Tramadol Hydrochloride and Acetaminophen

Boxed Warning 11/2023 Indications and Usage ( 1 ) 05/2023 Dosage and Administration ( 2.1 , 2.3 ) 05/2023 Warnings and Precautions; Opioid Induced Hyperalgesia and Allodynia ( 5.8 ) 05/2023

1 INDICATIONS AND USAGE Tramadol hydrochloride and acetaminophen tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use: Tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less. Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see Warnings and Precautions (5.1) ] , reserve tramadol hydrochloride and acetaminophen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: Have not been tolerated or are not expected to be tolerated, Have not provided adequate analgesia or are not expected to provide adequate analgesia. Tramadol hydrochloride and acetaminophen tablets should not be used for an extended period of time. Tramadol hydrochloride and acetaminophen tablets are a combination of tramadol hydrochloride, an opioid agonist, and acetaminophen, and is indicated for the management of acute pain, severe enough to require an opioid analgesic and for which alternative treatments are inadequate. ( 1 ) Limitations of Use: ( 1 ) Tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less. Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, reserve tramadol hydrochloride and acetaminophen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: Have not been tolerated or are not expected to be tolerated, Have not provided adequate analgesia or are not expected to provide adequate analgesia Tramadol hydrochloride and acetaminophen tablets should not be used for an extended period of time.

2 DOSAGE AND ADMINISTRATION Tramadol hydrochloride and acetaminophen tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of tramadol hydrochloride and acetaminophen tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5 ) Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. ( 2.1 ) Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. ( 2.1 , 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with tramadol hydrochloride and acetaminophen tablets. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.2 ) Initiate treatment with in a dosing range of two tablets every 4 to 6 hours as needed for pain relief, and at the lowest dosage necessary to achieve adequate analgesia. Titrate the dosage based upon the individual patient’s response to their initial dose of tramadol hydrochloride and acetaminophen tablets; maximum of 8 tablets per day. ( 2.3 , 5 ) Periodically reassess patients receiving tramadol hydrochloride and acetaminophen to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. (2.2 ) Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with tramadol hydrochloride and acetaminophen tablets, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. ( 2.2, 5.1 , 5.2 , 5.3 ) Do not use with other acetaminophen- or tramadol-containing products. ( 2 , 5.20 ) Severe Renal Impairment : Do not exceed 2 tablets every 12 hours. ( 2.4 ) Do not rapidly reduce or abruptly discontinue tramadol hydrochloride and acetaminophen tablets in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.5 , 5.21) 2.1 Important Dosage and Administration Instructions Tramadol hydrochloride and acetaminophen tablets are not approved for use for more than 5 days. Do not exceed the recommended dose of tramadol hydrochloride and acetaminophen tablets. Do not co-administer tramadol hydrochloride and acetaminophen tablets with other tramadol or acetaminophen containing products [see Warnings and Precautions (5.20) ] . Tramadol hydrochloride and acetaminophen tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions (5) ] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of tramadol hydrochloride and acetaminophen tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musc …

3 DOSAGE FORMS AND STRENGTHS Each tramadol hydrochloride and acetaminophen tablet, USP contains 37.5 mg of tramadol hydrochloride, USP and 325 mg of acetaminophen, USP. The tablets are beige colored, film-coated, biconvex capsule shaped tablets with “AN 617” debossed on one side and plain on the other side. Tablets: tramadol hydrochloride 37.5 mg and acetaminophen 325 mg. ( 3 )

4 CONTRAINDICATIONS Tramadol hydrochloride and acetaminophen tablets are contraindicated for: all children younger than 12 years of age. [see Warnings and Precautions (5.4) ] post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions (5.4) ] . Tramadol hydrochloride and acetaminophen tablets are also contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.3) ] . Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.13) ] . Patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.17) ] . Previous hypersensitivity to tramadol, acetaminophen, any other component of this product, or opioids [see Warnings and Precautions (5.18) ]. Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7) ]. Children younger than 12 years of age. ( 4 ) Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. ( 4 ) Significant respiratory depression. ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus. ( 4 ) Previous hypersensitivity to tramadol hydrochloride, acetaminophen, any other component of this product, or opioids. ( 4 ) Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days ( 4 )

