Tramadol Hydrochloride Drug Facts

Tramadol Hydrochloride

Trade Names:
Ultram
- Tablets 50 mg
- Tablets, extended-release 100 mg
- Tablets, extended-release 200 mg
- Tablets, extended-release 300 mg

Pharmacology

Binds to certain opioid receptors and inhibits reuptake of norepinephrine and serotonin; exact mechanism of action unknown.

Pharmacokinetics

Absorption

Mean absolute bioavailability of tramadol is 75%. High-fat meals increased T _max 3 h and decreased C _max and AUC 28% and 16%, respectively (ER). T _max is 2 to 3 h (IR) and 12 to 15 h for (ER). Steady-state plasma concentrations of both tramadol and the metabolite are achieved within 2 days (IR) and within 4 days (ER).

Distribution

Tramadol is 20% protein bound and is independent of concentrations up to 10 mcg/mL. Vd is approximately 2.7 L/kg. Tramadol follows linear kinetics.

Metabolism

There is no evidence of self-induction. Production of M1 (metabolite) is dependent on CYP-450 2D6. The O-demethylated metabolite is M1. Tramadol is extensively metabolized after administration. The major metabolic pathway is N- and O-demethylation, and glucuronidation or sulfation in liver.

Elimination

30% of a dose is excreted unchanged in urine; 60% is excreted as metabolites. The t _½ is 6.3 h for tramadol IR and 7.4 h for the metabolite. The t _½ is 7.9 h for tramadol ER and 8.8 h for the metabolite.

Onset

The onset of action is 1 h (IR).

Peak

Time to peak effect is 2 to 3 h (IR) and 12 to 15 h (ER).

Special Populations

In patients with renal function impairment, there is a decreased rate and extent of excretion of tramadol and M1. In patients with Ccr less than 30 mL/min, dose adjustment is recommended.

Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis. In cirrhotic patients, dose adjustment is recommended.

In patients older than 75 yr of age, dose adjustment is recommended.

Indications and Usage

Relief of moderate to moderately severe pain (IR); relief of moderate to moderately severe chronic pain for patients who require around-the-clock treatment for an extended period of time (ER).

Unlabeled Uses

Premature ejaculation.

Contraindications

Acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids, or psychotropic agents; hypersensitivity.

Dosage and Administration

PO Start with 25 mg/day in the morning and titrate in 25 mg increments as separate doses every 3 days to reach 100 mg/day (25 mg 4 times daily). Thereafter, increase the dose by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg 4 times daily). After titration, administer 50 to 100 mg every 4 to 6 h as needed for pain relief (max, 400 mg/day).

PO Start with low end of dosing (max, 300 mg/day in patients 75 yr of age and older).

PO Increase the dosing interval to 12 h (max, 200 mg/day).

PO 50 mg every 12 h.

PO 100 mg once daily initially, then titrate as necessary by 100 mg increments every 5 days to relief of pain and depending on tolerability (max, 300 mg/day).

PO Use cautiously, starting at the low end of the dosing range.

Do not administer.

Do not administer.

Storage/Stability

Store at 59° to 86°F in a tightly closed container.

Drug Interactions

May reduce serum tramadol levels, leading to decreased efficacy.

Risk of CNS and respiratory depression may be increased.

Digoxin toxicity has been reported.

Risk of seizures may be increased.

Tramadol plasma levels may be increased; however, the clinical importance of this interaction is not known.

Increased risk of serotonin syndrome; increased risk of seizures (ER).

Anticoagulant effect of warfarin may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Postural hypotension (5%); vasodilation (1% to less than 5%).

CNS

Dizziness/vertigo (33%); headache (32%); somnolence (25%); stimulation (14%); asthenia (12%); insomnia (11%); weakness (4%); anxiety, confusion, coordination disturbance, depression, euphoria, hypoesthesia, lethargy, malaise, miosis, nervousness, paresthesia, restlessness, sleep disorder, tremor (1% to less than 5%).

Dermatologic

Flushing (16%); pruritus (12%); sweating (9%); dermatitis, skin rash (1% to less than 5%).

EENT

Blurred vision, nasal congestion, nasopharyngitis, rhinorrhea, sneezing, sore throat, visual disturbance (1% to less than 5%).

GI

Constipation (46%); nausea (40%); vomiting (17%); dyspepsia (13%); diarrhea, dry mouth (10%); anorexia (6%); abdominal pain, flatulence, viral gastroenteritis (1% to less than 5%).

Genitourinary

Menopausal symptoms, urinary frequency, urinary retention, urinary tract infection (1% to less than 5%).

Lab Tests

Increased blood CPK (1% to less than 5%).

Metabolic-Nutritional

Decreased appetite, decreased weight (1% to less than 5%).

Musculoskeletal

Rigors (4%); arthralgia, back pain, hypertonia, limb pain, neck pain (1% to less than 5%).

Respiratory

Bronchitis, cough, dyspnea, sinus congestion, sinusitis, upper respiratory tract infection (1% to less than 5%).

Miscellaneous

Influenza, influenza-like symptoms (2%); chest pain, fall, feeling hot, fever, pain, (1% to less than 5%).

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

IR: Safety and efficacy not established in children younger than 16 yr of age.

ER: Safety and efficacy not established in children younger than 18 yr of age.

Elderly

In elderly patients 75 yr of age and older, concentrations may be slightly elevated; may have less ability to tolerate adverse reactions; use reduced dosage.

Hypersensitivity

Serious and, rarely, fatal anaphylactoid reactions may occur.

Renal Function

Dosage adjustments may be required.

Hepatic Function

Dosage adjustments may be required in patients with cirrhosis.

Acute abdominal conditions

Tramadol may complicate the assessment of acute abdominal conditions.

CNS depressants

Use with caution and in reduced dosage when administering to patients receiving CNS depressants or SSRIs.

Drug abuse

May induce psychic and physical dependence of the morphine type. Do not use in opioid-dependent patients.

Head trauma

Use with caution in patients with increased intracranial pressure or head trauma.

MAOIs (eg, isocarboxazid)

Use with great caution in patients taking MAOIs.

Opioid dependence

Not recommended for patients who are opioid-dependent; use caution when administering to patients who have recently received substantial amounts of opioids.

Respiratory depression

Use with caution.

Seizures

Seizures may occur within the recommended dosage range.

Suicide risk

Do not use in patients who are suicidal or addiction prone (ER only).

Withdrawal

If tramadol is discontinued abruptly, withdrawal symptoms may occur.

Overdosage

Symptoms

Cardiac arrest, coma, death, lethargy, respiratory depression, seizure.

Patient Information

• Instruct patient to take the prescribed dose at the recommended intervals.
• Advise patient to swallow the ER tablet whole and not to break, cut, or crush the tablet.
• Instruct patient to report any serious side effects to health care provider.
• Advise patient not to wait until pain level is high to self-medicate; drug will not be as effective.
• Advise patient to avoid using alcohol or other CNS depressants (eg, sleeping pills).
• Advise patient that this medication may cause drowsiness and to use caution while driving or using heavy equipment, or performing other tasks requiring mental alertness.
• Advise patient not to abruptly discontinue this medication; when discontinuing treatment, taper the dose.
• Advise patient to notify health care provider if pain is not relieved by the medication at prescribed dosage.