Isoniazid

The drug "Isoniazid" is one of the effective means to combat pathogens of such a serious disease as tuberculosis, regardless of the form and localization of the latter. But tuberculosis is considered one of the most common infectious diseases in the world, which affect both animals and humans. Moreover, you can become infected with the disease in various ways: airborne during verbal communication with a sick person or being in close proximity to him, while eating meat from animals affected by the disease or contaminated products, through direct contact with a bacterial infection, in utero.

In the absence of vaccination or vaccination without taking into account contraindications, it will not be difficult to get tuberculosis, but getting rid of it is much more difficult. This is where Isoniazid comes to the rescue.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ]

Indications Isoniazid

In most cases, tuberculosis affects the respiratory system, giving preference to the lungs, bronchi, and pleura.

Treatment with Isoniazit is indicated for any active form of pulmonary tuberculosis: disseminated, miliary, focal, infiltrative, cavernous, fibro-cavernous, cirrhotic, caseous pneumonia and tuberculoma (caseous tuberculosis).

Slightly less frequently, tuberculosis affects the joints and bones in the spine. In some cases, doctors diagnose other types of tuberculosis affecting the gastrointestinal tract (mainly the small intestine and the "cecum"), the genitourinary system (kidneys, urinary tract, genitals), the brain and central nervous system (the brain and spinal cord itself, the dura mater of the brain, when they say that tuberculous meningitis is developing), eyes, skin, lymph nodes. In these cases, therapy with this drug may also be prescribed.

Indications for the use of the drug "Isoniazid" are considered to be various forms in which tuberculosis can occur. This can be either primary (during infection entry into the body) or secondary (complication of an existing pathology) infection, acute and chronic active form of pathology, open and closed tuberculosis.

Isoniazid is also used for preventive purposes:

• To prevent disease in people who have had contact with patients with active tuberculosis,
• If there is a positive reaction to tuberculin in the form of redness and compaction after vaccination of more than 5 mm in size, and an X-ray confirms the presence of a non-progressive process,
• If the reaction to the tuberculosis test in children under 4 years of age is more than 1 cm and there is a possibility of further development of the inflammatory process in the lungs or other organs.

For the treatment of tuberculosis, the drug is most often prescribed as part of complex therapy. If there is a mixed infection, antibiotics and other drugs are added to anti-tuberculosis drugs.

Sometimes "Isoniazid" is used for other purposes, for example, to exterminate dogs. This is due to the fact that in large doses the drug has a high toxic effect.

[ 6 ], [ 7 ], [ 8 ]

Release form

The main active ingredient of the drug "Isoniadide" is a white powder with a bitter taste and the same name, which has a selective effect on bacteria that cause tuberculosis.

The following forms of the anti-tuberculosis drug "Isoniazid" are available:

• Tablets with a dosage of 100, 200 and 300 mg
• 10% isoniazid solution in ampoules (volume 5 ml)
• Powder substance for solution preparation.

Tablets with different dosages, containing isoniazid plus auxiliary substances (surfactant polysorbate 80, calcium stearate, crospovidone, which improves the dissolution of tablets, potato starch), are packaged in 10 pieces in blisters, which can be placed in cardboard boxes (from 5 to 100 blisters in each).

You can also find Isoniazid tablets on sale in a dark glass jar (number of tablets – 100 pcs.).

The injection solution contains 500 mg of the active substance. The auxiliary substance is water for injection. It is produced in cardboard boxes with 10 ampoules in each.

The powder for the solution is not intended for home use. It is packed in large polyethylene bags. The net weight of a bag with powder is 25 or 50 kg.

You can buy tablets and injection solution at the pharmacy. But for this you will need a prescription from a doctor with his signature and seal, as well as a stamp of the medical institution.

[ 9 ], [ 10 ], [ 11 ], [ 12 ], [ 13 ]

Pharmacodynamics

Isoniazid is a popular anti-tuberculosis drug based on an isonicotinic acid derivative.

The culprit of the development of various forms and types of tuberculosis is considered to be mycobacterium (Mycobacterium tuberculosis). It is in relation to this type of bacteria that the active substance of the drug exhibits a bactericidal effect, while it is neutral to other microorganisms. The chemotherapeutic effect in relation to other infectious agents is weakly expressed.

