Previous ban overturned, allowing kava products to apply for new licenses, but products not yet on market
by Mark Blumenthal
An important new development in the situation regarding the safety of kava has occurred in Germany. On May 12, 2005, the German health authorities (BfArM, German Federal Institute for Drugs and Medical Devices) repealed the ban of registered kava drug products in Germany.1,2 The BfArM had instituted the ban in June 2002 based on concern about the potential hepatotoxicity of kava in the wake of various adverse event reports of liver toxicity and liver failure allegedly associated with the use of various kava preparations.3,4
The reconsideration was based on persistent appeals by kava producers against the ban. According to a press release from the International Kava Executive Council (IKEC), the kava ban was revoked, as stated by the BfArM, “for reasons of appropriateness.”1 However, the government’s decision to revoke the cancellation of drug registrations does not mean that kava is again available on the German market. According to IKEC, the kava registrations in question are still inactivated until further notice, but now there is a process by which kava products can be appropriately reconsidered for future registration and sale instead of their being a priori banned altogether.
The 2002 decision to temporarily inactivate kava registrations was based on a classic drug review process of a risk-benefit evaluation. In its review of kava safety and efficacy studies, as well as the adverse event reports, the BfArM came to the somewhat surprising conclusion that there was a lack of adequate proof of anxiolytic (anxiety-reducing) efficacy of kava products; BfArM made this assessment because it determined that all existing clinical studies were either conducted with higher doses of kava than allowed within the respective products’ official drug registrations with the government, were used in indications that were not consistent with the approved registrations, or had been the subject of a non-controlled clinical study.2 The producers have been asked to provide new clinical data until June 2007, in which case a reinstitution of the kava products on the market might again be possible.
IKEC, which presents the interests of the South Pacific kava-producing countries, has produced what it considers to be a fair evaluation of kava risks based on a scientific review and evaluation of factual data related to kava safety and efficacy.5 IKEC has been working to provide new data to expose, what it considered, the inappropriateness of the 2002 kava ban, which also occurred in several other countries (Austria, France, Canada, Ireland, Singapore, Switzerland, UK). A significant amount of positive scientific evidence on kava safety was assembled by international scientists and kava experts and was presented at the International Kava Conference in Suva, Fiji, in December 2004.6
“We believe that the new scientific evidence and the constant political background work of the governments of the South Pacific states contributed to this new development,” said Joerg Gruenwald, PhD, Executive Director of the IKEC.1 “The new decision is, of course, not the end of the story,” he continued, “mainly because there does not seem to be a change for the situation of the consumers and physicians. When kava was banned, the withdrawal of the products from the market created a distinct gap in the therapeutic arsenal of physicians for the treatment of mild-to-moderate stress and anxiety-related disorders. With the new decision, kava is still not available for therapy.”
“Despite kava’s not being put back on the shelves for now, the decision is still a milestone, as now the administrative way to regular kava registrations is again open,” explained the kava scientist Mathias Schmidt, PhD, a consultant to the IKEC.1 Only a few days ago, he noted, an application for a kava preparation would not even have been considered for the German drug registration process. “We are glad that the discussion is now re-opened, and we hope to finally come to a constructive dialogue with the BfArM.”
The question of efficacy of kava is still a matter of debate. Among knowledgeable scientists, there is little question that kava is efficacious, and that the vast quantity and quality of pharmacological and clinical evidence in the published scientific and medical literature is of sufficient quality to adequately document the clinical efficacy of many kava preparations. A systematic review of published clinical trials has determined that a particular standardized kava preparation from Germany was safe and effective for treating anxiety.7
According to Dr. Gruenwald, “The doubts raised by the BfArM do not concern efficacy of kava as such, but of individual products, based on technical flaws in published data.”1 He stated that the BfArM’s offer to re-evaluate the risk-benefit ratio based on valid new clinical data shifts the focus from toxicity to efficacy. If proper clinical evidence of efficacy is sufficient to overcome the current unavailability of kava products as treatments for anxiety, the dangers from potential kava toxicity finally seem to be regarded as acceptable. In various reviews scientists have always asserted that the alleged kava toxicity—if it can be clearly demonstrated, which to date is equivocal—has occurred in an extremely low number of patients, by far below the incidence rates observed with many other freely available drugs.8,9 “The kava drug producers will now discuss the possible ways forward, and evaluate the chances to provide data from a new, state-of-the-art clinical trial,” he said.
The German change of policy may be indicative of a trend toward more rational evaluations of kava safety. Last year the British Medicines Control Agency agreed to begin a review of kava safety starting in January 2005.10 New toxicological data and evaluations of the risk-benefit ratio could be submitted until April 30, 2005. The data collection period is now concluded, and the evaluation process has been started. It is not yet certain if the German government’s new position will have an impact on the UK re-assessment.
1. Gruenwald J. German Kava discussion re-opened [press release]. Berlin: International Kava Executive Council; May 24, 2005.
2. German Federal Institute for Drugs and Medical Devices. Ruling on the appeal against the kava ban of June 25, 2002. Bonn, May 12, 2005.
3. German Federal Institute for Drugs and Medical Devices: Ruling on the cancellation of registrations for kava containing drugs. Bonn, June 14, 2002.
4. Blumenthal M. Kava safety questioned due to case reports of liver toxicity. HerbalGram. 2002;No. 55:26-32. Available at: http://www.herbalgram.org/herbalgram/articleview.asp?a=2147.
5. Gruenwald J, Mueller C, Skrabal J. In-depth investigation into EU market restrictions on kava products. Berlin: Phytopharm Consulting, Report for Centre for Development of Enterprises—Brussels; March 2003.
6. Gruenwald J. International Kava Conference Held in Fiji: Attendees Request Removal of All International Restrictions for Kava. HerbalGram. 2005;No. 66:69.
7. Pittler MH, Ernst E. Kava extract for treating anxiety (Cochrane Review). In: The Cochrane Library, Issue 1, 2002.
8. Schmidt M, Nahrstedt A, L9Fpke P. Piper methysticum (Kava) under debate: Considerations of quality, efficacy and safety. Wiener Med Wschr. 2002;152(15/16):382-388.
9. Clouatre DL. Kava kava: examining new reports of toxicity. Toxicol Lett. 2004; 150(1):85-96.
10. Medicines Control Agency (UK). Consultation document MLX 319: The Medicines for Human Use (Kava-kava) (Prohibition) Order 2002. January 31, 2005. Available at: http://medicines.mhra.gov.uk/inforesources/publications/mlx319.pdf.