TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

TRAMADOL HYDROCHLORIDE (UNII: 9N7R477WCK) (TRAMADOL - UNII:39J1LGJ30J), ACETAMINOPHEN (UNII: 362O9ITL9D) (ACETAMINOPHEN - UNII:362O9ITL9D)

Available from:

Aurobindo Pharma Limited

INN (International Name):

TRAMADOL HYDROCHLORIDE

Composition:

TRAMADOL HYDROCHLORIDE 37.5 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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 contraindicated for: - all children younger than 12 years of age [see Warnings and Precautions (5.6)] - post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions (5.6)] . Tramadol hydrochloride and acetaminophen 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 (5.13)] . - Patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.18)] . - Previous hypersensitivity to tramadol, acetaminophen, any other component of this product, or opioids [see Warnings and Precautions (5.19)] . - 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 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 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 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 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 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 and acetaminophen, if any, on the later growth, development, and functional maturation of the child is unknown. Data Animal Data No drug-related teratogenic effects were observed in the progeny of rats treated orally with tramadol and acetaminophen. The tramadol/acetaminophen combination product was shown to be embryotoxic and fetotoxic in rats at a maternally toxic dose, 50/434 mg/kg tramadol/acetaminophen (1.6 times the maximum daily human tramadol/acetaminophen dosage), but was not teratogenic at this dose level. Embryo and fetal toxicity consisted of decreased fetal weights and increased supernumerary ribs. 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, 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 alone was evaluated in peri- and post-natal studies in rats. Progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (300 mg/m2 or 1.6 times the maximum daily human tramadol dosage) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (480 mg/m2 or 2.6 times the maximum daily human tramadol dosage). Studies in pregnant rats that received oral acetaminophen during organogenesis at doses up to 1.3 times the maximum human daily dose (MHDD = 2.6 grams/day, based on a body surface area comparison) showed evidence of fetotoxicity (reduced fetal weight and length) and a dose-related increase in bone variations (reduced ossification and rudimentary rib changes). Offspring had no evidence of external, visceral, or skeletal malformations. When pregnant rats received oral acetaminophen throughout gestation at doses of 1.9-times the MHDD (based on a body surface area comparison), areas of necrosis occurred in both the liver and kidney of pregnant rats and fetuses. These effects did not occur in animals that received oral acetaminophen at doses 0.5-times the MHDD, based on a body surface area comparison. In a continuous breeding study, pregnant mice received 0.25, 0.5, or 1.0% acetaminophen via the diet (357, 715, or 1430 mg/kg/day). These doses are approximately 0.7, 1.3, and 2.7 times the MHDD, respectively, based on a body surface area comparison. A dose-related reduction in body weights of fourth and fifth litter offspring of the treated mating pair occurred during lactation and post-weaning at all doses. Animals in the high dose group had a reduced number of litters per mating pair, male offspring with an increased percentage of abnormal sperm, and reduced birth weights in the next generation pups. Risk Summary Tramadol hydrochloride and acetaminophen 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 (12.1)]. 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 and acetaminophen. Clinical Considerations If infants are exposed to tramadol hydrochloride and acetaminophen 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 and acetaminophen 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 and acetaminophen is contraindicated for all children younger than age 12 years of age [see  Contraindications (4)] . •       Tramadol hydrochloride and acetaminophen 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 and acetaminophen 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. Elderly patients (65 years of age or older) may have increased sensitivity to tramadol. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. 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 and acetaminophen slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.2)] . Tramadol and acetaminophen are 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. The pharmacokinetics and tolerability of tramadol hydrochloride and acetaminophen in patients with impaired hepatic function have not been studied. Based on information using tramadol immediate-release tablets in subjects with advanced cirrhosis of the liver, tramadol exposure was higher and half-lives of tramadol and active metabolite M1 were longer than in subjects with normal hepatic function [see Clinical Pharmacology (12.3)] . As tramadol and acetaminophen are both extensively metabolized by the liver, the use of tramadol hydrochloride and acetaminophen in patients with hepatic impairment is not recommended [see Warnings and Precautions (5.9)] . The pharmacokinetics and tolerability of tramadol hydrochloride and acetaminophen in patients with renal impairment has not been studied. Based on studies using tramadol extended-release tablets, the excretion of tramadol and metabolite M1 is reduced in patients with creatinine clearance of less than 30 mL/min. In patients with creatinine clearances of less than 30 mL/min, it is recommended that the dosage of tramadol hydrochloride and acetaminophen not exceed 2 tablets every 12 hours. [see Dosage and Administration (2.3)] . The total amount of tramadol and M1 removed during a 4 hour dialysis period is less than 7% of the administered dose based on studies using tramadol alone. Monitor closely for signs of respiratory depression, sedation, and hypotension. Tramadol clearance was 20% higher in female subjects compared to males in four Phase 1 studies of tramadol hydrochloride and acetaminophen in 50 male and 34 female healthy subjects. The clinical significance of this difference is unknown. Tramadol hydrochloride and acetaminophen tablets contain tramadol, a Schedule IV controlled substance. Tramadol hydrochloride and acetaminophen tablet contains 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 and acetaminophen 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 and acetaminophen 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 and acetaminophen 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 and acetaminophen 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 and acetaminophen, 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 and acetaminophen   Abuse of tramadol hydrochloride and acetaminophen poses a risk of overdose and death. The risk is increased with concurrent use of alcohol and/or other CNS depressants. Tramadol hydrochloride and acetaminophen is 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 and acetaminophen in a patient physically dependent on opioids. Rapid tapering of tramadol hydrochloride and acetaminophen 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 and acetaminophen, gradually taper the dosage using a patient specific plan that considers the following: the dose of tramadol hydrochloride and acetaminophen 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), and Warnings and Precautions (5.21)]. 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 and Acetaminophen Tablets USP containing 37.5 mg of tramadol hydrochloride USP and 325 mg of acetaminophen USP are light yellow, capsule shaped, biconvex film-coated tablets debossed with “I90” on one side and plain on the other side and are available as follows.         Bottles of 30                           NDC 65862-922-30         Bottles of 100                         NDC 65862-922-01         Bottles of 500                         NDC 65862-922-05         Bottles of 1,000                      NDC 65862-922-99         10 x 10 Unit-dose Tablets       NDC 65862-922-78 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight container. Store tramadol hydrochloride and acetaminophen tablets USP securely and dispose of properly [see Patient Counseling Information (17)] .

