MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Due to polypharmacy and the rising popularity of so-called alternative medicines (SCAM), oncology patients are particularly at risk of drug-drug interactions (DDI) or herb-drug interactions (HDI). The aims of this study were to assess DDI and HDI in outpatients taking oral anticancer drugs.

All prescribed and non-prescribed medications, including SCAMs, were prospectively collected by hospital pharmacists during a structured interview with the patient. DDI and HDI were analyzed using four interaction software programs: Thériaque®, Drugs.com®, Hédrine, and Memorial Sloan Kettering Cancer Center (MSKCC) database. All detected interactions were characterized by severity, risk, and action mechanism. The need for pharmaceutical intervention to modify drug use was determined on a case-by-case basis.

A total of 294 patients were included, with a mean age of 67 years [55-79]. The median number of chronic drugs per patient was 8 [1-29] and 55% of patients used at least one SCAM. At least 1 interaction was found for 267 patients (90.8%): 263 (89.4%) with DDI, 68 (23.1%) with HDI, and 64 (21.7%) with both DDI and HDI. Only 13% of the DDI were found in Thériaque® and Drugs.com® databases, and 125 (2.5%) were reported with a similar level of risk on both databases. 104 HDI were identified with only 9.5% of the interactions found in both databases. 103 pharmaceutical interventions were performed, involving 61 patients (20.7%).

The authors concluded that potentially clinically relevant drug interactions were frequently identified in this study, showing that several databases and structured screening are required to detect more interactions and optimize medication safety.

These data imply that DDIs are more frequent than HDIs. This does, however, not tell us which are more important. One crucial difference between DDIs and HDIs is that the former are usually known to the oncology team who should thus be able to prevent them or deal with them appropriately; in contrast, HDIs are often not known to the oncology team because many patients fail to disclose the fact that they take herbal remedies. Some forget, some do not think of herbals as medicine, others may be worried about their physician’s reaction.

It follows that firstly, conventional healthcare practitioners should always ask about the usage of herbal remedies, and secondly, they need to be informed about which herbal remedy might interact with which drug. The first can easily be implemented into routine history-taking; the second is more problematic, not least because our knowledge about HDIs is still woefully incomplete. In view of this, it might often be wise to tell patients to stop taking herbal remedies while they are on prescription drugs.

2 Responses to Herb-drug interactions in patients taking anticancer drugs

  • There is another important reason why doctors should always enquire about herbal and other medicines, and that is that they may not be quite what they seem.

    Some years ago there was a preparation on the market for treating metastatic prostate cancer called PC Spes, which purported to be a mixture of Chinese herbs. A number of oncologists had noted apparent responses in patients who had admitted to taking it, prompting a prospective randomised clinical trial to investigate further. As part of this, the preparation was analysed chemically, and found to contain (in addition to various plants) diethylstilboestrol (DES), warfarin and indomethacin.

    DES is a standard treatment for metastatic prostate cancer in the UK, though it is not available in the US. It is a synthetic oestrogen, though I suspect it has other properties as there were supply problems once and a number of oncologists switched their patients to ethanyl oestradiol (another oestrogen) instead, which in my own patients appeared to be less effective. However, DES is quite strongly prothrombotic, and when it was first introduced the reduction in deaths from prostate cancer was increased by deaths from thromboembolic disease. It is now only ever given in conjunction with some sort of anticoagulant (at the time of my retirement four years ago this was aspirin).

    Which brings me onto warfarin, a widely-prescribed anticoagulant, but one which isn’t at all straightforward to manage as it has a narrow therapeutic ratio (i.e. too little doesn’t work and too much causes uncontrolled bleeding). Furthermore people differ widely in their dose requirements, with 1mg being enough to anticoagulate some people completely, and thers requiring 12mg or more. Finally it has a long duration of action, which means that whatever dose you take today mainly has its effect in 2 – 3 days’ time. To prescribe it safely requires a loading dose with blood tests to determine how that person handles it, individualised dose modification and regular blood tests for monitoring (alll haematology departments have a warfarin clinic specifically for this purpose).

    Indomethacin is a painkiller in the non-steroidal antiinflammatory group (NSAID). All NSAID’s are potentially toxic, with gastric irritation and internal bleeding being the most common problem. Indomethacin is the strongest drug in this group, and its use is generally reserved for very short-term problems (gout is the most common indication) or else by rheumatologists in patients where nothing else is suitable. NSAID’s are contraindicated in combination with anticoagulants due to the very high risk of a serious internal bleed, and any doctor prescribing indomethacin and warfarin together is likely to find themselves facing some sort of fitness to practice investigation.

    However, for somebody with serious bone pain from metastatic prostate cancer, the initial improvement with indomethacin is likely to be dramatic, and DES would build on this and also bring their PSA down.

    The manufacturers of PC Spes claimed that there was some kind of contamination in the manufacture of the product. Given the specific “contaminants” and what they do, this seems to be rather a coincidence to me.

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