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| ADR REPORT |
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| Year : 2014 | Volume
: 60
| Issue : 2 | Page : 189-191 |
Cardiovascular abnormalities with single dose of tapentadol
A Vachhani1, M Barvaliya2, V Naik1, CB Tripathi1
1 Department of Pharmacology, Government Medical College, Bhavnagar, Gujarat, India
2 Department of Pharmacology, Gujarat Medical Education and Research Society Medical College, Patan, Gujarat, India
| Date of Submission | 30-Sep-2013 |
| Date of Decision | 08-Oct-2013 |
| Date of Acceptance | 21-Oct-2013 |
| Date of Web Publication | 13-May-2014 |
Correspondence Address:
Dr. C B Tripathi
Department of Pharmacology, Government Medical College, Bhavnagar, Gujarat
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0022-3859.132341
This case represents the development of dizziness, palpitation, tightness in chest, flushing, and tremor on consumption of a single dose of tapentadol (100 mg) for acute lower back pain. The patient was admitted in the intensive cardiac care unit for continuous monitoring. At admission, electrocardiogram showed tachycardia (140/min) along with ST segment elevation in second chest lead (V 2 ). The patient was monitored and advised not to take further doses of tapentadol. He was discharged after 36 hours of admission. Tapentadol should be used cautiously in patients with cardiovascular diseases and receiving sympathomimetic drugs.
Keywords: Adverse drug reaction, palpitation, structure activity relationship, tapentadol
How to cite this article:
Vachhani A, Barvaliya M, Naik V, Tripathi C B. Cardiovascular abnormalities with single dose of tapentadol. J Postgrad Med 2014;60:189-91 |
| :: Introduction | |  |
Tapentadol(_)-{[1R,2R)-3-(3-dimethylamino)-1-ethyl-2-methyl-propyl]-phenolhydrochloride} is a novel μ-opioid receptor agonist and norepinephrine reuptake inhibitor. It is indicated for acute moderate-to-severe pain relief. [1] Its side-effect profile is similar to other opioids. It also has an abuse liability and risk of psychological and physical dependence. [2],[3],[4] To the best of our knowledge, serious cardiovascular adverse reactions with tapentadol are not reported yet in clinical practice. In one reported case, a patient died due to tapentadol toxicity. [5] We report a case of cardiovascular abnormalities produced on administration of a single dose of tapentadol, and the patient required hospital admission.
| :: Case Report | | |
A 24-year-old male patient, weighing 62 kg consumed a single 100 mg tablet of tapentadol for acute lower back pain. After two hours, he developed dizziness, palpitation, tightness in chest, flushing, and tremor in fingers. On examination, pulse was 140/minute, blood pressure130/90 mmHg, and respiratory rate 15/minute. He was admitted in the medical ward of Sir Takhtsinhji General Hospital, Bhavnagar, Gujarat, and shifted to the intensive cardiac care unit (ICCU) for observation. Electrocardiogram (ECG) showed tachycardia (140/min) along with ST segment elevation in second chest lead (V 2 )[Figure 1]. Laboratory investigations like hemoglobin, total leukocyte count, differential leukocyte count, peripheral smear, platelet count, red blood cell count, erythrocyte sedimentation rate, serum bilirubin, blood urea, serum protein, serum glutamic pyruvic transaminase, and serum glutamic oxaloacetic transaminase were normal except serum potassium (5.6 mEq/L, reference value: 3.5-5.5 mEq/L) and sodium (147 mEq/L, reference value: 135-145 mEq/L) - were slightly altered.On detailed history and examination, there were no clinical features suggestive of any psychiatric, cardiovascular, or endocrinal disorders. There was no history of similar reactions or intake of any opioid analgesics. At the time of reaction, he was not on any other treatment. On admission, tapentadol was discontinued and he was treated with injection dexamethasone 4 mg single dose, injection chlorpheniramine maleate 25mg 12hourly for one day, injection pantoprazole 40mg for a single day, injection ondansetron hydrochloride 8 mg intravenously stat. On starting the rescue treatment, tremors, palpitation, and tightness in chest were relieved after 2 hours. His pulse rate became normal after 4 hours.ECG recorded after 10 hours of admission was normal. Intensity of dizziness was reduced, but it resolved completely after 48 hours. The patient was discharged from the hospital after 36 hours with tablet cinnarizine (25 mg) three times a day for relief of dizziness. Causality assessment with Naranjo's scale and the World Health Organization-Uppsala Monitoring Centre(WHO-UMC) scale showed the relationship with tapentadol; the reaction was probable and likely, respectively. [6],[7] The modified Hartwig and Siegel's scale showed that the reaction was moderate (level: 4b). [8]
| :: Discussion | | |
Tapentadol is a centrally acting opioid analgesic, which acts by activating μ receptors and by inhibiting norepinephrine reuptake. However, its main efficacy is due to the latter mechanism, and it is devoid of adverse effects like dose-related hypotension, confusion, ureteric or biliary spasm, and muscle rigidity caused by other opioid analgesics. [5] It is known to cause nausea, vomiting, headache, somnolence, dizziness, dryness of mouth, dyspepsia, obstipation, and pruritus. To the best of our knowledge, palpitation, tightness in chest, and tachycardia have not been reported yet. Tapentadol is rapidly absorbed and reaches maximum plasma concentration within 2 hours. In a study of healthy volunteers, the maximum plasma concentration (0.03-0.1 mg/L) was achieved after 1.25-1.5 hours of administration of a single dose of 100 mg tapentadol. [9] In one reported case, death occurred due to tapentadol overdose, and the person was found dead after gasping for some time. One day before death, he had neck stiffness and flulike symptoms. On autopsy, plasma concentration of tapentadol was found to be 1.05 mg/L in femoral and 3.2 mg/L in heart blood, respectively. [5]
In our case, the development of the reaction after 2 hours of consumption of the drug indicates temporal relation with an event. Absence of pre-existing diseases, concomitant medications, and recovery of reaction on avoiding further intake of tapentadol indicates the probable role of tapentadol in causing the reaction. However, rechallenge was not performed due to ethical reasons.
