hin 14 days of stopping such treatment.
Examples:
phenelzine, tranylcypromine, linezolid
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
Clinical Impact:
May reduce the analgesic effect of tramadol hydrochloride and acetaminophen and/or precipitate withdrawal symptoms.
Intervention:
Avoid concomitant use.
Examples:
butorphanol, nalbuphine, pentazocine, buprenorphine
Muscle Relaxants
Clinical Impact:
Tramadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Intervention:
Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of tramadol hydrochloride and acetaminophen and/or the muscle relaxant as necessary.
Diuretics
Clinical Impact:
Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Intervention:
Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs
Clinical Impact:
The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Intervention:
Monitor patients for signs of urinary retention or reduced gastric motility when tramadol hydrochloride and acetaminophen is used concomitantly with anticholinergic drugs.
Digoxin
Clinical Impact:
Post-marketing surveillance of tramadol has revealed rare reports of digoxin toxicity.
Intervention:
Follow patients for signs of digoxin toxicity and adjust dosage of digoxin as needed.
Warfarin
Clinical Impact:
Post-marketing surveillance of tramadol has revealed rare reports of alteration of warfarin effect, including elevation of prothrombin times.
Intervention:
Monitor the prothrombin time of patients on warfarin for signs of an interaction and adjust the dosage of warfarin as needed.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see WARNINGS AND PRECAUTIONS (5.3)]. 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 th |
