Mefloquine in Pregnancy and Breastfeeding

Risk Factor: CM
Class: Anti-infectives / Antimalarials

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Mefloquine is a quinoline-methanol antimalarial agent used in the prevention and treatment of malaria caused by Plasmodium falciparum, including chloroquine-resistant strains, or by Plasmodium vivax. At high doses (80160 mg/kg/day), mefloquine is teratogenic in mice, rats, and rabbits, and, at one dose (160 mg/kg/day), it is embryotoxic in rabbits (1). Smaller doses (2050 mg/kg/day) impaired fertility in rats, but no adverse effect was observed on spermatozoa in humans taking 250 mg/week for 22 weeks (1).

A study published in 1990 examined the pharmacokinetics of mefloquine during the 3rd trimester of pregnancy (2). Twenty women were treated with either 250 mg of mefloquine base (N=10) or 125 mg of base (N=10) weekly until delivery at term. Peak and trough concentrations of mefloquine were lower than those measured in nonpregnant adults, and the terminal elimination half-life was 11.6 7.9 days. The half-life reported in nonpregnant adults is 1533 days (1). No obstetric complications were observed at either dosage level, including during labor, and no toxicity was observed in the exposed infants. Normal infant development was observed during a 2-year follow-up.

The risks of complications from malarial infection occurring during pregnancy are increased, especially in women not living in endemic areas (i.e., nonimmune women) (3,4,5 and 6). Infection is associated with a number of severe maternal and fetal outcomes: maternal death, anemia, abortion, stillbirth, prematurity, low birth weight, fetal distress, and congenital malaria (3,4,5,6 and 7). However, one of these outcomes, low birth weight with the resulting increased risk of infant mortality, may have other causes inasmuch as it has not been established that antimalarial chemoprophylaxis can prevent this complication (4). Increased maternal morbidity and mortality includes adult respiratory distress syndrome, pulmonary edema, massive hemolysis, disseminated intravascular coagulation, acute renal failure, and hypoglycemia (5,6 and 7). Severe P. falciparum malaria in pregnant nonimmune women has a poor prognosis and may be associated with asymptomatic uterine contractions, intrauterine growth retardation, fetal tachycardia, fetal distress, placental insufficiency because of intense parasitization, and hypoglycemia (4,7). The exacerbation of this latter adverse effect has not been reported with mefloquine (7), but it occurs frequently with quinine (7,8 and 9). Because of the severity of this disease in pregnancy, chemoprophylaxis is recommended for women of childbearing age traveling in areas where malarial is present (3,4 and 5). However, some authors state that mefloquine should not be used for prophylaxis during pregnancy, especially during the 1st trimester, because of the potential for fetotoxicity (3,4 and 5,7,10,11,12,13 and 14), except in areas where chloroquine-resistant P. falciparum is present (11). An editorial comment to one Reference stated that recent data indicated the use of mefloquine during early pregnancy could result in congenital defects, but no other information was provided (15).

Two reports have described the therapeutic use of mefloquine during pregnancy without causing adverse fetal effects (4,16). A 24-year-old woman presented at 33 weeks' gestation with fever, scleral icterus, and tender splenomegaly secondary to P. falciparum infection involving 3% of her erythrocytes (16). After two attempts to administer doses of mefloquine (750 and 500 mg), both of which were vomited, predosing with IV metoclopramide allowed the woman to tolerate three 250-mg doses spaced 4 hours apart and two 250-mg doses the following day (total dose 1250 mg). Maternal fever resolved the day after therapy and, at 5 days, no parasites were observed in the mother's blood. Two months later, a 3405-g infant (sex not specified) was delivered by cesarean section for pelvic disproportion and poor beat-to-beat fetal heart rate variability. Apgar scores at 1 and 5 minutes were 6 and 9, respectively. The child was developing normally at 2 months.

