Mefloquine is an antimalarial medication used to prevent and treat malaria, a serious and potentially life-threatening mosquito-borne disease caused by Plasmodium parasites. It's often prescribed for travellers going to areas where malaria is prevalent. Mefloquine works by interfering with the growth of the parasite within the red blood cells.

Mefloquine (Lariam), an antimalarial medication, is used to treat and prevent malaria without complications. It might be applied in the prevention of infections caused by plasmodium falciparum strains that are resistant to chloroquine.

Mefloquine (Lariam) Uses:

• Acute malaria infections:
  • It is used to treat mild to moderate acute malaria brought on by Plasmodium falciparum mefloquine responsive strains. Additionally, it can be exploited by Plasmodium vivax and strains that are both vulnerable to and resistant to chloroquine.
• Prophylaxis of malaria:
  • Additionally, it is employed in the prophylaxis of P. falciparum and P. vivax malaria infections, as well as the prophylaxis of P. falciparum chloroquine-resistant strains.

Note: The CDC recommendations for prophylaxis should be examined because they vary by area.

• Off Label Use f Mefloquine in Adults:
  • Additionally, it is employed in the management of simple, chloroquine-resistant P. vivax malaria.

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Mefloquine (Lariam) Dose in Adults:

Mefloquine Dose for treating Malaria: Oral (dose expressed as mg of mefloquine hydrochloride):

Mild-to-Moderate Malaria Treatment:

• Take 1,250 mg (which is 5 tablets) as a single dose. If you don't feel better within 48 to 72 hours, you might need a different treatment.

Uncomplicated Malaria Treatment:

• For this, you take 750 mg (3 tablets) first, then 6 to 12 hours later, take 500 mg (2 tablets).

Treatment for Chloroquine-Resistant Malaria (a specific type):

• It's the same as the uncomplicated treatment: 750 mg first, then 6 to 12 hours later, take 500 mg. But in this case, you'll also take another medicine called primaquine.

Preventive Measure (Chemoprophylaxis):

• Take 250 mg once a week, starting one week before you enter an area where malaria is common.
• Keep taking it weekly while you're there and continue for 4 weeks after you leave.
• You might want to start taking it 2 to 3 weeks before you travel to make sure your body can handle it..

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Mefloquine (Lariam) Dose in Children:

Note: Mefloquine hydrochloride, the salt, is used to express dose. In light of geographic resistance and cross-resistance, where necessary, refer to the most recent CDC or WHO recommendations.

Mefloquine (Lariam) Dose in the treatment of Malaria, treatment; chloroquine-resistant (independent of HIV status):

Infants, Children, and Adolescents:

• Take orally, with the first dose being 15 mg per kilogram of body weight (up to a maximum dose of 750 mg), followed by a second dose of 10 mg per kilogram of body weight (up to a maximum dose of 500 mg) after 6 to 12 hours.
• It's usually combined with other anti-malarial drugs, depending on the local resistance patterns and guidelines.
• If there's no improvement within 48 to 72 hours, the doctor might consider a different treatment.

Remember, it's crucial to use this medication under close medical supervision, especially in children, due to the risk of severe reactions.

Mefloquine (Lariam) Dose in the chemoprophylaxis of malaria; (independent of HIV status):

Infants, Children, and Adolescents:

• Weight-based dosing:
  • Oral: Take 5 milligrams per kilogram of body weight once a week, with a maximum dose of 250 milligrams per dose.

Fixed dosing:

• Oral:
  • For children weighing between 9 to 19 kilograms: Take 62.5 milligrams (which is a quarter of a 250 milligram tablet) once a week.
  • For children weighing between 19 to 30 kilograms: Take 125 milligrams (half of a 250 milligram tablet) once a week.
  • For children weighing between 30 to 45 kilograms: Take 187.5 milligrams (three-quarters of a 250 milligram tablet) once a week.
  • For children weighing more than 45 kilograms: Take 250 milligrams once a week.

Remember to start taking mefloquine at least two weeks before entering the area where malaria is common. Take it on the same day each week while you're there and continue for four weeks after leaving.

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Pregnancy Risk Factor B

• Mefloquine has a pregnancy risk factor of B, meaning it crosses the placenta but hasn't shown increased risk of harm to pregnant women based on clinical experience.
• However, malaria in pregnant women can be more severe and may lead to adverse pregnancy outcomes.
• CDC guidelines provide recommendations for using mefloquine to treat malaria during pregnancy.
• Women who aren't pregnant but could become pregnant are advised to use contraception and avoid pregnancy during mefloquine treatment and for three months afterward.

