Cocaine Hydrochloride (Page 4 of 4)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term animal studies to evaluate the carcinogenic potential of cocaine have not been conducted.

Mutagenesis

In published studies, cocaine was genotoxic in the in vitro chromosomal aberration assay, the in vitro sister chromatid exchange assay, the in vitro micronucleus assay, and the in vitro hypoxanthine-guanine phosphoribosyltransferase (hgprt) assay. Cocaine was equivocal in a published in vivo micronucleus assay and the in vivo comet assay (liver). Cocaine was not mutagenic in the in vitro bacterial reverse mutation assay (Ames assay).

Impairment of Fertility

No adverse effects on fertility or early embryonic development were reported in a study where male rats were administered up to 20 mg/kg cocaine hydrochloride via subcutaneous injection for 28 days prior to mating and female rats were treated with the same dose for 14 days prior to mating through Gestation Day 7. The 20 mg/kg/dose resulted in AUC exposures that were 31 times (males) and 47 times (females) the adult human AUC following administration of pledgets containing 160 mg of cocaine.

14 CLINICAL STUDIES

A double-blind, multicenter, single-dose, placebo- and dose-controlled, parallel-group study was conducted in 648 subjects undergoing diagnostic procedures and surgeries on or through the mucous membranes of the nasal cavities. Subjects were randomized to receive COCAINE HYDROCHLORIDE nasal solution (n=278), cocaine hydrochloride solution 8% (n=275), to explore the dosing range, or placebo (n=95). Nasal endoscopy, nasal laryngoscopy, nasopharyngeal laryngoscopy, and nasal debridement comprised 88% of all procedures performed in the COCAINE HYDROCHLORIDE nasal solution (n=278), cocaine hydrochloride solution 8% (n=275), to explore the dosing range, or placebo (n=95). Nasal endoscopy, nasal laryngoscopy, nasopharyngeal laryngoscopy, and nasal debridement comprised 88% of all procedures performed in the COCAINE HYDROCHLORIDE nasal solution group and 85% of all procedures performed in the placebo group. All subjects completed the diagnostic or surgical procedure.

In the COCAINE HYDROCHLORIDE nasal solution group, two 40 mg pledgets were applied to the septum in each nasal cavity (160 mg cocaine hydrochloride total dose) and left in place for up to 20 minutes. Similarly, pledgets were applied in the placebo group. Topical anesthesia was assessed using the visual numeric rating scale (VNRS) during a von Frey Filament test prior to the diagnostic procedure or surgery. After subject-reported pain scores were collected, the blind to placebo was broken and placebo subjects were provided the option of receiving anesthesia. The primary efficacy endpoint was analgesic success, defined in the COCAINE HYDROCHLORIDE nasal solution group as a subject-reported pain score of 0 (no pain) on the VNRS during the von Frey Filament test, and no additional anesthetic or analgesic medication administration during the diagnostic procedure or surgery. Analgesic success was defined in the placebo group as a subject-reported pain score of 0 on the VNRS during the von Frey Filament test. Subjects did not receive supplemental intravenous sedation or general anesthesia during the study.

Table 2 provides the efficacy results for the primary endpoint of analgesic success showing a significant difference in the analgesic success rate between placebo and COCAINE HYDROCHLORIDE nasal solution.

Table 2: Analgesic Success
Event COCAINE HYDROCHLORIDE (N=278) n (%) Placebo (N=95) n (%)
Success 215 (77%) 14 (15%)
Failure 63 (23%) 81 (85%)

Of the 63 (23%) failures in the COCAINE HYDROCHLORIDE nasal solution group, 4 subjects requested additional anesthetic medication. Of these 4 subjects, 1 subject reported 0 on the VNRS during the von Frey Filament test. Of the 81 (85%) failures in the placebo group, 50 subjects required additional anesthetic medication.

16 HOW SUPPLIED/STORAGE AND HANDLING

COCAINE HYDROCHLORIDE nasal solution is a clear, green colored liquid available as one dosage strength:

160 mg/4 mL (40 mg/mL or 4%) cocaine hydrochloride, equivalent to 142.4 mg/4 mL (35.6 mg/mL) cocaine

NDC # 64950-362-04: Single-unit 4 mL bottle

Store upright at 20° to 25°C (68° to 77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP, Controlled Room Temperature (CRT)]. Avoid freezing.

17 PATIENT COUNSELING INFORMATION

Potential for Abuse and Dependence

Advise patients that COCAINE HYDROCHLORIDE nasal solution is a controlled substance and it can be abused and lead to dependence [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9)] .

Toxicology Screening

Advise patients that the cocaine hydrochloride in COCAINE HYDROCHLORIDE nasal solution 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)] .

Seizures

Advise patients that COCAINE HYDROCHLORIDE nasal solution may lower the seizure threshold. Patients should be monitored for development of seizures. [see Warnings and Precautions (5.2)] .

Blood Pressure and Heart Rate Increase

Advise patients that COCAINE HYDROCHLORIDE nasal solution can cause increases in blood pressure and heart rate and should be avoided in patients with recent or active history of uncontrolled hypertension, unstable angina, myocardial infarction, coronary artery disease, or congestive heart failure [see Warnings and Precautions (5.3)] .

Headache and/or Epistaxis

Inform patients that headache and/or epistaxis are the most frequently experienced side effects that should resolve without treatment. Instruct patients to contact their health care professional if these symptoms persist [see Adverse Reactions (6)] .

Pregnancy

Inform female patients of reproductive potential that COCAINE HYDROCHLORIDE nasal solution 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 nursing woman that breastfeeding is not recommended during treatment with COCAINE HYDROCHLORIDE nasal solution and to pump and discard breastmilk for 48 hours after administration of COCAINE HYDROCHLORIDE nasal solution nasal solution [see Use in Specific Populations (8.2)] .

Manufactured by and Distributed by:
Genus Lifesciences Inc.
514 North 12 th Street
Allentown, PA 18102

PRINCIPAL DISPLAY PANEL — 4 mL Bottle Carton

NDC 64950-362-04
COCAINE
HYDROCHLORIDE
nasal solution

CII

160 mg/4 mL

For Topical Use Only.
Not for Injection or Ophthalmic Use

Single-unit

Each 1 mL contains:
Cocaine Hydrochloride, USP
40 mg

(equivalent to 142.4 mg/4 mL [35.6 mg/mL] cocaine)

Rx Only
4 mL

Genus Lifesciences Inc.

PRINCIPAL DISPLAY PANEL -- 4 mL Bottle Carton
(click image for full-size original)
COCAINE HYDROCHLORIDE cocaine hydrochloride solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64950-362
Route of Administration NASAL DEA Schedule CII
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
COCAINE HYDROCHLORIDE (COCAINE) COCAINE HYDROCHLORIDE 40 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
ANHYDROUS CITRIC ACID
D&C YELLOW NO. 10
FD&C GREEN NO. 3
SODIUM BENZOATE
WATER
Product Characteristics
Color green Score
Shape Size
Flavor Imprint Code
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:64950-362-04 1 BOTTLE, GLASS in 1 CARTON contains a BOTTLE, GLASS
1 4 mL in 1 BOTTLE, GLASS This package is contained within the CARTON (64950-362-04)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA authorized generic NDA209963 06/04/2018
Labeler — Genus Lifesciences Inc. (113290444)
Establishment
Name Address ID/FEI Operations
Genus Lifesciences Inc. 113290444 manufacture (64950-362)

Revised: 03/2024 Genus Lifesciences Inc.

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