A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Ultracet Side Effects, and Drug Interactions - Tramadol hydrochloride / Acetaminophen
Ultracet Side Effects, and Drug Interactions - Tramadol hydrochloride / Acetaminophen
SIDE EFFECTS
Table 2 reports the incidence rate of treatment-emergent adverse
events over five days of ULTRACET use in clinical trials (subjects took an average
of at least 6 tablets per day).
Table 2: Incidence of Treatment-Emergent Adverse Events (³
2.0%)
|
ULTRACET (N=142)
|
|
Body System
|
|
Preferred Term
|
%
|
|
Gastrointestinal System
|
|
Constipation
|
6
|
|
Diarrhea
|
3
|
|
Nausea
|
3
|
|
Dry Mouth
|
2
|
|
Psychiatric Disorders
|
|
Somnolence
|
6
|
|
Anorexia
|
3
|
|
Insomnia
|
2
|
|
Central & Peripheral Nervous System
|
|
Dizziness
|
3
|
|
Skin and Appendages
|
|
Sweating Increased
|
4
|
|
Pruritus
|
2
|
|
Reproductive Disorders, Male*
|
|
Prostatic Disorder
|
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 ULTRACET.
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 ULTRACET clinical trials.
Body as a Whole Chest pain, rigors, syncope, withdrawal
syndrome
Cardiovascular Disorders Hypertension, aggravated
hypertension, hypotension
Central and Peripheral Nervous System Ataxia, convulsions,
hypertonia, migraine, aggravated migraine, involuntary muscle contractions,
paraesthesia, stupor, vertigo
Gastrointestinal System Dysphagia, melena, tongue edema
Hearing and Vestibular Disorders Tinnitus
Heart Rate and Rhythm Disorders Arrhythmia, palpitation,
tachycardia
Liver and Biliary System Hepatic function abnormal
Metabolic and Nutritional Disorders Weight decrease
Psychiatric Disorders Amnesia, depersonalization,
depression, drug abuse, emotional lability, hallucination, impotence, paroniria,
abnormal thinking
Red Blood Cell Disorders Anemia
Respiratory System Dyspnea
Urinary System Albuminuria, micturition disorder,
oliguria, urinary retention
Vision Disorders Abnormal vision
Other clinically significant adverse experiences previously
reported with tramadol hydrochloride.
Other events which have been reported with the use of tramadol
products and for which a causal association has not been determined include:
vasodilation, ortho-static hypotension, myocardial ischemia, pulmonary edema,
allergic reactions (including anaphylaxis and urticaria, Stevens-Johnson syndrome/TENS),
cognitive dysfunction, difficulty concentrating, depression, suicidal tendency,
hepatitis liver failure and gastrointestinal bleeding. Reported laboratory abnormalities
included elevated creatinine and liver function tests. Serotonin syndrome (whose
symptoms may include mental status change, hyperreflexia, fever, shivering,
tremor, agitation, diaphoresis, seizures and coma) has been reported with tramadol
when used concomitantly with other sero-tonergic agents such as SSRIs and MAOIs.
Other clinically significant adverse experiences previously
reported with acetaminophen.
Allergic reactions (primarily skin rash) or reports of hypersensitivity
secondary to acetaminophen are rare and generally controlled by discontinuation
of the drug and, when necessary, symptomatic treatment.
DRUG ABUSE AND DEPENDENCE
Tramadol may induce psychic and physical dependence of the
morphine-type (µ-opioid). (See WARNINGS.)
Dependence and abuse, including drug-seeking behavior and taking illicit actions
to obtain the drug are not limited to those patients with a prior history of
opioid dependence. The risk in patients with substance abuse has been observed
to be higher. Tramadol is associated with craving and tolerance development.
Withdrawal symptoms may occur if tramadol is discontinued abruptly. These symptoms
may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea,
upper respiratory symptoms, piloerection, and rarely hallucinations. Clinical
experience suggests that withdrawal symptoms may be relieved by reinstitution
of opioid therapy followed by a gradual, tapered dose reduction of the medication
combined with symptomatic support.
DRUG INTERACTIONS
In vitro studies indicate that tramadol is unlikely to inhibit
the CYP3A4-mediated metabolism of other drugs when tramadol is administered
concomitantly at therapeutic doses. Tramadol does not appear to induce its own
metabolism in humans, since observed maximal plasma concentrations after multiple
oral doses are higher than expected based on single-dose data. Tramadol is a
mild inducer of selected drug metabolism pathways measured in animals.
Use With Carbamazepine
Patients taking carbamazepine may have a significantly
reduced analgesic effect of tramadol. Because carbamazepine increases tramadol
metabolism and because of the seizure risk associated with tramadol, concomitant
administration of ULTRACET and carba-mazepine is not recommended.
Use With Quinidine
Tramadol is metabolized to M1 by CYP2D6. Quinidine is
a selective inhibitor of that isoenzyme; so that concomitant administration
of quinidine and tramadol results in increased concentrations of tramadol and
reduced concentrations of M1. The clinical consequences of these findings are
unknown. In vitro drug interaction studies in human liver microsomes indicate
that tramadol has no effect on quinidine metabolism.
Use With Inhibitors of CYP2D6
In vitro drug interaction studies in human liver microsomes
indicate that concomitant administration with inhibitors of CYP2D6 such as fluoxetine,
paroxetine, and amitripty-line could result in some inhibition of the metabolism
of tramadol.
Use With Cimetidine
Concomitant administration of ULTRACET and cime-tidine has
not been studied. Concomitant administration of tramadol and cimetidine does
not result in clinically significant changes in tramadol pharmacokinetics. Therefore,
no alteration of the ULTRACET dosage regimen is recommended.
Use With MAO Inhibitors
Interactions with MAO Inhibitors, due to interference
with detoxification mechanisms, have been reported for some centrally acting
drugs (see WARNINGS, Use With MAO Inhibitors).
Use With Digoxin
Post-marketing surveillance of tramadol has revealed rare reports
of digoxin toxicity.
Use With Warfarin Like Compounds
Post-marketing surveillance of both tramadol and acetaminophen
individual products have revealed rare alterations of warfarin effect, including
elevation of pro-thrombin times.
While such changes have been generally of limited clinical
significance for the individual products, periodic evaluation of prothrombin
time should be performed when ULTRACET and warfarin-like compounds are administered
concurrently.
top
