TRAMADOL HYDROCHLORIDE tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

Golden State Medical Supply, Inc.

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, which can occur at any dosage or duration [see Warnings and Precautions ( 5.1)] , reserve tramadol hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: - 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 tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. Tramadol hydrochloride tablets are contraindicated for: - all children younger than 12 years of age [see Warnings and Precautions ( 5.6)] . - postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions ( 5.6)] . Tramadol hydrochloride tablets are also contraindicated in patients with: - Significant respiratory depression [see Warnings and Precautions ( 5.2)] . - 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 and Precautions ( 5.16)] . - Hypersensitivity to tramadol, any other component of this product or opioids [see Warnings and Precautions ( 5.17)] . - Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions ( 7)] . Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4)] . Available data with tramadol hydrochloride tablets 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 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time 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 ( 5.4)] . 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 tablets are 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 tablets, 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 tablets, 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 tablets are 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 tablets  [see Warnings and Precautions ( 5.6)] . 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 Use of opioids for an extended period of time 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 tablets in pediatric patients have not been established. Life-threatening respiratory depression and death have occurred in children who received tramadol [see Warnings and Precautions ( 5.6)] . 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 tablets are contraindicated for all children younger than 12 years of age [see Contraindications ( 4)] . - Tramadol hydrochloride tablets are 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 tablets 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 tablets 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 tablets slowly in geriatric patients starting at the low end of the dosing range and frequently reevaluate the patient 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 contain tramadol, a Schedule IV controlled substance. Tramadol hydrochloride tablets contain tramadol, a substance with potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions ( 5.1)] . Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of tramadol hydrochloride tablets increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of tramadol hydrochloride tablets with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction. All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of tramadol hydrochloride tablets abuse include those with a history of prolonged use of any opioid, including products containing tramadol, those with a history of drug or alcohol abuse, or those who use tramadol hydrochloride tablets in combination with other abused drugs. “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 healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. Tramadol hydrochloride tablets, like other opioids, can be diverted for nonmedical 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 reevaluation 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 Tablets Abuse of tramadol hydrochloride tablets poses a risk of overdose and death. The risk is increased with concurrent use of tramadol hydrochloride tablets with alcohol and/or other CNS depressants. Tramadol hydrochloride tablets are approved for oral use only. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Both tolerance and physical dependence can develop during use of opioid therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. Do not abruptly discontinue tramadol hydrochloride tablets in a patient physically dependent on opioids. Rapid tapering of tramadol hydrochloride tablets 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 tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of tramadol hydrochloride tablets 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 an extended period of time 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 ( 5.18)] . 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 available as white, film-coated, unscored, oval-shaped tablets, debossed “TV” on one side and debossed “58” on the other side. They are available in bottles of 100 (NDC 60429-588-01) and 500 (NDC 60429-588-05). Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). Keep this and all medications out of the reach of children. Store tramadol hydrochloride tablets securely and dispose of properly [see Patient Counseling Information ( 17)] .

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Golden State Medical Supply, Inc.
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Dispense with Medication Guide available at: www.tevausa.com/medguides
MEDICATION GUIDE
Tramadol Hydrochloride ( tram′ a dol hye″ droe klor′ ide)
Tablets, C-IV
Tramadol hydrochloride tablets are:
•
A strong prescription pain medicine that contains an opioid (narcotic)
that is used for the management of 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 them. 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
years of age after surgery to remove the tonsils and

Summary of Product characteristics

TRAMADOL HYDROCHLORIDE- TRAMADOL HYDROCHLORIDE TABLET, FILM COATED
GOLDEN STATE MEDICAL SUPPLY, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
TRAMADOL HYDROCHLORIDE TABLETS. 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, C-IV
INITIAL U.S. APPROVAL: 1995
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL
HYDROCHLORIDE TABLETS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
TRAMADOL HYDROCHLORIDE TABLETS EXPOSE 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 TABLETS, AND MONITOR REGULARLY FOR
THESE
BEHAVIORS OR CONDITIONS. ( 5.1)
SERIOUS, LIFE-THREATENING, OR FATAL RESPIRATORY DEPRESSION MAY OCCUR.
MONITOR CLOSELY,
ESPECIALLY DURING INITIATION OR FOLLOWING A DOSE INCREASE. ( 5.2)
ACCIDENTAL INGESTION OF TRAMADOL HYDROCHLORIDE TABLETS, ESPECIALLY BY
CHILDREN, CAN
RESULT IN A FATAL OVERDOSE OF TRAMADOL. ( 5.2)
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. RESERVE CONCOMITANT PRESCRIBING FOR USE
IN PATIENTS
FOR WHOM ALTERNATIVE TREATMENT OPTIONS ARE INADEQUATE; LIMIT DOSAGES
AND DURATIONS
TO THE MINIMUM REQUIRED; AND FOLLOW PATIENTS FOR SIGNS AND SYMPTOMS OF
RESPIRATORY
DEPRESSION AND SEDATION. ( 5.3, 7)
PROLONGED USE OF TRAMADOL HYDROCHLORIDE TABLETS, DURING PREGNANCY CAN
RESULT IN
NEONATAL OPIOID WITHDRAWAL SYNDROME, WHICH MAY BE LIFE THREATENING IF
NOT
RECOGNIZED AND TREATED. IF PROLONGED OPIOID USE IS REQUIRED IN A
PREGNANT WOMAN,
ADVISE THE PATIENT OF THE RISK OF NEONATAL OPIOID WITHDRAWAL SYNDROME
AND ENSURE
THAT APPROPRIATE TREATMENT WILL BE AVAILABLE. ( 5.4)
TO ENSURE THAT THE BENEFITS OF OPIOID ANALGESICS OUTWEIGH THE RISKS OF
ADDIC