Mechanism of the Cardiotoxic Actions of Terfenadine

Woosley, Raymond L.; Chen, Yiwang; Freiman, Joel; Gillis, Richard A.

doi:10.1001/jama.1993.03500120070028

Cited by 536 publications

(160 citation statements)

References 25 publications

(6 reference statements)

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“…With 25 cases of torsade de pointes reported to the FDA following the use of terfenadine, there was much caution about its use 75. Similar findings were reported for astemizole and norastemizole 76.…”

Section: Antihistaminesmentioning

confidence: 83%

Drug-related cardiac pathology

2009

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Many commonly used drugs, with each causing changes that may be potentially lethal, can adversely affect the function of the heart. In addition some drugs have synergistic effects that can also damage cardiovascular tissues. The drug-related cardiotoxic effects of antineoplastic agents, psychotropic medications, heavy metals, substances of abuse, promotility agents, antihistamines, antimicrobials and antiarrhythmic agents are discussed. Hypersensitivity myocarditis is also discussed.

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Section: Antihistaminesmentioning

confidence: 83%

Drug-related cardiac pathology

2009

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“…Similarly the rationale for not withdrawing an anti-histamine from the market as soon as researchers clearly identified it as causing deaths has not been explained. 6 It is surprising that the drug was not removed from the market when the adverse effects were identified, but only after the manufacturer had developed a new product to substitute for it. For some relatively rare conditions practicing doctors may know little more than they knew when they first qualified.…”

Section: Prescribing Habits and Therapeutic Advancementioning

confidence: 99%

Doctors and Medical Science

Jiwa

2012

AMJ

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“…It is not cardiotoxic and does not cause the rare but potentially fatal adverse reaction associated with certain drug interactions involving terfenadine [61]. Fexofenadine is a widely used probe substrate for P-gp, as it does not undergo significant metabolic biotransformation with 95% of the dose excreted as an unchanged form either in the urine or feces after biliary excretion [62].…”

Section: Antihistamine Agent: Fexofenadinementioning

confidence: 99%

An Update on Clinical Drug Interactions with the Herbal Antidepressant St. Johns wort

Zhou

Lai

2008

CDM

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St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. Limited clinical trials suggest that hypericum and standard antidepressants have similar beneficial effects, but current evidence regarding the antidepression effects of SJW extracts is inconsistent. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs. This review highlights and updates the knowledge regarding drug interactions with SJW by a systematic review of all the available evidence, including worldwide published literature and spontaneous case reports. A number of clinically significant interactions of SJW have been identified with conventional drugs. These interactions often result in a decrease in the concentration or effect of the combined drug, most probably due to the induction of cytochrome P450s (CYPs) and the key drug transporter P-glycoprotein (P-gp) by the major active constituents in SJW. SJW is a potent inducer of human CYP3A4 and P-gp in vitro and in vivo. In addition, pharmacodynamic interactions of SJW with some drugs (e.g. selective serotonin re-uptake inhibitors) have been identified, which are associated with an increased risk of adverse reactions. Since potential interactions of SJW with conventional drugs is a major safety concern, it is important to minimize and avoid these interactions by taking appropriate approaches. These include systematic research to identify SJW-drug interaction; close therapeutic drug monitoring when SJW is combined with conventional drugs with a narrow therapeutic window; proper dose and regimen adjustment; patient education and communication between the patient and physician; design of new preparations of SJW without inducing ability of CYP3A4 and P-gp while retaining its bioactivity; and appropriate regulation in herbal safety and efficacy. Further clinical and mechanistic studies are warranted to explore the interaction of SJW with other important drugs and clinical significance.

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Mechanism of the Cardiotoxic Actions of Terfenadine

Cited by 536 publications

References 25 publications

Drug-related cardiac pathology

Drug-related cardiac pathology

Doctors and Medical Science

An Update on Clinical Drug Interactions with the Herbal Antidepressant St. Johns wort

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