operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of tramadol hydrochloride and acetaminophen and know how they will react to the medication [see PATIENT COUNSELING INFORMATION (17)].
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed, or described in greater detail, in other sections:
Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS (5.1)]
Life-Threatening Respiratory Depression [see WARNINGS AND PRECAUTIONS (5.2)]
Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS (5.3)]
Hepatotoxicity [see WARNINGS AND PRECAUTIONS (5.5)]
Interactions with Benzodiazepines and Other CNS Depressants [see WARNINGS AND PRECAUTIONS (5.6)]
Serotonin Syndrome [see WARNINGS AND PRECAUTIONS (5.7)]
Seizures [see WARNINGS AND PRECAUTIONS (5.8)]
Suicide [see WARNINGS AND PRECAUTIONS (5.9)]
Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS (5.10)]
Severe Hypotension [see WARNINGS AND PRECAUTIONS (5.12)]
Gastrointestinal Adverse Reactions [see WARNINGS AND PRECAUTIONS (5.15)]
Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS (5.16)]
Withdrawal [see WARNINGS AND PRECAUTIONS (5.18)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The most common incidence of treatment-emergent adverse events (≥3.0%) in subjects from clinical trials was constipation, diarrhea, nausea, somnolence, anorexia, dizziness, and sweating increased.
Table 1 shows the incidence rate of treatment-emergent adverse events reported in ≥2.0% of subjects over five days of tramadol hydrochloride and acetaminophen use in clinical trials (subjects took an average of at least 6 tablets per day).
Table 1: Incidence of Treatment-Emergent Adverse Events (≥2.0%)
Body System
Preferred Term
Tramadol Hydrochloride and Acetaminophen
(N=142)
(%)
Gastrointestinal System Disorders
Constipation
Diarrhea
Nausea
Dry Mouth
Psychiatric Disorders
Somnolence
Anorexia
Insomnia
Central & Peripheral Nervous System
Dizziness
Skin and Appendages
Sweating Increased
Pruritus
Reproductive Disorders, Male*
Prostatic Disorder
6
3
3
2
6
3
2
3
4
2
2
* Number of males = 62
Incidence at least 1%, causal relationship at least possible or greater:
The following lists adverse reactions that occurred with an incidence of at least 1% in single-dose or repeated-dose clinical trials of tramadol hydrochloride and acetaminophen.
Body as a Whole – Asthenia, fatigue, hot flushes
Central and Peripheral Nervous System – Dizziness, headache, tremor
Gastrointestinal System – Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, dry mouth, nausea, vomiting
Psychiatric Disorders – Anorexia, anxiety, confusion, euphoria, insomnia, nervousness, somnolence
Skin and Appendages – Pruritus, rash, increased sweating
Selected Adverse events occurring at less than 1%:
The following lists clinically relevant adverse reactions that occurred with an incidence of less than 1% in