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN - TRAMADOL HYDROCHLORIDE AND
ACETAMINOPHEN TABLET, FILM COATED
Aurobindo Pharma Limited
----------
MEDICATION GUIDE
Tramadol Hydrochloride and Acetaminophen Tablets USP CIV
(tram' a dol hye'' droe klor' ide and a seet'' a min' oh fen)
Tramadol hydrochloride and acetaminophen tablets are:
•
A strong prescription pain medicine that contains an opioid (narcotic)
that is used for the short-
term (five days or less) management of acute pain, 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 and acetaminophen
tablets:
•
Get emergency help or call 911 right away if you take too much
tramadol hydrochloride and
acetaminophen (overdose). When you first start taking tramadol
hydrochloride and acetaminophen
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.
•
Tramadol hydrochloride and acetaminophen tablets can cause severe
drowsiness, breathing
problems (respiratory depression), coma and death when taken with
benzodiazepines or other
medicines that depress consciousness.
•
Never give anyone else your tramadol hydrochloride and acetaminophen
tablets. They could die
from taking it. Selling or giving away tramadol hydrochloride and
acetaminophen tablets is
against the law.
•
Store tramadol hydrochloride and acetaminophen tablets securely, out
of sight and reach of
children, and in a location not accessible by others, including
visitors to the home.
•
Get emergency help right away if you take more than 4,000 mg of
acetaminophen in 1 day. T

Summary of Product characteristics

TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN - TRAMADOL HYDROCHLORIDE
AND ACETAMINOPHEN TABLET, FILM COATED
AUROBINDO PHARMA LIMITED
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TRAMADOL
HYDROCHLORIDE AND ACETAMINOPHEN TABLETS SAFELY AND EFFECTIVELY. SEE
FULL PRESCRIBING
INFORMATION FOR TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN TABLETS.
TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN TABLETS, FOR ORAL USE, CIV
INITIAL U.S. APPROVAL – 2001
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL
HYDROCHLORIDE AND ACETAMINOPHEN
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN 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 ACETAMINOPHEN,
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 AND ACETAMINOPHEN,
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 AND ACETAMINOPHEN, 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 WIL