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primobolan depot

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

 Falciparum may develop resistance to mefloquine, mainly in Southeast Asia. In some regions, marked cross-resistance between mefloquine and halofantrine, mefloquine and quinine.

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

Pharmacokinetics

Suction

The absolute bioavailability after oral administration of mefloquine has not been evaluated (no intravenous form of release). Bioavailability tablet form is more than 85% of that ingestion of the solution. Eating significantly accelerate the speed and increase the extent of absorption by 40%. The mean time to maximum concentration of mefloquine after a single reception – 17 hours (6-24 hours). Maximum plasma concentrations in g / L roughly equal to the dose in mg (e.g., 1000 mg single dose gives a maximum concentration of about 1000 mg / L). After receiving the 250 mg once a week equilibrium maximum plasma concentration equal to 1000-2000 mg / l is reached after 7-10 weeks. To achieve 95% efficiency mefloquine prophylaxis necessary blood concentration, equal to 620 ng / ml.

Distribution

Mefloquine volume of distribution of 20 l / kg, indicating that the tissue penetration of many drug. It accumulates in erythrocytes, in which malaria parasites are at concentrations approximately twice the plasma. It penetrates through the placenta and breast milk. Excretion in breast milk appears to be minimal (see. “Pregnancy and lactation” section). Communication preparation with 98% of the plasma proteins.

Metabolism

The metabolism of mefloquine mostly in the liver, with the participation of cytochrome P450. The in vitro and in vivo studies have shown that mefloquine metabolized mainly isoenzyme CYP3A4 metabolites to form 2: the main metabolite – 2,8-bis-trifluoromethyl-4-quinoline karboksikisloty and alcohol. The primary metabolite is inactive against P. falciparum, appears in the plasma within 2-4 hours after a single oral administration of the drug, its maximum concentration in the plasma by 50% higher than those achieved mefloquine and 2 weeks. Thereafter, the main metabolite concentrations decrease and of mefloquine in the plasma at the same rate. The area under the curve “concentration-time” of the main metabolite is 3-5 times higher than for the original formulation. Another metabolite of alcohol, is present in very small amounts.

breeding

The average half-life of mefloquine – 3 weeks (2 to 4 weeks) does not change during long-term prevention of malaria. Displays in the form of metabolic products mainly in the bile and feces. Total clearance, most of which is liver, equal to 30 ml / min. Excretion of unchanged mefloquine and its major metabolite in the urine is about 9% and 4%, respectively. Other metabolites in urine can not be detected.

Pharmacokinetics in special cases

Children and elderly patients

Age did not affect the pharmacokinetics of mefloquine.

kidney failure

Pharmacokinetic studies in patients with renal impairment have not been conducted since the kidneys displayed a very small amount of the drug. In any significant quantities of mefloquine and its main metabolite by hemodialysis is not deduced. No dose adjustment for patients on hemodialysis are required.

Liver failure

Patients with hepatic impairment elimination of mefloquine may be delayed, resulting primobolan depot in increased plasma concentrations of the drug.

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

Race

Pharmacokinetic differences have very little clinical significance in comparison with the immune status of the infected patient and pathogen sensitivity.

testimony

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

Prevention of malaria in those who depart in dangerous regions of malaria, especially in areas with high risk of infection with strains of P. falciparum, resistant to other antimalarials.

Emergency treatment (self-help): self-administration as an emergency treatment for suspected malaria when to receive urgent medical treatment is not possible.

Contraindications

Hypersensitivity to mefloquine, any components of the drug, or close to it drugs (quinine, quinidine).
Co-administration with halofantrine, taking halofantrine after mefloquine therapy for 15 weeks after discontinuation of the latter.
Co-administration with ketoconazole, receiving ketoconazole after mefloquine therapy for 15 weeks after discontinuation of the latter.
The depression, psychosis, schizophrenia, anxiety, seizures (including history).

 

Carefully

Hepatic insufficiency, during lactation, epilepsy, mental illness, the age of 6 months, weighing up to 5 kg, heart disease, age older than 65 years. In combination with quinine and quinidine.

 

Pregnancy and lactation

The drug is a category C (classification FDA – US Food and Drug Administration).

When assigning mefloquine in doses 5-20 times higher than therapeutic for humans, it is teratogenic in mice and rats and embryotoxic effect in rabbits. However, clinical experience with the drug Lariam ® did not show him any embryotoxic or teratogenic effects. Nevertheless, Lariam ® should be administered during the first trimester of pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Women of reproductive age should be given treatment only if the use of reliable contraception during the entire time receiving mefloquine and 3 months after the last dose. But in the event of pregnancy with chemoprophylaxis of malaria drug  indication for its interruption there.

