MAK-PAS plus - instructions for use, dose, side effects, contraindications

Active substanceAminosalicylic acid + IsoniazidAminosalicylic acid + Isoniazid

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Isopascus

pills inwards

FARMASINTEZ, JSC (Irkutsk) Russia

IAC-PAS Plus

granules inwards

McLeodz Pharmaceuticals Co., Ltd. India

Dosage form: & nbspgranules coated with enteric coating, pineapple

Composition:

1 g of granules contains:

Active substances:

Sodium aminosalicylate dihydrate 800.0 mg.

Isoniazid 23.3 mg.

Excipients:

vegetable hydrogenated water (1.30 mg), crospovidone (27.22 mg), sodium disulfite (8.0 mg), microcrystalline cellulose (34.4 mg), methylcellulose (15.0 mg), quinoline yellow dye (0, 45 mg).

Composition of the shell of granules: ethyl cellulose (2.16 mg), stearic acid (19.18 mg), dibutyl phthalate (6.208 mg), methyl acrylate and methyl methacrylate type B copolymer (56.08 mg), titanium dioxide (1.68 mg), quinolinoline yellow dye (0.135 mg), vegetable hydrogenated oil (1.48 mg), pineapple flavour (1.35 mg).

Description:

Granules of cylindrical (rod-like) form of various sizes from pale yellow to bright yellow with a fruity smell.

Pharmacotherapeutic group:Anti-tuberculosis means combined

ATX: & nbsp

J.04.A.C.01 Isoniazid

J.04.A.A.01 Aminosalicylic acid

Pharmacodynamics:

Aminosalicylic acid. It acts bacteriostatically. Competitively suppresses the synthesis of folate in a bacterial cell.Slightly affects the pathogen, located intracellularly. Under the influence of gastric juice aminosalicylic acid quickly turns into an inactive metabolite. Acid-resistant shell protects the granules from the destructive effects of gastric juice. In a neutral environment, for example, in the small intestine, the granule membrane dissolves and the drug releases.

Isoniazid in vivo and in vitro acts bactericidal on the process of cell division M.tuberculosis. The primary mechanism is to inhibit the synthesis of long chain mikolievyh acids which are part of the cell wall of mycobacteria.

To inhibit Gram-positive and Gram-negative bacteria, an isoniazid concentration of at least 600 mg / ml is required, and the minimum concentration for inhibition M.tuberculosis is 0.05-0.025 mg / ml. Resistance to isoniazid is manifested spontaneously and amounts to the growth of mutant bacilli, equal to 1 x 10⁶ bacteria on generation.

Pharmacokinetics:

Aminosalicylic acid. Characterized by high absorption; moderately penetrates into the cerebrospinal fluid (only with inflammation of the meninges).Easily passes other histohematological barriers and is distributed in tissues. Binding to proteins - 50-60 %. After a single dose of 4.0 g, the concentration of the drug in the plasma is 20 mg / ml (it can vary from 9 to 35 mg / ml). The mean time to reach the maximum plasma concentration (Tcmax) is 6 hours (varies from 1.5 to 24 hours). The concentration of the drug 2 mg / ml in plasma persists for 7.9 hours (variability from 5 to 9 hours), and 1 mg / ml - on average, for 8.8 hours (variability from 6 to 11.5 hours).

Metabolised, half the dose is determined in the urine in the form of an acetylated derivative. Half-life (T_1/2) is 30 minutes. The total clearance depends on both the metabolic rate and the excretion of the kidneys. 80% of aminosalicylic acid is excreted by the kidneys, while 50% or more is excreted in the acetylated form. Isoniazid quickly and completely absorbed when ingested, food reduces absorption and bioavailability. The effect of "first passage" through the liver has a great influence on the bioavailability index. Time to reach the maximum concentration of the drug in the blood plasma (T_Сmах) - 1-2 hours The maximum concentration of the drug in the blood (T_Сmах) after oral administration of a single dose of 300 mg - 3-7 μg / ml. The connection with proteins is insignificant - up to 10%. The volume of distribution is 0.57-0.76 l / kg. Well distributed throughout the body, penetrating all tissues and fluids, including spinal, pleural, ascitic; high concentrations are created in the lung tissue, kidneys, liver, muscles, saliva and sputum. Penetrates through the placental barrier and into breast milk. It is metabolized in the liver by acetylation with the formation of inactive products. The liver is acetylated with N-acetyltransferase to form N-acetylisoiniazide, which is then converted to isonicotinic acid and monoacetylhydrazine, which has a hepatotoxic effect by forming a mixed oxidase system of cytochrome P450 upon N-hydroxylation of the active intermediate metabolite. The rate of acetylation is genetically determined; in people with "slow" acetylation, there is little N-acetyltransferase. It is an inhibitor of CYP2C9 and CYP2E1 isoenzymes in the liver.

