Tramadol and Acetaminophen (Systemic )


VA CLASSIFICATION
Primary: CN101

Commonly used brand name(s): Ultracet.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Analgesic—

Indications

Accepted

Acute pain (treatment)—Tramadol and acetaminophen combination is indicated for short-term (five days or less) management of acute pain {01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Tramadol hydrochloride: 299.84 {01}
    Acetaminophen: 151.17 {01}

Mechanism of action/Effect:

Tramadol is a centrally-acting synthetic opioid analgesic.{01}. The mechanism of action of tramadol is not completely understood, but it may bind to μ-opioid receptors and inhibit the reuptake of norepinephrine (NE) and serotonin {01}. . Some opioid activity is derived from low-affinity binding of the parent compound and higher-affinity binding of the mono- O-desmethyltramadol (M1) metabolite to the opioid receptors {01}. The analgesic potency of M1 is about six times greater than that of tramadol in animal models and 200 times more potent in μ-opioid receptor binding {01}.

Absorption:

Oral—. Mean absolute bioavailability of a 100-mg dose of tramadol and acetaminophen is approximately 75%. The absorption of acetaminophen occurs primarily in the small intestine.{01}..

Note:  Peak plasma concentrations of tramadol and acetaminophen were delayed about 35 minutes and almost one hour, respectively, when administered with food. However, the extent of absorption is not significantly affected by administration with food {01}


Distribution:

The volume of distribution of tramadol is 2.6 and 2.9 liters per kilogram of body weight (L/kg) in males and females, respectively, following a 100-mg intravenous dose. Acetaminophen appears to be widely distributed throughout most body tissues except fat. Its apparent volume of distribution is about 0.9 liters per kilogram of body weight (L/kg){01}. Tramadol has been shown to cross the placenta. In women given tramadol during labor, the mean ratio of tramadol concentration in the umbilical veins compared to maternal veins was 0.83 {01}. Following a single 100 mg intravenous dose of tramadol, the cumulative distribution in breast milk within 16 hours post-dose was 100 micrograms (mcg) of tramadol ( 0.1% of the maternal dose) and 27 micrograms of the M1 metabolite.{01}.

Protein binding:

Low (20%) for both acetaminophen and tramadol{01}. Tramadol binding appears to be independent of concentration up to 10 micrograms per mL (mcg/mL); saturation of tramadol plasma protein binding occurs only at concentrations outside of the clinically relevant range. {01}.

Biotransformation:


Tramadol::

Hepatic: extensively (60%) metabolized via N- and O-demethylation utilizing the CYP2D6 and CYP3A4 pathways and glucuronidation or sulfation {01}. The production of the active metabolite mono- O-desmethyltramadol (M1) is dependent on the CYP2D6 isoenzyme of cytochrome P450. {01}.



Acetaminophen:

Acetaminophen is primarily metabolized in the liver by first order kinetics via three separate pathways. The pathways are conjugation with glucuronide, conjugation with sulfate and oxidation via the cytochrome P450-dependent, mixed function oxidase enzyme pathway. This pathway forms a reactive intermediate metabolite which conjugates with glutathione and is then further metabolized to cysteine and mercapturic acid conjugates. The principal cytochrome P450 isoenzyme involved appears to be CYP2E1 with CYP1A2 and CYP3A4 also involved. In adults, the majority of acetaminophen is conjugated with glucuronic acid and, to a lesser extent, with sulfate. The glucuronide, sulfate and glutathione-derived metabolites are inactive. In premature infants, newborns, and young infants, the sulfate conjugate predominates {01}.


Half-life:


Plasma Elimination:


Individuals with normal renal function—

Racemic tramadol—Approximately 5 to 6 hours (increased to 7 to 9 hours with multiple dosing [not clinically significant]{01}.

M1 metabolite—Approximately 7 hours{01}.

Acetaminophen—Approximately 2 to 3 hours in adults. It is somewhat shorter in children and somewhat longer in neonates and in cirrhotic patients {01}.



Onset of action:

The onset of pain relief after tramadol and acetaminophen was faster than tramadol alone. Onset of analgesia occurred in less than one hour {01}.

