[indices] Herbal-ARV drug interactions - new data

["INDICES Moderator" <indices@healthnet.org>]

Herbal-ARV drug interactions - new data
----------------------------------

Cross posted from DRUG-INFO with thanks, very long email  

 Hi all,

 That herbal preparations may be implicated in clinically relevant
 drug-drug interactions is well known - the Liverpool HIV Pharmacology
 Group site (http://www.hiv-druginteractions.org/) shows clearly that St
 John's Wort containing complementary medicines and supplements should
 not be used together with the non-nucleoside reverse transcriptase
 inhibitors (NNRTIs, such as nevirapine and efavirenz) and the protease
 inhibitors (PIs, such as lopinavir and saquinavir). Due to induction of
 metabolising enzymes and/or transport proteins, the concentrations of
 the ARVs are reduced significantly, which may result in clinical failure
 and possibly the development of resistance. Caution is advised with
 Echinacea products, Garlic supplements and Milk Thistle. Echinacea
 causes inhibition of CYP1A2 and intestinal CYP3A activity and induction
 of hepatic CYP3A activity. The assessment is that it "could contribute
 to inter-patient variability in protease inhibitor levels". In vitro,
 garlic components can affect CYP2C, 2D and 3A mediated metabolism. The
 assessment is thus that "there may be the potential for interactions and
 further studies need to be carried out in vivo".The data presented on
 milk thiste are less definite - but some changes in PI troughs were
 noted. Other herbal products have been shown to have less significant
 effects - e.g. "typical doses of valerian are unlikely to produce
 clinically significant effects on the disposition of drugs metabolised
 by CYP2D6 and CYP3A4" (Donovan JL, DeVane CL, Chavin KD, et al. Multiple
 night-time doses of Valerian (Valeriana officinalis) had minimal effects
 on CYP3A4 activity and no effect on CYP2D6 activity in healthy
 volunteers. Drug Metab Dis, 2004, 32: 1333-1336.  - see

<http://www.hiv-druginteractions.org/frames.htm?new/Content.asp?ID=198&TDM=Fa>http://www.hiv-druginteractions.org/frames.htm?new/Content.asp?ID=198&TDM=Fa
 
 The Liverpool Groups comment on the AIDS paper (abstract below -
 unfortunately low on detail) which sparked media comment in this country
 (IOL story below, as "fair use") was as follows: "The authors examined
 the effects of extracts from Hypoxis hemercallidea (African potato) and
 Sutherlandia on CYP3A4 metabolism, PXR activations and P-gp expression.
 Aliquots of water and methanol extracts of Hypoxis inhibited CYP3A4
 activity at a concentration of 100 mg/ml: Sutherlandia extracts showed
 even greater inhibition with almost complete inhibition with the
 methanol extract. In the PXR assay, there was significant activation
 with extracts of both Hypoxis and Sutherlandia. P-gp activity was also
 inhibited, although this was less than with the known P-gp inhibitor
 verapamil. Although the concentrations used in this in vitro study were
 high, these data certainly raise the possibility of interactions in the
 clinical setting. Clinical pharmacokinetic data will be required to
 assess the magnitude of any interactions."

 From this it would appear that the concern would be toxicity rather
 than loss of efficacy. Nonetheless, the correct advice is provided in
 the IOL story.

 regards
 Andy Gray
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<http://www.iol.co.za/index.php?set_id=1&click_id=125&art_id=vn20050130113157524C569683>

 Study casts doubt on African potato remedy
 January 30 2005 at 01:47PM
 By Caroline Hooper-Box

 The special mixture prescribed by Manto Tshabalala-Msimang, the
 minister of health, for fighting HIV and Aids looks as though it could
 be a recipe for disaster.

 A new study published this month by Aids, one of the world's leading
 HIV journals, said that the African potato (Hypoxis hemerocallidea)
 might significantly weaken the power of anti-HIV medicines
 (antiretrovirals or ARVs) by altering their concentration in the
 bloodstream.

 The African potato is just part of the concoction of garlic, onions and
 virgin olive oil Tshabalala-Msimang has repeatedly advocated as an
 immune-boosting combination for people living with HIV and Aids. The
 minister has been widely criticised and teased about these statements by
 medical practitioners and in the media.

 The new study ran the results of laboratory tests examining the effects
 of capsules, tablets and teas infused with African potato and
 Sutherlandia (cancer bush) on the metabolisation of ARVs.

 Both herbs, but the African potato in particular, were found to inhibit
 the effectiveness of ARVs "significantly". So much so, said the
 researchers, that "extreme caution" should be taken in treating HIV
 patients with any herbal "drugs".

 They write that their results "highlight the extreme caution that
 should be taken in introducing herbal drugs into routine care of HIV
 patients in any setting, including the developing world, and underscore
 the need for appropriately designed pharmacokinetic studies to unveil
 the true interaction potential of herbal drugs with antiretroviral
 drugs".

