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Lariam

Lariam
Lariam is effective against malaria pathogens that are resistant to other antimalarial drugs, such as chloroquine, proguanil, pyrimethamine, and the combination of pyrimethamine with sulfonamides.

Brand: Mefloquine

Availability: In Stock
Average Delivery Time: 9 Days
Exp. Date: December 2023
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Lariam 250 mg
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Product description

Pharmacological action of the drug Lariam

Buy Lariam in Canada

Lariam - hematocide, acts on asexual intracellular erythrocytic forms of human malaria pathogens: Plasmodium falciparum, Plasmodium vivax, circulating schizonts Plasmodium malariae and Plasmodium ovale. Not active against hepatic stages of parasites. Effective against malaria pathogens that are resistant to other antimalarial drugs such as chloroquine, proguanil, pyrimethamine, and pyrimethamine / sulfonamides.

For P. falciparum may develop resistance to mefloquine, mainly in Southeast Asia. In some regions, cross-resistance has been reported between mefloquine and halofantrine, mefloquine and quinine.

The drug does not cause hemolysis associated with a deficiency of glucose-6-phosphate dehydrogenase.

Pharmacokinetics

Absorption

Absolute bioavailability of mefloquine after oral administration has not been evaluated (no i / v form). The bioavailability of the tablet form is over 85% of that when the solution is taken orally. Eating food significantly speeds up the speed and increases the degree of absorption by 40%. The average time to reach Cmax of mefloquine after a single dose is 17 hours (6-24 hours). TheCmax plasma, measured in μg / L, is approximately equal to the dose taken, measured in mg (for example, a single dose of 1000 mg gives a Cmax of about 1000 μg / L). After regular intake of 250 mg of mefloquine 1 time / week, Cssmax , equal to 1000-2000 μg / l, is reached after 7-10 weeks. To achieve 95% effectiveness of prophylaxis, a blood concentration of mefloquine of 620 ng / ml is required.

The distribution of Vd of mefloquine 20 l / kg, which indicates the penetration of the drug into many tissues. It accumulates in erythrocytes, inside of which there are malaria parasites, at concentrations approximately twice the plasma concentration. Penetrates through the placental barrier, as well as into breast milk. The connection of the drug with plasma proteins is 98%.

Metabolism

Metabolized to form 2 metabolites: the main metabolite, 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid, and alcohol. The main metabolite is inactive against P. falciparum, appears in plasma 2-4 hours after a single oral administration of the drug, its Cmax in plasma is 50% higher than that of mefloquine and is reached after 2 weeks. Thereafter, the decrease in plasma concentrations of the main metabolite and mefloquine occurs at the same rate. AUC of the main metabolite is 3-5 times higher than that of the parent drug. Another metabolite, alcohol, is present in very small amounts.

Withdrawal

The average T1/2 of mefloquine is 3 weeks (from 2 to 4 weeks), does not change during long-term antimalarial prophylaxis. It is excreted in the form of metabolic products mainly with bile and feces. The total clearance, most of which is hepatic, is 30 ml / min. Excretion of unchanged mefloquine and its main metabolite by the kidneys is about 9% and 4%, respectively. Other metabolites are not found in urine.

Pharmacokinetics in special cases.

Children and elderly patients: age does not affect the pharmacokinetics of mefloquine.

Pharmacokinetic studies in patients with renal insufficiencynot havebeen carried out, since a very small amount of the drug is excreted in the kidneys. In any significant amounts, mefloquine and its main metabolite are not excreted by hemodialysis. No dose adjustment is required for patients on hemodialysis.

Hepatic failure: in patients with impaired liver function, the elimination of mefloquine may be slowed down, as a result of which the concentration of the drug in the plasma increases.

Pregnancy has no clinically significant effect on the pharmacokinetics of mefloquine.

Race. Pharmacokinetic differences are of very little clinical significance compared to the immune status of an infected patient and susceptible pathogen.

