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Tramacet and Zuplenz

Determining the interaction of Tramacet and Zuplenz and the possibility of their joint administration.

Check result:
Tramacet <> Zuplenz
Relevance: 26.09.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Combining these medications can increase the risk of serotonin syndrome and an irregular heart rhythm, both rare but potentially life-threatening effects of these drugs. Serotonin syndrome may include symptoms such as confusion, hallucination, seizure, extreme changes in blood pressure, increased heart rate, fever, excessive sweating, shivering or shaking, blurred vision, muscle spasm or stiffness, tremor, incoordination, stomach cramp, nausea, vomiting, and diarrhea. Severe cases may result in coma and even death. You should seek immediate medical attention if you experience these symptoms while taking the medications. You may be more susceptible to the irregular heart rhythm if you have a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). In addition, ondansetron may reduce the effects of traMADol in some patients. Your doctor may be able to adjust the dose of traMADol or prescribe alternatives that do not interact. Contact your doctor if your symptoms worsen, your condition changes, or if you have any questions or concerns. Your doctor may already be aware of the risks, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with these medications, whether together or alone. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

MONITOR CLOSELY: Concomitant use of 5-HT3 receptor antagonists with tramadol may potentiate the risk of serotonin syndrome and/or reduce the analgesic efficacy of tramadol. Serotonin syndrome has been reported with both 5-HT3 receptor antagonists and tramadol, and combined use of these drugs may increase the risk of this rare but serious and potentially fatal condition. Meanwhile, 5-HT3 receptor antagonists may inhibit serotonin-mediated analgesia of tramadol at the spinal level. According to the manufacturers, development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, primarily during concomitant use of serotonergic drugs but also in overdose. Some of the reported cases were fatal. In a randomized, double-blind study of 40 patients undergoing lumbar laminectomy, patients who were administered ondansetron 4 mg at induction of anesthesia required more tramadol postsurgery than control patients who had been given saline. Cumulative tramadol use via a PCA pump was 26% to 35% higher in the ondansetron group the first 4 hours postoperatively and 22% to 25% higher thereafter. Tramadol use on an hourly basis did not differ significantly between the two groups except in the first postoperative hour, probably because of the relatively short plasma half-life of ondansetron. The 4 mg dose of ondansetron did not reduce the 24-hour incidence of postoperative nausea and vomiting.

MONITOR CLOSELY: Treatment with 5-HT3 receptor antagonists has been associated with dose-dependent prolongation of the QT interval. Tramadol may also prolong the QT interval, and theoretically, coadministration of multiple agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias such as torsade de pointes and sudden death. Cases of torsade de pointes have been specifically reported with dolasetron and ondansetron during postmarketing use. It is uncertain whether palonosetron also causes significant prolongation of the QT interval. A thorough QT/QTc study in healthy volunteers demonstrated no relevant effect on QT/QTc interval duration or any other ECG interval at doses up to 2.25 mg. However, non-clinical studies have shown that palonosetron possesses the ability to block ion channels involved in ventricular de- and re-polarization and to prolong action potential duration. The effect of tramadol on the QT interval was evaluated in a randomized, double-blind, 4-way crossover, placebo- and positive-controlled, multiple-dose ECG study of 62 healthy subjects. The maximum placebo-adjusted mean change from baseline in the Fridericia-corrected QT interval (QTcF) was 5.5 msec in the 400 mg/day treatment arm (100 mg every 6 hours on days 1 through 3 with a single 100 mg dose on day 4) and 6.5 msec in the 600 mg/day treatment arm (150 mg every 6 hours on days 1 through 3 with a single 150 mg dose on day 4), both occurring at the 8-hour time point. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Also, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of 5-HT3 receptor antagonists with tramadol should generally be avoided. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is warranted when initiating or increasing the dosages of these agents. In addition, the potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures. The possibility of a diminished therapeutic response to tramadol should also be considered during concomitant therapy with 5-HT3 receptor antagonists. Due to the potential for additive effects on the QT interval, ECG monitoring may also be appropriate. Particular care should be exercised in patients suspected to be at an increased risk of torsade de pointes. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References
  • "Product Information. Anzemet (dolasetron)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  • DeWitte JL, Schoenmaekers B, Sessler DI, DeLoof T "The analgesic efficacy of tramadol is impaired by concurrent administration of ondansetron." Anesth Analg 92 (2001): 1319-21
  • Cerner Multum, Inc. "Australian Product Information." O 0
  • "Product Information. Sancuso (granisetron)." ProStrakan Group, Bedminster, NJ.
  • "Product Information. Akynzeo (netupitant-palonosetron)." Eisai Inc, Woodcliff Lake, NJ.
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  • Canadian Pharmacists Association "e-CPS. Available from: URL: http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink."
  • "Product Information. Aloxi (palonosetron)." MGI Pharma Inc, Minnetonka, MN.
Tramacet

Generic Name: acetaminophen / tramadol

Brand name: Ultracet

Synonyms: Acetaminophen and tramadol, Acetaminophen and Tramadol

Zuplenz

Generic Name: ondansetron

Brand name: Zofran, Zofran ODT, Zuplenz

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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