Though this article refers to Lariam/Mefloquine,
hepatic toxicities, undetected by the usual
diagnositic tests, can also cause CYPs polymorphisms
leading to inability to metabolize medications, herbs,
coffee, alcohol, chemicals in foods, anesthetics (local
and GA) and so forth.
Note Diazepam mention in the article.
Mefloquine and the liver
Mefloquine is an aryl amino alcohol which accumulates in both the liver and the lungs, and is subject to enterohepatic circulation. [29] It has recently been found to cause acute hepatitis.[30]
Mefloquine does not appear to cause florid signs of liver disease. However, transient subclinical disturbances of liver function are a common feature of many drugs metabolised in the liver, and this may explain the frequent finding of transaminase changes in safety studies of new drugs; these biochemical findings are usually dismissed as meaningless noise, but they may in fact be sensitive or oversensitive markers of vulnerability, of low specificity.
That mefloquine induces liver enzymes is well documented. Jaspers et al reported significantly raised transaminases in Dutch marines who took mefloquine during 3 months in Cambodia, and who were not drinking alcohol at the time. [31] Takeshima found that of a cohort of healthy Japanese soldiers who took prophylactic mefloquine for 36 weeks without drinking alcohol, one-quarter developed symptoms compatible with liver pathology and four showed disturbed liver function. [32] Reisinger et al observed the same phenomenon in a cohort of short-stay European travellers to Africa, but it is not clear whether alcohol could have contributed to this effect.[33] One of the travellers, who was concurrently taking a liver-damaging agent, sulfadoxine,[34] showed gross morphological changes in his liver which were attributed to his use of prophylactic mefloquine. Liver biopsy showed intralobular cellular infiltrates consisting of macrophages and eosinophils as well as sporadic eosinophilic cell necroses; virology was negative. [33] Grieco et al described a 46-year-old woman who drank wine daily while taking mefloquine, and who became nervous and depressed, with nausea, vomiting and diarrhoea. She was dehydrated and in severe liver failure, with negative virology. Liver biopsy showed diffuse macrovesical hepatic steatosis. [35]
‘Heavy sun exposure’ is noted in a case report of a 60-year-old Frenchman who reacted acutely to his second mefloquine tablet; it is likely that this sun exposure would have caused dehydration.[5] A 20-year old French traveller, concurrently taking an oral contraceptive, had epileptic seizures in her sixth week of mefloquine prophylaxis, directly after ‘severe exertion’.[5] It seems likely that in some mefloquine users dehydration will impose an added burden on the liver, and that this could contribute to a severe reaction to the drug. Many long-haul travellers using mefloquine are mildly dehydrated from in-flight alcohol and air conditioning, followed by hot and dry conditions, and more alcohol consumption, at their holiday or business destination.
Of the 516 case reports we reviewed, eleven cited alcohol as possibly contributing to the adverse drug effects described. Wittes et al reported a remarkable challenge-rechallenge experiment where a healthy male geologist took both his third and his fourth weekly mefloquine tablet together with half a bottle of whisky, and on both occasions experienced acute paranoid delusions, depression and suicidal ideation; a fellow geologist who shared the same whisky bottle (and who was taking no antimalaria medication) experienced no such effects.[36]
Vuurman et al, sponsored by Hoffmann-La Roche, tested in healthy volunteers whether or not alcohol might interact adversely with mefloquine.[37] They found psychomotor performance unimpaired, but their study design had important limitations. Only 20 participants took mefloquine and of these, two women dropped out due to adverse events (one with nausea, vomiting and dizziness, the other with malaise, fever and headache). The study protocol forbade ‘strenuous physical activity’ and any prescribed medications. Alcohol was given under strict laboratory conditions 24 h after mefloquine ingestion, and then in small and interrupted doses, such that the blood alcohol concentration in any participant never exceeded 0.50 mg ml-1. The authors admit that their study did not address ‘the question of what might happen should (mefloquine users) consume intoxicating amounts of alcohol. [37] Their findings can thus not be generalised to the broad population of tourists and business travellers.
Approximately half of the case reports listed in the Cochrane review note some co-medication taken along with mefloquine.[26] Other quinoline derivatives (chiefly chloroquine and quinine) are the commonest co-medications mentioned in the case reports. After antimalaria drugs, an oral contraceptive (noted in 8 reports) is the next most commonly reported co-medication, followed by sodium valproate (7) and diazepam (4). All these drugs can cause liver damage.[34] Diazepam is also a thyroid hormone antagonist, and we discuss below the possible significance of this. Meszaros et al reported a male traveller who in addition to mefloquine took thioridazine, amitriptyline and fluphenazine (all capable of damaging the liver), and whose mefloquine-associated neuropsychiatric symptoms persisted for over a year. [38] Gullahorn et al reported a series of patients who experienced delirium on emerging from anaesthesia, possibly because in addition to mefloquine they had received isoflurane, an anaesthetic known to cause hepatocellular necrosis. [34,39]
One report describes an acute reaction in a man who took one mefloquine tablet each week together with two aspirin tablets. One hour after taking his fifth mefloquine tablet he experienced acute amnesia lasting approximately one hour.[40] Aspirin can cause hepatocellular necrosis,[34] and in addition can aggravate acute thyroid disturbance (discussed below) by competing with thyroid hormones for sites on binding proteins.[53]
homecomingvets.com/2010/08/02/mefloquine-lariam-linked-to-liver-and-thyroid-damage/
Read more:
health-quest.proboards.com/thread/197/lariam-mefloquine?page=1#ixzz3JckjziGN