Mefloquine use during breastfeeding:

• Mefloquine can be found in breast milk in small amounts, approximately 3% to 4% of a 250 mg dose.
• While caution is advised when giving mefloquine to breastfeeding women, exposure to these small quantities through breast milk is generally considered safe for infants according to the CDC.

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Mefloquine Dose in Kidney Disease:

• No dosage adjustment is typically needed for mefloquine because only a small portion of it is eliminated through the kidneys.
• Therefore, the standard dosage is usually suitable for individuals with normal kidney function.

Mefloquine Dose in Liver disease:

• The manufacturer's labeling for mefloquine doesn't specify dosage adjustments for patients with hepatic impairment.
• However, it's important to note that in individuals with liver problems, the half-life of mefloquine may be prolonged, and their plasma levels may be higher compared to those with normal liver function.

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Common Side Effects of Mefloquine (Lariam):

• Central nervous system:
  • Abnormal dreams
  • Insomnia

Less Common Side Effects of Mefloquine (Lariam):

• Gastrointestinal:
  • Vomiting

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Contraindications to Mefloquine (Lariam):

• If someone has had a hypersensitivity reaction to mefloquine or related compounds like quinine or quinidine, or if they are allergic to any component of the medication, they should not use mefloquine.
• Additionally, mefloquine is not recommended for prophylactic use in individuals with a history of seizures or psychiatric disorders, including depression, anxiety disorders, psychosis, schizophrenia, or other major psychiatric conditions.
• While there's limited documentation of cross-reactivity with quinine derivatives, due to similarities in chemical structure and pharmacological actions, there's a possibility of cross-sensitivity.
• Therefore, caution should be exercised, and alternative medications may be considered in such cases.

Warnings and precautions

Agranulocytosis, aplastic anemia

• Agranulocytosis and aplastic anemia, which are severe blood disorders, have been reported in association with mefloquine use.

Modified cardiac conduction

• Mefloquine can affect the heart's electrical activity, which may show up on an ECG (electrocardiogram) as changes like slow heart rate, irregular heart rhythm, and abnormalities in specific waves.
• It's important to be cautious or avoid taking other medications that are known to prolong the QT interval, a measure of heart rhythm, such as halofantrine, quinine, or quinidine, at the same time as mefloquine to reduce the risk of serious heart problems.

Hypersensitivity reactions

• Some people may experience hypersensitivity reactions while taking mefloquine.
• This means they might have allergic reactions or other unexpected responses to the medication.

Neuropsychiatric effects: [US Boxed Warn]

• Mefloquine carries a significant warning about potential neuropsychiatric effects, which can persist even after stopping the medication.
• These effects can occur early in treatment and may include anxiety, paranoia, depression, hallucinations, psychosis, and in severe cases, suicidal thoughts or actions.
• Neurological symptoms like dizziness, ringing in the ears, and loss of balance may also occur, and in some cases, they can be permanent.
• If such symptoms arise, especially in children, it's crucial to monitor closely and consider alternative treatments.
• During prophylactic use, symptoms like anxiety or depression may be an early sign of more serious neuropsychiatric reactions.
• Individuals should be cautious with activities requiring focus and coordination, like driving or operating machinery, if experiencing neurological symptoms.

Cardiovascular disease

• Individuals with significant heart conditions should use mefloquine cautiously because it can lead to changes in the heart's electrical activity, as seen on an ECG.
• These changes might include a slower heart rate (sinus bradycardia), irregular heart rhythm (sinus arrhythmia), or abnormalities in the heart's conduction system (such as first-degree AV block).
• Additionally, mefloquine can prolong the QT interval on the ECG and cause abnormal T waves.

Hepatic impairment

• In individuals with liver problems, mefloquine should be used cautiously because their bodies might take longer to eliminate the medication.
• This prolonged elimination can increase the amount of mefloquine in the bloodstream, potentially leading to higher levels of the drug in the body.

Neuropsychiatric disorders [US Boxed Warning]

• Mefloquine should not be prescribed for preventing malaria in individuals with major psychiatric disorders like depression, anxiety disorders, psychosis, or schizophrenia, including those with active symptoms or recent history.
• It's strictly contraindicated in such cases due to the potential to worsen psychiatric symptoms.
• Additionally, caution is advised when using mefloquine in individuals with a previous history of depression.

