Drug information of Mefloquine

Mechanism of effect

Mefloquine has been found to produce swelling of the Plasmodium falciparum food vacuoles. It may act by forming toxic complexes with free heme that damage membranes and interact with other plasmodial components.

Pharmacodynamic

Mefloquine is an antimalarial agent which acts as a blood schizonticide. Mefloquine is active against the erythrocytic stages of Plasmodium species. However, the drug has no effect against the exoerythrocytic (hepatic) stages of the parasite. Mefloquine is effective against malaria parasites resistant to chloroquine. Mefloquine is a chiral molecule. It is reported that while the (+) enantiomer primarily mediates an antimalarial activity, the (-) enantiomer contribute to the psychotrophic effects by specifically binding to adenosine receptors in the central nervous system.

Pharmacokinetics

Bioavailability: Well absorbed; >85%; food enhances bioavailability by ~40%

Peak plasma time: 17 hr (range 6-24 hr)

Peak plasma concentration: 1000-2000 mcg/L (after 7-10 wk of 250 mg once weekly dosing)

Vd: 20 L/kg; blood, urine, CSF, tissues; enters breast milk

Protein Bound: 98%

Metabolism: Extensively metabolized in liver by CYP3A4

Metabolites: 2,8-bistrifluoromethyl-4-quinoline carboxylic acid is inactive

Half-life: 21-22 days

Total clearance (hepatic): 30 mL/min

Excretion: Mainly in bile and feces; urine (~1.5-9% as unchanged drug)

Dosage

Adult

Acute Malaria Infections

1250 mg PO once

Malaria Prevention

250 mg PO qWeek

Start 1-2 weeks before arrival in endemic area; continue 4 weeks after leaving endemic area

Pediatric

Acute Malaria Infections

<6 months old: Safety and efficacy not established

>6 months old: 20-25 mg/kg PO as single dose or may divide in 2 doses 

Malaria Prevention

5 to <10 kg: 31.25 mg (1/8 tablet) PO qWeek

10 to <20 kg: 62.5 mg (1/4 tablet) PO qWeek

20 to <30 kg: 125 mg (1/2 tablet) PO qWeek

30-45 kg: 187.5 mg (3/4 tablet) PO qWeek

>45 kg: 250 mg (1 tablet) PO qWeek

Start 1-2 weeks before arrival in endemic area; continue 4 weeks after leaving endemic area

Drug contraindications

Hypersensitivity

Side effects

Anxiety , Insomnia , Diarrhea , Headache , nausea , vomiting , vertigo , lightheadedness , stomach pain

Interactions

Octreotide acetate , Pregabalin , Carbamazepine , Atazanavir , Toremifene , ritonavir , nelfinavir , Zileuton , Dolasetron , vandetanib , Chloroquine , sparfloxacin , Procainamide , Aripiprazole , Amantadine , Amitriptyline , Amiodarone , Olanzapine , Ondansetron , lumefantrine , bosutinib , vemurafenib , Typhoid vaccine (live), oral , Fluticasone and Vilanterol , silodosin , Venetoclax , Apalutamide , ivosidenib , Moexipril , Vorinostat , riociguat , conivaptan , Paliperidone , Pazopanib , Isradipine , Iloperidone , Dosulepin , Foscarnet , Fosphenytoin , Idelalisib , cobicistat , Delavirdine , Asenapine , Artemether , Quinine , Indinavir , Dofetilide , Ibutilide , Eribulin , Loxapine , Fosamprenavir , Enflurane , Mifepristone , Afatinib , pomalidomide , Lopinavir , Ziprasidone , protriptyline , Nefazodone , dronedarone , saquinavir , Mirtazapine , Trimethoprim , Quetiapine , Desflurane , Tamoxifen , Quinidine , Amoxapine , Clarithromycin , Chloramphenicol , Clomipramine , Solifenacin , escitalopram , Darunavir , Nilotinib , Vardenafil , Venlafaxine , Voriconazole , Vincristin , Ketoconazole , Fluoxetine , Galantamine , Lithium carbonate , Lidocaine , Maprotiline , Nortriptyline , Sertraline , Sotalol , Sevoflurane , Ciprofloxacin , Citalopram , Famotidin , Dapsone , Doxepin , Disopyramide , Diphenhydramin , Risperidone , Salmeterol , Trimipramine , Topotecan , Tolterodine , Tizanidine , Thiothixene , Thioridazine , Paroxetine , Promethazine , Posaconazole , Pimozide , Tacrolimus , Tetrabenazine , Everolimus , Oxytocin , Itraconazole , Isoflurane , Imipramine , Bortezomib , Indapamide , Felbamate , Arsenic trioxide , Chloral hydrate , Tipranavir , Dabrafenib , Halofantrine , Grepafloxacin , Nicardipine , Amisulpride , Edoxaban , Bretylium , Bepridil , bedaquiline , talazoparib , ethotoin , Bacampicillin , Halaven

