day 0 to 9. Cerebral hemorrhage and endematous fetuses were noted at 2.2 times the HRD and above).
Developmental delays and altered spontaneous exploratory behavior in response to cocaine were reported in rat pups born to dams treated intravenously with 6 mg/kg cocaine (1.5 times the HRD) from Gestation Day 8 to 20 in the absence of maternal toxicity. Reduced fetal body a…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on the use of cocaine hydrochloride 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, found exposure was associated with reduced fetal growth compared with non-drug-abuse populations. Published data from a large number of studies of women with chronic cocaine abuse during pregnancy are inconsistent in their findings with regard to congenital malformations, prematurity, miscarriage, premature rupture of membranes and gestational hypertension.
The applicability of the findings from these studies of chronic abuse in pregnancy to a single topical exposure is limited. Animal Data Formal animal reproduction and development studies have not been conducted with intranasal cocaine hydrochloride. However, reproduction and development studies with cocaine have been reported in the published literature.
Exposure margins below are based on body surface area comparison to the human reference dose (HRD) of 37.5 mg (estimated amount absorbed from the 160 mg (4%) cocaine-soaked pledgets). Hydronephrosis was noted in embryos from pregnant rats treated wtih cocaine 2.1 mg/kg (0.5 times the HRD) and higher from Gestation Day 0 to 9. Cerebral hemorrhage and endematous fetuses were noted at 2.2 times the HRD and above).
Developmental delays and altered spontaneous exploratory behavior in response to cocaine were reported in rat pups born to dams treated intravenously with 6 mg/kg cocaine (1.5 times the HRD) from Gestation Day 8 to 20 in the absence of maternal toxicity. Reduced fetal body and brain weights and alterations in fetal central neurotransmitter levels were noted following treatment of pregnant mice with 20 mg/kg cocaine from gestation days 8 to 12 or 12 to 18 (2.6 times the HRD). Reduced fetal survival was noted when pregnant nonhuman primates were dosed with 0.3 mg/kg/h cocaine (3.7 times the HRD on per day basis) via a subcutaneous minipump from Gestation Day 24 to birth.
Exencephaly, cryptochidism, hydronephrosis, anophthalmia, delayed ossification, limb anomalies, and cerebral and intra-abdominal hemorrhage were reported following a single subcuta…
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of cocaine hydrochloride in pediatric patients under the age of 18 have not been established. Published studies state that in juvenile male rats, 30 mg/kg subcutaneous cocaine administration for longer than 7 days (7.8 times the HRD) produced testicular necrosis. Treatment of juvenile male rats with 15 mg/kg (3.9 times the HRD) for 100 days resulted in abnormal sperm morphology and reduced pregnancy rates.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 802 subjects in the two Phase 3 studies with cocaine hydrochloride 13 subjects (1.6%) were age 65 and older, and one subject (0.1%) was 75 years of age or older. No untoward or unexpected adverse reactions were seen in elderly patients who received cocaine hydrochloride compared to those subjects that were under the age of 65. However, hypertension was observed in all geriatric subjects receiving cocaine hydrochloride.
Special precaution should be given when determining the dose of cocaine hydrochloride for geriatric patients, commensurate with their age and physical status.
🆘 Overdosage ▾
10 OVERDOSAGE No cases of overdose with cocaine hydrochloride were reported in clinical trials. Reported blood pressure and heart rate increases were greater with cocaine hydrochloride nasal solution 10% than with cocaine hydrochloride 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Cocaine hydrochloride is a local anesthetic of the ester type. Cocaine hydrochloride 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.
12.2Pharmacodynamics Cardiac Electrophysiology The effect of cocaine hydrochloride topical solution on the QTc interval was evaluated in a randomized, positive- and placebo-controlled four-period crossover thorough QTc study in 32 healthy subjects. Cocaine hydrochloride is associated with concentration-dependent QTc prolongation. Based on the concentration-QTc relationship, the mean placebo corrected change from the baseline QTcF (90% two-sided upper confidence interval) are 4.7 ms (6.2 ms) and 15.4 ms (20.1 ms) 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 QTc prolongation observed with cocaine hydrochloride (4% single dose) was found to be below the regulatory threshold for concern. Cocaine hydrochloride is associated with increases in heart rate.