6 ADVERSE REACTIONS The following serious adverse reactions are discussed, or described in greater detail, in other sections: Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions (5.8) ] Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1) ] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2) ] Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.3) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4) ] Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children [see Warnings and Precautions (5.6) ] Hepatotoxicity [see Warnings and Precautions (5.9) ] Serotonin Syndrome [see Warnings and Precautions (5.10) ] Seizures [see Warnings and Precautions (5.11) ] Suicide [see Warnings and Precautions (5.12) ] Adrenal Insufficiency [see Warnings and Precautions (5.14) ] Severe Hypotension [see Warnings and Precautions (5.15) ] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.18) ] Hypersensitivity Reactions [see Warnings and Precautions (5.19) ] Withdrawal [see Warnings and Precautions (5.21) ] The most common incidence of treatment-emergent adverse events (≥ 3%) in patients from clinical trials were constipation, diarrhea, nausea, somnolence, anorexia, dizziness, and sweating increased. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials 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. The most common incidence of treatment-emergent adverse events (≥ 3%) in subjects from clinical trials was constipation, diarrhea, nausea, somnolence, anorexia, dizziness, and sweating increased. Table 1 shows the incidence rate of treatment-emergent adverse events reported in ≥ 2% of subjects over five days of tramadol hydrochloride and acetaminophen use in clinical trials (subjects took an average of at least 6 tablets per day). Table 1: Incidence of Treatment-Emergent Adverse Events (≥ 2%) Body System Preferred Term Tramadol Hydrochloride and Acetaminophen (N=142) (%) Gastrointestinal System Disorders Constipation Diarrhea Nausea Dry Mouth 6 3 3 2 Psychiatric Disorders Somnolence Anorexia Insomnia 6 3 2 Central & Peripheral Nervous System Dizziness 3 Skin and Appendages Sweating Increased Pruritus 4 2 Reproductive Disorders, Male * Prostatic Disorder 2 * Number of males = 62 Incidence at least 1%, causal relationship at least possible or greater: The following lists adverse reactions that occurred with an incidence of at least 1% in single-dose or repeated-dose clinical trials of tramadol hydrochloride and acetaminophen. Body as a Whole – Asthenia, fatigue, hot flushes Central and Peripheral Nervous System – Dizziness, headache, tremor Gastrointestinal System – Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, dry mouth, nausea, vomiting Psychiatric Disorders – Anorexia, anxiety, confusion, euphoria, insomnia, nervousness, somnolence Skin and Appendages – Pruritus, rash, increased sweating Selected Adverse events occurring at less than 1%: The following lists clinically relevant adverse reactions that occurred with an incidence of less than 1% in tramadol hydrochloride and acetaminophen clinical trials. Body as a Whole – Chest pain, rigors, syncope, withdrawal syndrome Cardiovascular Disorders – Hypertension, aggravated hypertension, hypotension Central and Peripheral Nervous System – Ataxia, convulsions, hypertonia, migraine, aggravated migraine, involuntary muscle contractions, paresthesias, stupor, vertigo Gastrointestinal System – Dysphagia, melena, tongue edema Hearing and Vestibular Disorders – Tinnitus Heart R …

