Nevigramon® (Nevigramon®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceNalidixic acidNalidixic acid
Dosage form: & nbspcapsules
Composition:

1 capsule contains:

active substance: nalidixic acid - 500.0 mg;

Excipients: silicon colloidal dioxide - 19.0 mg, stearic acid-11.0 mg.

The composition of the capsule (body and lid): dye quinoline yellow (E 104) - 0.75%, dye sunset yellow (E 110) - 0.0059%, titanium dioxide (E 171) - 2.00%, gelatin to 100.00%.
Description:

The contents of the capsules are white to white powder with a yellowish hue of color.

Pharmacotherapeutic group:Antimicrobial agent, quinolone
ATX: & nbsp

J.01.M.B.02   Nalidixic acid

Pharmacodynamics:

Nalidixic acid selectively inhibits the function of the subunit A of the gyrase enzyme, which plays an important role in the synthesis of bacterial DNA. Suppression of gyrase function prevents the formation of a double helix of bacterial DNA or disrupts its location in a microbial cell, which leads to the destruction of the bacterium. The drug has bactericidal properties and a pronounced postantibiotic effect. In low concentrations nalidixic acid It acts only on multiplying microorganisms by suppressing DNA replication.The minimum inhibitory concentration (MIC) of nalidixic acid ranges from 5 to 75 μg / ml, but for bacteria that are sensitive to it nalidixic acid is effective even at a concentration of less than 10 μg / ml.

Nalidixic acid has a pronounced antimicrobial activity against gram-negative bacteria, such as Proteus mirabilis, Proteus morganii, Proteus vulgaris and Proteus rettgeri; Escherichia coli, Enterobacter (Aerobacter) spp. and Klebsiella spp.

The drug is ineffective in relation to Pseudomonas spp. and Gram-positive microorganisms.

When using the drug in microorganisms, resistance to nalidixic acid may develop, especially with prolonged intake of the drug, although resistance may develop during the first 48 hours of its administration.

There was cross-resistance between nalidixic acid and other quinolone derivatives, such as oxolinic acid, cinoxacin.
Pharmacokinetics:

Absorption

Nalidixic acid is rapidly absorbed from the gastrointestinal tract, its bioavailability is 96%. The maximum plasma concentration after taking 1 g of nalidixic acid on an empty stomach is achieved after 2 hours and is 20-50 μg / ml. Eating slows the absorption of nalidixic acid.

Distribution

The half-life of the plasma is 1 to 2.5 hours. The association with plasma proteins is about 93% for nalidixic acid and 63% for hydroxyanalidic acid (an active metabolite of nalidixic acid).

Nalidixic acid, along with its active metabolite, is rapidly excreted through the kidneys. After taking 1 g of nalidixic acid, its maximum concentrations in the urine are on average 150-250 μg / ml and are reached after 3-6 hours.

Nalidixic acid penetrates the placenta and is excreted in small quantities into the mother's milk.

Metabolism

Nalidixic acid is partially metabolized in the liver.

The active metabolite of nalidixic acid is hydroxyanaldihydric acid, which has antibacterial activity similar to nalidixic acid.

Excretion

Nalidixic acid and its active metabolite are excreted mainly by the kidneys, about 4% of nalidixic acid is excreted by the intestine.

Indications:

Infectious diseases caused by microorganisms sensitive to nalidixic acid.

  • Pyelonephritis, cystitis, urethritis, prostatitis.
  • Bacterial dysentery.
  • Prevention of infections during surgery or invasive diagnostic tests carried out on the kidneys, ureters, bladder.

Contraindications:
  • Known hypersensitivity to nalidixic acid or other components of the drug.
  • Epilepsy.
  • Parkinson's disease.
  • Severe form of cerebral arteriosclerosis.
  • Liver failure.
  • Deficiency of glucose-6-phosphate dehydrogenase (a risk of hemolysis).
  • Porphyria.
  • Children under 18 years of age (the risk of joint disorders during the growth of the skeleton, which until now have been shown only in animal experiments).
  • First trimester and last trimester of pregnancy. Breastfeeding period.
  • Simultaneous reception of bacteriostatic antibiotics (antagonistic interaction and loss of efficacy).
Carefully:

  • Simultaneous reception of indirect anticoagulants (possibly strengthening the effects of indirect anticoagulants).
  • Renal insufficiency with creatinine clearance less than 20 ml / min (dose reduction is required, see section "Method of administration and dose").

Pregnancy and lactation:

Safety of the drug Nevigramon® during pregnancy not installed. Apply the drug during pregnancy, it is possible second trimester of pregnancy and Only if the expected The benefits for the mother surpasses potential risk to the fetus. During the first trimester of pregnancy, it was shown that nalidixic acid in some species of animals it penetrates the placental barrier and is captured by growing cartilage, and in the last trimester of pregnancy its fetotoxic action is possible. Intrauterine nalidixic acid from the mother to the fetus can lead to the creation of high concentrations of nalidixic acid in the blood of the newborn.

Dosing and Administration:

Capsules Nevigramon® should be taken one hour before meals.

Patients with normal kidney function and with kidney failure with creatinine clearance greater than 20 ml / min

The average dose for adults (including the elderly) is 4 g (2 capsules (1 g) - 4 times a day) for 7-10 days. If it is necessary to take the drug longer (for another 7-10 days), its dose can be reduced to 1 capsule (0.5 g) - 4 times a day.

Patients with renal insufficiency with creatinine clearance less than 20 ml / min

When the creatinine clearance is less than 20 ml / min, the doses are reduced by a factor of 2.

Side effects:

Disturbances from the nervous system

Drowsiness, weakness, dizziness, vertigo, headaches, myalgia, paresthesia. Toxic psychosis or short-term convulsions and increased intracranial pressure, especially when using high doses. Typically, seizures were observed in patients with predisposing diseases, such as epilepsy or cerebral atherosclerosis.

