Abaktal, 400 mg 10 pcs

Antimicrobial agent – fluoroquinolone.

ATX code: J01MA03

Pharmacodynamics

Pefloxacin is a synthetic antimicrobial agent of the group of fluoroquinolones. It acts bactericidally by inhibiting the enzyme DNA-Giase and bacterial DNA replication; it also disrupts ribonucleic acid A-subunit replication and protein synthesis by the bacterial cell. With respect to Gram-negative bacteria, it acts on cells in both resting and dividing phases; with respect to Gram-positive bacteria, it acts only on cells in the process of mitotic division.

Pefloxacin has a broad spectrum of antimicrobial action.

The following microorganisms are sensitive to pefloxacin: Aeromonas hydrophila, Campylobacter jejuni, Citrobacter spp, Enterobacter spp, Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Klebsiella spp., Legionella pneumophilla, Moraxella catarrhalis, Morganella morganii, Pasteurella multocida, Proteus mirabilis, indole positive Proteus, Providencia stuartii, Salmonella spp, Serratia spp., Shigella spp., Vibrio cholerae.

Moderate sensitivity to the drug has: Streptococcus spp, except Streptococcus pneumoniae; Acinetobacter spp., Neisseria gonorrhoeae, Neisseria meningitidis, Staphylococcus aureus, Chlamydia trachomatis.

Clostridium perfringens, Enterococcus spp, Gardnerella vaginalis, Gram-negative anaerobic microorganisms, spirochetes (Treponema spp., Borrelia spp, Leptospira spp.), Pseudomonas aeruginosa, Mycoplasma spp, Ureaplasma urealyticum and Mycobacterium tuberculosis.

Pharmacokinetics

Absorption

Absorption is high: within 20 minutes after oral administration 90% of pefloxacin is absorbed in the gastrointestinal tract (GIT). After a single oral intake of 200 or 400 mg of pefloxacin per day by healthy volunteers within 1-1.5 hours the maximum plasma concentrations (Cmax) were 2.5 and 4.3 mcg/ml, respectively.

When repeated oral administration of 400 mg of pefloxacin twice daily, maximum and residual concentrations of pefloxacin are reached after 48 hours: maximum serum concentrations range from 7.9 to 10 mcg/ml, residual serum concentrations, just before the next dose, are 3.8 mcg/ml.

The area under the curve “drug concentration/time” (AUC) when administered orally and intravenously is the same, indicating complete absorption of pefloxacin and is 29.5 mg/ml/h.

Distribution

The degree of binding to plasma proteins is 20-30 %, volume of distribution – 1.7 l/kg, providing uniform distribution in organs and tissues. Due to the high volume of distribution the drug penetrates quickly and is well distributed in the tissues, organs and body fluids.

Metabolism

Pefloxacin is metabolized in the liver to form 5 metabolites, 4 of which are found in the urine. The 2 main metabolites are pefloxacin-N-oxide, which has minimal antibacterial activity, and N-dimethyl-pefloxacin, which has antibacterial properties.

However, its concentration is minimal and amounts to 2-3% of pefloxacin concentration.

Excretion

In patients with normal renal and hepatic function 59% of the dose taken is excreted by the kidneys unchanged and as two major metabolites. In general, 60% of the dose is excreted by the kidneys and 40% by the intestine. 20% of the administered dose was excreted as N-dimethyl-pefloxacin and 16.2% as pefloxacin-N-oxide.

The drug is reabsorbed in renal tubules. Renal clearance of pefloxacin is low, varying from 0.11 to 0.21 ml per second depending on the dose. The half-life (T½) of the drug after single administration is 10.5 hours, and increases to 12.3 hours with multiple oral administration. However, pefloxacin and its metabolites are detected in the urine within 48 hours after usage.

Also 20-30% of pefloxacin is excreted with the bile as pefloxacin-glucuronide and N-oxide derivatives. Within 12 hours after oral administration of 400 mg of pefloxacin its concentration in bile reached 83 µg/ml.

Pharmacokinetics in special patient groups

In renal disorders plasma concentration of pefloxacin and T½ is almost unchanged due to the fact that hepatic clearance of the drug is the main excretion mechanism.

In impaired liver function, plasma clearance of pefloxacin is significantly reduced and T½ is correspondingly increased.

