Ultram (tramadol HCl)

Available as tramadol hydrochloride; dosage expressed in terms of the salt.

Use the lowest effective dosage and shortest duration of therapy consistent with the treatment goals of the patient.

Individualize initial dosage based on severity of pain, response, prior analgesic use, and risk factors for addiction, abuse, and misuse. Dosage should be titrated to a level that provides adequate analgesia and minimizes adverse effects. If level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the dosage.

Tramadol hydrochloride is administered orally as immediate- or extended-release preparations.

Tramadol is commercially available as a single-entity preparation in various dosage forms and in fixed combination with acetaminophen. Consult the prescribing information for additional information on the fixed combination product.

No dosing information is available for this tab.

No dosing information is available for this tab.

Tramadol hydrochloride is extensively metabolized by cytochrome P-450 (CYP) isoenzymes 2D6 and 3A4, as well as by conjugation. The formation of the active metabolite, O-desmethyl tramadol (M1), is dependent on CYP2D6.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known hypersensitivity (e.g., anaphylaxis) to tramadol, any ingredient in the formulation, or opioid agonists.

*Significant respiratory depression.

*Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.

*Known or suspected GI obstruction, including paralytic ileus.

*Current or recent (within 14 days) therapy with a monoamine oxidase inhibitor (MAOI).

*In children <12 years of age for pain.

*In children <18 years of age for postoperative pain following tonsillectomy and/or adenoidectomy.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

The most common adverse effects of tramadol hydrochloride immediate-release preparations (>=15%) reported in clinical trials were dizziness/vertigo, nausea, constipation, headache, somnolence, vomiting, and pruritus.

The most common adverse effects of tramadol hydrochloride extended-release tablets (>=10% and >=2 times that of placebo) include dizziness, constipation, nausea, headache, somnolence, flushing, pruritus, vomiting, insomnia, and dry mouth.

The most common adverse effects of tramadol hydrochloride extended-release capsules (>=10% and >=2 times that of placebo) include nausea, constipation, dry mouth, somnolence, dizziness, and vomiting.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

The safety and efficacy of tramadol has not been established in pediatric patients. Life-threatening respiratory depression and death have occurred in pediatric patients who have received tramadol. In some cases, these events followed tonsillectomy and/or adenoidectomy, and one patient had evidence of being an ultrarapid metabolizer. Children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol.

Because of the risk of life-threatening respiratory depression and death, tramadol is contraindicated in all pediatric patients <12 years of age and for the post-operative management of pain in pediatric patients <18 years of age following tonsillectomy and/or adenoidectomy. Risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.

There are insufficient data available regarding tramadol in pregnant females to establish the associated risk of major birth defects and spontaneous abortion. Tramadol has been shown to be embryotoxic and fetotoxic in mice, rats, and rabbits at maternally toxic doses 1.4, 0.6, and 3.6 times, respectively, the maximum daily human dosage (120 mg/kg in mice, 25 mg/kg in rats, and 75 mg/kg in rabbits). Embryo and fetal toxicity consisted mainly of decreased fetal weights, decreased skeletal ossification, and increased supernumerary ribs at maternally toxic dose levels. Transient delays in developmental or behavioral parameters also were seen in pups from rat dams allowed to deliver. Embryo and fetal lethality was reported in only one rabbit study, in which rabbits received tramadol hydrochloride 300 mg/kg, a dose that would cause extreme maternal toxicity in rabbits. No drug-related teratogenic effects were observed in progeny of mice, rats, or rabbits receiving tramadol (up to 140, 80, or 300 mg/kg or 1.7, 1.9, or 14.6 times, respectively, the maximum daily human dosage) by various routes. In perinatal and postnatal studies in rats, progeny of dams receiving oral (gavage) tramadol doses of 50 mg/kg (1.2 times the maximum human dose) or higher had decreased weights, and pup survival was decreased early in lactation at tramadol doses of 80 mg/kg (1.9 times the maximum human dose).