Alerts

May increase QT interval; caution with other drugs known to prolong QT interval

Strong CYP3A4 inhibitors (eg, ketoconazole) should do not coadminister with or within 15 weeks after the last mefloquine dose

Caution with hepatic impairment

Agranulocytosis and aplastic anemia reported

Geographical drug resistance patterns of P. falciparum occur and the preferred choice of malaria prophylaxis might be different from one area to another

Periodic ophthalmic examinations recommended; retinal abnormalities seen in humans with long-term chloroquine use have not been observed with mefloquine use; however, long- term feeding of mefloquine to rats resulted in dose-related ocular lesions

Psychiatric and neurologic adverse effects

• May cause neuropsychiatric adverse reactions, which may be difficult to identify in children; monitor for symptoms, especially in nonverbal children
• Psychiatric symptoms ranging from anxiety, paranoia, and depression to hallucinations and psychotic behavior can occur; symptoms may occur early in the course of mefloquine use and in some cases, these symptoms have been reported to continue for months or years after mefloquine has been stopped
• Cases of suicidal ideation and suicide have been reported
• Should not be prescribed for prophylaxis in patients with active depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders
• Dizziness or vertigo, tinnitus, and loss of balance reported; these symptoms were reported to be permanent in some cases
• May increase the risk of convulsions in patients with epilepsy; prescribed only for curative treatment in such patients and only if there are compelling medical reasons for its use
• Concomitant administration of mefloquine and quinine or chloroquine may increase the risk of convulsions
• During prophylactic use, if symptoms emerge, discontinue and substitute treatment with a different antimalarial agent

 

Black Box Warnings

May cause neuropsychiatric adverse reactions that can persist after mefloquine has been discontinued

Should not be prescribed for prophylaxis in patients with major psychiatric disorders

During prophylactic use, if psychiatric or neurologic symptoms occur, the drug should be discontinued and an alternative medication should be substituted

Points of recommendation

• Tell all of your health care providers that you take mefloquine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how mefloquine affects you.
• Have your blood work checked if you are on mefloquine for a long time. Talk with your doctor.
• Have an eye exam as you have been told by your doctor.
• This medicine may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to your doctor to see if you have a greater chance of seizures while taking mefloquine.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking mefloquine with your other drugs.
• Use birth control to prevent pregnancy while taking mefloquine and for 3 months after the last dose.
• If you get pregnant while taking mefloquine or within 3 months after your last dose, call your doctor right away.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Preventing malaria:

• Other measures are needed along with mefloquine including using screens, bed netting, insect repellent (10% to 35% DEET), and permethrin spray on clothing and nets. Avoid spraying most insect repellents on children. Lower evening and night-time outdoor activity.
• If you have a fever after leaving a malaria area, call your doctor right away.
• If you are a pregnant woman and traveling to a malaria infested place, talk to your doctor about the risks first.

For all uses of mefloquine:

• Take mefloquine with the largest meal of the day.
• Do not take on an empty stomach.
• Take with a full glass of water.
• Tablet can be crushed and mixed with water, milk, or other liquid.
• To gain the most benefit, do not miss doses.
• Keep using mefloquine as you have been told by your doctor or other health care provider, even if you feel well.

Preventing malaria:

• Use as you have been told to prevent malaria.
• If using to prevent malaria, start mefloquine before traveling to the high risk place.

What do I do if I miss a dose?

Treating malaria:

• Most of the time, 1 dose of mefloquine is needed. If you miss the dose, take it as soon as you think about it with food. If you need to take more than 1 dose of mefloquine, follow what your doctor has told you to do.

Preventing malaria:

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• If you miss a dose before leaving for your trip, call your doctor to find out what to do.

Related drugs

primaquine , Chloroquine , Hydroxychloroquine , Quinine , Tafenoquine , Lumefantrine / artemether , Halofantrine , Atovaquone