7 DRUG INTERACTIONS Table 2 includes clinically significant interactions with tramadol hydrochloride and acetaminophen. Table 2: Clinically Significant Drug Interactions with Tramadol Hydrochloride and Acetaminophen Inhibitors of CYP2D6 Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophen and CYP2D6 inhibitors may result in an increase in the plasma concentration of tramadol and a decrease in the plasma concentration of M1, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride and acetaminophen is achieved. Since M1 is a more potent μ-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. After stopping a CYP2D6 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease and the M1 plasma concentration will increase which could increase or prolong therapeutic effects but also increase adverse reactions related to opioid toxicity, and may cause potentially fatal respiratory depression [see Clinical Pharmacology (12.3) ] . Intervention: If concomitant use of a CYP2D6 inhibitor is necessary, follow patients closely for adverse reactions including opioid withdrawal, seizures and serotonin syndrome. If a CYP2D6 inhibitor is discontinued, consider lowering tramadol hydrochloride and acetaminophen dosage until stable drug effects are achieved. Follow patients closely for adverse events including respiratory depression and sedation. Examples: Quinidine, fluoxetine, paroxetine and bupropion Inhibitors of CYP3A4 Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophen and CYP3A4 inhibitors can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1. Follow patients closely for increased risk of serious adverse events including seizures and serotonin syndrome, and adverse reactions related to opioid toxicity including potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride and acetaminophen is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease [see Clinical Pharmacology (12.3) ] , resulting in decreased opioid efficacy and possibly signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. Intervention: If concomitant use is necessary, consider dosage reduction of tramadol hydrochloride and acetaminophen until stable drug effects are achieved. Follow patients closely for seizures and serotonin syndrome, and signs of respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the tramadol hydrochloride and acetaminophen dosage until stable drug effects are achieved and follow patients for signs and symptoms of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophen and CYP3A4 inducers can decrease the plasma concentration of tramadol [see Clinical Pharmacology (12.3) ] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the tramadol plasma concentration will increase [see Clinical Pharmacology (12.3) ] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depressio …

8 USE IN SPECIFIC POPULATIONS Pregnancy : May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.5) ] . Available data with tramadol hydrochloride and acetaminophen in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, the combination of tramadol and acetaminophen decreased fetal weights and increased supernumerary ribs at 1.6 times the maximum recommended human daily dosage (MRHD). In separate animal reproduction studies, tramadol administration alone during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (MRHD). Tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the MRHD. Reproductive and developmental studies in rats and mice from the published literature identified adverse events at clinically relevant doses with acetaminophen. Treatment of pregnant rats with doses of acetaminophen approximately 1.3 times the maximum human daily dose (MRHD) showed evidence of fetotoxicity and increases in bone variations in the fetuses. In another study, necrosis was observed in the liver and kidney of both pregnant rats and fetuses at doses approximately 1.9 times the MHDD. In mice treated with acetaminophen at doses within the clinical dosing range, cumulative adverse effects on reproduction were seen in a continuous breeding study. A reduction in number of litters of the parental mating pair was observed as well as retarded growth and abnormal sperm in their offspring and reduced birth weight in the next generation [see Data] . Based on animal data, advise pregnant women of the potential risk to a fetus. 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% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms and signs of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.5) ] . Neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported with tramadol hydrochloride during postmarketing. Labor or Delivery Tramadol hydrochloride and acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in the neonate. Tramadol hydrochloride and acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including tramadol hydrochloride and acetaminophen, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is …

12.1 Mechanism of Action Tramadol hydrochloride and acetaminophen tablets contains tramadol, an opioid agonist and inhibitor of norepinephrine and serotonin re-uptake, and acetaminophen. Although the mode of action of tramadol is not completely understood, the analgesic effect of tramadol is believed to be due to both binding to μ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity of tramadol is due to both low affinity binding of the parent compound and higher affinity binding of the O -demethylated metabolite M1 to μ-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in μ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound [see Clinical Pharmacology (12.3) ] . Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro , as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol. Acetaminophen is a non-opioid, non-salicylate analgesic. The site and mechanism for the analgesic effect of acetaminophen has not been determined but is thought to primarily involve central actions.

