Oxycodone Hydrochloride (Page 9 of 10)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies have not been performed in animals to evaluate the carcinogenic potential of oxycodone HCl tablets or oxycodone.

Mutagenesis

Oxycodone hydrochloride was genotoxic in an in vitro mouse lymphoma assay in the presence of metabolic activation. There was no evidence of genotoxic potential in an in vitro bacterial reverse mutation assay (Salmonella typhimurium and Escherichia coli) or in an assay for chromosomal aberrations (in vivo mouse bone marrow micronucleus assay).

Impairment of Fertility

Studies in animals to evaluate the potential impact of oxycodone on fertility have not been conducted.

16 HOW SUPPLIED/STORAGE AND HANDLING

Oxycodone HCl tablets, USP 5 mg are supplied as white, round, biconvex tablets debossed with “A” on the left and “04” on the right of the score on one side and plain on the other side.

They are available as follows:

Carton of 100 tablets (10 tablets per blister pack x 10), NDC 0904-6966-61

Oxycodone HCl tablets, USP 15 mg are supplied as green, round, biconvex tablets debossed with “A” on the left and “49” on the right of the score on one side and plain on the other side.

They are available as follows:

Carton of 100 tablets (10 tablets per blister pack x 10), NDC 0904-7180-61

DEA Order Form Required.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure.

Protect from moisture.

Store at 20° to 25°C (68° to 77°F); excursions are permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Store oxycodone HCl securely and dispose of properly [see Patient Counseling Information (17)].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Storage and Disposal

Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store oxycodone HCl securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions (5.1, 5.3), Drug Abuse and Dependence (9.2)]. Inform patients that leaving oxycodone HCl unsecured can pose a deadly risk to others in the home.

Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused oxycodone HCl should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.

Addiction, Abuse and Misuse

Inform patients that the use of oxycodone HCl, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.1)]. Instruct patients not to share oxycodone HCl with others and to take steps to protect oxycodone HCl from theft and misuse.

Life-Threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting oxycodone HCl or when the dosage is increased, and that it can occur even at recommended dosages.

Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Warnings and Precautions (5.3)].

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with oxycodone HCl. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) [see Dosage and Administration (2.2), Warnings and Precautions (5.3)].

Educate patients and caregivers on how to recognize the signs and symptoms of an overdose.

Explain to patients and caregivers that naloxone’s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered [see Overdosage (10)].

If naloxone is prescribed, also advise patients and caregivers:

•

How to treat with naloxone in the event of an opioid overdose

•

To tell family and friends about their naloxone and to keep it in a place where family and friends can access it in an emergency

•

To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do.

Accidental Ingestion

Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.3)].

Interactions with Benzodiazepines and Other CNS Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if oxycodone HCl is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.6), Drug Interactions (7)].

Serotonin Syndrome

Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare providers if they are taking, or plan to take serotonergic medication [see Drug Interactions (7)].

MAOI Interaction

Inform patients to avoid taking oxycodone HCl while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking oxycodone HCl [see Drug Interactions (7)].

Adrenal Insufficiency

Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions (5.8)].

Important Administration Instructions

Instruct patients how to properly take oxycodone HCl. Patients should be advised not to adjust the dose of oxycodone HCl without consulting the prescribing healthcare provider [see Dosage and Administration (2), Warnings and Precautions (5.13)].

Important Discontinuation Instructions

In order to avoid developing withdrawal symptoms, instruct patients not to discontinue oxycodone HCl without first discussing a tapering plan with the prescriber [see Dosage and Administration (2.4)].

Hypotension

Inform patients that oxycodone HCl may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from sitting or lying position) [see Warnings and Precautions (5.9)].

Anaphylaxis

Inform patients that anaphylaxis has been reported with ingredients contained in oxycodone HCl. Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications (4), Adverse Reactions (6.2)].

Pregnancy

Neonatal Opioid Withdrawal Syndrome

Inform female patients of reproductive potential that prolonged use of oxycodone HCl during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)].

Embryo-Fetal Toxicity

Inform female patients of reproductive potential that oxycodone HCl can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

Lactation

Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see Use in Specific Populations (8.2)].

Infertility

Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Use in Specific Populations (8.3)].

Driving or Operating Machinery

Inform patients that oxycodone HCl may impair the ability to perform potentially hazardous activities such as driving a car or operating dangerous machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.14)].

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6),Clinical Pharmacology (12.1)].

Manufactured by:
Amneal Pharmaceuticals of NY, LLC Brookhaven, NY 11719

Distributed By:

MAJOR® PHARMACEUTICALS

Livonia, MI 48152

Refer to package label for Distributor’s NDC Number

Rev. 12-2021-08