TRAMADOL HYDROCHLORIDE tablet, extended release

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

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

Tilgjengelig fra:

Lupin Pharmaceuticals, Inc.

INN (International Name):

TRAMADOL HYDROCHLORIDE

Sammensetning:

TRAMADOL HYDROCHLORIDE 100 mg

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

Tramadol hydrochloride extended-release tablet is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. Limitations of Use - Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosages or duration, and because of the greater risks of overdose and death with extended-release opioid formulations [see Warnings and Precautions (5.1)] , reserve tramadol hydrochloride extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - Tramadol hydrochloride extended-release tablet is not indicated as an as-needed (prn) analgesic. Tramadol hydrochloride extended-release 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 extended-release 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 (5.12)] - Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.15)] - Hypersensitivity to tramadol (e.g., anaphylaxis) [see Warnings and Precautions (5.16), Adverse Reactions (6.2)] - 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 extended-release 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 to 4% and 15 to 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 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 (5.4)] . Neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported with tramadol during post-approval use of tramadol immediate-release products. 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 extended-release tablets are not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including tramadol hydrochloride extended-release 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 extended-release 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/m2 basis are 1.9, 0.8, and 4.9 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 2.3, 2.6, and 19 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 (1.6 times the MRHD) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (2.6 times the MRHD). Risk Summary Tramadol hydrochloride extended-release 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-desmethyl tramadol (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 (12.1)] . 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 extended-release tablets. 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), Clinical Pharmacology (12.2), Nonclinical Toxicology (13.1)] . The safety and effectiveness of tramadol hydrochloride extended-release 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 extended-release tablets are contraindicated for all children younger than 12 years of age [see Contraindications (4)] . - Tramadol hydrochloride extended-release tablets are contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)]. - Avoid the use of tramadol hydrochloride extended-release 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. [see Warnings and Precautions (5.6)]. Nine-hundred-one elderly (65 years of age or older) subjects were exposed to tramadol hydrochloride extended-release tablets in clinical trials. Of those subjects, 156 were 75 years of age and older. In general, higher incidence rates of adverse events were observed for patients older than 65 years of age compared with patients 65 years and younger, particularly for the following adverse events: constipation, fatigue, weakness, postural hypotension and dyspepsia. For this reason, tramadol hydrochloride extended-release tablets should be used with caution in patients over 65 years of age, and with even greater caution in patients older than 75 years of age [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)] . 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 extended-release tablets slowly in geriatric patients 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 regularly evaluate renal function. Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of the liver. Tramadol hydrochloride extended-release tablet has not been studied in patients with severe hepatic impairment. The limited availability of dose strengths and once daily dosing of tramadol hydrochloride extended-release tablets do not permit the dosing flexibility required for safe use in patients with severe hepatic impairment (Child-Pugh Class C). Therefore, tramadol hydrochloride extended-release tablets should not be used in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)] . Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1. Tramadol hydrochloride extended-release tablet has not been studied in patients with severe renal impairment (CLcr < 30 mL/min). The limited availability of dose strengths and once daily dosing of tramadol hydrochloride extended-release tablets do not permit the dosing flexibility required for safe use in patients with severe renal impairment (Child-Pugh Class C). Therefore, tramadol hydrochloride extended-release tablets should not be used in patients with severe renal impairment [see Clinical Pharmacology (12.3)] . Tramadol hydrochloride extended-release tablet contains tramadol, a scheduled IV controlled substance. Tramadol hydrochloride extended-release tablet contains tramadol, a substance with high 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 extended-release tablet 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 extended-release tablet 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 extended-release tablet 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 extended-release tablet 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 extended-release 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 Extended-Release Tablets Abuse of tramadol hydrochloride extended-release tablets poses a risk of overdose and death. This is increased with concurrent use of tramadol hydrochloride extended-release tablets with alcohol and/or other CNS depressants. Tramadol hydrochloride extended-release tablets are approved for oral use only. Inappropriate intravenous, intramuscular, or subcutaneous use of tramadol hydrochloride extended-release tablets can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism. With parenteral abuse the inactive ingredients can result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis and valvular heart injury, embolism, and death. 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 also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), 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 opioid usage. Do not abruptly discontinue tramadol hydrochloride extended-release tablets in a patient physically dependent on opioids. Rapid tapering of tramadol hydrochloride extended-release 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 extended-release tablets, gradually taper the dosage using a patient specific plan that considers the following: the dose of tramadol hydrochloride extended-release 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 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 (2.1), 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)].

