TRAMADOL HYDROCHLORIDE tablet, coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

TRAMADOL HYDROCHLORIDE (UNII: 9N7R477WCK) (TRAMADOL - UNII:39J1LGJ30J)

Available from:

American Health Packaging

INN (International Name):

TRAMADOL HYDROCHLORIDE

Composition:

TRAMADOL HYDROCHLORIDE 50 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Tramadol hydrochloride tablets are indicated in adults for the management of pain 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 and Precautions (5.1)] , reserve tramadol hydrochloride 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 is contraindicated for: - all children younger than 12 years of age [see Warnings and Precautions (5.4)] . - postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions (5.4)] . Tramadol hydrochloride is 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 (5.12)] . - Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings andPrecautions (5.15)] . - Hypersensitivity to tramadol, any other component of this product or opioids [see Warnings andPrecautions (5.16)] . - Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7)] . Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with tramadol hydrochloride in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, tramadol administration 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 [see Data] . Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 can present 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 still birth have been reported during postmarketing. Labor or Delivery 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 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, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor. The effect of tramadol hydrochloride, if any, on the later growth, development, and functional maturation of the child is unknown. Data Animal Data Tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg), rats (25 mg/kg) and rabbits (75 mg/kg) at maternally toxic dosages, but was not teratogenic at these dose levels. These doses on a mg/m 2 basis are 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (MRHD) for mouse, rat and rabbit, respectively. No drug-related teratogenic effects were observed in progeny of mice (up to 140 mg/kg), rats (up to 80 mg/kg) or rabbits (up to 300 mg/kg) treated with tramadol by various routes. Embryo and fetal toxicity consisted primarily of decreased fetal weights, decreased skeletal ossification and increased supernumerary ribs at maternally toxic dose levels. Transient delays in developmental or behavioral parameters were also seen in pups from rat dams allowed to deliver. Embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit. The dosages listed for mouse, rat and rabbit are 1.7, 1.9 and 14.6 times the MRHD, respectively. Tramadol was evaluated in pre- and post-natal studies in rats. Progeny of dams receiving oral (gavage) dose levels of 50 mg/kg 1.2 times the MRHD) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (1.9 times the MRHD). Risk Summary Tramadol hydrochloride is not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. Tramadol and its metabolite, O -desmethyltramadol (M1), are present in human milk. There is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. The M1 metabolite is more potent than tramadol in mu opioid receptor binding [see Clinical Pharmacology (12)] . Published studies have reported tramadol and M1 in colostrum with administration of tramadol to nursing mothers in the early post-partum period. Women who are ultra-rapid metabolizers of tramadol may have higher than expected serum levels of M1, potentially leading to higher levels of M1 in breast milk that can be dangerous in their breastfed infants. In women with normal tramadol metabolism, the amount of tramadol secreted into human milk is low and dose-dependent. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with tramadol hydrochloride [see Warnings and Precautions (5.4)] . Clinical Considerations If infants are exposed to tramadol hydrochloride through breast milk, they should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. Data Following a single IV 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours post dose was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of M1. Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6.2)] . The safety and effectiveness of tramadol hydrochloride in pediatric patients have not been established. Life-threatening respiratory depression and death have occurred in children who received tramadol [see Warnings and Precautions (5.4)] . In some of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being an ultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6). Children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol. Because of the risk of life-threatening respiratory depression and death: - Tramadol hydrochloride is contraindicated for all children younger than 12 years of age [see Contraindications (4)] . - Tramadol hydrochloride is contraindicated for postoperative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)] . Avoid the use of tramadol hydrochloride in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. Risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression. A total of 455 elderly (65 years of age or older) subjects were exposed to tramadol hydrochloride in controlled clinical trials. Of those, 145 subjects were 75 years of age and older. In studies including geriatric patients, treatment-limiting adverse events were higher in subjects over 75 years of age compared to those under 65 years of age. Specifically, 30% of those over 75 years of age had gastrointestinal treatment-limiting adverse events compared to 17% of those under 65 years of age. Constipation resulted in discontinuation of treatment in 10% of those over 75. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of tramadol hydrochloride slowly in geriatric patients starting at the low end of the dosing range and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.12)] . Tramadol is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. 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, dosing reduction is recommended [see Dosage and Administration (2.3)] . Metabolism of tramadol and M1 is reduced in patients with severe hepatic impairment based on a study in patients with advanced cirrhosis of the liver. In patients with severe hepatic impairment, dosing reduction is recommended [see Dosage and Administration (2.3)] . With the prolonged half-life in these conditions, achievement of steady-state is delayed, so that it may take several days for elevated plasma concentrations to develop. Tramadol hydrochloride tablets contains tramadol, a Schedule IV controlled substance. Tramadol hydrochloride tablets contains tramadol, a substance with a high potential for abuse similar to other opioids. Tramadol hydrochloride can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions (5.1)] . All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful, or potentially harmful, consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction. Tramadol hydrochloride, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Risks Specific to Abuse of Tramadol Hydrochloride Tramadol hydrochloride is intended for oral use only. Abuse of tramadol hydrochloride poses a risk of overdose and death. The risk is increased with concurrent abuse of tramadol hydrochloride with alcohol and other central nervous system depressants. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of drugs to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. Do not abruptly discontinue tramadol hydrochloride in a patient physically dependent on opioids. Rapid tapering of tramadol hydrochloride in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. When discontinuing tramadol hydrochloride, gradually taper the dosage using a patient-specific plan that considers the following: the dose of tramadol hydrochloride the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see Dosage and Administration (2.5), Warnings and Precautions (5.17)] . Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)] .

