TRAMADOL HYDROCHLORIDE- tramadol hydrochloride tablet, coated 
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Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Addiction, Abuse, and Misuse

Inform patients that the use of tramadol hydrochloride, 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 tramadol hydrochloride tablets with others and to take steps to protect tramadol hydrochloride tablets from theft or misuse.

Life-Threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting tramadol hydrochloride or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions (5.3)]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.

Accidental Ingestion

Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.3)]. Instruct patients to take steps to store tramadol hydrochloride tablets securely and to dispose of unused tramadol hydrochloride tablets in accordance with the local state guidelines and/or regulations.

Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children

Advise caregivers that tramadol hydrochloride is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Advise caregivers of children ages 12 to 18 years of age receiving tramadol hydrochloride to monitor for signs of respiratory depression [see Warnings and Precautions (5.4)].

Interactions with Benzodiazepines and Other CNS Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if tramadol hydrochloride is used with benzodiazepines, CNS depressants, including alcohol, or some illicit drugs and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.7); 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 provider if they are taking, or plan to take serotonergic medications [see Warnings and Precautions (5.8)].

Seizures

Inform patients that tramadol hydrochloride may cause seizures with concomitant use of serotonergic agents (including SSRIs, SNRIs, and triptans) or drugs that significantly reduce the metabolic clearance of tramadol [see Warnings and Precautions (5.9)].

MAOI Interaction

Inform patients not to take tramadol hydrochloride while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking tramadol hydrochloride [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 (5.11)].

Important Administration Instructions

Instruct patients how to properly take tramadol hydrochloride tablets [see Dosage and Administration (2)].
Advise patients not to adjust the dose of tramadol hydrochloride tablets without consulting with a physician or other healthcare professional.
If patients have been receiving treatment with tramadol hydrochloride tablets for more than a few weeks and cessation of therapy is indicated, counsel them on the importance of safely tapering the dose as abrupt discontinuation of the medication could precipitate withdrawal symptoms. Provide a dose schedule to accomplish a gradual discontinuation of the medication [see Dosage and Administration (2.4)].

Hypotension

Inform patients that tramadol hydrochloride 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 a sitting or lying position) [see Warnings and Precautions (5.13)].

Anaphylaxis

Inform patients that anaphylaxis has been reported with ingredients contained in tramadol hydrochloride. Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications (4); Warnings and Precautions (5.16); Adverse Reactions (6)].

Pregnancy

Neonatal Opioid Withdrawal Syndrome

Inform female patients of reproductive potential that prolonged use of tramadol hydrochloride during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated and that the patient should inform their healthcare provider if they have used opioids at any time during their pregnancy, especially near the time of birth [see Warnings and Precautions (5.5); Use in Special Populations (8.1)].

Embryo-Fetal Toxicity

Inform female patients of reproductive potential that tramadol hydrochloride may cause fetal harm and to inform the healthcare provider of a known or suspected pregnancy [see Use in Special Populations (8.1)].

Lactation

Advise women that breastfeeding is not recommended during treatment with tramadol hydrochloride [see Warnings and Precautions (5.4); Use in Special 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 Special Populations (8.3)].

Driving or Operating Heavy Machinery

Inform patients that tramadol hydrochloride may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.18)].

Constipation

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

Disposal of Unused Tramadol Hydrochloride Tablets

Advise patients to throw the unused tramadol hydrochloride tablets in the household trash following these steps.

1) Remove the drugs from their original containers and mix with an undesirable substance, such as used coffee grounds or kitty litter (this makes the drug less appealing to children and pets, and unrecognizable to people who may intentionally go through the trash seeking drugs).

2) Place the mixture in a sealable bag, empty can, or other container to prevent the drug from leaking or breaking out of a garbage bag.

Maximum single-dose and 24-hour dose

Advise patients not to exceed the single-dose and 24-hour dose limit and the time interval between doses, since exceeding these recommendations can result in respiratory depression, seizures and death [see Dosage and Administration (2); Warnings and Precautions (5.3)].

Manufactured by:

Amneal Pharmaceuticals of NY LLC

Brookhaven, NY 11719

Distributed by:

Amneal Pharmaceuticals LLC

Glasgow, KY 42141

Rev. 04-2019-08

Revised: 7/2019
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