Activity mefloquine small amounts falling in breast milk is unknown. When lactation the drug is prescribed only if the expected benefit to the mother outweighs the potential risk is not a child. In breast-fed infants whose mothers took, adverse reactions are noted.

Dosing and Administration

Inside, after meals, with plenty of fluids (not less than 200 ml) to 2-3 hours.

Mefloquine primobolan depot has a bitter and slightly burning taste. The tablets should be swallowed whole. When assigning children or people who can not swallow the tablet whole, it can be crushed and dissolved in a small amount of water, milk or other drink.

Until the reception of a tablet should not be removed from the blisters, since they are sensitive to moisture.

prevention

Adults and children weighing more than 45 kg – 5 mg / kg (250 mg, 1 tablet) 1 time per week. Adults and children weighing 30-45 kg – 3/4 a tablet; 20-30 kg – 1/2 a tablet; 10-20 kg – 4.1 tablets and 5.10 kg of body weight -. 1.8 tablets (tablets approximate proportion of 5 mg / kg body weight The exact dosage for children weighing less than 10 kg should be possible to prepare issued and pharmacists).

Weekly dose Lariam ® should be always in the same day of the week. The first time the drug should be taken at least one week before arrival in the malaria-endemic area. If this is not possible, you must assign a loading dose of the drug, consisting of weekly doses of the drug Lariam ® , for 3 consecutive days and then switch to the standard dose regimen. To reduce the risk of malaria after leaving an endemic region, prophylaxis was continued for 4 weeks. If the patient is taking other drugs, it is desirable to start prophylaxis 2-3 weeks prior to departure to ensure good tolerability of concomitant medications.

 

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Blocks the synthesis final stage of hydrochloric acid to decrease both basal and stimulated secretion regardless of the nature of the stimulus. With highly lipophilic, easily penetrates the gastric parietal cells, concentrated therein has a cytoprotective effect, increases the secretion of bicarbonates. Inhibition of production of hydrochloric acid at a dose of 30 mg – 80-97%. No effect on the motility of the gastrointestinal tract. The inhibitory effect of increases in the first four days of admission. The secretory activity is restored in 3-4 days after ingestion.

Pharmacokinetics. Absorption – high (eating reduces the absorption and bioavailability, but the inhibitory effect on gastric secretion remains the same, regardless of the meal). Occurrence of a maximum concentration (C max ) after oral administration of 30 mg – 1.5-2.2 hours C max – 0,75-1,15 mg / l. Connection with the plasma protein – 97,7-99,4%. Actively metabolized during the initial passage through the liver. Half-life of 1.3-1.7 h excretion by the kidneys (in the form of metabolites.) – 14-23%, and through the intestines. In hepatic insufficiency and in elderly patients elimination slows.

INDICATIONS

Gastric ulcer and duodenal ulcer.

  • Reflux esophagitis
  • Erosive – ulcerative lesions of gastric and duodenal ulcers associated with NSAID, stress ulcers
  • Erosive-ulcerative lesions of gastric and duodenal ulcers associated with Helicobacter pylori (in the complex therapy).
  • Ellison – Syndrome Zollinger.DOSAGE AND ADMINISTRATION
    The capsules should be swallowed whole without chewing. Peptic ulcer duodenal ulcer exacerbation – 30 mg daily for 2-4 weeks (in resistant cases up to 60 mg per day). Peptic ulcer in the acute phase and the erosive -yazvenny esophagitis – 30 -. 60 mg daily for 4-8 weeks Erosive and ulcerative lesions of the gastrointestinal tract caused by NSAIDs – 30 mg daily for 4-8 weeks. Eradication of Helicobacter pylori – on 30 mg 2 times day for 10-14 days in combination with antibacterial agents. anti-treatment of gastric ulcer and 12 duodenal ulcer -. 30 mg a day of anti-treatment of reflux esophagitis – 30 mg per day for a long time (up to 6 months). Zollinger-Ellison syndrome – the dose selected individually to achieve the level of basal secretion less than 10 mmol / h.

     

    SIDE EFFECTS
    Diarrhea, abdominal pain, constipation, headache, dizziness, drowsiness, pharyngitis, rhinitis, skin rashes, depression, myalgia, and allergic reactions.

    CONTRAINDICATIONS
    : Hypersensitivity to the drug, pregnancy, lactation, liver and / or kidney failure, children’s age.

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