Time to peak concentration:


Plasma—:


Following a 1–tablet (37.5 mg tramadol/ 325 mg acetaminophen) dose—

(+) Tramadol—1.8 hours {01}.

(-) Tramadol—1.8 hours {01}.

(+) M1 metabolite—2.1 hours {01}.

(-) M1 metabolite—2.2 hours {01}.

Acetaminophen— 0.9 hours{01}.




Following a 2–tablet (75 mg tramadol/ 650 mg acetaminophen) dose :

Tramadol—2 hours {01}.

M1 metabolite—3 hours {01}.

Acetaminophen— within one hour; not affected by co-administration with tramadol {01}.


Peak serum concentration:


Peak plasma concentrations:


Following a single 37.5 mg tramadol/ 325 mg acetaminophen dose—

(+) enantiomer of tramadol—64.3 nanograms per mL ± 9.3 nanograms/mL {01}.

(-) enantiomer of tramadol—55.5 nanograms per mL ± 8.1 nanograms/mL {01}.

(+) enantiomer of M1 metabolite—10.9 nanograms per mL ± 5.7 nanograms/mL {01}.

(-) enantiomer of M1 metabolite—12.8 nanograms per mL ± 4.2 nanograms/mL {01}.

Acetaminophen—4.2 nanograms per mL ± 0.8 nanograms/mL {01}.



Elimination:


Renal—
        Tramadol: 60% as metabolites and 30% as unchanged drug. Clearance rate is 20% higher in females than in males {01}.
        Acetaminophen: Less than 9% unchanged {01}.



In dialysis—
        Less than 7% of an administered dose of tramadol is removed by hemodialysis within a 4-hour period {01}.



Precautions to Consider

Carcinogenicity

There are no studies done on the combination of tramadol and acetaminophen to evaluate carcinogenicity.{01}

Tumorigenicity

Evidence of a statistically significant increase in two common murine tumors (pulmonary and hepatic) was observed in mice receiving oral doses of tramadol up to 30 mg per kg of body weight (mg/kg) (90 mg per square meter of body surface area [mg/m2] or 0.5 times the maximum daily dose of 185 mg/m2) for approximately 2 years {01}. However, no tumors were observed in a rat carcinogenicity study at doses of 30 mg/kg or 180 mg/m 2 (one times the maximum daily human tramadol dose) {01}.

Mutagenicity

There are no studies done on the combination of tramadol and acetaminophen to evaluate mutagenicity. {01}No evidence of tramadol mutagenicity was found in the Ames test, CHO/HPRT mammalian cell assay, mouse lymphoma assay, dominant lethal mutation Salmonella microsomal activation test in mice, chromosome aberration test in Chinese hamsters, or bone marrow micronucleus tests in mice and Chinese hamsters {01}. Weakly mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and micronucleus test in rats {01}.

Pregnancy/Reproduction
Fertility—
There are no studies done on the combination of tramadol and acetaminophen to evaluate impairment of fertility.{01}

No impairment of fertility was observed at oral dose levels up to 50 mg/kg (350 mg/m2 ) in male rats and 75 mg/kg (450 mg/m2) in female rats. These dosages are 1.6 and 2.4 times the maximum daily human tramadol dosage of 185 mg/m 2{01}.

Pregnancy—
Tramadol has been shown to cross the placenta {01}. Well-controlled studies in humans have not been done. Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported with tramadol hydrochloride in post-marketing surveillance{01}.Long-term use of tramadol during pregnancy may lead to physical dependence and postpartum withdrawal symptoms in the newborn. {01}

Studies have shown the tramadol/acetaminophen combination product to be embryotoxic and fetotoxic in rats at maternally toxic doses 50/434 mg/kg tramadol/acetaminophen or 300/2604 mg/m2 ( 1.6 time the maximum daily human tramadol/acetaminophen dosage); however, it was found not to be teratogenic at these levels. Studies done in progeny of rats and rabbits treated orally with tramadol and acetaminophen found no drug-related teratogenic effects. Embryo and fetal toxicity consisted of decreased fetal weights and increased supernumerary ribs. In peri- and postnatal studies of tramadol alone in rats, decreased weights were observed in the progeny of dams that received oral (gavage) doses of 50 mg/kg (300 mg/m 2 or 1.6 times the maximum daily human tramadol dosage) or greater. At doses of 80 mg/kg (480 mg/m2) or 2.6 times the maximum daily human tramadol dosage), pup survival was decreased early in lactation{01}.