The mean placebo corrected change from baseline heart rate (90% two-sided upper confidence interval) are 12 (14) bpm and 20 (22) bpm for the 4% and 10%, respectively. Effects on Cardiovascular System Cocaine can potentiate central and peripheral sympathetic effects on the cardiovascular system, resulting in increased inotropic and chronotropic effects, increased cardiac activity, and tachycardia. Intense peripheral vasoconstriction may result in elevated systolic and diastolic blood pressure.
Effects on Vascular System The relationship between local anesthetic effectiveness and toxicity of cocaine is a function of the patient’s state of health, medical condition, nasal mucosa integrity and extent of systemic absorption of cocaine (from the pledgets). When applied to mucous membranes by pledget administration, topical anesthesia develops rapidly and persists for 30 minutes or longer depending on the concentration of cocaine hydrochloride solution used, the dose, and on the vascularity of the tissue.
12.3Pharmacokinetics Cocaine hydrochloride is an aqueous solution of cocaine hydrochloride for topical use only. Absorption Application of cocaine hydrochloride for 20 minutes by pledget administration to the nasal mucosa in healthy adults may reduce the systemic absorption of the applied dose of cocaine hydrochloride compared to the systemic absorption after non-pledget administration. The estimated mean systemic absorption of cocaine from a single 160 mg dose (4 mL, 4%) was 23.44% of the topically applied dose.
( Table 2 ). Table 2. Systemic Absorption of Cocaine Hydrochloride in Healthy Adult Subjects Minimized by Pledget Administration (single nasal dose of 160 mg Cocaine Hydrochloride Topical Solution over 20 minutes) Cocaine Hydrochloride Dose (4 mL) Age Range (yr) Application Time (min) Estimated 1 Systemic Absorption Mean C max (ng/mL) Median T max (min) C max (ng/mL) 160 mg (4%) 20-40 20 23.44% 142.68 n=33 30 142.7 1 Estimated absorbed dose was calculated by subtracting the residual amount of drug in the pledgets from the administered dose; T max includes time 0 (the start of pledget insertion to pledget removal (20 minutes) to the time C max was observed, i.e.
10 minutes after removal of the pledgets. Distribution Cocaine has been described in literature as approximately 84-92% bound to human plasma proteins. Cocaine is extensively distributed to tissues and crosses the blood brain barrier.
Its volume of distribution is approximately 2 L/kg. Cocaine crosses the placenta by simple diffusion and accumulates in the fetus after repeated use. Elimination Metabolism Cocaine is metabolized by two major hydrolytic pathways.
Cocaine is metabolized by hydrolysis to benzoylecgonine (majo…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Cocaine hydrochloride is a local anesthetic of the ester type. Cocaine hydrochloride 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Cocaine Hydrochloride nasal solution is a clear, blue-green solution available as follows: 4% (40 mg/ mL) Nasal Solution NDC 81665-301-02: 4mL Single-use Bottles NDC 81665-301-03: 10mL Multi-use Bottles
16.2Storage 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].
📋 Description ▾
11 DESCRIPTION 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 Cocaine hydrochloride 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
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Pregnancy Inform female patients of reproductive potential that cocaine hydrochloride may cause fetal harm and to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations ( 8.1 )] . Lactation Advise a woman that breastfeeding is not recommended during treatment with cocaine hydrochloride and to pump and discard breastmilk for 48 hours after administration of cocaine hydrochloride [see Use in Specific Populations ( 8.2 )] . Blood Pressure and Heart Rate Increase Advise patients that cocaine hydrochloride can cause increases in blood pressure and heart rate.
Instruct patients to contact their health care professional if these symptoms persist [see Warnings and Precautions ( 5.3 )] . Seizures Advise patients that cocaine hydrochloride may lower the seizure threshold. Patients should be monitored for the development of seizures [see Warnings and Precautions ( 5.2 )] .
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. Advise patients that cocaine hydrochloride and its metabolites in cocaine hydrochloride may be detected in plasma for up to one week after administration. Cocaine hydrochloride and its metabolites may be detected in urine toxicology screening for longer than one week after administration [see Warnings and Precautions ( 5.4 )] .
Concomitant CNS Stimulants Advise patients to inform their health care professional if they are taking CNS stimulants, alpha-modifying agents, monoamine oxidase inhibitors, or tricyclic antidepressants [see Drug Interactions ( 7.1 )] . Hypersensitivity Reactions Advise patients of the signs and symptoms of hypersensitivity reactions and to seek immediate medical attention should they occur [see Warnings and Precautions ( 5.5 )] . Distributed by: Omnivium Pharmaceuticals Rahway, NJ 07065 CIB72181A Rev.
08/2023