Product summary:

Tramadol Hydrochloride Tablets USP, 50 mg are supplied as unscored, white, round film-coated tablets debossed “AN” over “627” on one side and plain on the other side. They are supplied as follows: Unit dose packages of 100 (10 x 10) NDC 68084-808-01 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]. Store tramadol hydrochloride tablets securely and dispose of properly [see Patient Counseling Information (17)] . FOR YOUR PROTECTION: Do not use if blister is torn or broken.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

American Health Packaging
----------
MEDICATION GUIDE
Dispense with Medication Guide.
To order more Medication Guides call American Health Packaging at
1‐800‐707‐4621.
8280801/0223
Tramadol Hydrochloride (tram’ a dol hye” droe klor’ ide)
Tablets, USP CIV
Tramadol hydrochloride 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 hydrochloride tablets:
•
Get emergency help or call 911 right away if you take too many
tramadol hydrochloride tablets
(overdose). When you first start taking tramadol hydrochloride
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. Talk to your healthcare provider about
naloxone, a medicine for the
emergency treatment of an opioid overdose.
•
Taking tramadol hydrochloride 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 hydrochloride tablets. They could
die from taking it.
Selling or giving away tramadol hydrochloride tablets is against the
law.
•
Store tramadol hydrochloride tablets securely, out of sight and reach
of children, and in a location
not accessible by others, including visitors to the home.
Important Information Guiding Use in Pediatric Patients:
•
Do not give tramadol hydrochloride tablets to a child younger than 12
years of age.
•
Do not give tramadol hydrochloride tablets to a child younger than 18

Summary of Product characteristics

TRAMADOL HYDROCHLORIDE- TRAMADOL HYDROCHLORIDE TABLET, COATED
AMERICAN HEALTH PACKAGING
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TRAMADOL
HYDROCHLORIDE TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
TRAMADOL HYDROCHLORIDE TABLETS.
TRAMADOL HYDROCHLORIDE TABLETS, FOR ORAL USE, CIV
INITIAL U.S. APPROVAL: 1995
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION
STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
INGESTION; ULTRA-RAPID METABOLISM OF TRAMADOL AND OTHER RISK FACTORS
FOR
LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID
WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450
ISOENZYMES; AND RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR
OTHER
CNS DEPRESSANTS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
TRAMADOL HYDROCHLORIDE EXPOSES USERS TO THE RISKS OF ADDICTION, ABUSE
AND MISUSE,
WHICH CAN LEAD TO OVERDOSE AND DEATH. ASSESS EACH PATIENT’S RISK
PRIOR TO
PRESCRIBING TRAMADOL HYDROCHLORIDE, AND MONITOR REGULARLY FOR THESE
BEHAVIORS OR
CONDITIONS. ( 5.1)
TO ENSURE THAT THE BENEFITS OF OPIOID ANALGESICS OUTWEIGH THE RISKS OF
ADDICTION,
ABUSE, AND MISUSE, THE FOOD AND DRUG ADMINISTRATION (FDA) HAS REQUIRED
A RISK
EVALUATION AND MITIGATION STRATEGY (REMS) FOR THESE PRODUCTS. ( 5.2)
SERIOUS, LIFE-THREATENING, OR FATAL RESPIRATORY DEPRESSION MAY OCCUR.
MONITOR CLOSELY,
ESPECIALLY DURING INITIATION OR FOLLOWING A DOSE INCREASE. ( 5.3)
ACCIDENTAL INGESTION OF TRAMADOL HYDROCHLORIDE, ESPECIALLY BY
CHILDREN, CAN RESULT IN
A FATAL OVERDOSE OF TRAMADOL. ( 5.3)
LIFE-THREATENING RESPIRATORY DEPRESSION AND DEATH HAVE OCCURRED IN
CHILDREN WHO
RECEIVED TRAMADOL. SOME OF THE REPORTED CASES FOLLOWED TONSILLECTOMY
AND/OR
ADENOIDECTOMY; IN AT LEAST ONE CASE, THE CHILD HAD EVIDENCE OF BEING
AN ULTRA-RAPID
METABOLIZER OF TRAMADOL DUE TO A CYP2D6 POLYMORPHISM. ( 5.4)
TRAMADOL HYDROCHLORIDE IS CONTRAINDICATED IN CHILDREN YOUNGER THAN 12
YEARS