Ultracet (tramadol HCl/acetaminophen)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

*Tramadol/acetaminophen should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.

*Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of tramadol/acetaminophen for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.

*Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.

*Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse.

*Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with tramadol hydrochloride and acetaminophen tablets. Consider this risk when selecting an initial dose and when making dose adjustments.

*Initiate treatment with 2 tablets every 4 to 6 hours as needed for pain relief up to a maximum of 8 tablets per day and at the lowest dosage necessary to achieve adequate analgesia. Titrate the dosage based upon the individual patient's response to their initial dose of tramadol/acetaminophen tablets; maximum of 8 tablets per day.

*Periodically reassess patients receiving tramadol/acetaminophen to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse.

*Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with tramadol/acetaminophen, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose.

*Do not use with other acetaminophen- or tramadol-containing products.

*In patients with severe renal impairment, do not exceed 2 tablets every 12 hours.

*Do not rapidly reduce or abruptly discontinue tramadol/acetaminophen in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Children younger than 12 years of age.

*Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy.

*Significant respiratory depression.

*Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment.

*Known or suspected GI obstruction, including paralytic ileus.

*Previous hypersensitivity to tramadol hydrochloride, acetaminophen, any other component of this product, or opioids.

*Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

The most common incidence of treatment-emergent adverse events (>=3%) in patients from clinical trials were constipation, diarrhea, nausea, somnolence, anorexia, dizziness, and increased sweating

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

The safety and effectiveness of tramadol/acetaminophen in pediatric patients have not been established.

Life-threatening respiratory depression and death have occurred in children who received tramadol. 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/acetaminophen is contraindicated for all children younger than 12 years of age. Tramadol/acetaminophen is contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of tramadol/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 post-operative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.

Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with tramadol/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 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 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 MRHD. 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. 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.

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.

Neonatal seizures, neonatal withdrawal syndrome, fetal death, and stillbirth have been reported with tramadol hydrochloride during post-marketing.

Tramadol/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 overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid induced respiratory depression in the neonate. Tramadol/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/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/acetaminophen, if any, on the later growth, development, and functional maturation of the child is unknown.

Tramadol/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 on milk production. The M1 metabolite is more potent than tramadol in mu opioid receptor binding. 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/acetaminophen.

If infants are exposed to tramadol/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.

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/acetaminophen slowly in geriatric patients and frequently reevaluate the patient for signs of CNS and respiratory depression.

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.