Prolonged maternal use of opioid agonists during pregnancy can result in neonatal opioid withdrawal syndrome with manifestations of irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. In contrast to adults, the withdrawal syndrome in neonates may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Females who require prolonged opioid therapy during pregnancy should be advised of the risk of neonatal opioid withdrawal syndrome, and availability of appropriate treatment should be ensured. The onset, duration, and severity of the syndrome vary depending on the specific opioid agonist used, duration of use, timing and amount of last maternal use, and rate of drug elimination by the neonate. Neonatal seizures, neonatal withdrawal syndrome, fetal death, and stillbirth have been reported with tramadol during postmarketing experience. The effect of tramadol, if any, on the later growth, development, and functional maturation of the child is unknown.

Use of opioids in pregnant females during labor can result in neonatal respiratory depression. Use of tramadol is not recommended immediately before or during labor, when other analgesic techniques may be more appropriate. Opioid agonists may prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is inconsistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Neonates exposed to opioids during labor should be monitored for excessive sedation and respiratory depression. An opioid antagonist must be available for reversal of opioid-induced respiratory depression.

Tramadol and its metabolite, O-desmethyl tramadol (M1), are distributed into human milk. Following a single IV tramadol dose of 100 mg, the cumulative distribution into milk within 16 hours after dosing was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of M1. Published studies have reported tramadol and M1 in colostrum with administration of tramadol to nursing mothers in the early postpartum period. Females who are ultrarapid metabolizers of tramadol may have higher than expected serum levels of M1, potentially leading to higher levels of M1 in breast milk that can be dangerous to breast-fed infants. In females with normal tramadol metabolism, the amount of tramadol distributed into human milk is low and dose-dependent. There is no information on the effects of tramadol on the breast-fed infant or the effects on milk production. Because of the potential for serious adverse effects, including excess sedation and respiratory depression in a breast-fed infant, advise patients that breast-feeding is not recommended with tramadol. Infants exposed to tramadol through breast milk should be monitored closely for clinical manifestations of opioid toxicity (e.g., excess sedation, respiratory depression). Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped or when breast-feeding is stopped.

Select the dosage of tramadol with caution and consider regular evaluation of renal function. Titrate the dosage carefully, starting at the low end of the dosage range and monitor closely for signs of CNS and respiratory depression.

Do not exceed a total daily dosage of 300 mg in patients >75 years of age.

In controlled clinical trials of tramadol immediate-release tablets, 455 patients who received tramadol were >=65 years of age and 145 patients were >=75 years of age. In patients >=75 years of age receiving immediate-release tramadol, maximum serum tramadol concentrations were elevated (208 ng/mL) and the elimination half-life was prolonged (7 hours) compared with patients 65-75 years of age (162 ng/mL and 6 hours, respectively). Treatment-limiting adverse GI effects occurred in 30% of patients >75 years of age compared with 17% of those <65 years of age, and constipation resulted in discontinuance of treatment in 10% of those >75 years of age.

In clinical trials of tramadol extended-release tablets, 901 patients who received tramadol were >=65 years of age and 156 patients were >=75 years of age. In these studies, the incidence of adverse effects was higher in patients >65 years of age compared with younger adults; adverse effects reported more frequently in older adults included constipation, fatigue, weakness, postural hypotension, and dyspepsia.

In clinical trials of tramadol extended-release capsules, 812 patients who received tramadol were >=65 years of age and 240 patients were >=75 years of age. In these studies, the incidence of adverse effects was higher in patients >65 years of age compared with younger adults; adverse effects reported more frequently in older adults included nausea, constipation, somnolence, dizziness, dry mouth, vomiting, asthenia, pruritus, anorexia, sweating, fatigue, weakness, postural hypotension, and dyspepsia.

Tramadol is known to be substantially excreted by the kidney, and the risk of adverse effects may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, select the dosage of tramadol with caution and consider regular evaluation of renal function. Titrate the dosage carefully, starting at the low end of the dosage range and monitor closely for signs of CNS and respiratory depression.