An unpublished double-blind, randomized, controlled study from Thailand conducted between 1983 and 1989 was briefly described in a World Health Organization (WHO) publication (4) and a 1993 review (13). A total of 178 pregnant women were randomized to two groups; one group received mefloquine 500 mg every 8 hours for two doses (N=87), and the other group received quinine 600 mg every 8 hours for 7 days (N=91). Although the exact stages of pregnancy at the time of treatment were not specified, a small number of the women in the mefloquine group were in the 1st trimester (4,13). All of the women were followed to term. The incidence of uterine contractions, premature labor, and fetal distress in the mefloquine and quinine groups were 18% vs. 25%, 1% vs. 5%, and 2% vs. 4%, respectively (4). None of the differences were statistically significant. No stillbirths occurred, but one spontaneous abortion was observed in each group, 21 days after mefloquine and 37 days after quinine; neither was thought to be related to drug treatment (4). The 21-day cure rate was 97% among those treated with mefloquine compared with 86% of those treated with quinine. Three newborns had congenital malformations, but these were believed to be unrelated to the drug therapy (13). The study investigators concluded that the therapeutic use of mefloquine during pregnancy was safe and effective. The WHO Scientific Group concluded, however, that, because of the small number of patients, treatment with mefloquine should be undertaken cautiously during the first 1214 weeks of gestation (4).

Two trials of mefloquine prophylaxis in pregnancy were reviewed in a 1993 Reference (13). An unpublished study compared weekly prophylaxis with either mefloquine (N=468) or chloroquine (N=1312) in asymptomatic pregnant women (13). Mefloquine was more effective than chloroquine in preventing fetal growth retardation and was also effective in reducing placental P. falciparum infections. In another double-blind, placebo-controlled trial, prophylaxis during the second half of pregnancy with 250 mg/week for 1 month followed by 125 mg/week until delivery in 360 Karen women was 95% effective in preventing malaria (13). The incidence of stillbirths was similar between mefloquine (N=4) and placebo (N=5).

A presentation made at a 1991 conference described the follow-up of 98 prospectively recorded pregnancy exposures to mefloquine (17). Five diverse congenital malformations were observed, an incidence that does not support mefloquine-induced teratogenicity.

Breast Feeding Summary

Mefloquine is excreted in human milk (1,18). Two women, who were not breast-feeding, were given a single 250-mg dose, 23 days after delivery (18). Milk samples were collected from both women during the first 4 days after dosing, and from one woman at various intervals up to 56 days. The milk:plasma ratios in the two women during the first 4 days were 0.13 and 0.16, respectively. In one woman, the ratio was 0.27 calculated over 56 days. The investigators estimated that a 4-kg infant consuming 1000 mL of milk daily would ingest 0.08 mg/day of the mother's dose (18), or approximately 4% of the dose would be recovered from the milk (1,18). Although these amounts are not thought to be harmful to the nursing infant, they are insufficient to provide adequate protection against malaria (3).

Long-term effects of mefloquine exposure via breast milk have not been studied. Because the antimalarial agent has a long plasma half-life, averaging nearly 12 days during pregnancy (2) and 14.418.0 days during and after lactation (18), weekly prophylactic doses of mefloquine will result in continuous exposure of a nursing infant. Moreover, higher milk concentrations of mefloquine than those reported should be expected after therapeutic or weekly prophylactic doses (18).