FDA Pregnancy Category C {01}.


Labor and delivery—

Tramadol is not recommended for use in pregnant women prior to or during labor unless the potential benefits outweigh the risks, because safe use in pregnancy has not been established {01}. .

Breast-feeding

Following a single intravenous 100-mg dose of tramadol, the cumulative distribution in breast milk within 16 hours postdose was 100 micrograms (mcg) of tramadol (0.1% of the maternal dose) and 27 mcg of the M1 metabolite {01}. Use of oral tramadol is not recommended for obstetrical preoperative medication or postdelivery analgesia in nursing mothers because of lack of studies on its safety in infants and newborns {01}.

Pediatrics

No information is available on the relationship of age to the effects of tramadol in patients under 16 years of age {01}. Safety and efficacy have not been established {01}.


Geriatrics


Studies have shown no significant changes in pharmacokinetics of tramadol and acetaminophen in elderly patients with normal renal and hepatic function. In general, dosage selection in the elderly should be cautious, reflecting the greater frequency of decreased hepatic, renal, cardiac function, concomitant disease or multiple drug therapy {01}.


Pharmacogenetics

Studies have shown a 20% higher tramadol clearance in female patients compared to males. The clinical significance of this difference is unknown {01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.


For tramadol and acetaminophen
» Alcohol    (Tramadol and acetaminophen combination should no be used concomitantly with alcohol due to the possibility of hepatotoxicity.{01})


» Anticoagulants, coumadin    (post-marketing surveillance of both tramadol and acetaminophen have revealed rare alterations of anticoagulant effect, including elevation of prothrombin times {01}.)


For acetaminophen
» Acetaminophen-containing products    (Due to the possibility of hepatotoxicity at cumulative doses)


For tramadol
» Analgesics, Opioid or
» Antidepressants, Tricyclic (TCA) or
» Neuroleptics or
» Tricyclic compounds, other, such as cyclobenzaprine or promethazine    (concomitant use of tramadol has resulted in seizures during post-market reporting{01})


» Alcohol or
» Anesthetic agents or
» Central nervous system (CNS) depression–producing medications, other (see Appendix II ), such as:
Antidepressants, tricyclics
Opioid analgesics
Phenothiazines
Sedative hypnotics
Tranquilizers     (caution is recommended because concurrent use may potentiate the CNS depressant effects, including respiratory depression; {01})


» Carbamazepine    (causes an increase in tramadol metabolism and increased risk of seizures; concomitant administration is not recommended{01}.)


CYP2D6 inhibitors, such as
Amitriptyline or
Fluoxetine or
Paroxetine    (concurrent administration may result in inhibition of tramadol metabolism, resulting in increased plasma levels of tramadol{01}.)


Digoxin    (post marketing surveillance of tramadol has revealed rare reports of digoxin toxicity {01})


» Monoamine oxidase (MAO) inhibitors, including furazolidone and procarbazine, or
» Selective serotonin reuptake inhibitors (SSRI), including citalopram, fluoxetine, fluvoxamine and sertraline,    (tramadol inhibits the uptake of norepinephrine and serotonin {01}; concurrent use with MAO inhibitors and serotonin reuptake inhibitors may decrease seizure threshold or induce serotonin syndrome; caution is recommended.{01})


Quinidine    (concurrent use may increase concentrations of tramadol and decrease concentration of the M1 metabolite by competitively inhibiting the CYP2D6 isoenzyme {01} )



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Prothrombin times    (Tramadol and acetaminophen in post-marketing surveillance have revealed rare alterations including elevation of prothrombin times.{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Acute intoxication with alcohol, hypnotics, centrally-acting analgesics, opioids, or psychotropic drugs    ( central nervous system and respiratory depression may be worsened {01})


» Drug abuse or dependence, current or history of, including alcoholism    (patient predisposition to drug abuse {01})


» Hypersensitivity to acetaminophen or
» Hypersensitivity to opioids or
» Hypersensitivity to tramadol    (increased risk of anaphylactoid reactions {01}.)


