Complete SPL Sections#
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFETHREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
BOXED WARNING SECTION
ADDICTION, ABUSE AND MISUSE Tramadol HCl exposes patients and other users to the risks of opioid addiction, abuse and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing tramadol HCl, and monitor all patients regularly for the development of these behaviors and conditions (see WARNINGS ). LIFE-THREATENING RESPIRATORY DEPRESSION Serious, life-threatening, or fatal respiratory depression may occur with use of tramadol HCl. Monitor for respiratory depression, especially during initiation of tramadol HCl or following a dose increase (see WARNINGS ). ACCIDENTAL INGESTION Accidental ingestion of tramadol HCl, especially by children, can be fatal (see WARNINGS ). NEONATAL OPIOID WITHDRAWAL SYNDROME Prolonged use of tramadol HCl during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (see WARNINGS ). INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with Tramadol HCl requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1 (see WARNINGS , PRECAUTIONS; Drug Interactions ). RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death (see WARNINGS , PRECAUTIONS; Drug Interactions ). Reserve concomitant prescribing of tramadol HCl and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit treatment to the minimum effective dosages and durations. Follow patients for signs and symptoms of respiratory depression and sedation.
DESCRIPTION
DESCRIPTION SECTION
Tramadol hydrochloride (HCl) tablets, USP are an opioid agonist. The chemical name for tramadol HCl, USP is (±) cis -2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride. The structural formula is: The molecular weight of tramadol HCl, USP is 299.8. Tramadol HCl, USP is a white, bitter, crystalline and odorless powder. It is readily soluble in water and ethanol and has a pKa of 9.41. The n-octanol/water log partition coefficient (logP) is 1.35 at pH 7. Tramadol HCl tablets, USP contain 50 mg of tramadol HCl, USP and are white in color. Inactive ingredients in the tablet are hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, pregelatinized starch, sodium starch glycolate, and titanium dioxide.
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
CLINICAL STUDIES
CLINICAL STUDIES SECTION
Tramadol HCl has been given in single oral doses of 50, 75 and 100 mg to patients with pain following surgical procedures and pain following oral surgery (extraction of impacted molars). In single-dose models of pain following oral surgery, pain relief was demonstrated in some patients at doses of 50 mg and 75 mg. A dose of 100 mg tramadol HCl tended to provide analgesia superior to codeine sulfate 60 mg, but it was not as effective as the combination of aspirin 650 mg with codeine phosphate 60 mg. Tramadol HCl has been studied in three long-term controlled trials involving a total of 820 patients, with 530 patients receiving tramadol HCl. Patients with a variety of chronic painful conditions were studied in double-blind trials of one to three months duration. Average daily doses of approximately 250 mg of tramadol HCl in divided doses were generally comparable to five doses of acetaminophen 300 mg with codeine phosphate 30 mg (TYLENOL with Codeine #3) daily, five doses of aspirin 325 mg with codeine phosphate 30 mg daily, or two to three doses of acetaminophen 500 mg with oxycodone hydrochloride 5 mg (TYLOX) daily. Titration Trials In a randomized, blinded clinical study with 129 to 132 patients per group, a 10-day titration to a daily tramadol HCl dose of 200 mg (50 mg four times per day), attained in 50 mg increments every 3 days, was found to result in fewer discontinuations due to dizziness or vertigo than titration over only 4 days or no titration. In a second study with 54 to 59 patients per group, patients who had nausea or vomiting when titrated over 4 days were randomized to re-initiate tramadol HCl therapy using slower titration rates. A 16-day titration schedule, starting with 25 mg qAM and using additional doses in 25 mg increments every third day to 100 mg/day (25 mg four times per day), followed by 50 mg increments in the total daily dose every third day to 200 mg/day (50 mg four times per day), resulted in fewer discontinuations due to nausea or vomiting and fewer discontinuations due to any cause than did a 10-day titration schedule.
INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Tramadol HCl tablets are indicated for the management of pain in adults that is severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses (see WARNINGS ), reserve tramadol HCl 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.
CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
Tramadol HCl tablets contraindicated in patients with: Significant respiratory depression (see WARNINGS ). Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see WARNINGS ). Known or suspected gastrointestinal obstruction, including paralytic ileus (see WARNINGS ). Hypersensitivity to tramadol, any other component of this product or opioids (see WARNINGS ). Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (see PRECAUTIONS; Drug Interactions ).