Indications

Lung inflammation (pneumonia), Biliary tract infections, Sinusitis, Prostatitis, Bronchitis, Osteomyelitis, Adnexitis, Otitis, Salmonellosis, Intestinal infections, Skin infections, Urinary tract infections, Guaymonitis

Treatment of infection and inflammatory diseases caused by microorganisms sensitive to pefloxacin:

• complicated urinary tract infections;
• bacterial prostatitis;
• lower respiratory tract infections (exacerbation in cystic fibrosis, nosocomial pneumonia);
• infections of the abdominal organs and hepatobiliary system;
• bacterial infections of the gastrointestinal tract with a severe course, including salmonellosis;
• bone and joint infections (osteomyelitis caused by Gram-negative microorganisms);
• skin and soft tissue infections;
• bacterial endocarditis;
• meningitis (if the pathogen is sensitive only to pefloxacin);
• gonorrhea.

Pefloxacin may only be used as an alternative to other antimicrobial agents for treatment of the following infectious and inflammatory diseases:

• acute sinusitis;
• acute chronic bronchitis;
• uncomplicated urinary tract infections.

Pefloxacin is used as monotherapy or in combination therapy with other antimicrobial agents.
Pefloxacin is effective in therapy and prophylaxis of infections in immunocompromised patients.

Active ingredient

Pefloxacin

Composition

1 tablet contains:

active ingredient:

pefloxacin mesylate dihydrate 558.50 mg (equivalent to pefloxacin 400.00 mg);

excipients:

lactose monohydrate 79.50 mg,

corn starch 32.00 mg,

povidone 32.00 mg,

sodium carboxymethyl starch 32.00 mg,<

talc 27.00 mg,

colloidal silica (anhydrous) 2.00 mg,

magnesium stearate 7.00 mg;

shell composition: Hypromellose 13.166 mg, titanium dioxide 2.090 mg, talc 0.854 mg, macrogol 400 1.790 mg, carnauba wax 0.100 mg.

How to take, the dosage

The duration of treatment is set individually, depending on the localization and severity of the infection, as well as the sensitivity of the microorganisms.

To be taken orally, to avoid gastrointestinal distress, the tablets should be taken with food.

The drug is used in 1 tablet (400 mg) twice a day, every 12 hours. The average daily dose is 800 mg per day and the maximum daily dose is 1200 mg.

Infections of the urinary tract may be treated with Abactal® in a dose of 1 tablet (400 mg) once daily, morning or evening.

For treatment of uncomplicated gonorrhea in men and women 800 mg of Abactal® once daily is used.

In patients with hepatic impairment: Use is contraindicated in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment excretion of pefloxacin is significantly slower; therefore the recommended daily dose of the drug is 400 mg every 24-48 hours with determination of serum concentrations.

In patients with renal impairment excretion of pefloxacin is almost unchanged because part of the drug is excreted by liver. In this regard, there is no need to reduce the average daily dose of pefloxacin for patients with impaired renal function.

Pefloxacin is not excreted during hemodialysis; therefore, no additional use of Abactal® is required after hemodialysis.

In elderly patients (over 65 years), due to age-related changes in distribution and excretion, a dose reduction of pefloxacin is recommended.

Interaction

Synergistic and additive effects are achieved when combining pefloxacin with rifampicin (remember that rifampicin significantly increases the plasma clearance of pefloxacin, so serum plasma concentrations of pefloxacin should be controlled when using these drugs together), beta-lactam antibiotics (when treating staphylococcal infection).

The aminoglycosides, piperacillin, azlocillin, ceftazidime increase antibacterial effect (including in case of infection with Pseudomonas aeruginosa).

Pefloxacin reduces metabolism of theophylline in liver, which leads to increase of its concentration in blood plasma and CNS. This may lead to an increase in the frequency and/or severity of side effects which in rare cases may be life-threatening or fatal. Therefore, when concomitant use of theophylline and pefloxacin, plasma concentrations of theophylline should be monitored and the dose should be reduced if necessary.

Pefloxacin may decrease prothrombin index (in patients taking oral (indirect) anticoagulants). The degree of anticoagulant effect may vary depending on the nature of the disease, age and general condition of the patient. Therefore it is necessary to monitor the International Normalized Ratio (INR) during and some time after co-administration of pefloxacin and oral anticoagulants.

Cimetidine, ranitidine and other microsomal liver enzyme inhibitors increase T1/2 of pefloxacin and increase its toxicity.

The antacids (containing aluminum or magnesium) and preparations containing iron and zinc, as well as didanosine (only didanosine dosage forms containing aluminum or magnesium compounds as a buffer) slow the absorption of pefloxacin. In this regard, pefloxacin should be taken at least 2 hours before or 4-6 hours after the use of these drugs. No clinically significant interaction of pefloxacin and calcium carbonate has been found.

In co-administration of fluoroquinolones and cyclosporine may increase plasma concentrations of creatinine and cyclosporine.

Caution should be exercised when co-administering isoniazid.