Observed individual cases of paralysis of the sixth pair of cranial nerves, which is manifested by internal strabismus. The mechanism of these reactions is unknown, but the signs and symptoms of them are usually fast pass without consequences after discontinuation of the drug.

Disturbances on the part of the organ of sight

Reversible subjective visual impairment without objective damage to the organ of vision, such as excessive brightness color perception, color irregularityperception, difficulty focusing vision, loss of vision and diplopia (bifurcated image). Usually these effects quickly disappeared with a decrease dose or cancellation of the drug.

Disorders from the gastro-intestinal tract

Abdominal pain, nausea, vomiting and diarrhea; can develop gastrointestinal bleeding and cholestasis.

Disorders from the immune system system (allergic reactions)

Rash, itching, hives, eosinophilia, arthralgia with stiffness and swelling joints, angioedema, anaphylactic shock and anaphylactoid reaction.

Disturbances from the skin and subcutaneous tissue

Photosensitivity: redness and the appearance of bubbles on the skin arising under the influence of sunlight, completely passing during the period from two weeks to two months after cancellation nalidixic acid. However, during three months after the abolition of nalidix acid bubbles can continue occur on the skin, subject to subsequent exposure to sunlight or minor skin damage.

Violations from the blood and lymphatic system

Thrombocytopenia, leukocytopenia, hemolytic anemia, sometimes in patients with insufficiency of glucose-6-phosphate dehydrogenase (see section "Contraindications"),

Disorders from the metabolism and supply

Metabolic acidosis.

Disorders from the side of the skeletal-muscular and connective tissue

Damage to tendons, including rupture tendons.

Overdose:

Symptoms

Patients who took a dose exceeding the recommended dose may experience: toxic psychosis, seizures, increased intracranial pressure, or metabolic acidosis. Also after an overdose can be observed: nausea, vomiting and lethargy. These reactions pass fairly quickly, since nalidixic acid usually quickly excreted by the kidneys.

Treatment

In case of symptoms of overdose, careful medical supervision of the patient in a hospital environment is recommended. Treatment should be symptomatic and supportive.

Interaction:

With indirect anticoagulants

Nalidixic acid may enhance the effect of indirect anticoagulants, such as warfarin as a result of a significant displacement of indirect anticoagulants from the bond with the protein, resulting in an increase in the concentration of their free (not protein-bound) fraction in the blood. In case of simultaneous use, careful monitoring of prothrombin time or of the international normalized ratio (INR) isthere is a need to reduce the dose of anticoagulant.

With bacteriostatic antibiotics, such as tetracycline, chloramphenicol or nitrofurantoin

Since antibacterial action of nalidixic acid is necessary to multiply bacterial cells, the action of nalidixic acid can be suppressed in the presence of other antimicrobial agents, especially with bacteriostatic effects, such as: tetracycline, chloramphenicol or nitrofurantoin (the latter is an antagonist of nalidixic acid in vitro).

With a probenicide

The probenicide suppresses the secretion of nalidixic acid in the renal tubules and can reduce its effectiveness in relation to infections of the genitourinary system, while increasing the risk of systemic side effects.

With melphalan

The combined use of nalidixic acid and melphalan was accompanied by toxic effects from the gastrointestinal tract.

Impact on laboratory tests

Analysis for glucose in the urine

If urine glucose analysis is used in patients receiving Nevigramon®, methods based on copper reduction are used, such as, for example,use of solutions of Benedict or Felling, a false positive reaction to glucose can be obtained. Therefore, it is recommended to use specific glucose-oxidase methods of investigation.

Determination of 17-keto and ketogenic steroids in the urine

False values ​​can be obtained by determining 17-keto and ketogenic steroids in urine in assays based on the measurement of vanillminal acid in urine. In such cases, you can use the Porter-Silber test for 17-hydroxycorticosteroids.

Special instructions:

Shown, that nalidixic acid and Related compounds cause erosion in cartilage tissue of the joints and others arthropathy in most animals, not reached puberty. Clinical The significance of this phenomenon for a person is not installed. Therefore it is contraindicated application of nalidixic acid patients who have not reached eighteen years of age. If manifested arthralgia, treatment nalidixic acid should be terminated.

Reported damage to tendons, including the rupture of tendons, upon admission nalidixic acid. If you suspect a development of tendinitis treatment of nalidix acid should be immediately terminated.

Patients should be warned about need to avoid exposure direct sunlight, and when developing photosensitivity treatment with drug Nevigramon® should be discontinued.

If a patient shows signs or symptoms of increased intracranial pressure, development of psychosis or other toxic manifestations should immediately stop taking Nevigramon ®.

Perhaps the development of resistance to nalidixic acid, which usually develops within 48 hours after the start of its administration. There is cross-resistance between nalidixic acid and other quinolone derivatives.

If treatment with nalidixic acid lasts more than 2 weeks, then the total blood test and liver and kidney function should be monitored periodically.

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Capsules 500 mg.

Packaging:

For 56 capsules in a polystyrene bottle, closed with a plastic stopper.

1 bottle with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use the drug after the expiration date. the expiration date printed on the package.

Terms of leave from pharmacies:On prescription
Registration number:П N012374 / 01
Date of registration:27.09.2011
Expiration Date:Unlimited
The owner of the registration certificate:HINOIN Pharmaceutical and Chemical Products Plant, ZAO HINOIN Pharmaceutical and Chemical Products Plant, ZAO Hungary
Manufacturer: & nbsp
Representation: & nbspHINOIN Pharmaceutical and Chemical Products Plant ZAOHINOIN Pharmaceutical and Chemical Products Plant ZAO
Information update date: & nbsp26.06.2018
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