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.
8.3 Females and Males of Reproductive Potential
Infertility
Chronic use of opioids 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)].
8.4 Pediatric Use
The safety and efficacy of tramadol hydrochloride and acetaminophen in patients under 18 years of age have not been established. The use of tramadol hydrochloride and acetaminophen in the pediatric population is not recommended.
8.5 Geriatric Use
Elderly patients (aged 65 years 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 monitor closely 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 monitor renal function.
8.6 Hepatic Impairment
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 (5.5)].
8.7 Renal Impairment
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 (2.2)]. 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.
8.8 Sex
Tramadol clearance was 20% higher in female subjects compared to males in four Phase 1 stu |
