tramadol

Contraindicated in:

Hypersensitivity;
Cross-sensitivity with opioids may occur;
Significant respiratory depression;
Acute or severe bronchial asthma (in unmonitored setting or in absence of resuscitative equipment);
Known or suspected GI obstruction (including paralytic ileus);
Concurrent use of MAO inhibitors (or use within the past 14 days);
Patients who are acutely intoxicated with alcohol, sedatives/hypnotics, centrally acting analgesics, opioid analgesics, or psychotropic agents;
Patients who are physically dependent on opioid analgesics (may precipitate withdrawal);
Ultra-rapid metabolizers of CYP2D6 (↑ risk of respiratory depression and death)
;
Severe renal impairment (extended release);
Hepatic impairment (extended release).
Lactation: Lactation;
Pedi:
Children <12 yr, children <18 yr following tonsillectomy and/or adenoidectomy, and children 12–18 yr who are postoperative; have obstructive sleep apnea, obesity, severe pulmonary disease, or neuromuscular disease; or are taking other medications that cause respiratory depression (↑ risk of respiratory depression and death)
.

Use Cautiously in:

Personal or family history of substance use disorder or mental illness;
History of epilepsy or risk factors for seizures;
Diabetes mellitus (↑ risk of hypoglycemia);
Severe renal impairment (immediate release) (↑ dosing interval);
Hepatic impairment (immediate release) (↑ dosing interval in patients with cirrhosis);
Suicidal or prone to addiction (↑ risk of suicide);
Excessive use of alcohol (↑ risk of suicide);
↑intracranial pressure or head trauma;
OB:
Use during pregnancy only if potential maternal benefit justifies potential fetal risk. Chronic maternal treatment with opioids during pregnancy may result in neonatal opioid withdrawal syndrome
;
Geri: Appears on Beers list. May worsen or cause hyponatremia in older adults. Use with caution in older adults and monitor sodium concentrations closely when initiating therapy or ↑ the dose. Use extended-release formulation with extreme caution in patients >75 yr.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: pruritus, sweating

EENT: visual disturbances

Endo: hypoglycemia

F and E: hyponatremia

GI: constipation, nausea, abdominal pain, anorexia, diarrhea, dry mouth, dyspepsia, flatulence, vomiting

GU: ↓fertility, menopausal symptoms, urinary retention/frequency

Neuro: dizziness, headache, somnolence, anxiety, confusion, coordination disturbance, euphoria, hypertonia, malaise, nervousness, SEIZURES, sleep disorder, stimulation, weakness

Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA)

Misc: allodynia, opioid-induced hyperalgesia, physical dependence, psychological dependence, tolerance

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors↑ risk of adverse reactions; concurrent use or use within previous 14 days contraindicated.
Use with benzodiazepines or other CNS depressants, including other opioids, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
Mixed agonist/antagonist analgesics, including nalbuphine or butorphanol, and partial agonist analgesics, including buprenorphine, may ↓ tramadol's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.
↑risk of seizures with high doses of penicillins, cephalosporins, phenothiazines, opioid analgesics, or antidepressants.
CYP2D6 inhibitors, including quinidine, fluoxetine, paroxetine, and bupropion, may ↓ levels of active metabolite (M1) and lead to ↓ analgesic effects.
CYP3A4 inhibitors, including erythromycin, clarithromycin, ketoconazole, itraconazole, and protease inhibitors, may allow for a greater degree of metabolism via CYP2D6 and ↑ levels of the active metabolite (M1), leading to respiratory depression.
CYP3A4 inducers may ↓ levels and effectiveness.
Drugs that affect serotonergic neurotransmitter systems, including SSRIs, SNRIs, MAO inhibitors, TCAs, trazodone, mirtazapine, 5-HT3 receptor antagonists, linezolid, methylene blue, and triptans, may ↑ risk of serotonin syndrome.

Drug-Natural Products:

Kava-kava, valerian, or chamomile can ↑ risk of CNS depression.
↑risk of serotonin syndrome with St. John's wort.

Availability ⬆ ⬇

(Generic available)

Immediate-release tablets: 25 mg; 50 mg; 100 mg
Extended-release capsules (Conzip): 100 mg; 200 mg; 300 mg
Extended-release tablets: 75 mg; 100 mg; 150 mg; 200 mg; 300 mg; 400 mg
Oral solution grape flavor: 5 mg/mL
In combination with: acetaminophen (generic only).

