Mefloquine
Clinical data | |
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Trade names | Lariam, Mephaquin, Mefliam, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a603030 |
License data |
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Pregnancy category |
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Routes of administration | By mouth |
ATC code | |
Legal status | |
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Pharmacokinetic data | |
Metabolism | Extensive liver; main metabolite is inactive |
Elimination half-life | 2 to 4 weeks |
Excretion | Primarily bile and feces; urine (9% as unchanged drug, 4% as primary metabolite) |
Identifiers | |
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JSmol) | |
Chirality | Racemic mixture |
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Mefloquine, sold under the brand name Lariam among others, is a medication used to prevent or treat malaria.[4] When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure.[4] It can be used to treat mild or moderate malaria but is not recommended for severe malaria.[4] It is taken by mouth.[4]
Common side effects include vomiting, diarrhea, headaches, sleep disorders, and a rash.[4] Serious side effects include potentially long-term mental health problems such as depression, hallucinations, and anxiety and neurological side effects such as poor balance, seizures, and ringing in the ears.[4] It is therefore not recommended in people with a history of mental health problems or epilepsy.[4] It appears to be safe during pregnancy and breastfeeding.[1]
Mefloquine was developed by the United States Army in the 1970s and came into use in the mid-1980s.
Medical uses
Mefloquine is used to both prevent and treat certain forms of malaria.[10]
Malaria prevention
Mefloquine is useful for the prevention of malaria in all areas except for those where parasites may have
Malaria treatment
Mefloquine is used as a treatment for chloroquine-sensitive or resistant Plasmodium falciparum malaria, and is deemed a reasonable alternative for uncomplicated chloroquine-resistant Plasmodium vivax malaria.[10][16] It is one of several drugs recommended by the United States' Centers for Disease Control and Prevention.[17] It is not recommended for severe malaria infections, particularly infections from P. falciparum, which should be treated with intravenous
Resistance to mefloquine
Resistance to mefloquine is common around the west border in Cambodia and other parts of Southeast Asia.[18] The mechanism of resistance is by increase in Pfmdr1 copy number.[19]
Adverse effects
Common side effects include vomiting, diarrhea, headaches, and a rash.
Neurologic and psychiatric
In 2013, the U.S.
Central nervous system events requiring hospitalization occur in about one in 10,000 people taking mefloquine for malaria prevention, with milder events (e.g., dizziness, headache, insomnia, and vivid dreams) in up to 25%.[23] When some measure of subjective severity is applied to the rating of adverse events, about 11–17% of travelers are incapacitated to some degree.[14]
Cardiac
Mefloquine may cause abnormalities with heart rhythms that are visible on
Contraindications
Mefloquine is contraindicated in those with a previous history of seizures or a recent history of psychiatric disorders.[10]
Pregnancy and breastfeeding
Available data suggests that mefloquine is safe and effective for use by pregnant women during all trimesters of pregnancy,[24] and it is widely used for this indication.[25] In pregnant women, mefloquine appears to pose minimal risk to the fetus,[25][26] and is not associated with increased risk of birth defects or miscarriages.[27] Compared to other malaria chemoprophylaxis regimens, however, mefloqinone may produce more side effects in non-pregnant travelers.
Mefloquine is also safe and effective for use during breastfeeding,[24] though it appears in breast milk in low concentrations.[11][16]: 9 The World Health Organization (WHO) gives approval for the use of mefloquine in the second and third trimesters of pregnancy and use in the first trimester does not mandate termination of pregnancy.[11]
Pharmacology
Elimination
Mefloquine is metabolized primarily through the liver. Its elimination in persons with impaired liver function may be prolonged, resulting in higher plasma levels and an increased risk of adverse reactions. The mean elimination plasma half-life of mefloquine is between two and four weeks. Total clearance is through the liver, and the primary means of excretion is through the bile and feces, as opposed to only 4% to 9% excreted through the urine. During long-term use, the plasma half-life remains unchanged.[28][29]
Liver function tests should be performed during long-term administration of mefloquine.[30] Alcohol use should be avoided during treatment with mefloquine.[31]
Chemistry
Specifically it is used as mefloquine hydrochloride.