References

  1. Product information. Lariam. Roche Laboratories, 1993.
  2. Nosten F, Karbwang J, White NJ, Honeymoon, Na Bangchang K, Bunnag D, Harinasuta T. Mefloquine antimalarial prophylaxis in pregnancy: dose finding and pharmacokinetic study. Br J Clin Pharmacol 1990;30:7985.
  3. Centers for Disease Control. Recommendations for the prevention of malaria among travelers. MMWR 1990;39:110.
  4. World Health Organization. Practical chemotherapy of malaria. WHO Tech Rep Ser 1990;805:1141.
  5. Subramanian D, Moise KJ Jr, White AC Jr. Imported malaria in pregnancy: report of four cases and review of management. Clin Infect Dis 1992;15:40813.
  6. World Health Organization. Severe and complicated malaria. Trans R Soc Trop Med Hyg 1990;84(Suppl 2):165.
  7. Nathwani D, Currie PF, Douglas JG, Green ST, Smith NC. Plasmodium falciparum malaria in pregnancy: a review. Br J Obstet Gynaecol 1992;99:11821.
  8. Phillips RE, Looareesuwan S, White NJ, Silamut K, Kietinun S, Warrell DA. Quinine pharmacokinetics and toxicity in pregnant and lactating women with falciparum malaria. Br J Clin Pharmacol 1986;21:67783.
  9. White NJ, Warrell DA, Chanthavanich P, Looareesuwan S, Warrell MJ, Krishna S, Williamson DH, Turner RC. Severe hypoglycemia and hyperinsulinemia in falciparum malaria. N Engl J Med 1983;309:616.
  10. Bradley D. Prophylaxis against malaria for travellers from the United Kingdom. Br Med J 1993;306:124752.
  11. Barry M, Bia F. Pregnancy and travel. JAMA 1989;261:72831.
  12. Lackritz EM, Lobel HO, Howell BJ, Bloland P, Campbell CC. Imported Plasmodium falciparum malaria in American travelers to Africa. JAMA 1991;265:3835.
  13. Palmer KJ, Holliday SM, Brogden RN. Mefloquine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1993;45:43075.
  14. Baker L, Van Schoor JD, Bartlett GA, Lombard JH. Malaria prophylaxisthe South African viewpoint. S Afr Med J 1993;83:1269.
  15. Raccurt CP, Le Bras M, Ripert C, Cuisinier-Raynal JC, Carteron B, Buestel ML. Paludisme d'importation Bordeaux: valuation du risque d'infectation par Plasmodium falciparum en fonction de la destination. Bull WHO 1991;69:8591.
  16. Collignon P, Hehir J, Mitchell D. Successful treatment of falciparum malaria in pregnancy with mefloquine. Lancet 1989;1:967.
  17. Elefant E, Boyer M, Roux C. Presentation at the 4th International Conference of Teratogen Information Services, Chicago, Il., April 1820, 1991 (F Rosa, personal communication, 1993).
  18. Edstein MD, Veenendaal JR, Hyslop R. Excretion of mefloquine in human breast milk. Chemotherapy (Basel) 1988;34:1659.

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Questions and Answers

What side effects have people suffered from taking mefloquine?, I have to take malarial prophylaxis for a 2 1/2 month trip to Peru. I have three choices of malarial prophylaxis. Malarone (way too expensive for me), doxycycline and mefloquine. My doctor recomends mefloquine as doxycyclin give a rash in the sun and he doesn't reccomend it for Peru.

So what I want to know is has anyone taken mefloquine? and what side effects have you had from it?

I have read to British National Formulary and have read all the possible side effects so I do not need a list. Just what people have actually suffered.

Thanks

unless u r going to be in the jungle, u really don't need mefloquine in Peru.
but if u really wanna take malaria medication take a pill with u to take as soon as u feel the symptoms.
i dont have the name with me right now, but if u contact me i´ll tell u.
i went to kenya last april and did a whole research about malaria.
another good option is mosquito repellent..

Can patients with Multiple Sclerosis on Avonex take Mefloquine for malaria chemoprophylaxis?,

Only your doctor can give that judgement

Has anybody taken Mefloquine, what side effects did you get?, I have to take malarial prophylaxis for a 2 1/2 month trip to Peru. I have three choices of malarial prophylaxis. Malarone (way too expensive for me), doxycycline and mefloquine. My doctor recomends mefloquine as doxycyclin give a rash in the sun and he doesn't reccomend it for Peru.

So what I want to know is has anyone taken mefloquine? and what side effects have you had from it?

I have read to British National Formulary and have read all the possible side effects so I do not need a list. Just what people have actually suffered.

Thanks

i went to kenya last april and i was going to take mefloquine but i read a lot about it and it really doesnt prevent u from malaria, bc i read that there´s a lot of people that a year after got malaria (even with medication) so i didnt take anything and instead i bought a medicine that cures malaria in 72 hrs..
mefloquine makes u allucinate and i dont know what else..
if u r interested contact me and i´ll tell u about this medicine.

whats the difference between mefloquine lariam & mefliam mefloquine hydrochloride tablets?, i am travelling to india and heard that the female mosquito has become immune to the mefloquine lariam is this true, what should i use

Hi, These drugs are exactly the same, just different brand names. Lariam and Mefliam are the brand names. Both drugs contain Mefloquine hydrochloride.