Pefloxacin can be used in combination with metronidazole and vancomycin.

Antagonism is observed when used together with tetracycline and chloramphenicol.

Pefloxacin co-administration with glucocorticosteroids (especially in patients older than 60 years old, in patients with renal dysfunction and in patients with dyslipidemia) increases the risk of adverse events (tendinitis and in very rare cases of Achilles tendonitis). In view of this, co-administration of pefloxacin and glucocorticosteroids should be avoided.

Because of decrease of microsomal oxidation activity in hepatocytes increases concentration and prolongs T1/2 of oral hypoglycemic agents.

Pefloxacin may prolong QT interval; therefore caution should be exercised when concomitant use with agents that may prolong QT interval (e.g., antiarrhythmic agents of classes IA and III; antipsychotic agents (pimozide, haloperidol, phenothiazine derivatives) tricyclic antidepressants, some antimicrobials (erythromycin, sparfloxacin, moxifloxacin, antimalarials, macrolides); some antihistamines (astemizole), as the risk of life-threatening arrhythmias increases.

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Special Instructions

Abactal® is used as monotherapy or in combination therapy with other antimicrobials.

In mixed infections, in perforating processes in abdominal cavity, in bacterial infections of the gastrointestinal tract with severe course Abactal® is combined with drugs active against anaerobes (metronidazole, clindamycin).

Patients should get plenty of fluids during treatment (to prevent crystalluria).

Photo-sensitivity

Due to the possible occurrence of photosensitivity reactions during treatment with Abactal® , patients should not be exposed to UV radiation or prolonged exposure to direct sunlight. Treatment should be discontinued if any changes on the skin occur. Direct sunlight should be avoided for 4 days after discontinuation of therapy, otherwise protective clothing or cream (with high UV protection) should be used.

Hepatic failure

For patients with severe liver disease, dosage adjustment is required in proportion to the degree of damage (see section “Dosage and administration”).

Muscular system

Tendinitis occurring during treatment with pefloxacin can lead to tendon rupture (e.g., Achilles tendon). Bilateral tendinitis can sometimes occur within 48 hours after the start of treatment with Abactal® and several months after discontinuation of treatment with the drug. Risk factors of tendinitis development during therapy with fluoroquinolones include: age over 60 years, renal insufficiency, dialysis, concomitant therapy with glucocorticosteroids, dyslipidemia. In case of initial signs of tendinitis, treatment with pefloxacin should be discontinued, load on the affected limb should be excluded and the patient should consult a physician.

To reduce the risk of tendinopathy:

• Treatment of elderly patients is recommended after careful assessment of benefit-risk ratio. The risk can be reduced by using half doses of the drug;
• Pefloxacin is contraindicated in patients with a history of tendinitis, and use in patients receiving glucocorticosteroids or who engage in strenuous physical activity is recommended to be avoided.

The risk of rupture is greater in patients who start walking after prolonged bed rest.

When therapy with pefloxacin is initiated, it is recommended to monitor pain and swelling in the Achilles tendon area, especially in patients at risk. If these symptoms are detected, the use of pefloxacin should be discontinued, load on the affected tendons should be avoided, and they should be supported with a suitable orthosis or orthopedic shoe, even if the lesion is unilateral. Specialist advice should be sought.

Dysglycemia

As with other fluoroquinolones, changes in blood glucose concentrations, including hypo- and hyperglycemia, are possible with the use of pefloxacin. During pefloxacin therapy, dysglycemia may occur more often in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic agents (such as sulfonylureas) or insulin. When using pefloxacin in these patients the risk of hypoglycemia increases, up to hypoglycemic coma.

Patients should be informed about the symptoms of hypoglycemia (confusion, dizziness, wolfish appetite, headache, nervousness, palpitations or increased pulse rate, pale skin, sweating, trembling, weakness). If the patient develops hypoglycemia, treatment with pefloxacin should be stopped immediately and appropriate therapy should be started. In these cases it is recommended to switch to therapy with another antibiotic other than fluoroquinolones, if possible. When treating with pefloxacin in elderly patients, in patients with diabetes mellitus close monitoring of blood glucose concentration is recommended.

Nervous system disorders

In patients receiving fluoroquinolones, including pefloxacin, sensory and sensory-motor peripheral neuropathy have been reported, the onset of which may be rapid. If the patient presents with symptoms of peripheral neuropathy, the use of pefloxacin should be discontinued (minimizing the possible risk of developing irreversible changes). Pefloxacin should be used with caution in patients with pseudoparalytic myasthenia gravis.

Pefloxacin should be used with caution in elderly patients with impaired cerebral circulation, organic brain changes or stroke.