Half-life (T_1/2) for "fast acetylators" is 0.5-1.6 hours; for "slow" - 2-5 hours With renal failure T_1/2 can increase to 6.7 hours. T_1/2 for children aged 1.5 to 15 years - 2.3-4.9 hours, and in newborns - 7.8-19.8 hours (which is due to the imperfection of the processes of acetylation in newborns). Despite the fact that the indicator T_1/2 varies considerably depending on the individual intensity of the acetylation processes, the average value T_1/2 is 3 hours (intake of 600 mg) and 5.1 hours (900 mg). With repeated appointments T_1/2 is shortened to 2-3 hours. It is excreted mainly by the kidneys: within 75 hours 75-95 % of the drug, mainly in the form of inactive metabolites - N-acetylisiniazide and isonicotinic acid. At the same time, "fast acetylators" contain N-acetylisiniazide content of 93%, while "slow" - not more than 63%. Small amounts are excreted with feces. The drug is removed from the blood during hemodialysis; Hemodialysis, conducted for 5 hours, allows you to remove from the blood to 73% of the drug.

Indications:Tuberculosis of various forms and localizations with multiple drug resistance, acutely progressive, widespread pulmonary tuberculosis.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- Kidney and liver diseases (chronic renal failure, hepatic insufficiency, hepatitis, cirrhosis of the liver);

- Peptic ulcer of stomach and duodenum, enterocolitis (exacerbation);

- Amyloidosis of internal organs;

- Myxedema (exacerbation);

- Epilepsy;

- Poliomyelitis (including in history);

- Chronic heart failure;

- Thrombophlebitis;

- Hypocoagulation;

- Psoriasis;

- Children under 3 years old or weighing less than 30 kg;

- Lactation period.

Carefully:

With caution, the drug is used with concomitant diseases of the gastrointestinal tract, amyloidosis, decompensated diseases of the cardiovascular system, hypothyroidism, patients over 60 years old and weighing less than 50 kg, patients with a history of cramps and alcoholism.

Pregnancy and lactation:

The use of the drug Mak-Paz plus in pregnancy is possible if the expected benefit for the mother exceeds the potential risk to the fetus.

If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Assign inside the form of granules, which should be taken after meals, washed down with water, 2-3 times a day. Adults 9-12 g per day or as prescribed by the doctor (at the rate of 10 mg / kg body weight per day for aminosalicylic acid).Children older than 3 years (for this dosage form) from the calculation of 0.2 mg / kg body weight per day for aminosalicylic acid, but not more than 10.0 g. For ease of use, a sufficient amount of water can be added to the required amount of water, well shake and drink the resulting mixture.

To the packing 100,0 g for the convenience of dosing is attached a measuring spoon.

Each measuring spoon (total 4.3 g of granules) contains:

Sodium aminosalicylate dihydrate 3.44 g, Isoniazid 0.1 g

It is also recommended to take isoniazid 0.3 g once after breakfast. Used in combination with more active anti-TB drugs.

Features of the drug at the first admission or when it is canceled

The drug does not have the features of the action at the first reception or upon its cancellation.

Description of the actions of the medical worker and patient if one or several doses of the drug are missed

You should not stop prematurely or temporarily discontinue the course of treatment started, and also take the medication irregularly.

If you miss a single dose, take the next dose of the drug at the set time, or, in consultation with your doctor, take the next dose at a time when you remembered taking the drug,smoothly shifting the next time the drug is taken; do not take twice the dose of the drug.

Side effects:

Determination of the frequency of adverse reactions: often (> 1/100 and <1/10), sometimes (> 1/1000 and <1/100), rarely (> 1/10 000 and <1/1000), very rarely (<1 / 10 000).

Adverse reactions are possible as a result of the action of individual active components included in the drug.

Aminosalicylic acid

Decreased appetite, nausea, vomiting, flatulence, abdominal pain, diarrhea or constipation, hepatomegaly, increased activity of "liver" transaminases, hyperbilirubinemia; proteinuria, hematuria, crystalluria, malabsorption syndrome.

Rarely, thrombocytopenia, leukopenia (up to agranulocytosis), drug-induced hepatitis, B₁₂-deficient megaloblastic anemia.

Allergic reactions: fever, dermatitis (urticaria, purpura, enanthema), eosinophilia, arthralgia, bronchospasm.

With prolonged use in high doses - hypothyroidism, goiter, myxedema.

Isoniazid

From the nervous system: headache, dizziness, rarely excessive fatigue or weakness, irritability, euphoria, insomnia, paresthesia, numbness of limbs, peripheral neuropathy, optic neuritis, polyneuritis, psychosis, mood change, depression. In patients with epilepsy, convulsions may become more frequent.

From the side of the cardiovascular system: palpitation, angina, increased blood pressure.

From the digestive system: nausea, vomiting, gastralgia, toxic hepatitis.

Allergic reactions: skin rash, itching, hyperthermia, arthralgia.

Other: very rarely - gynecomastia, menorrhagia, a tendency to bleeding and hemorrhage.

Overdose:

Symptoms: may increase dose-related side effects.

Treatment: withdrawal of the drug, symptomatic therapy (including: washing stomach, reception of activated carbon and laxatives, osmotic diuretics, forced diuresis, hemodialysis).

Interaction:

Aminosalicylic acid

Compatible with other antituberculous drugs.