Indications of the drug Lariam

Lariam for the treatment of malaria

  • treatment of mild and moderate forms of malaria caused by strains of P. falciparum resistant to other antimalarial drugs, P. vivax, and malaria of mixed etiology;

  • prevention of malaria in persons traveling to malaria-prone regions, especially to regions with a high risk of infection with P. falciparum strains resistant to other antimalarial drugs;

  • emergency care (self-help): self-admission as an emergency treatment for suspected malaria, if urgent medical attention is not possible.

Dosing regimen of the drug Lariam

Inside, after meals, drinking plenty of liquid (at least 200 ml) in 2-3 doses.

Mefloquine has a bitter and slightly pungent taste. The tablets should be swallowed whole. When used in children or people who cannot swallow the tablet whole, it can be crushed and dissolved in a little water, milk or other beverage.

The tablets should not be removed from the blister until they are taken, as they are sensitive to moisture.

Prevention

Adults and children weighing more than 45 kg: 5 mg / kg (250 mg, 1 tablet of Lariam) 1 time / week.

Adults and children weighing from 30 to 45 kg - 3/4 tablets, children weighing from 20 to 30 kg - 1/2 tablets, children weighing from 10 to 20 kg - 1/4 tablets, children weighing body from 5 to 10 kg - 1/8 tablet.

Weekly doses of Lariam should always be taken on the same day of the week. The first time the drug should be taken at least one week before arriving in a malaria-endemic region. If this is not possible, a loading dose of the drug must be prescribed. For adults weighing more than 45 kg, it is 1 tablet of Lariam (250 mg) per day for 3 consecutive days, and then 1 tablet / week. To reduce the risk of malaria after leaving the endemic region, prophylaxis continues for another 4 weeks. If the patient is taking other medications, it is advisable to start prophylaxis 2-3 weeks before departure to ensure that the concomitant medications are well tolerated.


Contraindications to the use of

  • depression;

  • psychosis;

  • schizophrenia;

  • anxious states;

  • convulsions (including a history);

  • pregnancy;

  • co-administration with halofantrine, administration of halofantrine after mefloquine therapy;

  • hypersensitivity to the components of the drug or drugs close to it (quinine, quinidine).

With care: liver failure, I trimester of pregnancy, breastfeeding period, mental illness, age under 6 months, body weight up to 5 kg, heart disease, age over 65 years, combination with quinine and quinidine.

Application during pregnancy and lactation

Contraindicated in the II and III trimesters of pregnancy. With caution in the first trimester.

When using mefloquine in doses 5-20 times higher than therapeutic for humans, it had a teratogenic effect in mice and rats and an embryotoxic effect in rabbits. However, the experience of clinical use of Lariam did not reveal any embryotoxic or teratogenic effects in him. However, Lariam should be prescribed in the first trimester of pregnancy only if the intended benefit to the mother outweighs the potential risk to the fetus. Women of reproductive age should be prescribed treatment only if they use reliable contraception for the entire period of mefloquine intake and for 3 months after the last dose. But if pregnancy occurs against the background of chemoprophylaxis of malaria by Lariam, there is no indication for its termination.

The activity of small amounts of mefloquine in breast milk is unknown. During breastfeeding, the drug is prescribed only if the intended benefit to the mother outweighs the potential risk to the child. In children whose mothers took Lariam during breastfeeding, no adverse reactions were noted.

Application for violations of liver function

The drug is prescribed with caution in patients with hepatic insufficiency.

Application for impaired renal function

There is no data on the use of Lariam in patients with impaired renal function.

Use in children

The drug is prescribed with caution to children under 6 months of age, as well as to children weighing up to 5 kg (the experience of using Lariam in this category of patients is limited).

Use in elderly patients

The drug is prescribed with caution to patients over 65 years of age.

Specific guidance

Lariam may increase the risk of seizures in patients with epilepsy. Therefore, the drug can be prescribed to such patients only for the purpose of treatment and in the presence of absolute indications for its use (see also "Interactions").

After quinine or quinidine, you can take mefloquine no earlier than 12 hours later. With prophylactic administration for a long time (taking the drug for more than 1 year is undesirable), periodic analysis of liver function indicators and an ophthalmological examination are required.

