Elderly patients and patients with chronic respiratory disorders may be at greater risk of adverse events. Use with caution in patients with increased intracranial pressure or head injury. Use tramadol with caution and reduce dosage in patients with liver disease or renal dysfunction and in patients with myxedema, hypothyroidism, or hypoadrenalism. Not recommended during pregnancy or in nursing mothers. Tolerance or drug dependence may result from extended use (withdrawal symptoms have been reported); abrupt discontinuation should be avoided. Tapering of dose at the time of discontinuation limits the risk of withdrawal symptoms. Safety and efficacy in pediatric patients have not been established.

>10%:

Central nervous system: Dizziness, headache, somnolence, vertigo

Gastrointestinal: Constipation, nausea

1% to 10%:

Cardiovascular: Vasodilation

Central nervous system: Agitation, anxiety, confusion, coordination impaired, emotional lability, euphoria, hallucinations, malaise, nervousness, sleep disorder, tremor

Dermatologic: Pruritus, rash

Endocrine & metabolic: Menopausal symptoms

Gastrointestinal: Abdominal pain, anorexia, diarrhea, dry mouth, dyspepsia, flatulence, vomiting

Genitourinary: Urinary frequency, urinary retention

Neuromuscular & skeletal: Hypertonia, spasticity, weakness

Ocular: Miosis, visual disturbance

Miscellaneous: Diaphoresis

<1%: Abnormal gait, allergic reaction, amnesia, anaphylactoid reactions, anaphylaxis, angioedema, bronchospasm, cognitive dysfunction, concentration difficulty, death, depression, dyspnea, dysuria, hallucinations, menstrual disorder, orthostatic hypotension, paresthesia, seizure, serotonin syndrome, Stevens-Johnson syndrome, suicidal tendency, syncope, taste perversion, tachycardia, toxic epidermal necrolysis, tremor, urticaria, vesicles, weight loss

Postmarketing and/or case reports: Abnormal ECG, cataracts, creatinine increased, deafness, gastrointestinal bleeding, hemoglobin decreased, hepatitis, hyper-/hypotension, liver enzymes elevated, liver failure, migraine, myocardial ischemia, palpitation, proteinuria, pulmonary edema, pulmonary embolism, speech disorders, stomatitis, tinnitus

A withdrawal syndrome may occur with abrupt discontinuation; includes anxiety, diarrhea, hallucinations (rare), nausea, pain, piloerection, rigors, sweating, and tremor. Uncommon discontinuation symptoms may include severe anxiety, panic attacks, or paresthesia.

Amphetamines: May increase the risk of seizures with tramadol.

Carbamazepine: Decreases half-life of tramadol by 33% to 50%.

CYP2D6 inhibitors: May decrease the effects of tramadol. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Digoxin: Rare reports of digoxin toxicity with concomitant tramadol use.

Linezolid: May be associated with increased risk of seizures (due to MAO inhibition)

MAO inhibitors: May increases the risk of seizures.

Naloxone: May increase the risk of seizures (if administered in tramadol overdose)

Neuroleptic agents: May increase the risk of tramadol-associated seizures and may have additive CNS depressant effects.

Opioids: May increase the risk of seizures, and may have additive CNS depressant effects.

Quinidine: May increase the tramadol serum concentrations.

Selegiline: An increased risk of seizures has been associated with MAO inhibitors. It is not clear if drugs with selective MAO type B inhibition are safer than nonselective agents.

SSRIs: May increase the risk of seizures with tramadol. Includes citalopram, fluoxetine, paroxetine, sertraline.

Tricyclic antidepressants: May increase the risk of seizures.

Warfarin: Concomitant use may lead to an elevation of prothrombin times; monitor.

Ethanol: Avoid ethanol (may increase CNS depression).

Food: Does not affect the rate or extent of absorption.

Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).

Onset of action: ~1 hour

Duration of action: 9 hours

Absorption: Rapid and complete

Distribution: Vd: 2.5-3 L/kg

Protein binding, plasma: 20%

Metabolism: Extensively hepatic via demethylation, glucuronidation, and sulfation; has pharmacologically active metabolite formed by CYP2D6

Bioavailability: 75%

Half-life elimination: Tramadol: ~6 hours; Active metabolite: 7 hours; prolonged in elderly, hepatic or renal impairment

Time to peak: 2 hours

Excretion: Urine (as metabolites)

Adults: Moderate to severe chronic pain: 50-100 mg every 4-6 hours, not to exceed 400 mg/day

For patients not requiring rapid onset of effect, tolerability may be improved by starting dose at 25 mg/day and titrating dose by 25 mg every 3 days, until reaching 25 mg 4 times/day. Dose may then be increased by 50 mg every 3 days as tolerated, to reach dose of 50 mg 4 times/day.

Elderly: >75 years: 50-100 mg every 4-6 hours (not to exceed 300 mg/day); see dosing adjustments for renal and hepatic impairment

Dosing adjustment in renal impairment: Clcr<30 mL/minute: Administer 50-100 mg dose every 12 hours (maximum: 200 mg/day)

Dosing adjustment in hepatic impairment: Cirrhosis: Recommended dose: 50 mg every 12 hours

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