WARNINGS
WARNINGS SECTION
PRECAUTIONS
PRECAUTIONS SECTION
ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse (see WARNINGS ) Life-Threatening Respiratory Depression (see WARNINGS ) Neonatal Opioid Withdrawal Syndrome (see WARNINGS ) Interactions with Benzodiazepines or Other CNS Depressants (see WARNINGS ) Serotonin Syndrome (see WARNINGS ) Seizures (see WARNINGS ) Suicide (see WARNINGS ) Adrenal Insufficiency (see WARNINGS ) Severe Hypotension (see WARNINGS ) Gastrointestinal Adverse Reactions (see WARNINGS ) Hypersensitivity Reactions (see WARNINGS ) Withdrawal (see WARNINGS )
DRUG ABUSE AND DEPENDENCE
DRUG ABUSE AND DEPENDENCE SECTION
OVERDOSAGE
OVERDOSAGE SECTION
Clinical Presentation Acute overdosage with tramadol HCl 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, hypotension, partial or complete airway obstruction, atypical snoring, seizures, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations. Deaths due to overdose have been reported with abuse and misuse of tramadol (see WARNINGS; Addiction, Abuse, and Misuse ). 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. Treatment of Overdose 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 serious arrhythmias will require advanced life-supporting measures. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to tramadol overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to tramadol overdose. While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, the risk of seizures is also increased with naloxone administration. In animals, convulsions following the administration of toxic doses of tramadol HCl 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 tramadol HCl, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
HOW SUPPLIED
HOW SUPPLIED SECTION
Tramadol HCl tablets, USP, 50 mg, are supplied as unscored, white, round film-coated tablets debossed AN over 627. They are supplied as follows: NDC 68071-4119-5 Bottles of 15 NDC 68071-4119-3 Bottles of 30 NDC 68071-4119-4 Bottles of 40 NDC 68071-4119-6 Bottles of 60 NDC 68071-4119-7 Bottles of 84 NDC 68071-4119-9 Bottles of 90 NDC 68071-4119-1 Bottles of 120 NDC 68071-4119- 8 Bottles of 180 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight container as defined in the USP. Manufactured by: Amneal Pharmaceuticals of NY LLC Brookhaven, NY 11719 Distributed by: Amneal Pharmaceuticals LLC Glasgow, KY 42141 Rev. 03-2017-04
Medication Guide
SPL MEDGUIDE SECTION
Tramadol (TRAM-a-dol) Hydrochloride Tablets, USP, CIV Tramadol HCl tablets are: A strong prescription pain medicine that contains an opioid (narcotic) that is used for the management pain in adults, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them. An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death. Important information about tramadol HCl tablets: Get emergency help right away if you take too much tramadol HCl tablets (overdose). When you first start taking tramadol HCl tablets, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Taking tramadol HCl tablets with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death. Never give anyone else your tramadol HCl tablets. They could die from taking it. Store tramadol HCl tablets away from children and in a safe place to prevent stealing or abuse. Selling or giving away tramadol HCl tablets is against the law. Do not take tramadol HCl tablets if you have: Severe asthma, trouble breathing, or other lung problems. A bowel blockage or have narrowing of the stomach or intestines. An allergy to tramadol. Taken a Monoamine Oxidase Inhibitor, MAOI, (medicine used for depression) within the last 14 days. Before taking tramadol HCl tablets, tell your healthcare provider if you have a history of: head injury, seizures problems urinating abuse of street or prescription drugs, alcohol addiction, or mental health problems. liver, kidney, thyroid problems pancreas or gallbladder problems Tell your healthcare provider if you are: pregnant or planning to become pregnant. Prolonged use of tramadol HCl tablets during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. breastfeeding. Tramadol HCl passes into breast milk and may harm your baby. taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking tramadol HCl tablets with certain other medicines can cause serious side effects that could lead to death. When taking tramadol HCl tablets: Do not change your dose. Take tramadol HCl tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed. Take your prescribed dose as indicated by your health care provider. The maximum dosage is 1 or 2 tablets every 4 to 6 hours, as needed for pain relief. Do not take more than your prescribed dose and do not take more than 8 tablets per day. If you miss a dose, take your next dose at your usual time. Call your healthcare provider if the dose you are taking does not control your pain. If you have been taking tramadol HCl tablets regularly, do not stop taking tramadol HCl tablets without talking to your healthcare provider. After you stop taking tramadol HCl tablets, ask your pharmacist how to dispose of any unused tablets. While taking tramadol HCl tablets DO NOT: Drive or operate heavy machinery, until you know how tramadol HCl affects you. Tramadol HCl tablets can make you sleepy, dizzy, or lightheaded. Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with tramadol HCl tablets may cause you to overdose and die. The possible side effects of tramadol HCl tablets: constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe. Get emergency medical help if you have: trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion. These are not all the possible side effects of tramadol HCl tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov Manufactured by: Amneal Pharmaceuticals of NY LLC Brookhaven, NY 11719 Distributed by: Amneal Pharmaceuticals LLC Glasgow, KY 42141 Rev. 03-2017-00 This Medication Guide has been approved by the U.S. Food and Drug Administration.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