Risk-benefit should be considered when the following medical problems exist
Acute abdominal conditions {01}    (diagnosis may be obscured)


» Alcohol or drug withdrawal or
» Central nervous system infection or
» Epilepsy, or history of or
» Head trauma or
» Metabolic disorders {01}    (tramadol may increase the risk of seizures)


» Hepatic function impairment    (use in patients with hepatic impairment has not been studied and is not recommended{01}.)


Increased intracranial pressure or
Head trauma    (tramadol causes pupillary changes [miosis] that may obscure the existence, extent, or course of intracranial pathology. Carbon dioxide retention and elevation of cerebrospinal fluid pressure may be exaggerated due to respiratory depressant effects. Clinicians should consider the possibility of an adverse drug reaction when evaluating altered mental status {01})


Opioid dependent patients    (Tramadol has been shown to reinitiate physical dependence in some patients that have been previously dependent of other opioids)


» Renal function impairment    (decreased rate and extent of excretion of tramadol and its active metabolite M1; dosage interval increase to not exceed 2 tablets every twelve hours is recommended in patients with creatinine clearance of less than 30 mL per minute [mL/min]. {01})


» Respiratory depression, risk of    ( caution is recommended with administration of oral tramadol in patients at risk for respiratory depression. Respiratory depression should be treated as an overdose; if naloxone is administered, use cautiously because it may precipitate seizures{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Prothrombin time    (Periodic evaluation of prothrombin times should be performed when tramadol/ acetaminophen is concurrently administered with warfarin-like compounds.{01})




Side/Adverse Effects

Note: Tramadol can produce drug dependence of the morphine (μ-opioid type) and may potentially be abused. Tolerance development, drug-seeking behavior and craving have been associated with the use of tramadol. Withdrawal symptoms may occur with abrupt discontinuation of tramadol therapy. These symptoms may be relieved by reinstitution of opioid therapy followed by a gradual, tapered dose reduction of the medication combined with symptomatic support{01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Allergic reaction (burning, itching, and redness of skin; vomiting )
    
anaphylactoid reactions ( cough; difficulty swallowing; dizziness; fast heartbeat; hives; itching; puffiness or swelling of the eyelids or around the eyes, face, lips or tongue; shortness of breath; skin rash; tightness in chest; unusual tiredness or weakness; wheezing )
    
chest pain
    
seizures (muscle spasm or jerking of all extremities; sudden loss of consciousness)

{01}

Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Abdominal pain
    
anorexia (loss of appetite; weight loss)
    
anxiety (severe nervousness)
    
asthenia (loss of strength or energy; muscle pain or weakness)
    
confusion (mood or mental changes)
    
constipation
    
diarrhea (increase in bowel movements; loose stools; soft stools)
    
dizziness
    
dry mouth
    
dyspepsia ( acid or sour stomach; belching; heartburn; indigestion; stomach discomfort )
    
euphoria (false or unusual sense of well-being)
    
fatigue ( unusual tiredness or weakness)
    
flatulence (bloated full feeling; excess air or gas in stomach or intestines )
    
headache
    
hot flashes (feeling of warmth; redness of the face, neck, arms, and occasionally the upper chest)
    
insomnia (sleeplessness; trouble sleeping; unable to sleep)
    
increased sweating
    
nausea
    
nervousness
    
prostatic disorder (painful or difficult urination )
    
pruritus (itching skin)
    
rash
    
somnolence (sleepiness or unusual drowsiness)
    
tremor ( aches, pains or weakness of muscles; numbness or tingling of hands, legs, and feet)
    
vomiting
{01}
Incidence rare
    
Abnormal hepatic function (yellow eyes or skin)
    
abnormal thinking
    
abnormal vision (change in vision )
    
albuminuria
    
amnesia ( loss of memory; problems with memory)
    
anemia (unusual tiredness or weakness )
    
ataxia (shakiness and unsteady walk; clumsiness, unsteadiness, trembling, or other problems with muscle control or coordination)
    
depersonalization (loss of sense of reality )
    
depression (mood or mental changes)
    
drug abuse and dependence
dysphagia (difficulty swallowing )
    
