Tramadol (ULtram)

Today's med: Tramadol  (TRA ma dole) 
(brand names: ConZip, Rybix ODT, Ryzolt, Ultram, Ultram ER)

Drug Class: Analgesic, Opiod

Other Drugs in this class: Oxycodone,Acetaminophen,Hydrocodone/Acetaminophen, 
Gabapentin,Codeine, Ibuprofen, Morphine,Buprenorphine,Oxycodone/Acetaminophen, Ketoprofen,Methadone, Tapentadol, Aspirin,Hydroxyzine, Hydromorphone, Meperidine,Fentanyl, Loperamide,
Phenazopyridine,Butorphanol, Oxymorphone,Hydrocodone/ibuprofen, Remifentanil,Menthol, Sufentanil, Magnesium salicylate, Alfentanil, Loperamide Hydrochloride, Ziconotide, Levorphanol,Oxycodone Hydrochloride,
Propoxyphene,Gabapentin enacarbil,Hydrocodone/Chlorpheniramine,
Codeine/Guaifenesin,Hydrocodone/Homatropine,Tramadol/Acetaminophen,Oxycodone/Ibuprofen,Morphine/naltrexone, Fentanyl Citrate,Hydromorphone Hydrochloride, Meperidine Hydrochloride, Propoxyphene Napsylate,Propoxyphene/Acetaminophen,Oxymorphone Hydrochloride, Tapentadol hydrochloride, Methadone hydrochloride,Levorphanol tartrate, Propoxyphene Hydrochloride, Sufentanil citrate, …

Indications: 

Use: Labeled Indications

Relief of moderate to moderately-severe pain

Extended release formulations are indicated for patients requiring around-the-clock management of moderate to moderately-severe pain for an extended period of time

Contraindications: Hypersensitivity to tramadol, opioids, or any component of the formulation

Additional contraindications for Ultram®, Rybix™ ODT, and Ultram® ER: Any situation where opioids are contraindicated, including acute intoxication with alcohol, hypnotics, centrally-acting analgesics, opioids, or psychotropic drugs

Additional contraindications for ConZip™, Ryzolt™: Severe/acute bronchial asthma, hypercapnia, or significant respiratory depression in the absence of appropriately monitored setting and/or resuscitative equipment

Canadian product labeling:

Tramadol is contraindicated during or within 14 days following MAO inhibitor therapy

Extended release formulations: Additional contraindications:

Ralivia™, Tridural™: Severe (Cl_cr <30 mL/minute) renal dysfunction, severe (Child-Pugh class C) hepatic dysfunction

Durela™ and Zytram® XL: Severe (Cl_cr <30 mL/minute) renal dysfunction, severe (Child-Pugh class C) hepatic dysfunction; known or suspected mechanical GI obstruction or any disease/condition that affects bowel transit; mild, intermittent or short-duration pain that can be managed with other pain medication; management of peri-operative pain; obstructive airway, acute respiratory depression, cor pulmonale, delirium tremens, seizure disorder, severe CNS depression, increased cerebrospinal or intracranial pressure, head injury, breast-feeding, pregnancy; use during labor and delivery

Actions: Tramadol and its active metabolite (M1) binds to μ-opiate receptors in the CNS causing inhibition of ascending pain pathways, altering the perception of and response to pain; also inhibits the reuptake of norepinephrine and serotonin, which also modifies the ascending pain pathway

Warnings: 

Concerns related to adverse effects:

• Anaphylactoid reactions: Rare but serious anaphylactoid reactions (including fatalities) often following initial dosing have been reported. Pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome also have been reported with use. Previous anaphylactoid reactions to opioids may increase risks for similar reactions to tramadol.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Seizures: Even when taken within the recommended dosage seizures may occur; risk is increased in patients receiving serotonin reuptake inhibitors (SSRIs or anorectics), other opioids, tricyclic antidepressants or other cyclic compounds (including cyclobenzaprine, promethazine), neuroleptics, MAO inhibitors, drugs which may lower seizure threshold, or drugs which impair metabolism of tramadol (ie, CYP2D6 and 3A4 inhibitors). Patients with a history of seizures, or with a risk of seizures (head trauma, metabolic disorders, CNS infection, malignancy, or during alcohol/drug withdrawal) are also at increased risk.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists.

• Ethanol use: Use with caution in heavy alcohol users.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.

• Hepatic impairment: Use with caution and reduce dosage in patients with mild-to-moderate hepatic impairment; extended release formulations should not be used in severe hepatic impairment (Child-Pugh class C); Ryzolt™ (extended release tablet) should not be used in any degree of hepatic impairment.

• Renal impairment: Use with caution and reduce dosage in patients with mild-to-moderate renal impairment; extended release formulations should not be used in severe renal impairment Cl_cr <30 mL/minute.