DESCRIPTION Tramadol hydrochloride and acetaminophen tablets, USP combine two analgesics, tramadol, USP 37.5 mg and acetaminophen, USP 325 mg. The chemical name for tramadol hydrochloride, USP is (±) cis -2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride. Its structural formula is: The molecular weight of tramadol hydrochloride, USP is 299.84. Tramadol hydrochloride, USP is a white, bitter, crystalline and odorless powder. The chemical name for acetaminophen, USP is N -acetyl- p -aminophenol. Its structural formula is: The molecular weight of acetaminophen, USP is 151.17. Acetaminophen, USP is an analgesic and antipyretic agent which occurs as a white, odorless, crystalline powder, possessing a slightly bitter taste. Tramadol hydrochloride and acetaminophen tablets, USP contain 37.5 mg tramadol hydrochloride, USP and 325 mg acetaminophen, USP and are beige in color. Inactive ingredients in the tablets are carnauba wax, crospovidone, iron oxide black, iron oxide red, iron oxide yellow, microcrystalline cellulose, pregelatinized starch, polyethylene glycol, polyvinyl alcohol, povidone, sodium starch glycolate, stearic acid, talc and titanium dioxide. Dissolution Method: Test 2 24f1bdbc-figure-01 24f1bdbc-figure-02

10 OVERDOSAGE Clinical Presentation Tramadol hydrochloride and acetaminophen tablet is a combination drug. The clinical presentation of overdose may include the signs and symptoms of tramadol toxicity, acetaminophen toxicity or both. The initial symptoms of tramadol overdosage may include respiratory depression and/or seizures. The initial symptoms seen within the first 24 hours following an acetaminophen overdose are: anorexia, nausea, vomiting, malaise, pallor and diaphoresis. Tramadol Acute overdosage with tramadol can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, QT prolongation, hypotension, partial or complete airway obstruction, atypical snoring, seizures, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2) ] . Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Deaths due to overdose have been reported with abuse and misuse of tramadol [see Warnings and Precautions (5.1) ] . Review of case reports has indicated that the risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol or other CNS depressants, including other opioids. Acetaminophen In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia also occur. Plasma acetaminophen levels > 300 mcg/mL at 4 hours after oral ingestion were associated with hepatic damage in 90% of patients; minimal hepatic damage is anticipated if plasma levels at 4 hours are < 150 mcg/mL or < 37.5 mcg/mL at 12 hours after ingestion. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. Treatment of Overdose A single or multiple drug overdose with tramadol and acetaminophen is a potentially lethal polydrug overdose. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Oxygen, intravenous fluids, vasopressors, assisted ventilation, and other supportive measures should be employed as indicated. Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control center (where available) to determine the latest recommendations for the management of an overdose. Tramadol In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures. For clinically significant respiratory or circulatory depression secondary to opioid overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. While an opioid overdose reversal agent will reverse some, but not all, symptoms caused by overdosage with tramadol, the risk of seizures is also increased with reversal agent administration. In animals, convulsions following the administration of toxic doses of tramadol hydrochloride and acetaminophen could be suppressed with barbiturates or benzodiazepines but were increased with naloxone. Naloxone administration did not change the lethality of an overdose in mice. Hemodialysis is not expected to be helpful in an overdose because it removes less than 7% of the administered dose in a 4-hour dialysis period. Because the duration of opioid reversal is expected to be less than the duration of action of tramadol in tramad …

16 HOW SUPPLIED/STORAGE AND HANDLING Tramadol hydrochloride and acetaminophen tablets USP, 37.5 mg/325 mg, are supplied as beige colored, film-coated, biconvex capsule shaped tablets with “AN 617” debossed on one side and plain on the other side. NDC: 71335-0111-1: 30 Tablets in a BOTTLE NDC: 71335-0111-2: 60 Tablets in a BOTTLE NDC: 71335-0111-3: 90 Tablets in a BOTTLE NDC: 71335-0111-4: 120 Tablets in a BOTTLE NDC: 71335-0111-5: 20 Tablets in a BOTTLE NDC: 71335-0111-6: 40 Tablets in a BOTTLE NDC: 71335-0111-7: 100 Tablets in a BOTTLE NDC: 71335-0111-8: 15 Tablets in a BOTTLE Dispense in a tight container. Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight container as defined in the USP. Store tramadol hydrochloride and acetaminophen tablets securely and dispose of properly [see PATIENT COUNSELING INFORMATION (17)]. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504