tramadol (Rx)

Brand and Other Names:Ultram, Ultram ER, more...ConZip
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet: Schedule IV

  • 50mg

suspension reconstituted

  • 10 mg/mL

capsule, extended release: Schedule IV

  • 100mg (ConZip, Ultram ER)
  • 150mg (ConZip)
  • 200mg (ConZip, Ultram ER)
  • 300mg (ConZip, Ultram ER)
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Moderate-to-Severe Pain

Immediate release

  • Chronic: 25 mg PO every morning initially; increased by 25-50 mg/day every 3 days up to 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
  • Acute: 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day

Extended release

  • 100 mg PO once daily initially; increased by 100 mg/day every 5 days; not to exceed 300 mg/day
  • Conversion from immediate release to extended release: Round total daily dose down to nearest 100 mg
  • Do not chew, crush, split, or dissolve

Limitations of Use

Because of risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve therapy for use in patients for whom alternative treatment options [eg, non-opioid analgesics] have not been tolerated, or are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia

Dosing Considerations

Extended-release capsule/tablet must not be chewed, crushed, split, or dissolved

Also given in combination with acetaminophen

Dosing Modifications

Severe renal impairment (CrCl <30 mL/min): Immediate release, 50-100 mg PO q12hr; extended release not recommended

Severe hepatic impairment: Immediate release, 50 mg PO q12hr; extended release not recommended

HIV-Associated Neuropathy (Orphan)

Orphan indication sponsor

  • TheraQuest Biosciences, LLC, 146 Medinah Drive, Blue Bell, PA 19422-3212

Postherpetic Neuralgia (Orphan)

Orphan indication sponsor

  • TheraQuest Biosciences, LLC, 146 Medinah Drive, Blue Bell, PA 19422-3212

Dosage Forms & Strengths

tablet: Schedule IV

  • 50mg

suspension reconstituted

  • 10 mg/mL
more...

Moderate-to-Severe Pain

Immediate release

  • <17 years: Safety and efficacy not established
  • ≥17 years (acute): 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
  • ≥17 years (chronic): 25 mg PO every morning initially; increased by 25-50 mg/day every 3 days as separate doses up to 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day

Extended release

  • <18 years: Safety and efficacy not established

>65 years: Initiate at lower end of dosing range; not to exceed 300 mg/day if >75 years

>75 years: Not to exceed 300 mg/day immediate release; use great caution with extended release

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Interactions

Interaction Checker

and tramadol

No Results

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Constipation (24-46%)

            Nausea (24-40%)

            Dizziness (10-33%)

            Vertigo (26-33%)

            Headache (18-32%)

            Somnolence (7-25%)

            Vomiting (9-17%)

            Agitation (7-14%)

            Anxiety (7-14%)

            Emotional lability (7-14%)

            Euphoria (7-14%)

            Hallucinations (7-14%)

            Nervousness (7-14%)

            Spasticity (7-14%)

            Dyspepsia (5-13%)

            Asthenia (6-12%)

            Pruritus (8-11%)

            1-10%

            Diarrhea (5-10%)

            Dry mouth (5-10%)

            Sweating (6-9%)

            Hypertonia (1-5%)

            Malaise (1-5%)

            Menopausal symptoms (1-5%)

            Rash (1-5%)

            Urinary frequency (1-5%)

            Urinary retention (1-5%)

            Vasodilation (1-5%)

            Visual disturbance (1-5%)

            <1%

            Abnormal gait

            Amnesia

            Cognitive dysfunction

            Depression

            Difficulty in concentration

            Dysphoria

            Dysuria

            Fatigue

            Hallucinations

            Menstrual disorder

            Motor system weakness

            Orthostatic hypotension

            Paresthesia

            Seizures

            Suicidal tendencies

            Syncope

            Tachycardia

            Tremor

            Frequency Not Defined

            Abnormal electrocardiogram (ECG)