Isoniazid pays special attention to mycobacteria in a state of active reproduction, which occurs through cell division. It is assumed that the drug negatively affects the synthesis of mycolic acids, which are components of the bacterial cell wall, as a result of which the microorganisms die.

[ 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ]

Pharmacokinetics

Isoniazid is characterized by almost complete absorption after entering the digestive tract when administered orally. It easily enters all kinds of tissues and fluids of the body, and also has a unique ability to penetrate the protective (hematocephalic) barrier of the brain, exerting a bactericidal effect on bacteria that have entered the brain.

It takes 1 to 4 hours after taking the tablets to reach the maximum concentration of the drug in the blood plasma, and its effect on pathogenic microorganisms after taking a single dose can last from 6 to 24 hours.

Isoniazid is metabolized in the liver by acetylation, which produces inactive substances. The drug is excreted from the body mainly by the kidneys. The half-life of the drug is:

• with a fast metabolism, which is a physiological feature of patients, from half an hour to an hour and a half,
• at a slow pace – about 2-5 hours,
• In severe cases of kidney failure it can reach 6 or even 7 hours.

[ 19 ], [ 20 ], [ 21 ], [ 22 ], [ 23 ]

Dosing and administration

The drug "Isoniazid" can be administered in various ways:

• orally (tablets for internal use),
• intravenously
• intramuscularly
• by inhalation
• intracavernous method, when the solution is delivered directly to the affected area where necrotic processes are observed.

The attending physician selects an effective method. He also determines the effective dose of the drug, as well as the duration of the therapeutic course, based on the severity of the disease, the condition and age of the patient.

The prescription and dose adjustment of the drug is carried out taking into account the characteristics of the patient's body, which determine the rapid or slow elimination of isoniazid through the blood and urine, in connection with which it may be necessary to increase the dosage or frequency of administration.

The dosage also depends on the route of administration of the drug and is calculated based on the patient's body weight.

Treatment with tablets for oral administration. The recommended average daily dose for adult patients is 15 mg per kilogram of weight. At this dosage, the drug should be taken once every 2-3 days. Sometimes daily tablet intake is prescribed at a maximum daily dose of 300 mg.

For children, the effective daily dose may range from 20 to 40 mg per 1 kg of weight, provided that the drug is taken 2 or 3 times a week. If the drug is taken daily, the daily dose will be 10-20 mg.

The frequency of administration will depend on the rate of isoniazid metabolism in the liver. The course of treatment is quite long, can reach 6 months.

Tuberculosis prevention is carried out only with the help of tablets. The recommended daily dose is 5-10 mg per 1 kg of the patient's weight. Tablets are taken 1 or 2 times a day.

If the patient with active forms of tuberculosis cannot use oral medications, for example, due to gastrointestinal pathologies, he is prescribed intravenous or intramuscular injections. The injection method of administering the drug is recommended for the treatment of adult patients with various types and forms of tuberculosis, but is not excluded in the treatment of young patients.

In this case, the effective single dose for intramuscular administration for adults is 5 mg per 1 kg of body weight. Injections should be given once a day.

Another treatment regimen is possible, when injections are given once every 2-3 days. Then the single dose is 15 mg per kilogram of the patient's weight.

For children, the effective single dose will be from 20 to 40 mg per kilogram of weight (for a once-every-2-3-day regimen) and from 10 to 20 mg (for daily administration once a day).

Intravenous administration of the drug "Isoniazid" is indicated for widespread forms of pulmonary tuberculosis with an increased level of infectivity. The daily dosage for adults is 10-15 mg per 1 kg of body weight. After the administration of the drug, the patient is recommended to stay in bed for about 1-1 ½ hours.

For intracavernous administration in forms of pulmonary tuberculosis with the formation of necrotic areas, as well as in preparation for surgical intervention, the same 10% solution of the drug is used as for intravenous and intramuscular injections. The effective dosage is 10-15 mg per kilogram of the patient's body weight.

