Lariam

Lariam is a medicine against malaria. The active component of the medicine is methanolquinoline.

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Indications Lariama

It is used for treatment in the following cases:

• therapy for uncomplicated malaria (which is caused by strains of Plasmodium falciparum and other pathogenic bacteria that are resistant to other antimalarial drugs);
• for malaria of mixed origin or caused by the bacterium Plasmodium vivax;
• to prevent the development of malaria in people who are planning to visit regions where there is a high risk of contracting it;
• as emergency aid or self-help – for people suspected of having malaria.

Release form

The product is produced in tablets, 4 pieces inside a blister plate. The pack contains 2 blister packs.

Pharmacodynamics

Lariam affects asexual types of pathology (of intraerythrocytic origin). This list includes Plasmodium vivax and Plasmodium falciparum, as well as Plasmodium malariae and Plasmodium ovale.

At the same time, the drug is effective against bacteria that have shown resistance to many other drugs. Among them are Proguanil with Chloroquine, as well as Pyrimethamine and a combination of Pyrimethamine with sulfonamides.

During the tests it was found that resistance of Plasmodium falciparum to mefloquine is found mainly in Southeast Asia, where bacterial resistance to many known drugs is often observed. There is information about cross-resistance of mefloquine with quinine and halofantrine.

Pharmacokinetics

The bioavailability level is more than 85%. Taking with food increases the degree and rate of absorption, and also the bioavailability index (by about 40%). Peak values in plasma, which are approximately the same as the dose taken, are reached after 6-24 hours. Equilibrium values in plasma (1000-2000 mcg/l) can be achieved by taking the drug in the amount of 250 mg once a week for a period of 7-10 weeks.

The distribution volume of mefloquine is approximately 20 l/kg. The substance can pass into tissues, through the placental barrier, and also enter the mother's milk in small quantities. Protein synthesis is 98%.

To achieve 95% prophylactic effectiveness of the drug, it is necessary to achieve the substance levels in the bloodstream of at least 620 ng/ml (inside erythrocytes containing malaria bacteria, these values should be 2 times higher).

Inside the body, mefloquine is converted by the hemoprotein P450 3A4 into two breakdown products – carboxymefloquine and hydroxymefloquine. The main one is 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid, which is inactive against the bacterium Plasmodium falciparum.

The average half-life is 3 weeks. Excretion occurs mainly in the feces and bile. The total clearance rate is 30 ml/minute (mainly within the liver). Urine eliminates 9% of unchanged mefloquine, as well as 4% of its main breakdown product.

Dosing and administration

The tablets are taken orally, after meals, with water (at least 200 ml). The tablet must be swallowed whole, because it has a bitter taste and is slightly burning. If the patient is unable to swallow the medicine whole, it is allowed to crush the tablet and add it to the liquid that he drinks.

Use for the prevention of malaria development.

The adult dosage (and for children weighing over 45 kg) is a maximum of 5 mg/kg once a week (taken on a strictly defined day). For weights in the range of 30-45 kg, the dosage is 3/4 of a tablet, for weights in the range of 20-30 kg - half a tablet, for weights in the range of 10-20 kg - a quarter of a tablet, and for weights in the range of 5-10 kg - a maximum of 0.125 tablets.

The first dose of Lariam should be taken before visiting a region with a high risk of contracting malaria (usually this is done 7 days before). If the dosage has not been taken in advance, shock treatment is required - the dosage intended for taking 1 time / week should be taken for 3 days in a row, and then switch to the usual regimen. To reduce the likelihood of developing the disease after leaving a potentially dangerous area, it is necessary to take the drug in a preventive mode during the first month. If a person is being treated with other drugs, prophylaxis should be started no later than 2-3 weeks before the trip to ensure the safety of the combination of drugs.

Treatment using Lariam.

The general standard dose that allows achieving the desired effect is 20-25 mg/kg, and may vary depending on the patient's weight, and also be distributed with some variations (using the general medicinal dose in 2-3 doses with an interval of 6-8 hours can prevent the occurrence of side effects).

People weighing over 60 kg should take 6 tablets (in 3 doses according to the scheme 3+2+1 tablets), and people weighing within 45-60 kg – 5 tablets (in 2 doses, scheme 3+2 tablets). With a weight in the range of 30-45 kg, you need to take 3-4 tablets (in 2 doses according to the scheme 2+2 tablets). Weight 20-30 kg – 2-3 tablets (in 2 doses, according to the scheme 2+1 tablets). With a weight of 10-20 kg, take 1-2 tablets in one dose, and with a weight of 5-10 kg – also in 1 dose 0.5-1 tablet.

Dose peculiarities in some situations:

• in case of weakened immunity, and in addition, people living in endemic malaria regions can take a reduced total dose;
• if the patient develops vomiting within half an hour after taking the tablets, he must take the full dose again, and if vomiting begins within 0.5-1 hour after taking them, he must take an additional half dose;
• if the bacterium that causes malaria is Plasmodium vivax, in order to remove Plasmodium from the liver, it is necessary to prevent relapses using derivatives of the substance 8-aminoquinoline (for example, the drug primaquine);
• if there is no improvement after 48-72 hours after completing the full course of treatment, or if malaria develops during prophylaxis, the doctor should select another medication;
• in severe forms of acute malaria, the drug may be used after 2-3 days of therapy with intravenous quinine. It is necessary to observe an interval of at least 12 hours between the use of these drugs in order to prevent the development of many pharmacological interactions;
• In areas where pathogenic microbes are cross-resistant, a regimen with initial use of artemisinin or its derivatives, followed by the use of Lariam, may yield results.