It is not recommended to have a joint reception with rifampicin, since aminosalicylic acid reduces its concentration. If you need co-therapy with rifampicin, taking medications should be divided: rifampicin before breakfast, sodium aminosalicylate after dinner and overnight.

Violates the absorption of erythromycin and lincomycin.

Disrupts the assimilation of cyanocobalamin (vitamin B₁₂) (risk of developing anemia).Suction of Vitamin B₁₂ when taking 5.0 g of aminosalicylic acid is disrupted by 55%, which leads to significant changes in erythrocytes. Thus, when treating patients with aminosalicylic acid for more than 1 month, vitamin therapy is necessary B₁₂.

Isoniazid

When combined with paracetamol, hepato- and nephrotoxicity increases; isoniazid induces a system of cytochrome P450, which increases the metabolism of paracetamol to toxic products.

Ethanol increases the hepatotoxicity of isoniazid and speeds up its metabolism.

Reduces metabolic transformations and increases the concentration in the blood of alfentanil. Cycloserine and disulfiram enhance the adverse effects of the central nervous system.

Increases hepatotoxicity of rifampicin.

The combination with pyridoxine reduces the risk of peripheral neuritis and side reactions from the central nervous system. Caution should be combined with potentially neuro-, hepato- and nephrotoxic drugs because of the risk of side effects.

Strengthens the action of coumarin and indanedione derivatives, benzodiazepines, carbamazepine, theophylline, as it reduces their metabolism by activating the cytochrome P450 system.

Glucocorticosteroids accelerate metabolism in the liver and reduce the active concentration of isoniazid in the blood.

It suppresses the metabolism of phenytoin, which leads to an increase in its concentration in the blood and an increase in the toxic effect (correction of the dosing regimen of phenytoin may be necessary, especially in patients with slow acetylation of isoniazid). Antatsida (especially aluminum-containing) slows down absorption and reduces the concentration of isoniazid in the blood (antacids should be taken no earlier than 1 hour after taking isoniazid).

When used simultaneously with enflurane isoniazid can increase the formation of inorganic fluoride metabolite, which has a nephrotoxic effect.

Reduces the concentration of kegonazole in the blood.

Isoniazid - an antagonist of hypoglycemic action of insulin, it increases the concentration of glucose in the blood.

Special instructions:

Alcohol and drug intake are incompatible.

Possible damage to the liver and kidneys due to the drug. Careful observation of patients during the first three months of therapy is necessary. Laboratory indicators - alanine aminotransferase, aspartate aminotransferase, serum bilirubin concentration can transiently increase without clinical manifestations.

When there are signs of toxic hepatitis caused by the drug, it is canceled. Decreased kidney function against tuberculous intoxication or specific damage is not a contraindication to the appointment. The development of proteinuria and hematuria require a temporary discontinuation of the drug.

In connection with the different metabolic rate before the use of isoniazid, it is expedient to determine the rate of its inactivation (by the dynamics of the content in the blood and urine). With rapid inactivation isoniazid used in higher doses.

At a risk of peripheral neuritis (patients over 65, patients with diabetes, pregnant women, patients with chronic renal failure in remission, alcoholics, eating disorders, concomitant anticonvulsant therapy), 10-25 mg / day of pyridoxine is recommended.

During the treatment, you should avoid eating cheese (especially Swiss or Cheshire), fish (especially tuna, sardinella, skipjack), since with the simultaneous use of them with isoniazid may cause reactions (skin hyperemia, itching, sensation of heat or cold, palpitations, increased sweating, chills, headache, dizziness) associated with the suppression of monoamine oxidase and diaminoxidase activity and leading to a disruption of the metabolism of tyramine and histamine contained in fish and cheese.

It should be borne in mind that isoniazid can cause hyperglycemia with secondary glucosuria; tests with the reduction of copper ions can be false positive, and the enzyme tests for glucose drug does not affect.

Special precautions for the destruction of an unused medicinal product or a drug with an expired shelf life is not required.

Effect on the ability to drive transp. cf. and fur:

The ability of the drug to influence the speed of psychomotor reactions and the ability to control transport or other technical means has not been studied. Care should be taken when dealing with potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

Form release / dosage:

Granules coated with enteric coating, pineapple, 800 mg / 23.3 mg per 1 g.

Packaging:

For 100 g of the drug in aluminum bags, laminated from the outside, tightly sealed.Each package in a plastic container together with instructions for use and a measuring spoon. The container is sealed with an aluminum membrane, the top is closed with a plastic cover.

By 4.3 g or 5.0 g of the drug in aluminum bags laminated from the outside. For 10, 25, 50 or 100 bags, together with instructions for use in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000301/10

Date of registration:25.01.2010 / 18.05.2012

Expiration Date:Unlimited

The owner of the registration certificate:McLeodz Pharmaceuticals Co., Ltd. McLeodz Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

MACLEODS PHARMACEUTICALS, Ltd. India

Representation: & nbspAdvansd Trading, OOOAdvansd Trading, OOO

Information update date: & nbsp25.03.2018

Illustrated instructions

Instructions

IAC-PAS Plus (MAC-PAS plus)