intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing tramadol hydrochloride and acetaminophen. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see PATIENT COUNSELING INFORMATION (17)]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
5.2 Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see OVERDOSAGE (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of tramadol hydrochloride and acetaminophen, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of tramadol hydrochloride and acetaminophen.
To reduce the risk of respiratory depression, proper dosing and titration of tramadol hydrochloride and acetaminophen are essential [see DOSAGE AND ADMINISTRATION (2)]. Overestimating the tramadol hydrochloride and acetaminophen dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of tramadol hydrochloride and acetaminophen, especially by children, can result in respiratory depression and death due to an overdose of tramadol.
5.3 Neonatal Opioid Withdrawal Syndrome
Prolonged use of tramadol hydrochloride and acetaminophen during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see USE IN SPECIFIC POPULATIONS (8.1) and PATIENT COUNSELING INFORMATION (17)].
5.4 Risks of Interactions with Drugs Affecting Cytochrome P450 Isoenzymes
The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors on levels of tramadol and M1 from tramadol hydrochloride and acetaminophen are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride and acetaminophen requires careful consideration of the effects on the parent drug, tramadol, which is a weak serotonin and norepinephrine reuptake inhibi |