            Angioedema

            Bronchospasm

            Flushing

            Hypertension

            Hypotension

            Myocardial ischemia

            Palpitation

            Urticaria

            Withdrawal syndrome

            Postmarketing Reports

            Life-threatening respiratory depression

            Neonatal opioid withdrawal syndrome

            Adrenal insufficiency

            Severe hypotension

            Gastrointestinal adverse reactions

            Abdominal pain

            Serotonin syndrome

            Anaphylaxis

            Androgen deficiency

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            Warnings

            Black Box Warnings

            Addiction, abuse, and misuse

            • Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death; assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation or following a dose increase

            Accidental ingestion

            • Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose

            Neonatal opioid withdrawal syndrome

            • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Ultra-rapid metabolism and other risk factors for life-threatening respiratory depression in children

            • Life-threatening respiratory depression reported in children who received tramadol; some reported cases occurred following tonsillectomy and/or adenoidectomy, and at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism; therapy is contraindicated in children <12 years and in children <18 years of age following tonsillectomy and/or adenoidectomy; avoid use in adolescents 12-18 years who have other risk factors that may increase sensitivity to respiratory depressant effects

            Interactions with Drugs Affecting Cytochrome P450 Isoenzymes

            • Effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex.
            • Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1

            Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

            • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation

            Contraindications

            Hypersensitivity to tramadol or opioids

            Known or suspected gastrointestinal obstruction, including paralytic ileus

            Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within last 14 days

            Children <12 years

            Postoperative management in children <18 years following tonsillectomy and/or adenoidectomy

            ER tablet formulation

            • Acute intoxication with alcohol
            • Concomitatn use with centrally acting analgesics, psychotropic drugs, opioids, hypnotics
            • Severe renal or hepatic impairment

            ER capsule formulation

            • Severe/acute bronchial asthma, significant respiratory depression, hypercapnia
            • Severe renal or hepatic impairment

            Cautions

            Therapy exposes users to risks of addiction, abuse and misuse; because extended-release products deliver opioid over extended period of time, there is greater risk for overdose and death due to arger amount of tramadol present; addiction can occur at recommended dosages and if drug is misused or abused; assess each patient’s risk for opioid addiction, abuse or misuse prior to prescribing therapy; risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); potential for risks should not prevent proper management of pain in any given patient; patients at risk may be prescribed opioids but use in such patients necessitates intensive counseling about risks and proper use along with intensive monitoring for signs of addiction, abuse and misuse; abuse or misuse by splitting, breaking, chewing, crushing, snorting, or injecting dissolved product will result in uncontrolled delivery of tramadol and can result in overdose and death; strategies to reduce these risks include prescribing drug in smallest appropriate quantity and advising patient on proper disposal of unused drug

            Use in patients with acute or severe bronchial asthma in unmonitored setting or in absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages

            Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

            In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma

            Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; may cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

            If anaphylaxis or other hypersensitivity occurs, stop therapy immediately, and do not rechallenge with any formulation of tramadol; advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction

            Avoid use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or may precipitate withdrawal symptoms; when discontinuing therapy, gradually taper dosage; do not abruptly discontinue therapy

            Warn patients not to drive or operate dangerous machinery unless they are tolerant to therapy and know how they will react to medication

            Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts

            If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible

            Renal impairment (reduce dose)

            Anaphylactoid/fatal reactions including pruritus, hives, angioedema, epidermal necrolysis, and Stevens-Johnson syndrome reported with use; risk higher in patients with previous anaphylactoid reactions to opioids

            Use caution when administering with other respiratory depressants and monoamine oxidase inhibitors (MAOIs); risk of respiratory depression or increased ICP

            Increased risk of respiratory depression in patients with respiratory disorders including COPD, hypercapnia, cor pulmonale, or hypoxia; while serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases; to reduce risk of respiratory depression, proper dosing and titration are essential; overestimating dosage when converting patients from another opioid product can result in a fatal overdose with the first dose

            Seizure risk even at recommended dosage, epilepsy patients, or recognized risks (head trauma, metabolic disorders, alcohol and drug withdrawal, central nervous system [CNS] infections), concomitant administraiton with other opioids, SSRIs, tricyclic antidepressants, cyclobenzaprine, promethazine, neuroleptics, MAO inhibitors, or drugs that impair metabolism of tramadol (CYP2D6, 3A4)

            Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency

            Use caution when selecting dosage for an elderly patient, usually starting at low end of dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy; because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function

            Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of liver; limited availability of dose strengths does not permit dosing flexibility required for safe use in patients with severe hepatic impairment (Child-Pugh Class C)

            Not recommended for obstetric preoperative medication or for postdelivery analgesia in nursing mothers

            May impair ability to diagnose or determine clinical course of patients with acute abdominal conditions

            Avoid use in patients who are suicidal; use caution in patients taking tranquilizers and/or antidepressants

            Off-label use in children

            • Severe respiratory depression reported with off-label use in children
            • Tramadol undergoes extensive hepatic metabolism; it is metabolized by CYP2D6 to the active metabolite O-desmethyltramadol (M1), which has a 200-fold greater affinity for opioid receptors than does tramadol
            • Avoid use in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of tramadol unless benefits outweigh risks; 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; when prescribing tramadol for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of opioid overdose
            • CYP2D6 poor metabolizers have shown a 20% increase in tramadol levels and a 40% decrease in O-desmethyltramadol (M1)

            Drug interactions overview

            • Concomitant use with all cytochrome P450 2D6 inhibitors (e.g., amiodarone, quinidine) may result in increased tramadol plasma levels and decreased levels of the active metabolite, M1; a decrease in M1 exposure in patients who have developed physical dependence to tramadol, may result in signs and symptoms of opioid withdrawal and reduced efficacy; increased tramadol levels may increase risk for serious adverse events including seizures and serotonin syndrome
            • Discontinuation of a concomitantly used cytochrome P450 2D6 inhibitor may result in a decrease in tramadol plasma levels and an increase in active metabolite M1 levels, which could increase or prolong adverse reactions related to opioid toxicity and may cause potentially fatal respiratory depression
            • Concomitant use with cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) or discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine, and phenytoin, may result in an increase in tramadol plasma concentrations, which could increase or prolong adverse reactions, increase the risk for serious adverse events including seizures and serotonin syndrome, and may cause potentially fatal respiratory depression
            • The concomitant use with all cytochrome P450 3A4 inducers or discontinuation of a cytochrome P450 3A4 inhibitor may result in lower tramadol levels; this may be associated with a decrease in efficacy, and in some patients, may result in signs and symptoms of opioid withdrawal
            • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation
            • Cases of serotonin syndrome, a potentially life-threatening condition, reported, particularly during concomitant use with serotonergic drugs; serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue); may occur within recommended dosage range; symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea); onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy if serotonin syndrome is suspected
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            Pregnancy & Lactation

            Pregnancy: Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported with tramadol during post-approval use of tramadol immediate-release products

            Pregnancy

            Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly  

            Labor and delivery

            • Use of tramadol during labor may lead to respiratory depression in the neonate
            • Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; use is not recommended in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate; opioid analgesics, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression

            Lactation

            Tramadol and its active metabolite, O-desmethyltramadol (M1), are present in human milk; there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk; women who are ultra-rapid metabolizers of tramadol achieve higher than expected serum levels of opioids, potentially leading to higher levels of M1 in breast milk that can be dangerous in their breastfed infants; in women with normal tramadol metabolism (normal CYP2D6 activity), the amount of tramadol secreted into human milk is low and dose-dependent

            Because of potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Non-opioid-derived synthetic opioid; centrally acting analgesic, but may act at least partially by binding to opioid mu receptors, causing inhibition of ascending pain pathways

            Absorption

            Bioavailability: Immediate release, 75%; extended release, 85-90%

            Onset: ~1 hr

            Duration: 9 hr

            Peak plasma time: Immediate release, 1.5 hr; extended release, 12 hr

            Distribution

            Protein bound: 20%

            Vd: 2.5-3 L/kg

            Metabolism

            Metabolized in liver by CYP2D6 and CYP3A4 via N- and O-demethylation and glucuronidation/sulfation

            Metabolites: M1 (O-desmethyltramadol; active); M1 metabolite has 200-fold greater affinity for opioid receptors than parent drug

            In CYP2D6 poor metabolizers, tramadol levels may increase by 20% and M1 levels decrease by 40%

            Elimination

            Half-life: 6-8 hr

            Excretion: Urine (90%)

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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