Route/Dosage ⬆ ⬇

Immediate Release

PO (Adults ≥18 yr): Rapid titration: 50–100 mg every 4–6 hr (not to exceed 400 mg/day [300 mg in patients >75 yr]). Gradual titration: 25 mg/day initially; ↑ by 25 mg/day every 3 days to reach dose of 25 mg 4 times daily; then ↑ by 50 mg/day every 3 days to reach dose of 50 mg 4 times daily; may then use 50–100 mg every 4–6 hr (maximum dose = 400 mg/day).

Renal Impairment

PO (Adults ): CCr <30 mL/min:↑ dosing interval to every 12 hr (not to exceed 200 mg/day).

Hepatic Impairment

PO (Adults ): Severe hepatic impairment: 50 mg every 12 hr.

Extended Release

PO (Adults ): Not currently receiving immediate release: 100 mg once daily initially; may then titrate every 5 days up to 300 mg/day; Currently receiving immediate release: Calculate 24-hr total dose of immediate-release product and give same dose (rounded down to next lowest 100-mg increment) of ER once daily (maximum dose = 300 mg/day).

US Brand Names ⬆ ⬇

ConZip, ~~Ultram,~~ ~~Ultram ER~~

Action ⬆ ⬇

Acts as a mu-opioid receptor agonist.
Inhibits reuptake of serotonin and norepinephrine in the CNS.

Therapeutic effects:

Decreased pain.

Classifications ⬆ ⬇

Therapeutic Classification: analgesics (centrally acting), opioid analgesics

Pharmacologic Classification: opioid agonists

Pharmacokinetics ⬆ ⬇

Absorption: Immediate release: 75% absorbed after oral administration; Extended release: 85–90% (compared with immediate release).

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Mostly metabolized by the liver (primarily by the CYP2D6 and CYP3A4 isoenzymes); primarily metabolized by the CYP2D6 isoenzyme to active metabolite with analgesic activity (M1); CYP2D6 enzyme system exhibits genetic polymorphism; ∼7% of population may be poor metabolizers and may have significantly ↑ concentrations of tramadol and ↓ concentrations of M1 metabolite. 1–10% of White patients, 3–4% of Black patients, and 1–2% of East Asian patients may be CYP2D6 ultra-rapid metabolizers and have significantly ↑ concentrations of M1 metabolite. 30% eliminated unchanged in the urine.

Half-Life: Tramadol (immediate release): 6–8 hr, Extended release: 7.9 hr; Active metabolite: 7–9 hr; both are ↑ in renal or hepatic impairment.

Contr. Subst. Schedule ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Durela, Ralivia, Tridural, Zytram XL

Time/Action Profile ⬆ ⬇

(analgesia)

ROUTE	ONSET	PEAK	DURATION
PO–immediate release	1 hr	2–3 hr	4–6 hr
PO–extended release	unknown	12 hr	24 hr

Patient/Family Teaching ⬆ ⬇

REMS: Explain purpose and side effects of tramadol to patient. Instruct them to take medication as directed and when to ask for pain medication. Never use household teaspoons or tablespoons to measure dose for oral solution; always use a calibrated measuring device. Do not share medication with others, even if they have similar symptoms; may be harmful. Do not stop taking without discussing with health care provider; may cause withdrawal symptoms if discontinued abruptly after prolonged use. Do not doses without discussing with health care provider; may lead to overdose. Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx. The Patient Counseling Guide is available at https://opioidanalgesicrems.com/patientCounselingGuide.htmlAdvise patient to read Patient Information before starting and with each Rx refill in case of changes.
May cause dizziness and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Emphasize the importance of aggressive prevention of constipation with the use of tramadol.
Advise patient that tramadol is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children and in a location not accessible by others.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Inform patients and caregivers about various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (Rx, direct from pharmacist, or state programs). OTC nasal spray is available at pharmacies nationwide for overdose or accidental ingestion.
Advise patient to change positions slowly to minimize orthostatic hypotension.
Caution patient to avoid concurrent use of alcohol or other CNS depressants, including other opioids, with this medication. Advise patient to notify health care provider before taking other RX, OTC, or herbal products concurrently.
Advise patient to notify health care provider if seizures or if symptoms of serotonin syndrome (agitation, confusion, fever, elevated BP, rapid heartbeat, sweating, nausea, vomiting, loss of coordination) occur.
Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
Rep:
Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal symptoms (irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, failure to gain weight); usually occur the 1st days after birth. Monitor infants exposed to tramadol through breast milk for excess sedation and respiratory depression. Neonatal seizures, fetal death, and stillbirth have been reported with tramadol immediate-release products. Chronic use may ↓ fertility in men and women.

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Indications ⬇

Contraind./Precautions ⬆ ⬇