Pefloxacin should be used with caution in patients with a history of seizures and conditions predisposing to their development, in patients with porphyria.

The development of adverse reactions associated with mental disorders is possible even after a single dose.

In case of any central nervous system adverse reactions, including mental disturbances, Abactal® should be discontinued immediately and appropriate therapy should be initiated. In these cases, it is recommended to switch to therapy with an antibiotic other than fluoroquinolones, if possible.

Visual disorders

If visual acuity decreases or other visual effects are observed, an ophthalmologist should be consulted immediately.

Gastrointestinal tract

Diarrhea (especially in cases of severe, persistent and/or mixed blood) during or after use of Abactal® may be a symptom of disease caused by Clostridium difficile, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, Abactal® should be stopped immediately and symptomatic treatment (e.g. oral vancomycin) given. Drugs that reduce peristalsis are contraindicated in this condition.

Cardiac disorders

There have been reports of prolongation of the QT interval in patients receiving fluoroquinolones. Despite the fact that pefloxacin can be referred to the group of fluoroquinolones characterized by very low potential, or there is insufficient information to assess their potential ability to cause QT interval prolongation, caution should be exercised in congenital QT interval prolongation syndrome, heart disease (heart failure, myocardial infarction, bradycardia) electrolyte imbalance (e.g., hypokalemia, hypomagnesemia), in concurrent use of pefloxacin with drugs that can prolong the QT interval (e.g., antiarrhythmic drugs of classes IA and III; antipsychotic drugs (pimozide, haloperidol, phenothiazine derivatives) tricyclic antidepressants, some antimicrobials (erythromycin, sparfloxacin, moxifloxacin, antimalarials, macrolides); some antihistamines (astemizole), as the risk of life-threatening arrhythmias increases.

Aortic aneurysm and dissection

Epidemiological studies have reported an increased risk of aortic aneurysm and aortic dissection after fluoroquinolones, especially in elderly patients.

. Therefore, fluoroquinolones should be used only after careful assessment of benefit-risk ratio and consideration of other therapy options in patients with a family history of aortic aneurysm or in patients with diagnosed aortic aneurysm and/or aortic dissection or in the presence of other risk factors or conditions, predisposing to the development of an aortic aneurysm or aortic dissection (e.g., Marfan syndrome, Ehlers-Danlos vascular syndrome, Takayasu arteritis, gigantocellular arteritis, Behcet’s disease, arterial hypertension, atherosclerosis).

In case of sudden pain in the abdomen, chest or back, patients should immediately see a physician in the emergency department.

Glucose-6-phosphate dehydrogenase deficiency

Hemolytic reactions have been reported with fluoroquinolones in patients with glucose-6-phosphate dehydrogenase deficiency. Although hemolysis has not been reported with pefloxacin, the use of this antibiotic in these patients should be avoided and an alternative treatment option, if available, is recommended.

Resistance

As with other antibiotics, use of pefloxacin, especially long-term use, can lead to the multiplication of insensitive microorganisms. Re-evaluation of the patient is mandatory. If secondary infection develops during treatment, appropriate measures should be taken.

Influence on laboratory tests

False-positive results may be observed in the determination of opiates in the urine. It may be necessary to confirm positive results with more specific methods.

Pefloxacin does not affect tests that determine the concentration of glucose in the urine.

Hypersensitivity

Hypersensitivity and allergic reactions, including anaphylactic reactions, may result from pefloxacin use and may be life-threatening.

If a hypersensitivity reaction develops, pefloxacin should be discontinued and appropriate therapy initiated.

Loss of function (disability) and potentially irreversible serious adverse reactions due to fluoroquinolones

. Patients using quinolones and fluoroquinolones, regardless of age or pre-existing risk factors, have had very rare cases of long-term (months or years), disabling and potentially irreversible serious adverse reactions affecting different body systems, sometimes multiple systems (musculoskeletal, nervous system, mental and sensory, including reactions such as tendinitis, tendon damage, arthralgia, limb pain, gait disturbance, neuropathies associated with pa

Pefloxacin administration should be discontinued immediately on appearance of the first signs or symptoms of any severe adverse reaction, patients are advised to consult a physician. The use of pefloxacin is not recommended in patients who have previously had serious adverse reactions with quinolones or fluoroquinolones.

Contraindications

• high sensitivity to fluoroquinolones and/or other drug components;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;
• severe hepatic dysfunction;
• deficiency of glucose-6-phosphate dehydrogenase;
• A history of tendon disorders from previous treatment with fluoroquinolones;
• children under 18 years of age (due to risk of severe arthropathy, especially of large joints);
• pregnancy and breastfeeding period.