Inhalations with a 10% solution are done daily. The daily dose will be 5-10 mg per 1 kg of weight. It is sometimes recommended to divide the daily dose into 2 doses.

In order to reduce the manifestation of side effects, in parallel with the introduction of Isoniazid, therapy with Pyridoxine (60-100 mg) and glutamic acid (1-1.5 g per day) is carried out.

The course of treatment usually lasts from 1 month to six months, the prophylactic course is about 2 months.

[ 30 ], [ 31 ], [ 32 ], [ 33 ], [ 34 ], [ 35 ], [ 36 ]

Use Isoniazid during pregnancy

The use of the drug "Isoniazid" during pregnancy implies taking the drug in a limited dosage (no more than 10 mg per 1 kg of the body weight of the expectant mother) and strictly according to the doctor's instructions. Exceeding the dose is fraught with intoxication of the fetus in the womb, the consequences of which can be very diverse, but definitely unpleasant.

Contraindications

It is prohibited to treat tuberculosis with the drug "Isoniazid" if the patient has the following pathologies:

• Severe forms of vascular atherosclerosis, in which harmful cholesterol is deposited in the lumen of the arteries
• Various serious liver pathologies, including previous cases of toxic hepatitis
• Severe renal failure
• The patient has a history of seizures or epilepsy
• Spinal cord paralysis, known to many as polio

The dosage of the drug is limited for diseases such as

• Hypertension (consistently high blood pressure) stages 2 and 3
• IHD
• Bronchial asthma
• Destruction (cirrhosis) of the liver
• Acute stage of eczema
• Various pathologies of the optic and peripheral nerves
• Psoriasis
• Widespread atherosclerosis
• Myxedema, or mucous edema, is the final stage of thyroid failure.
• And also at the stage of decompensated pulmonary heart disease.

The drug in the form of an injection solution is not used for inflammation of the venous vessel wall (phlebitis).

The drug therapy is not carried out if the patient has hypersensitivity to any of its components.

Pregnancy and childhood are not contraindications to the use of anti-tuberculosis drugs.

[ 24 ], [ 25 ], [ 26 ], [ 27 ]

Side effects Isoniazid

Therapy with the drug "Isoniazid" is not always cloudless. Sometimes various side effects from the organs and systems of the body are observed.

The cardiovascular system may react to the administration of the drug:

• increased blood pressure, including pulmonary pressure,
• heart pains,
• increased heart rate,
• symptoms of angina pectoris,
• increased ischemic processes in the heart muscle.

The nervous system can give its symptoms in the form of:

• intoxication psychosis,
• generalized convulsive seizures characteristic of epilepsy,
• tingling and numbness in various parts of the body, paralysis of the limbs,
• headaches and dizziness,
• multiple nerve damage due to intoxication when using large doses of the drug,
• inflammation or decreased function of the optic nerve,
• organic brain damage of a non-inflammatory nature, called encephalopathy,
• increased excitability,
• irritability and insomnia,
• inflammation of peripheral nerves
• temporary partial memory loss, etc.

From the gastrointestinal tract, the following unpleasant effects can be expected:

• nausea accompanied by vomiting,
• dryness of the mucous membranes of the mouth,
• hepatitis caused by the toxic effect of the drug,
• increased activity of some enzymes (ALT and AST) and increased production of bilirubin,
• initial symptoms of developing hepatitis,

The genitourinary system will remind you of itself:

• rare cases of menorrhagia (heavy periods) in women,
• dysmenorrhea (severe pain accompanying menstrual flow),
• enlargement and swelling of the mammary glands in women and men.

Various changes in the composition and properties of the blood, skin allergic reactions, fever, short-term muscle spasms manifested as twitching, inflammation of the venous wall during intravenous administration, muscle weakness, etc. are also possible.

[ 28 ], [ 29 ]

Overdose

The phenomenon of overdose with the drug "Isoniazid" may occur if the therapy is carried out in high doses, most often due to the fault of the patient himself, who believes that increased doses will speed up recovery.

A single intake of large doses can cause the development of such pathologies as:

• metabolic acidosis (increased acidity of the body),
• severe epileptic seizures,
• coma.