Mefloquine is a
History
Mefloquine was formulated at Walter Reed Army Institute of Research (WRAIR) in the 1970s shortly after the end of the Vietnam war. Mefloquine was number 142,490 of a total of 250,000 antimalarial compounds screened during the study.[5]
Mefloquine was the first Public-Private Venture (PPV) between the US Department of Defense and a pharmaceutical company. WRAIR transferred all its phase I and phase II clinical trial data to Hoffman-LaRoche and Smith Kline. FDA approval as a treatment for malaria was swift. Most notably, phase III safety and tolerability trials were skipped.[5]
The drug was first approved in Switzerland in 1984 by Hoffmann-LaRoche,[32] who brought it to market with the name Lariam.[33]
However, mefloquine was not approved by the FDA for prophylactic use until 1989. This approval was based primarily on compliance, while safety and tolerability were overlooked.
By 1991, Hoffman was marketing the drug on a worldwide basis.[33]
By the 1992
By 1994, medical professionals were noting "severe psychiatric side effects observed during prophylaxis and treatment with mefloquine", and recommending that "the absence of
The neuropsychiatric side effects of the antimalarial drug mefloquine are well documented. They include anxiety, depression, hallucinations, acute psychosis, and seizures. The incidence of these side effects is 1 in 13,000 with prophylactic use and 1 in 250 with therapeutic use.
The first randomized, controlled trial on a mixed population was performed in 2001. Prophylaxis with mefloquine was compared to prophylaxis with atovaquone-proguanil. Roughly 67% of participants in the mefloquine arm reported greater than or equal to one adverse event, versus 71% in the atovaquone-proguanil arm. In the mefloquine arm, 5% of the users reported severe events requiring medical attention, versus 1.2% in the atovaquone-proguanil arm.[5][37]
In August 2009, Roche stopped marketing Lariam in the United States.[38]
Retired soldier Johnny Mercer, who was later appointed Minister for Veterans Affairs by Boris Johnson, told in 2015 that he had received "a letter about once or twice a week" about ill-effects from the drug.[39] In July 2016, Roche took this brand off the market in Ireland.[38]
Military
In 2006, the Australian military deemed mefloquine "a third-line drug" alternative, and over the five years from 2011 only 25 soldiers had been prescribed the drug, and only in cases of their intolerance for other alternatives.
In early December 2016, the German defence ministry removed mefloquine from the list of medications it would provide to its soldiers.[38]
In autumn 2016, Canadian Surgeon General Brigadier General Hugh Colin MacKay told a parliamentary committee that faulty science supported the assertion that the drug has indelible noxious side effects. An expert from Health Canada named Barbara Raymond told the same committee that the evidence she had read failed to support the conclusion of indelible side effects.[38] Canadian soldiers who took mefloquine when deployed overseas have claimed they have been left with ongoing mental health problems.[40]
In 2020 the UK Ministry of Defence (MoD) admitted to a breach of duty regarding the use of Mefloquine.[41] by acknowledging numerous instances of failure to assess the risks and warn of potential side effects of the drug.
Research
In June 2010, the first case report appeared of a
Mefloquine alters
References
- ^ a b "Mefloquine (Lariam) Use During Pregnancy". Drugs.com. Retrieved 31 March 2019.
- ^ "Lariam 250 mg tablets - Summary of Product Characteristics (SmPC)". (emc). 3 April 2019. Retrieved 8 September 2020.
- ^ "Lariam brand of mefloquine hydrochloride tablets". DailyMed. Retrieved 9 October 2022.
- ^ a b c d e f g h i j k "Mefloquine Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 2015-12-08. Retrieved 27 Nov 2015.
- ^ PMID 17404338.
- ISBN 9783527326693.
- ISBN 9780702053061.
- hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
- ^ a b c d e "Lariam". The American Society of Health-System Pharmacists. Archived from the original on 7 January 2012. Retrieved 3 April 2011.
- ^ PMID 21143906.
- ^ "www.idsociety.org" (PDF). Archived (PDF) from the original on 2015-03-19.
- ^ "Malaria - Chapter 3 - 2014 Yellow Book | Travelers' Health | CDC". Archived from the original on 2014-12-26.
- ^ PMID 10381965.
- PMID 29083100.
- ^ a b c d e f "Lariam medication guide" (PDF). Hoffman La Roche. Archived (PDF) from the original on 2 October 2013. Retrieved 27 September 2013.
- ^ "www.cdc.gov" (PDF). Archived (PDF) from the original on 2015-02-09.
- ^ "Malaria Information". Traveldoctor. Archived from the original on 28 June 2016. Retrieved 9 July 2016.
- PMID 15288742.
- ^ "Mefloquine hydrochloride tablet". DailyMed. 31 May 2016. Retrieved 8 September 2020.
- ^ "www.fda.gov" (PDF). Food and Drug Administration. Archived (PDF) from the original on 2014-06-30.
- ^ "FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects". Food and Drug Administration.
- S2CID 7888082.
- ^ a b "Mefloquine" (PDF). Medicines for the Prevention of Malaria While Traveling. Atlanta, Georgia: Centers for Disease Control and Prevention. 2019. Retrieved 2019-03-30.
- ^ PMID 24581338.
- PMID 21418669.
- PMID 22495078.
- ^ "Lariam product monogram" (PDF). Hoffman La Roche Limited. p. 3. Archived from the original (PDF) on 17 December 2011. Retrieved 24 April 2011.
- ^ "Lariam product monogram" (PDF). Hoffman La Roche Limited. p. 4. Archived from the original (PDF) on 17 December 2011. Retrieved 24 April 2011.
- ^ "Lariam product monogram" (PDF). Hoffman La Roche Limited. p. 6. Archived from the original (PDF) on 17 December 2011. Retrieved 24 April 2011.
- ^ "Lariam product monogram" (PDF). Hoffman La Roche Limited. p. 18. Archived from the original (PDF) on 17 December 2011. Retrieved 24 April 2011.
- ^ "Roche Submission to Committee Secretary Senate Foreign Affairs Australia".
- ^ a b "'It's not a benign drug - it has ruined my life'". Guardian News & Media Limited. 24 October 2002.
- ^ Adams S (6 September 2017). "Cure or curse?". Canvet Publications Ltd. Legion Magazine.
- PMID 7944858.
- PMID 8202114.
- PMID 11528574.
- ^ a b c d e f g h "Germany bans drug linked to brain damage, ramps up pressure on Canada". iPolitics. 9 December 2016.
- ^ "Did Lariam send Cambridge student Alana Cutland to her death… and what anti-malarials should children take on their gap year?". Telegraph Media Group Limited. 3 August 2019.
- ^ Haines A (18 October 2019). "Canadian soldiers allege anti-malaria medication left them with intense rage, suicidal ideations". W5. Retrieved 16 April 2020.
- ^ "Lariam (Mefloquine) in the Armed Forces".
- S2CID 19877728. Archived from the originalon 2012-03-21. Retrieved 2011-10-16.
- S2CID 28938736.
- S2CID 13245990.
- S2CID 22205111.
Further reading
- Chen LH, Wilson ME, Schlagenhauf P (May 2007). "Controversies and misconceptions in malaria chemoprophylaxis for travelers". JAMA. 297 (20): 2251–2263. PMID 17519415.
- Schlagenhauf P, Adamcova M, Regep L, Schaerer MT, Rhein HG (December 2010). "The position of mefloquine as a 21st century malaria chemoprophylaxis". Malaria Journal. 9: 357. PMID 21143906.
External links
- "Mefloquine". Drug Information Portal. U.S. National Library of Medicine.