TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN

Seizure Risk

• Selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics),  
• Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), or
• Other opioids.

• MAO inhibitors (see also WARNINGS, Use with MAO Inhibitors and Serotonin Re-uptake Inhibitors),
• Neuroleptics, or  
• Other drugs that reduce the seizure threshold.

Suicide Risk

• Do not prescribe tramadol hydrochloride and acetaminophen tablets for patients who are suicidal or addiction-prone. 
• Prescribe tramadol hydrochloride and acetaminophen tablets with caution for patients taking tranquilizers or antidepressant drugs and patients who use alcohol in excess and who suffer from emotional disturbance or depression.

Serotonin Syndrome Risk

Hypersensitivity/Anaphylaxis

Respiratory Depression

Administer tramadol hydrochloride and acetaminophen tablets cautiously in patients at risk for respiratory depression. In these patients, alternative non-opioid analgesics should be considered. When large doses of tramadol are administered with anesthetic medications or alcohol, respiratory depression may result. Respiratory depression should be treated as an overdose. If naloxone is to be administered, use cautiously because it may precipitate seizures (see WARNINGS, Seizure Risk and OVERDOSAGE ).

Interaction With Central Nervous System (CNS) Depressants

Tramadol hydrochloride and acetaminophen tablets should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers, or sedative hypnotics. Tramadol increases the risk of CNS and respiratory depression in these patients.

Interactions With Alcohol and Drugs of Abuse

Increased Intracranial Pressure or Head Trauma

Tramadol hydrochloride and acetaminophen tablets should be used with caution in patients with increased intracranial pressure or head injury. The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure and may be markedly exaggerated in these patients. Additionally, pupillary changes (miosis) from tramadol may obscure the existence, extent, or course of intracranial pathology. Clinicians should also maintain a high index of suspicion for adverse drug reactions when evaluating altered mental status in these patients if they are receiving tramadol hydrochloride and acetaminophen tablets (see WARNINGS, Respiratory Depression ).

Use in Ambulatory Patients

Tramadol may impair the mental and or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. The patient using this drug should be cautioned accordingly.

Use With MAO Inhibitors and Serotonin Re-uptake Inhibitors

Use tramadol hydrochloride and acetaminophen tablets with great caution in patients taking monoamine oxidase inhibitors. Animal studies have shown increased deaths with combined administration of MAO inhibitors and tramadol. Concomitant use of tramadol with MAO inhibitors or SSRI's increases the risk of adverse events, including seizure and serotonin syndrome.

Use With Alcohol

Tramadol hydrochloride and acetaminophen tablets should not be used concomitantly with alcohol consumption. The use of tramadol hydrochloride and acetaminophen tablets in patients with liver disease is not recommended.

Use With Other Acetaminophen-containing Products

Due to the potential for acetaminophen hepatotoxicity at doses higher than the recommended dose, tramadol hydrochloride and acetaminophen tablets should not be used concomitantly with other acetaminophen-containing products.

Misuse, Abuse and Diversion

Risk of Overdosage

Withdrawal

Withdrawal symptoms may occur if tramadol hydrochloride and acetaminophen tablets is discontinued abruptly (see also DRUG ABUSE AND DEPENDENCE ). Reported symptoms have included: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Other symptoms that have been reported less frequently with tramadol hydrochloride and acetaminophen tablets discontinuation include:  panic attacks, severe anxiety, and paresthesias. Clinical experience suggests that withdrawal symptoms may be avoided by tapering tramadol hydrochloride and acetaminophen tablets at the time of discontinuation.

PRECAUTIONS

General

Pediatric Use

The safety and effectiveness of tramadol hydrochloride and acetaminophen tablets has not been studied in the pediatric population.

Geriatric Use

In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function; of concomitant disease; and multiple drug therapy.

Acute Abdominal Conditions

The administration of tramadol hydrochloride and acetaminophen tablets may complicate the clinical assessment of patients with acute abdominal conditions.

Use in Renal Disease

Tramadol hydrochloride and acetaminophen tablets has not been studied in patients with impaired renal function. Experience with tramadol suggests that impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1. In patients with creatinine clearances of less than 30 mL/min, it is recommended that the dosing interval of tramadol hydrochloride and acetaminophen tablets be increased, not to exceed 2 tablets every 12 hours.

Use in Hepatic Disease

Tramadol hydrochloride and acetaminophen tablets has not been studied in patients with impaired hepatic function. The use of tramadol hydrochloride and acetaminophen tablets in patients with hepatic impairment is not recommended (see WARNINGS, Use With Alcohol ).

Information for Patients

• Do not take tramadol hydrochloride and acetaminophen tablets if you are allergic to any of its ingredients. 
• If you develop signs of allergy such as a rash or difficulty breathing, stop taking tramadol hydrochloride and acetaminophen tablets and contact your healthcare provider immediately. 
• Do not take more than 4,000 milligrams of acetaminophen per day. Call your doctor if you took more than the recommended dose. 
• Do not take tramadol hydrochloride and acetaminophen tablets in combination with other tramadol or acetaminophen-containing products, including over-the-counter preparations.
• Tramadol hydrochloride and acetaminophen tablets may cause seizures and/or serotonin syndrome with concomitant use of serotonergic agents (including SSRIs, SNRIs, and triptans) or drugs that significantly reduce the metabolic clearance of tramadol.
• Tramadol hydrochloride and acetaminophen tablets may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. 
• Tramadol hydrochloride and acetaminophen tablets should not be taken concomitantly with alcohol-containing beverages during the course of treatment with tramadol hydrochloride and acetaminophen tablets.
• Tramadol hydrochloride and acetaminophen tablets should be used with caution when taking medications such as tranquilizers, hypnotics, or other opiate-containing analgesics.
• Inform the physician if you are pregnant, think you might become pregnant, or are trying to become pregnant (see PRECAUTIONS, Labor and Delivery ).
• Understand the single-dose and 24-hour dose limit and the time interval between doses, since exceeding these recommendations can result in respiratory depression, seizures, hepatic toxicity, and death.

Drug Interactions

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Teratogenic Effects: Pregnancy Category C

Non-teratogenic Effects

Labor and Delivery

Nursing Mothers

TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN ADVERSE REACTIONS

^*Number of males = 62

DRUG ABUSE AND DEPENDENCE

Abuse

Dependence

OVERDOSAGE

TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN DOSAGE AND ADMINISTRATION

HOW SUPPLIED

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 37.5 mg/325 mg (100 Tablet Bottle)

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 37.5 mg/325 mg Blister Carton (8 x 10 Unit-dose)