Mild intoxication will make itself known within half an hour after taking the drug in the form of increased heart rate, nausea and vomiting, dizziness and speech disorders.

In case of acute intoxication (20 mg or more per 1 kg of weight), its manifestations will be immediately noticeable in the form of epileptic seizures.

The following reactions are observed: increased body temperature, decreased blood pressure, the appearance of acetone in the urine, increased sugar levels in the blood and urine, renal failure, psychosis, ataxia, hallucinations.

In severe cases, a coma occurs for a period of 1 to 1.5 days.

With prolonged therapy in maximum doses, chronic overdose occurs, as a result of which the number of active hepatocytes decreases. At first, this manifests itself as an increase in AST and ALT indicators, and then in some cases, the development of hepatitis affecting the liver is diagnosed.

It is also possible that other pathologies may develop during treatment with increased doses. For example, optic neuritis with deterioration of visual perception or polyneuropathy as a result of damage to the peripheral nerves. Polyneuropathy manifests itself as loss of sensitivity in the hands and feet, muscle weakness, and ataxia.

In mild intoxication, only a dose adjustment and gastric lavage followed by administration of activated carbon may be required. The development of drug-induced hepatitis requires discontinuation of the drug.

If the symptoms of intoxication are clearly expressed and accompanied by convulsions, acid metabolism disorders, coma, intravenous sodium bicarbonate is used as first aid. To remove the remains of isoniazid from the gastrointestinal tract, the use of enterosorbents, in particular activated carbon, is indicated.

Neurological symptoms require different treatment. To reduce them, use Pyridoxine (both for prevention and for overdose treatment) and benzodiazepines (Diazepam). Pyridoxine is administered in the same dosage as the taken isoniazid. If the dosage of Isoniazid could not be determined, then the dosage of Pyridoxine for adults will be from 5 to 10 mg (for children - at the rate of 80 mg per 1 kg of weight).

[ 37 ], [ 38 ], [ 39 ], [ 40 ], [ 41 ]

Interactions with other drugs

Parallel administration of Paracetamol, Enflurane and Rifampicin during isoniazid therapy may increase the toxic effect of these drugs on the liver, resulting in an increased risk of drug-induced hepatitis. This combination is especially dangerous for patients with various liver pathologies.

But ethanol can speed up metabolism and increase the hepatotoxicity of isoniazid itself. Glucocorticosteroids can also speed up metabolism and reduce the concentration of isoniazid in the blood.

"Isoniazid" reduces the metabolism of "Theophylline", "Ethosuximide", "Phenytoin", "Carbamazepine", "Alfentanil", benzodiazepines, coumarin or indandione derivatives and indirect anticoagulants, as a result of which their concentration in the blood and therapeutic effect can increase significantly. At the same time, the toxic effect of the drugs also increases.

Taking Isoniazid simultaneously with other tuberculosis medications (Cycloseryl, etc.) causes a mutual enhancement of their effects. The central effects of isoniazid are also enhanced by the drug for treating alcohol dependence, Disulfiram.

Isoniazid can reduce the plasma concentration of Ketoconazole and increase the blood content of valproic acid, which requires dose adjustment.

When taken orally, antacids to reduce gastric acidity may reduce the absorption of isoniazid.

Pyridoxine, Diazepam, Thiamine and glutamic acid are able to reduce the neurotoxic effect of isoniazid.

[ 42 ], [ 43 ], [ 44 ], [ 45 ], [ 46 ], [ 47 ], [ 48 ]

Storage conditions

Thus, tablets and powder sealed in dark glass jars can be stored at room temperature (not higher than 25 degrees) and preferably away from light.

But ampoules with solution require maintaining a storage temperature of no higher than 10 degrees. It is also recommended to store them away from sunlight.

Solutions prepared from powder are also stored at temperatures up to 10 degrees.

[ 49 ], [ 50 ], [ 51 ], [ 52 ], [ 53 ], [ 54 ]

Shelf life

The tablets have a shelf life of 6 years if stored properly.

The ampoules have a shelf life of 2 years if stored properly.

The shelf life of freshly prepared Isoniazid solutions is only 1-2 days.

[ 55 ], [ 56 ]