With caution
Neurological disorders (epilepsy, seizure syndrome of undetermined etiology, severe organic lesions of the central nervous system, cerebral circulatory disorders, peripheral neuropathy); renal dysfunction; mild to moderate hepatic impairment, elderly patients, congenital QT interval prolongation syndrome, cardiac diseases (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (e.g., hypokalemia, hypomagnesemia), concurrent use of QT interval prolonging agents (including those of the following groups).ч. Class IA and III antiarrhythmic drugs, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungals, imidazole derivatives, some antihistamines), concurrent use with glucocorticosteroids, isoniazid, hypoglycemic oral medications, insulin porphyria; myasthenia gravis; diabetes mellitus; psychosis, history of mental illness; severe adverse reactions to other quinolones or fluoroquinolones; patients with a family history of aortic aneurysm, or patients with diagnosed aortic aneurysm and/or aortic dissection or in the presence of other risk factors or conditions, predisposing to the development of an aortic aneurysm or aortic dissection (e.g., Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, gigantocellular arteritis, Behcet’s disease, arterial hypertension, atherosclerosis) (see See section “Special indications”).

Side effects

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: Very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), rare (≥1/10000, < 1/1000) and very rare (< 1/10000); frequency unknown – the incidence could not be determined from available data.

Infectious and parasitic diseases: frequency unknown: candidiasis.

Blood and lymphatic system disorders

• infrequent: eosinophilia;
• rarely: thrombocytopenia;
• frequent unknown: anemia, leukopenia, neutropenia, pancytopenia, agranulocytosis.

Endocrine system disorders: frequency unknown: syndrome of inadequate secretion of antidiuretic hormone.

Immune system disorders: frequency unknown: angioedema, anaphylactic shock.

Metabolic and nutritional disorders: frequency unknown: severe hypoglycemia up to hypoglycemic coma, especially in elderly patients, patients with diabetes receiving oral hypoglycemic agents or insulin.

Mental disorders: frequency unknown: increased fatigue, depression, psychosis, attention disorders, disorientation, agitation, nervousness, memory impairment, delirium.

Nervous system disorders:

• often: insomnia;
• infrequently: headache, dizziness;
• frequently: increased irritability, hallucinations;
• frequent unknown: confusion, seizures (including epileptic seizures), intracranial hypertension (especially in young adults after long-term therapy with pefloxacin, characterized by a favorable prognosis; in most cases resolved after discontinuation of therapy and adequate treatment), paresthesia, myoclonia (sudden short-term twitching of individual muscles or entire body muscles), sensory or sensory-motor peripheral neuropathy, increased seizure alertness, anxiety, agitation, “nightmares” dreams, worsening myasthenia gravis, tremor.

Visual disorders: frequency unknown: visual disturbances.

Cardiac disorders: frequency unknown: prolongation of the QT interval.

Respiratory system, chest and mediastinum disorders: frequency unknown: bronchospasm.

Gastrointestinal tract disorders:

• often: nausea, vomiting, stomach pain;
• infrequently: Diarrhea;
• frequently: pseudomembranous colitis;
• frequently unknown: change in taste, decreased appetite, flatulence.

Disorders of the liver and biliary tract:

• rare: transient increase in the activity of “hepatic” transaminases, as well as alkaline phosphatase and plasma bilirubin concentration;
• frequency unknown: cholestatic jaundice, hepatitis, liver necrosis.

Skin and subcutaneous tissue disorders:

• often: skin rash, urticaria;
• infrequent: Photosensitivity reactions (to both sunlight and ultraviolet (UV) radiation);
• infrequently: skin itching, erythema;
• frequency unknown: exudative erythema multiforme, toxic epidermal necrolysis (Lyell syndrome), Stevens-Johnson syndrome, skin hyperemia, vascular purpura, photoionycholysis.

Musculoskeletal and connective tissue disorders:

• often: myalgia, arthralgia;
• frequency unknown: arthropathy, tendinitis, tendon rupture, joint effusion.

Renal and urinary tract disorders:

• very rare: acute renal failure;
• frequency unknown: crystalluria, glomerulonephritis, dysuria, interstitial nephritis.

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Overdose

Symptoms: nausea, vomiting, confusion, psychomotor agitation, in severe cases loss of consciousness, seizures, prolonged QT interval.

Treatment: the patient should be under medical control. It is necessary to ensure sufficient intake of fluids into the body. Treatment is symptomatic. Hemodialysis is ineffective.

Pregnancy use

Pefloxacin penetrates into breast milk in large amounts (75% serum concentration). Therefore, it is necessary to stop breastfeeding while using the drug.