There are two possible mechanisms for this reaction with tapentadol. Increased level of norepinephrine due to inhibition of norepinephrine reuptake can produce such cardiovascular abnormalities but in the present case, blood pressure was not elevated. Another possible mechanism is its structural similarity with catecholamines. [10] As shown in [Figure 2], [10],[11] tapentadol also contains a β-phenylethylamine structure. The various substitutions in the parent chemical structure of catecholamine at the aromatic ring, α and β carbons, and terminal amino groups generate a variety of sympathomimetic compounds with differences in potency and receptor selectivity. Two hydroxyl groups at the third and fourth positions of the aromatic ring are essential for maximal sympathomimetic activity. [10] Tapentadol has only one hydroxyl group at position 3 of the aromatic ring. It indicates the lesser potency of tapentadol than epinephrine for sympathomimetic activity. When the amino group is separated by two carbon atoms from the aromatic ring, sympathomimetic activity is the greatest. [10] In tapentadol, the amino group is separated by three carbons atoms from the aromatic ring that shows its tendency for good sympathomimetic effect. Increasing alkyl substitution on the amino group increases the β receptor selectivity of catecholamine. Tapentadol has -CH (CH 3 ) 2 substitution at the amino group. Substitutions on α and β carbon in catecholamine increase the duration of action and increase the peripheral rather than central action, respectively. [10] Tapentadol has methyl substitutions on α and β carbon atoms. Based on this structure activity analysis, tapentadol may act as β-selective sympathomimetic agents with less central nervous system (CNS) effect. It may have directly acted on β1 and β2 receptors leading to tachycardia, palpitation, tightness in chest, dizziness, and tremor. Effect on blood pressure was not evident, may be due to lack of effect on the α receptor. In the present case, the reaction was serious as the patient required admission in hospital. The use of tapentadol in patients with pre-existing cardiac disease and as a concomitant medication along with sympathomimetic drugs thus requires caution. | Figure 2: (a) Basic structure of catecholamine, arrow shows commonly present hydroxyl group at position 3 and 4 of the aromatic ring (b) Structure of tapentadol, arrow shows one hydroxyl group at position 3 of the aromatic ring
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| :: References | | |
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| 6. | Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions.Clin Pharmacol Ther 1981;30:239-45.
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| 7. | The use of WHO-UMC system for standardized case causality assessment [monograph on the Internet]. Uppsala: The Uppsala Monitoring Centre. Available from: http://www.who-umc.org/graphics/24734.pdf. [Last accessed on 2013 Aug 5].
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| 8. | Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm 1992;49:2229-32.
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| 9. | Wade WE, Spruill WJ. Tapentadol hydrochloride: A centrally acting oral analgesic. Clin Ther 2009;31:2804-18.
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| 10. | Thomas CW, David PW. Adrenergic agonist and antagonists. In: Laurence LB, Bruce AC, Bjorn CK, Goodman & Gilman′s The Pharmacological Basis of Therapeutics. 12 th ed. New York: McGraw Hill;2011.p. 277-330.
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| 11. | Australian Public Assessment Report for Tapentadol. Australian Government, Department of Health and Aging, Therapeutic Goods Administration Available from: http://www.tga.gov.au/pdf/auspar/auspar-palexia.pdf.
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[Figure 1], [Figure 2]
| This article has been cited by | | 1 |
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Toxicity of tapentadol: a systematic review |
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| Jessie S Channell, Stephan Schug | | Pain Management. 2018; 8(5): 327 | | [Pubmed] | [DOI] | |
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