Ocular effects

• Mefloquine treatment has been associated with eye disorders, such as optic neuropathy and retinal disorders.
• If someone experiences visual symptoms while taking mefloquine, it's important to seek prompt evaluation by an eye specialist.
• In some cases, discontinuing mefloquine therapy may be necessary to prevent further eye complications.
• Keeping a close watch on any changes in vision and acting swiftly can help ensure appropriate management of ocular effects associated with mefloquine use.

Plasmodium falciparum infection:

• In severe cases of malaria caused by Plasmodium falciparum, where the infection is life-threatening or serious, patients are usually treated initially with intravenous antimalarial drugs.
• Mefloquine can then be administered orally to complete the treatment course.
• This approach helps to swiftly combat the infection and ensure that the patient receives the necessary medication to fully recover from the illness.

Plasmodium virex infections:

• In cases of acute Plasmodium vivax infection treated with mefloquine, it's important to follow up with treatment using an 8-aminoquinoline derivative, such as primaquine.
• This additional medication is necessary to prevent the possibility of relapse after the initial treatment with mefloquine.

Seizure disorder:

• When mefloquine is used for treatment, it should be approached cautiously in patients with a history of seizures because it may increase the risk of experiencing seizures.
• However, the use of mefloquine for prophylaxis is contraindicated in patients with a seizure disorder, meaning it should not be used at all in such individuals due to the heightened risk it poses.

Mefloquine: Drug Interaction

Risk Factor C (Monitor therapy)
Amodiaquine	Mefloquine's negative or toxic effects could be exacerbated. Particularly, there may be an elevated risk for eyesight issues.
Antipsychotic Agents (Phenothiazines)	Antipsychotic Agents' serum concentration may rise in response to antimalarial drugs (Phenothiazines).
Aprepitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Celiprolol	Mefloquine may enhance the bradycardic effect of Celiprolol.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Haloperidol	QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTcprolonging effect of Haloperidol.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Palbociclib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
QT-prolonging Agents (Highest Risk)	The QTc-prolonging action of QT-prolonging Agents may be enhanced by QT-prolonging Agents (Indeterminate Risk - Caution) (Highest Risk). When using these medications together, watch out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.
Sarilumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Tocilizumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Risk Factor D (Consider therapy modification)
Anticonvulsants	Mefloquine may lessen the anticonvulsant's ability to treat seizures. Anticonvulsant serum concentrations may be reduced by mefloquine. Treatment: Mefloquine should not be used to prevent malaria in those who have a history of convulsions. With concurrent use, closely monitor anticonvulsant concentrations and therapeutic response.
CYP3A4 Inducers (Strong)	May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.
CYP3A4 Inhibitors (Strong)	May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).
Dabrafenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).
Dapsone (Systemic)	Antimalarial drugs could intensify the harmful or hazardous effects of dapsone (Systemic). In particular, the use of antimalarial medications concurrently with dapsone may raise the risk of hemolytic responses. Dapsone (Systemic) may make antimalarial agents more harmful or poisonous. More specifically, using dapsone at the same time as an antimalarial drug may make hemolytic responses more likely. Treatment: Carefully observe patients for any indications or symptoms of hemolytic responses while administering dapsone and antimalarial medications, especially in those who have haemoglobin M, glucose-6-phosphate dehydrogenase (G6PD), or methemoglobin reductase deficiencies.
Dapsone (Topical)	Antimalarial drugs could intensify the harmful or hazardous effects of dapsone (Topical). Particularly, there may be a higher risk of hemolytic responses. Treatment: Apply topical dapsone and antimalarial medications while closely monitoring for hemolytic reactions' signs and symptoms. Patients who lack glucose-6-phosphate dehydrogenase may be especially vulnerable to negative hematologic consequences.
Enzalutamide	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.
Lorlatinib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes.
MiFEPRIStone	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes.
Mitotane	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Risk Factor X (Avoid combination)
Aminoquinolines (Antimalarial)	Mefloquine's negative or toxic effects could be exacerbated. Particularly, there may be an increased risk for QTc-prolongation and convulsions. Aminoquinolines' serum concentration may rise in response to mefloquine (Antimalarial). Management: When possible, avoid concomitant usage and postpone the delivery of mefloquine until at least 12 hours after the final dosage of an antimalarial aminoquinoline.
Artemether	Could intensify the negative or hazardous effects of antimalarial drugs. Management: Unless there are no other treatment options available, artemether/lumefantrine (combination product) should not be used with other antimalarials.
Conivaptan	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fusidic Acid (Systemic)	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Halofantrine	Halofantrine's ability to extend QTc may be strengthened by mefloquine.
Idelalisib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Lumefantrine	Antimalarial drugs may intensify Lumefantrine's harmful or toxic effects. Management: Unless there are no other treatment options available, artemether/lumefantrine (combination product) should not be used with other antimalarials.
QuiNIDine	Mefloquine's negative or toxic effects could be exacerbated. Particularly, there may be an elevated risk for QTcprolongation and convulsions. Management: When possible, avoid taking two medications at the same time and postpone giving mefloquine until at least 12 hours have passed since the last dosage of quinidine.
QuiNINE	Mefloquine's negative or toxic effects could be exacerbated. Particularly, there may be an elevated risk for QTcprolongation and convulsions. The serum concentration of QuiNINE may rise in response to mefloquine. Avoid concomitant use, and hold off on giving mefloquine until at least 12 hours have passed since the last dosage of quinine.