Due to the danger of potentially life-threatening QT interval prolongation, halofantrine should not be administered with or after Lariam. There is no data on the use of Lariam after halofantrine.

With the development of anxiety, depression, anxiety or impaired consciousness during the prophylactic use of Lariam, the drug should be canceled.

The experience of using Lariam in children under the age of 6 months or with a case weight of less than 5 kg is limited.

Influence on the ability to drive vehicles and work with machines and mechanisms

During treatment, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: An overdose of Lariam is characterized by the manifestation of side effects in a more pronounced form.

Treatment: induce vomiting, wash out the stomach. If necessary, symptomatic and intensive supportive measures are carried out aimed at eliminating disorders of the cardiovascular system. It is necessary to monitor hemodynamic parameters, ECG and neuropsychic status for at least 24 hours.

Drug interactions

Simultaneous administration of Lariam and quinine, quinidine and chloroquine can cause changes in the ECG and increase the risk of seizures.

The use of halofantrine after mefloquine leads to a significant lengthening of the QTc interval (the QTc interval, corrected by heart rate, is calculated by the formula: QTc = QT / RR1/2). With mefloquine alone, there was no clinically significant QTc prolongation. The concomitant use of other drugs that affect cardiac conduction (antiarrhythmics, β-blockers, calcium channel blockers, antihistamines, in particular H1-histamine blockers, tricyclic antidepressants and phenothiazines) may also play a role in prolonging the QTc interval.

Reduces the effectiveness of anticonvulsants (valproic acid, carbamazepine, phenobarbital or phenytoin), decreasing their plasma concentrations. It is necessary to control the concentration of drugs in plasma. In some cases, dose adjustment of anticonvulsants may be required.

Lariam can reduce the immunogenicity of oral live typhoid vaccines when taken simultaneously, so vaccination with live attenuated vaccines should be completed at least 3 days before the first dose of Lariam.

No other drug interactions of Lariam are known. But persons receiving other drugs, in particular, anticoagulants or antihyperglycemic agents, must undergo medical control before leaving for the endemic region.

Side effects

When taking Lariam in doses prescribed for the treatment of acute malaria, side effects similar to the symptoms of the underlying disease may occur.

The incidence of adverse events during prophylaxis with mefloquine is comparable to that of other chemoprophylaxis regimens. The side effect profile of mefloquine is characterized by a predominance of reactions from the neuropsychic sphere.

The most common side effects are usually mild and decrease with continued use of the drug. These include nausea, vomiting, fecal incontinence, diarrhea, abdominal pain, dizziness, imbalance, headache, drowsiness, insomnia, nightmares.

The following side effects are less common.

From the side of the central nervous system and peripheral nervous system: sensory and motor neuropathy, paresthesia, tremor, ataxia, convulsions, agitation, anxiety, anxiety, depression, panic attacks, memory impairment, confusion, hallucinations, aggressive, psychotic and paranoid reactions, in rare cases - suicidal ideation (their connection with taking the drug has not been established), rarely - encephalopathy.

From the side of the cardiovascular system: a decrease or increase in blood pressure, hot flashes, fainting, chest pain, tachycardia, palpitations, bradycardia, arrhythmia, incl. extrasystole, transient conduction disturbances, rarely AV block.

Dermatological reactions: skin rash, exanthema, erythema, urticaria, itching, edema, alopecia, rarely - exudative erythema multiforme, Stevens-Johnson syndrome.

Musculoskeletal system: myasthenia gravis, muscle cramps, myalgia, arthralgia.

From the senses: visual impairment, disorders of the vestibular apparatus (dizziness), hearing impairment.

From the hematopoietic system: leukopenia or leukocytosis, thrombocytopenia, decreased hematocrit.

Others: shortness of breath, malaise, weakness, fever, sweating, chills, loss of appetite, transient increase in the activity of hepatic transaminases.

Due to the large T1/2 of mefloquine, side effects can develop or persist up to several weeks after the last dose of the drug.