• Respiratory disease: Patients with respiratory disorders (eg, significant chronic obstructive pulmonary disease (COPD), cor pulmonale, hypoxia, hypercapnia) may be at greater risk of respiratory depression.

• Suicide risk: Avoid use in patients who are suicidal; use with caution in patients taking tranquilizers and/or antidepressants, or those with an emotional disturbance including depression.

Concurrent drug therapy issues:

• CNS depressants: Use with caution and reduce dosage when administering to patients receiving other CNS depressants; may cause CNS depression and/or respiratory depression.

• Serotonin syndrome: Avoid, if possible, use with serotonergic agents such as TCAs, MAO inhibitors (use with extreme caution; contraindicated in Canadian product labeling), triptans, venlafaxine, trazodone, lithium, sibutramine, meperidine, dextromethorphan, St John’s wort, SNRIs, and SSRIs; use caution with drugs which impair metabolism of tramadol (ie, CYP2D6 and 3A4 inhibitors); concomitant use may increase the risk of serotonin syndrome.

Special populations:

• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

• Elderly: Extended-release formulation should be used with extreme caution in the elderly (particularly >75 years of age); may be more sensitive to adverse effects. Reduce initial dose.

Dosage form specific issues:

• Extended release tablets: Caution patients to swallow tablets whole. Rapid release absorption of tramadol from tablets that are broken, crushed, or chewed may lead to a potentially-lethal overdose.

• Phenylalanine: Some products may contain phenylalanine.

Other warnings/precautions:

• Abuse/misuse/diversion: Healthcare provider should be alert to problems of abuse, misuse, and diversion.

• Withdrawal: 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.

Monitoring Parameters

Pain relief, respiratory rate, blood pressure, and pulse; signs of tolerance, abuse, or suicidal ideation

Pregnancy Risk Factor  C

Standard Dosing: Oral: Moderate-to-severe pain:

Children ≥17 years and Adults:

Immediate release: 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. The total daily dose may then be increased by 50 mg every 3 days as tolerated, to reach dose of 50 mg 4 times/day. After titration, 50-100 mg may be given every 4-6 hours as needed up to a maximum 400 mg/day.

Orally-disintegrating tablet (Rybix™ ODT): 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 50 mg/day and titrating dose by 50 mg every 3 days, until reaching 50 mg 4 times/day. After titration, 50-100 mg may be given every 4-6 hours as needed up to a maximum 400 mg/day.

Adults: Extended release:

U.S. labeling: ConZip™, Ryzolt™, Ultram® ER:

Patients not currently on immediate-release tramadol: 100 mg once daily; titrate every 5 days (ConZip™, Ultram® ER) or every 2-3 days (Ryzolt™); maximum dose: 300 mg daily

Patients currently on immediate-release tramadol: Calculate 24-hour immediate release total dose and initiate total extended release daily dose (round dose to the next lowest 100 mg increment); titrate as tolerated to desired effect (maximum: 300 mg daily)

Canadian labeling: Note: Patients currently on immediate-release tramadol: When switching to extended release, initiate at the same or lowest nearest total daily tramadol dose. Not to exceed recommended maximum daily dosing.

Durela™, Ralivia™, Tridural™: Patients not currently on immediate-release tramadol or opioids: Initial: 100 mg once daily; titrate every 5 days (Durela™, Ralivia™) or every 2 days (Tridural™) as needed based on clinical response and severity of pain (maximum: 300 mg daily)

Zytram® XL: Patients not currently on immediate-release tramadol or opioids: 150 mg once daily; if pain relief is not achieved may titrate by increasing dosage incrementally, with sufficient time to evaluate effect of increased dosage; generally not more often than every 7 days (maximum: 400 mg daily)

Elderly >65 years: Use caution and initiate at the lower end of the dosing range

Elderly >75 years:

Immediate release: Do not exceed 300 mg/day; see dosing adjustments for renal and hepatic impairment.

Extended release: Use with great caution. See adult, renal, and hepatic dosing.

Lab Test Interferences

May interfere with urine detection of PCP (false-positive).

Drug interactions: Link: http://www.drugs.com/drug-interactions/tramadol.html 

A total of 660 drugs (3852 brand and generic names) are known to interact with tramadol.

• 349 major drug interactions (1774 brand and generic names)
• 307 moderate drug interactions (2063 brand and generic names)
• 4 minor drug interactions (15 brand and generic names)

Show all medications in the database that may interact with tramadol.

• SSRIs, MAO inhibitors and Tricyclic antidepressants may increase risk of seizure!!!
• Vit K antagonist
• Zolpidem may enhance CNS depressant effect and may increase diuretic effect of thiazide diuretics.
• DO NOT use with alcohol
• CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
• Monitor paitent for respiratory symptoms.  

               THIS IS A SCHEDULE IV DRUG!