Produkt oppsummering:

Tramadol hydrochloride extended-release tablets USP are supplied in the following package and dose strength forms: 100 mg tablets (white to off-white circular, biconvex, beveled edge, coated) imprinted with 'L010' on one side and plain on the other side. Bottles of 30 tablets:               NDC 68180-697-06 Bottles of 100 tablets:             NDC 68180-697-01 Bottles of 500 tablets:             NDC 68180-697-02 200 mg tablets (white to off-white circular, biconvex, beveled edge, coated) imprinted with 'L011' on one side and plain on the other side. Bottles of 30 tablets:               NDC 68180-698-06 Bottles of 100 tablets:             NDC 68180-698-01 Bottles of 500 tablets:             NDC 68180-698-02 300 mg tablets (white to off-white circular, biconvex, beveled edge, coated) imprinted with 'L012' on one side and plain on the other side Bottles of 30 tablets:               NDC 68180-699-06 Bottles of 100 tablets:             NDC 68180-699-01 Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Store tramadol hydrochloride extended release tablets securely and dispose of properly [see Patient Counseling Information (17) ].

Autorisasjon status:

Abbreviated New Drug Application

Informasjon til brukeren

TRAMADOL HYDROCHLORIDE- TRAMADOL HYDROCHLORIDE TABLET, EXTENDED
RELEASE
Lupin Pharmaceuticals, Inc.
----------
Medication Guide
Tramadol Hydrochloride Extended-Release Tablets , CIV
(tram' a dol hye'' droe klor' ide)
Tramadol hydrochloride extended-release tablets are:
•
A strong prescription pain medicine that contains an opioid (narcotic)
that is used to manage
severe and persistent pain that requires an extended treatment period
with a daily opioid pain
medicine, when other pain medicines do not treat your pain well enough
or you cannot tolerate
them.
•
A long-acting (extended-release) 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.
•
Not to be taken on an "as needed" basis.
Important information about tramadol hydrochloride extended-release
tablets:
•
Get emergency help or call 911 right away if you take too much
tramadol hydrochloride extended-
release tablets (overdose). When you first start taking tramadol
hydrochloride extended-release
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 extended-release 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 extended-release
tablets. They could die
from taking it. Selling or giving away tramadol hydrochloride
extended-release tablets is against
the law.
•
Store tramadol hydrochloride extended-release tablets securely, out of
sight and reach of children,
and in a location not accessible by others, including visitors to the
home.
Important In

Preparatomtale

TRAMADOL HYDROCHLORIDE- TRAMADOL HYDROCHLORIDE TABLET, EXTENDED
RELEASE
LUPIN PHARMACEUTICALS, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TRAMADOL
HYDROCHLORIDE EXTENDED-RELEASE TABLETS SAFELY AND EFFECTIVELY. SEE
FULL PRESCRIBING
INFORMATION FOR TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS.
TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS FOR ORAL USE, C IV
INITIAL U.S. APPROVAL: 1995
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL
HYDROCHLORIDE EXTENDED-RELEASE TABLETS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLET EXPOSES USERS TO RISKS
OF ADDICTION,
ABUSE, AND MISUSE, WHICH CAN LEAD TO OVERDOSE AND DEATH. ASSESS
PATIENT'S RISK
BEFORE PRESCRIBING AND MONITOR REGULARLY FOR THESE BEHAVIORS AND
CONDITIONS. (5.1)
SERIOUS, LIFE-THREATENING, OR FATAL RESPIRATORY DEPRESSION MAY OCCUR.
MONITOR CLOSELY,
ESPECIALLY UPON INITIATION OR FOLLOWING A DOSE INCREASE. INSTRUCT
PATIENTS TO SWALLOW
TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS WHOLE TO AVOID
EXPOSURE TO A
POTENTIALLY FATAL DOSE OF TRAMADOL. (5.2)
ACCIDENTAL INGESTION OF TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE
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 EXTENDED-RELEASE 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 O