Mefloquine works by attacking parasites once they have entered the red blood cells. It kills the parasites and prevents them from multiplying further. You need to start taking Mefloquine about a month before you travel.

You need to ensure you take the appropriate prophylactic drug regimen for the area you are visiting. Also, India is not a Mefloquinine resistant country, so you don't have to worry about that. The countries that are Mefloquinine resistant in Asia are; Cambodia, Thailand and areas of Burma.

Has anyone used the maleria propholaxis called Mefloquine, I heard that it?, really makes you sick. anyone out there please tell me your experience. I am going on a trip to INdia with my family and i had concerns about maleria.

what if i take 1/2 pill twice a week? will that decrease my night mares and dizziness and stuff like that??? I am very sensitive to medications. what about children? i am giving my 2-1/2 yr old 1/4 of the pill every week...as per the dr.

It is a form of Quinine..which is used in treatment for Malaria!! As you indicated, you have a doctor that gave you these, so follow what the Doctor has requested!! It's very important if you want to avoid contracting Malaria!!

Has anyone ever taken Mefloquine?, I am going to Kenya in September and having seen the cost of the recommended Malarone, me and my partner can't afford that and have opted for Mefloquine (Lariam). However, I have heard from a few people who've had it and would be interested in anyone who's had side effects? And what would be better is anyone who HASN'T had side effects - because I'm a bit concerned now.

yes theres lots of concern about lariam and the side effects - Inevitably you will always hear from the people who have the bad experience, not the majority who are fine. I'm sure if you do a websearch you can come up with lots of horror stories.

I took lariam when I went to Tanzania recently without any noticeable side effects - this was for a three week period (plus the one week either side back in the UK)

My sister who was out there for longer and on lariam said that she had some minor side effects -bad dreams etc- but these werent very major and they soon went after she stopped taking it on her return (she had been on for around six months).

Some of the people she was with had minor similar side effects but they did know of one or two people who had had bad reactions. These seemed to be people who had histories of depressions/ minor psychological problems. I would say that if you are well mentally you should have no problems - ask your doctor and keep on monitoring your condition whilst you are on it.

Another option if you dont want to take lariam is to be cautious and ensure that you are well protected - ie always wear long sleeves, put lots of antimalarial stuff on (get the stuff with deet in it) and make sure you always sleep under a malaria net.

Good luck - you will have a fabulous time in Kenya!

I have started a course of mefloquine, but have forgotten to take it are there any side effects?,

Among subjects who received Lariam (mefloquine) for treatment, the most frequently observed adverse experiences included: dizziness, myalgia, nausea, fever, headache, vomiting, chills, diarrhea, skin rash, abdominal pain, fatigue, loss of appetite, and tinnitus.

Long Term effects on Mefloquine?, Hello. I am leaving for Ethiopia this Saturday. I started my first Mefloquine tablet per my doctors prescription this last Sat. Last night I couldn't go to sleep. I felt tingly in my arms, small hallucinations, trouble sleeping, I was wide awake at 3am after going to bed at 12am. I was very sensitive to hearing. I woke up immediately after the sprinklers went off sometime in the middle of the night and when cars drove by. I felt really out of my normal realm. Today I feel not myself. I don't feel suicidal but just kina drugged up. Anyways, does anybody have any advice!?? Should I stop taking them?? Do the symptoms go away?? Is there long term effects?? Thank you.

Mefloquine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
* upset stomach
* vomiting
* diarrhea
* stomach pain
* loss of appetite
* muscle pain
* dizziness
* loss of balance
* ringing in ears
* headache
* sleepiness
* difficulty falling or staying asleep
* unusual dreams
Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor immediately:
* tingling in your fingers or toes
* difficulty walking
* seizures
* shaking of arms or legs that you cannot control
* nervousness or extreme worry
* depression
* changes in mood
* panic attack
* forgetfulness
* confusion
* hallucinations (seeing things or hearing voices that do not exist)
* violent behavior
* losing touch with reality
* feeling that others want to harm you
* thoughts of hurting or killing yourself
* rash
Mefloquine may cause other side effects. You may continue to experience side effects for some time after you take your last dose. Call your doctor if you have any unusual problems while taking this medication.
Please see the web pages for more details on Mefloquine.