Monitoring parameters:

Regular Monitoring During Prolonged Use of Mefloquine

• Liver Function Tests: Periodic tests to check how well the liver is working.
• Evaluation for Neuropsychiatric Effects: Regular assessments to monitor for any changes in mood, behavior, or mental health.
• Ocular Examinations: Routine eye check-ups to detect any potential eye problems or changes in vision.

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How to administer Mefloquine (Lariam)?

• Take with Food and Water: Always take mefloquine with food and at least 240 mL (8 ounces) of water to help with absorption.
• Dosage for Malaria Prophylaxis: Take the dose once a week on the same day each week to prevent malaria.
• Dealing with Vomiting After Dose:
  • If vomiting occurs within 30 minutes after taking the dose, take another full dose.
  • If vomiting occurs within 30 to 60 minutes after taking the dose, take an additional half-dose.
• Option for Those Who Can't Swallow Tablets: If someone can't swallow tablets, they can crush them and mix the powder in a small amount of water, milk, or another beverage for easier consumption.

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Mechanism of action of Mefloquine (Lariam):

• Mefloquine is a medication similar in structure to quinine, belonging to the quinoline-methanol compound family.
• It works by targeting and destroying the asexual blood forms of the malaria-causing parasites that affect humans, including Plasmodium falciparum and P.
• vivax.
• This destruction of the parasites is what makes mefloquine effective in both treating and preventing malaria infections.

Absorption:

• Mefloquine is well absorbed, but the rate of absorption can vary between individuals.
• Suspension forms are absorbed more completely compared to tablets.

Distribution:

• Mefloquine spreads throughout the body, including tissues, red blood cells, blood, urine, and cerebrospinal fluid (CSF).
• Volume of distribution:
  • Children (4 to 10 years): Approximately 18 to 19 liters per kilogram.
  • Adults: Around 20 liters per kilogram.

Protein Binding:

• Mefloquine is highly bound to proteins in the blood, with approximately 98% binding.

Metabolism:

• Mefloquine is mainly metabolized in the liver, primarily by an enzyme called CYP3A4.
• The main metabolite produced is inactive, along with other metabolites.

Bioavailability:

• Absorption of mefloquine is increased when taken with food.

Half-life Elimination:

• Children (4 to 10 years): Average half-life ranges from 11.6 to 13.6 days, but it can range from 6.5 to 33 days.
• Adults: Approximately 3 weeks, with a range of 2 to 4 weeks.
• Half-life may be shorter during infection, around 2 weeks.

Time to Peak, Plasma:

• It takes approximately 17 hours for mefloquine to reach peak levels in the blood, with a range of 6 to 24 hours.

Excretion:

• Mefloquine is primarily eliminated through bile and feces.
• A small portion (9% of total dose) is excreted unchanged in urine, along with 4% of the total dose as the primary metabolite.

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International Brand Names of Mefloquine:

• Eloquine
• Lariam
• Laricam
• Larimef
• Malariquin
• Malarium
• Malarivent T
• Mefliam
• Meflon
• Melophar
• Mephaquin
• Mequin
• Suton
• Tropicur
• Vexam

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Mefloquine Brand Names in Pakistan:

Mefloquine (HCl) Tablets 250 mg in Pakistan
Malarium	Global Pharmaceuticals
Meflogen	Genome Pharmaceuticals (Pvt) Ltd
Meflowan	Swan Pharmaceuticals(Pvt) Ltd