Acetaminophen with Tramadol (Tramacet®)

Controlled Substances

Only midwives who have completed the “Opioids and Benzodiazepines: Safe Prescribing for Midwives” course may independently prescribe controlled substances.

(Tramacet®) is not a controlled substance but has been included here because it contains Tramadol, a non-federally regulated opioid analgesic that appears to have a reduced addictive potential.

Acetaminophen and Tramadol is an analgesic, opioid combination medication. Tramadol is more potent than codeine and most closely resembles the opiates.

Acetaminophen component: Inhibits prostaglandin synthesis in the central nervous system and peripherally blocks pain impulse; it produces antipyresis from inhibition of the hypothalamic heat-regulating center.

Tramadol component: Binds to opiate receptors in the CNS causing inhibition of ascending pain pathways, altering pain perception and response to pain; also inhibits norepinephrine and serotonin uptake, and modifies ascending pain pathways.

Indications and Clinical Use:

Combined Acetaminophen and Tramadol is used for < 72 hours to relieve acute short-term moderate to severe pain in the postpartum period following vaginal and/or operative delivery.

Contraindications:

Hypersensitivity to acetaminophen, tramadol, opioids, or any component of the formulation; opioid-dependent patients; narcotics, centrally-acting analgesics or psychotropic drugs; hepatic dysfunction.

Tramadol is contraindicated during or within 14 days following monoamine oxidase (MAO) inhibitor therapy first generation antidepressant drugs. The MAO inhibitor antidepressants are older antidepressants, now reserved for extremely resistant cases of depression unresponsive to new agents: Isocarboxazid (Marplan®), Phenelzine (Nardil®), Tranylcypromine (Parnate®), Moclobemide (generics).

Warnings and Precautions:

Acetaminophen: Do not exceed the maximum recommended dose (4000 mg = 4 g) per 24 hours. Liver toxicity has been reported following chronic abuse of acetaminophen at > 200 mg/kg/day.

Tramadol: May cause CNS depression and/or respiratory depression and may impair physical or mental abilities.

Use with caution in patients taking tranquilizers and/or antidepressants, or those with an emotional disturbance including depression; history of seizure disorder.

*CNS depressants: Use with caution and reduce dosage when administering to patients receiving other CNS depressants.

Tramadol may enhance the neuroexcitatory and/or seizure-potentiating effect of MAO Inhibitors. Consider alternatives to combined treatment with tramadol and monoamine oxidase inhibitors due to an increased risk of serotonin syndrome and seizures.

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

A history of anaphylactoid reactions to opioids may increase risks for similar reactions to tramadol.

Healthcare provider should be alert to problems of abuse, misuse, and diversion.

Pregnancy:

Acetaminophen – Human Data Suggest Low Risk; Compatible 
Tramadol – Human Data Suggest Risk 

There is a risk of congenital birth defects if exposure occurs during organogenesis. Continuous intake leads to the potential complication of neonatal withdrawal. Long term neurobehavior effects of the neonate are unknown.

Lactation:

Acetaminophen – L1
Tramadol – L3 – Limited Data – Probably Compatible 

Tramadol is considered suitable for short term use in lactation as about 3% of the dose enters milk. However, the U.S. Food & Drug Administration has issued a warning against the use of Tramadol during lactation and in pediatric patients due to adverse events. This medication has an active metabolite via the CYP 2D6 enzyme, thus caution is recommended. In addition, experience with this medication is limited in the neonatal/pediatric population. If this medication is given in lactation, the lowest effective dose should be given for the shortest possible period of time. The neonate should also be monitored for signs of sedation, such as not waking up to feed at regular intervals. If ongoing narcotic is required postpartum consider other alternative agents such as hydromorphone.

Adverse Reactions:

Acetaminophen – Diarrhea, gastric upset with overdose.

Tramadol – Sedation, respiratory depression, nausea, vomiting, constipation, pruritus, hives, angioedema, bronchospasm, toxic epidermal necrolysis, Stevens-Johnson syndrome have been reported.

Rare reactions including anaphylactoid fatalities have been reported following initial dosing. Adverse events were observed in animal studies. Tramadol has been shown to cross the human placenta when administered during labor. Postmarketing reports following tramadol use during pregnancy include neonatal seizures, withdrawal syndrome, fetal death, and stillbirth. Not recommended for intrapartum use.

Dosage and Administration:

Tramacet® is a combination medication consisting of the following:

Acetaminophen: 325 mg plus Tramadol: 37.5 mg

Usual dose: PO1- 2 tablets every 4 to 6 hours as needed for pain

Maximum dose: PO 8 tablets per 24 hours

Note: if 8 tablets are taken daily, this equals: acetaminophen 2600 mg/day. Maximum dose of acetaminophen is 4,000 mg/day, a top up with plain acetaminophen (4 x 325 mg or 2 x 500 mg) per 24 hours is considered safe.

May be administered with or without food.

Onset of Action:

Acetaminophen: < less than 1 hour

Tramadol: 60-90 minutes.

Time to peak effect: Tramadol: 2-3 hours

Half-Life:

Adult – Acetaminophen – 2 hours, Tramadol – 6-8 hours, 7-9 for the active metabolite

Neonate – Acetaminophen – 7 hours, Tramadol – 3.6 hours in children (no data in neonates)

Prescription:

Acetaminophen with tramadol may be prescribed in hospital or in the community. It does not require a duplicate prescription pad. A prescription cannot exceed three days. No refills.