dyspnea (shortness of breath; difficult or labored breathing; tightness in chest; wheezing)
    
emotional lability (crying; depersonalization; dysphoria; euphoria; mental depression; paranoia; quick to react or overreact emotionally; rapidly changing moods)
    
hallucinations (seeing, hearing, or feeling things that are not there)
    
hypertension (blurred vision; dizziness; severe or continuing, dull headache; pounding in the ears; slow or fast heartbeat)
    
hypertonia (increased muscle tone)
    
hypotension (blurred vision; confusion; dizziness, faintness, or light-headedness when getting up from a lying or sitting position; sudden sweating; unusual tiredness or weakness)
    
impotence (loss in sexual ability, desire, drive, or performance; decreased interest in sexual intercourse; inability to have or keep an erection)
    
involuntary muscle contractions
    
melena ( bloody or black, tarry stools)
    
micturition disorder (trouble in holding or releasing urine; painful urination )
    
migraine headache
    
oliguria (decrease in amount of urine)
    
palpitation (fast, irregular, pounding, or racing heartbeat or pulse)
    
paresthesia (tingling sensation on skin.)
    
paroniria ( terrifying dreams causing sleep disturbances)
    
rigors (feeling unusually cold; shivering)
    
stupor (decreased awareness or responsiveness)
    
syncope ( high or low blood pressure; dizziness; light-headedness)
    
tachycardia (fainting; fast, pounding, or irregular heartbeat or pulse; palpitations)
    
tinnitus (continuing ringing or buzzing or other unexplained noise in ears )
    
tongue edema
    
urinary retention (decrease in urine volume; decrease in frequency of urination; difficulty in passing urine [dribbling]; painful urination)
    
vertigo (dizziness or light-headedness; feeling of constant movement of self or surroundings; sensation of spinning)
    
weight decrease {01}



Those indicating possible withdrawal and the need for medical attention if they occur after medication is discontinued
    
Anxiety
    
diarrhea
    
hallucinations (seeing, hearing, or feeling things that are not there)
    
insomnia ( difficulty sleeping)
    
nausea or vomiting
    
nervousness, restlessness, or irritability
    
pain
    
piloerection (goosebumps)
    
rigors (feeling unusually cold; shivering)
    
sweating, increased
    
tremors (trembling or shaking of hands or feet, shakiness in legs, arms, hands, feet)
    
upper respiratory symptoms (fever; runny nose or sneezing)



Note: The signs and symptoms of withdrawal listed above are characteristics of the withdrawal symptoms produced by abrupt discontinuation of tramadol. Tapering the dose of tramadol may prevent some of the signs and symptoms of withdrawal from occurring {01}.




Overdose
For specific information on the agents used in the management of acetaminophen overdose, see:    • Acetylcysteine (Systemic) monograph; and/or
   • Charcoal (Oral-Local) monograph.


For specific information on the agents used in the management of tramadol overdose, see:   • Naloxone (Systemic) monograph; and/or
   • Diazepam in Benzodiazepines (Systemic) monograph.

For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and chronic effects of tramadol
    
Cardiac arrest
    
central nervous system depression
; coma
    
death
    
lethargy
    
respiratory depression
    
seizures
{01}
Acute effects of acetaminophen
    
Gastrointestinal upset (diarrhea, loss of appetite, nausea or vomiting, stomach cramps or pain)
    
increased sweating


Note: Although gastrointestinal upset and increased sweating often do not occur, they sometimes occur within 6 to 14 hours after ingestion of an overdose and persist for about 24 hours.

Acetaminophen monographChronic effects of acetaminophen
    
cardiac arrhythmias
    
cardiovascular collapse
    
cerebral edema;
coagulation defects
    
coma
    
convulsions
    
disseminated intravascular coagulation
    
gastrointestinal bleeding
    
hepatic encephalopathy
    
hypoglycemia
    
metabolic acidosis
    
respiratory depression

Note: The first indications of overdosage may be signs and symptoms of possible liver damage and abnormalities in liver function tests, which may not occur until 2 to 4 days after the ingestion of the overdose. Maximal changes in liver function tests usually occur 3 to 5 days after ingestion of the overdose.