 Pharmacokinetic studies concern the the way drugs are metabolised.

 The two herbs were tested after reports by South African researchers in
 Western Cape last year that they were toxic.

 If tests are not carried out on herbs, say the investigators, there
 could be poisonous drug "interactions", together with failure of the
 treatment, and the HIV strain could also become resistant to the ARVs.

 Dr Rudy Onia, a pharmacologist with the South African Traditional
 Medicines Research Group at the University of Cape Town, said: "To my
 knowledge, no evidence currently exists to suggest that these effects,
 as demonstrated in the laboratory, are of significance within the live
 clinical context."

 But, he added, "research into the clinical significance of this
 potential interaction should be commissioned as a matter of urgency.

 "Until these investigations suggest otherwise, it would be prudent for
 patients to refrain from using these herbal medicines while being
 managed with ARVs."

 Meanwhile, the government is allowing 27 health-care centres to provide
 complementary and traditional medicines to HIV-positive patients. This
 follows a department of health estimate that 70 percent of South
 Africans consult traditional healers.

 But new legislation bans South Africa's 200 000 sangomas from
 diagnosing and treating terminal diseases such as Aids and cancer. How
 the government proposes to police the new law is unknown.

 Speaking this month at the first international conference on natural
 products and molecular therapy held at the University of Cape Town,
 Tshabalala-Msimang urged delegates to expose the split that had arisen
 between natural medicine and allopathic medicine.

 "This is a division fostered by the need to make money from patented
 drugs through discrediting the use of natural products," she said.

 The department of health has channelled a R6-million grant through the
 Medical Research Council (MRC) for research on the safety, efficacy and
 quality of traditional medicines used as immune boosters by people
 living with HIV and Aids.

 Dr Francois Venter of the University of the Witwatersrand, who works at
 a large ARV clinic in Johannesburg, said: "It's a difficult situation.
 People use the African potato plant and Sutherlandia frequently, as well
 as a range of other untested medications. We have very little
 information about the safety of these herbs and also understand very
 little about their interactions with anti-retrovirals and other drugs.

 "This study confirms that we need more research in the area, and the
 MRC is devoting significant resources to this. Practically, I tell my
 patients that combining these herbs with their antiretrovirals is a
 gamble, and that I do not know if it is safe. After that, it becomes
 their own decision."

 This article was originally published on page 1 of Sunday Independent
 on January 30, 2005

 --------------------------------------------------------------------------- 
 
<http://www.aidsonline.com/pt/re/aids/abstract.00002030-200501030-00013.
htm;jsessionid=CE4ocUXIzanp6R2j1AjSO5kGwGIAm2VdJNLdugCtgg2x7EdfZj5m!
1641739476!-949856032!9001!-1>  

Impact of African herbal medicines on antiretroviral metabolism.

 AIDS. 19(1):95-97, January 3, 2005.

 Mills, Edward a,e; Foster, Brian C b; Heeswijk, Rolf van c; Phillips,
 Elizabeth d; Wilson, Kumanan d; Leonard, Blair d; Kosuge, Kazuhiro d;
 Kanfer, Isadore f

 aDepartment of Clinical Epidemiology and Biostatistics, McMaster
 University, Hamilton, Ontario, Canada bUniversity of British Columbia,
 British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British
 Columbia, Canada cDivision of Infectious Diseases, Ottawa General
 Hospital, Ottawa, Ontario, Canada dDepartment of Medicine, University of
 Toronto, Toronto, Ontario, Canada eCanadian College of Naturapathic
 Medicine, Toronto, Ontario, Canada fFaculty of Pharmacy, Rhodes
 University, Grahamstown, South Africa.

 Abstract:
 We examined the effects of two African herbal medicines recommended for
 HIV/AIDS patients on antiretroviral metabolism. Extracts from Hypoxis
 and Sutherlandia showed significant effects on cytochrome P450 3A4
 metabolism and activated the pregnane X receptor approximately twofold.
 P-glycoprotein expression was inhibited, with Hypoxis showing 42-51% and
 Sutherlandia showing 19-31% of activity compared with verapamil.
 Initiating policies to provide herbal medicines with antiretroviral
 agents may put patients at risk of treatment failure, viral resistance
 or drug toxicity.
 ~~~~~~~~~~~~~~~~~~~
 Andy Gray MSc(Pharm) FPS
 * Senior Lecturer
 Dept of Therapeutics and Medicines Management
 * Study Pharmacist
 Centre for the AIDS Programme of Research
 in South Africa (CAPRISA)
 Nelson R Mandela School of Medicine
 University of KwaZulu-Natal
 PBag 7 Congella 4013
 South Africa
 Tel: +27-31-2604334/4298 Fax: +27-31-2604338
 email: graya1@ukzn.ac.za or andy@gray.za.net