Self-medication.

It is necessary to take the initial portion - at least 15 mg/kg. For example, if the weight indicator is more than 45 kg - take 3 tablets (the dose is 750 mg). If it is impossible to receive further medical care and there are no negative manifestations, after 6-8 hours it is necessary to take the 2nd half of the total portion - 2 tablets (the dose is 500 mg). If the weight is more than 60 kg, after another 6-8 hours, take another tablet.

To exclude or confirm the diagnosis, you need to visit a doctor, even if you feel well.

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Use Lariama during pregnancy

The use of Lariam in the first trimester is permitted only in situations where the probable benefit to the woman outweighs the risks of complications for the child.

Women of reproductive age should use reliable contraceptives when using the drug, as well as 3 months after the end of the course. However, if conception has already occurred during treatment, termination of pregnancy is not required.

Mefloquine passes into breast milk in small quantities. Since there is no information about its effect in such cases, it is necessary to stop breastfeeding during the period of taking Lariam.

Contraindications

Among the contraindications:

• states of anxiety or depression, as well as psychosis;
• a patient suffering from schizophrenia;
• presence of seizures (also if they are present in the anamnesis);
• therapy with Halofantrine, and in addition, its administration after the use of mefloquine (prolongation of QT interval values may occur, which will be life-threatening);
• manifestations of intolerance to elements of the drug or drugs with similar therapeutic effects, such as quinidine or quinine.

It is necessary to use the medicine with caution in the presence of liver failure or epilepsy (because the probability of seizures increases), and also in people with mental disorders and heart pathologies. Caution is also necessary when prescribing to infants under six months weighing less than 5 kg, and to the elderly (over 65 years).

Side effects Lariama

During therapy in the acute stage of malaria, side effects may appear, which are symptoms of the underlying pathology.

The most frequently observed disorders (they are often expressed rather weakly, and their manifestation decreases in the process of continuing the course of treatment): vomiting, headaches and abdominal pain, diarrhea, nausea, fecal incontinence, problems with balance, diarrhea, nightmares, dizziness, as well as insomnia and a feeling of drowsiness.

The following complications and disorders are occasionally observed:

• a state of depression, encephalopathy, motor or sensory neuropathy, ataxia, paresthesia with convulsions and tremor. There is a feeling of anxiety, agitation, confusion or restlessness, memory deterioration, hallucinations and panic attacks, suicidal thoughts, as well as manifestations of a paranoid psychotic and aggressive nature;
• increased or decreased blood pressure, tachycardia, increased heart rate, bradycardia, hot flashes, and also extrasystole with arrhythmia. AV blocks and transient problems with cardiac conduction may occur;
• urticaria, rashes on the skin surface, swelling, exanthema, alopecia, itching, as well as erythema (including exudative multiforme) and Stevens-Johnson syndrome;
• myalgia with myasthenia, as well as arthralgia;
• problems with hearing, vision or the vestibular system may develop;
• thrombocytopenia or leukopenia, decreased hematocrit and leukocytosis;
• a state of fever and a feeling of weakness, increased sweating, a feeling of chills and loss of appetite.

Due to the long period of excretion of the drug, negative effects may persist and manifest themselves for several weeks after the end of taking the drug.

Overdose

Among the characteristic signs of poisoning: increased severity of side effects.

Treatment in this case consists of the following: induction of vomiting and gastric lavage, as well as symptomatic procedures. In addition, intensive measures are taken to maintain the function of the cardiovascular system, hemodynamic values and ECG indicators are monitored, and the patient's neuropsychiatric state is assessed (during the first day).

Interactions with other drugs

When combining Lariam with chloroquine, quinidine, and quinine, changes in ECG parameters may be observed, and the likelihood of developing seizures increases.

Ca channel blockers, antiarrhythmic and antihistamine drugs, tricyclics, β-blockers, phenothiazines, and histamine (H1) blockers affect conduction processes within the heart and may also affect prolongation of the QT interval.

Since the combination with Lariam reduces the plasma levels of valproates, carbamazepine and phenytoin with phenobarbital, which weakens their effectiveness, it may be necessary to change the dosage of these drugs.

Combination of the drug with live typhoid vaccines for oral administration reduces the immunogenicity of the latter. For this reason, vaccination must be performed at least 3 days before starting to use Lariam.

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Storage conditions

Lariam should be kept in a place protected from moisture. The temperature should not exceed +30°C.

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Special instructions

Reviews

Lariam is a fairly popular drug that is often used as a preventive measure against the development of malaria in case of travel to countries with a high endemic level. Reviews about it are quite good, but, since the microbes that cause malaria in different regions have differences (for example, in Sri Lanka), treatment or prevention is prohibited to be carried out independently - they should be prescribed exclusively by a professional specialist who is able to assess the picture and select the dosage or another drug against malaria if necessary.

Shelf life

Lariam can be used for a period of 3 years from the date of release of the drug.