Treatment of overdose


To increase elimination:
For tramadol, hemodialysis is not expected to be helpful because it removes less than 7% of the administered dose in a 4–hour dialysis period {01}.



Specific treatment for tramadol:
Primary treatment should be given to maintaining adequate ventilation along with general supportive treatment. Administration of the opioid antagonist naloxone, which will reverse some, but not all, symptoms caused by overdosage with tramadol {01}. Administer naloxone with caution because it may precipitate seizures. See the package insert or Naloxone (Systemic) for specific dosing guidelines for use of this product.



Specific treatment for acetaminophen:
Standard treatment recommendations should be followed for an acetaminophen overdose. See the package insert or Acetaminophen (Systemic)Acetylcysteine (Systemic) and/or Charcoal, Activated (Oral-Local) monographs for specific dosing guidelines for use of this product.



Supportive care:
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation .



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Tramadol and Acetaminophen (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to tramadol, opioids or acetaminophen

Pregnancy— Tramadol crosses the placenta; not recommended for use during pregnancy





Breast-feeding— Tramadol is distributed into breast milk; use is not recommended
Other medications, especially alcohol, antidepressants (TCA and SSRI), carbamazepine, CNS depressants or anesthetic agents, MAO inhibitors, neuroleptics, other acetaminophen-containing products, other opioid analgesics or oral anticoagulants
Other medical problems, especially acute intoxication with alcohol, hypnotics, centrally-acting analgesics, opioids, or psychotropic drugs; alcohol or drug withdrawal; central nervous system infection; drug abuse or dependence; epilepsy; head trauma; hepatic function impairment; metabolic disorders; physical dependence on opioids; renal function impairment; or risk of respiratory depression

Proper use of this medication
» Importance of not taking more medication than the amount prescribed because of danger of overdose

» Proper dosing

» Proper storage

Precautions while using this medication
» Avoiding use of alcoholic beverages or other CNS depressants during therapy unless prescribed or otherwise approved by physician

» Caution if dizziness, drowsiness, or lightheadedness occurs

» Caution when getting up from a lying or sitting position

Lying down if nausea or vomiting, or dizziness or lightheadedness occurs

Informing physician or dentist of use of medication if any kind of surgery (including dental surgery) or emergency treatment is required

» Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief of dry mouth; checking with physician or dentist if dry mouth continues for more than 2 weeks

» Importance of not stopping medication abruptly without consulting physician


Side/adverse effects
Signs of potential side effects, especially allergic reaction, anaphylactoid reactions, chest pain, and seizures


Oral Dosage Forms

TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN TABLETS

Usual adult and adolescent dose
Analgesic
Oral, two tablets (75 mg tramadol, 650 mg acetaminophen) every four to six hours as needed for up to five days{01}.

Note: Patients with impaired renal function (creatinine clearance less than 30 mL/minute), the dosing interval should be increased not to exceed 2 tablets every twelve hours {01}.
.



Usual adult prescribing limits
Oral, 8 tablets per day ( 4 tablets per day in patients with creatinine clearance of less than 30 mL/min for up to five days.){01}

Usual Pediatric Dose
Children up to 16 years of age—Safety and efficacy have not been established.{01}.

Usual Geriatric Dose
See Usual adult and adolescent dose .

Note: In elderly patients, dose selection should be cautious, reflecting the greater frequency of decreased hepatic, renal, cardiac function, concomitant disease and multiple drug therapy {01}.


Strength(s) usually available
U.S.—


37.5 mg tramadol and 325 mg acetaminophen (Rx) [Ultracet (powdered cellulose) ( pregelatinized starch) (sodium starch glycolate ) (starch) (purified water ) (magnesium stearate) ( OPADRY light yellow) (carnauba wax)]

Canada—
Not commercially available.

Packaging and storage:
Store at 25°C (77 °F), in a tight container, excursions permitted between 15 and 30°C (59 and 86°F){01}.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.

Additional information:

Note: Tramadol is not a controlled substance in the U.S.




Revised: 05/06/2002



References
  1. Product Information: Ultracet™, tramadol and acetaminophen. Ortho McNeil, Raritan, NJ, (PI issued 08/2001) reviewed 09/2001.
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