Tarivid®

Nosological classification (ICD-10)

• A54 Gonococcal infection
• H60 Otitis externa
• H66 Suppurative and unspecified otitis media
• J04 Acute laryngitis and tracheitis
• J06 Acute upper respiratory tract infections of multiple and unspecified localization
• J18 Pneumonia without specifying the pathogen
• J22 Acute respiratory infection of the lower respiratory tract, unspecified
• J40 Bronchitis, not specified as acute or chronic
• J85 Abscess of the lung and mediastinum
• K65 Peritonitis
• K81 Cholecystitis
• L00-L08 Infections of the skin and subcutaneous tissue
• M60.0 Infectious myositis
• M65.0 Tendon sheath abscess
• M65.1 Other infectious tenosynovitis
• M71.0 Abscess of bursa
• M71.1 Other infectious bursitis
• N15 Other tubulointerstitial kidney diseases
• N39.0 Urinary tract infection without established location
• N49 Inflammatory diseases of the male genital organs, not elsewhere classified
• N70-N77 Inflammatory diseases of the female pelvic organs
• N74.3 Gonococcal inflammatory diseases of the female pelvic organs (A54.2+)
• O85 Puerperal sepsis
• O86 Other postpartum infections

Release form and composition

Dosage forms of Tarivida:

• film-coated tablets: biconvex, oblong, white with a yellowish tint, have a dividing groove, engraving is applied on both sides of the tablet - M and XI, on the left and right sides of the groove (respectively) (10 pcs each in contour strip packs , 1 package in a cardboard box);
• solution for infusion: greenish-yellow, transparent (100 ml in colorless glass bottles, 1 bottle in a cardboard box).

Composition of 1 tablet:

• active substance: ofloxacin – 200 mg;
• auxiliary components: polyethylene glycol (macrogol) 8000, starch, hypromellose (hydroxypropyl methylcellulose), lactose, titanium dioxide (E171), hydroxypropylcellulose (hyprolose), carboxymethylcellulose (carmellose), talc, magnesium stearate.

Composition of 100 ml infusion solution:

• active substance: ofloxacin – 200 mg (ofloxacin hydrochloride – 220 mg);
• auxiliary components: hydrochloric acid 1N (to adjust the pH level), sodium chloride, water for injection.

Side effects

Possible side effects identified on the basis of clinical data and extensive post-marketing experience with Tarivid (very often - 10%; often - 1-10%; infrequently - 0.1-1%; rarely - 0.01-0.1%; very rarely - up to 0.01%, taking into account individual cases):

• central nervous system: uncommon – headache, agitation, dizziness, insomnia/sleep disorders; rarely - confusion, psychotic reactions (for example, hallucinations), anxiety, nightmares, depression, drowsiness, disturbances of peripheral sensitivity (including paresthesia, disturbances of smell, taste, vision); very rarely - hearing impairment (including epileptic seizures, tinnitus or hearing loss), extrapyramidal disorders or other disorders of muscle coordination, tremor, hypoesthesia, convulsions; in some cases - psychotic reactions that occur with behavior dangerous for the patient (including increased intracranial pressure, suicidal tendencies);
• cardiovascular system: rarely – tachycardia, hypotension; with intravenous administration - tachycardia and a decrease in blood pressure (in rare cases it is pronounced; if there is a noticeable decrease in blood pressure, the administration is stopped);
• allergic reactions: infrequently - dry cough, itching, burning in the eyes, rash, rhinitis; rarely - angioedema, pustular rash, urticaria, bronchospasm/suffocation, sweating, hyperemia; very rarely - persistent drug rash, anaphylactic/anaphylactoid shock, toxic epidermal necrolysis, erythema multiforme, photosensitivity, vascular purpura, vasculitis, which in exceptional cases can lead to skin necrosis; in some cases - severe suffocation, Stevens-Johnson syndrome;
• musculoskeletal system: rarely – tendonitis; very rarely - myalgia, arthralgia, rupture of the Achilles tendon (usually within 2 days from the start of treatment; can be bilateral); in some cases - acute necrosis of skeletal muscles/myopathy, muscle weakness (especially important in the presence of myasthenia gravis);
• digestive system: uncommon – vomiting, abdominal pain, nausea, diarrhea, loss of appetite; rarely – flatulence, anorexia, enterocolitis; very rarely - pseudomembranous colitis;
• peripheral blood: very rarely - leukopenia, anemia, thrombocytopenia, hemolytic anemia, eosinophilia, agranulocytosis; in some cases – inhibition of bone marrow hematopoiesis, pancytopenia;
• kidneys: rarely - an increase in the concentration of urea and serum creatinine; very rarely - acute renal failure; in some cases – interstitial nephritis;
• liver: rarely - increase in bilirubin and/or liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase/alkaline phosphatase); very rarely - cholestatic jaundice; in some cases - hepatitis (can occur in severe forms);
• others: often - redness/pain at the injection site of the infusion solution and phlebitis; infrequently - the development of a secondary infection caused by microorganisms and fungi that are resistant to the action of the drug; in some cases - acute attacks of porphyria in patients with porphyria, allergic pulmonitis, hypoglycemia (with diabetes mellitus during therapy with hypoglycemic drugs).

Drug interactions

With the simultaneous use of certain drugs/substances, the following effects may develop:

• aluminum phosphate, iron, zinc, antacids containing aluminum hydroxide (including sucralfate) and magnesium: decreased absorption of ofloxacin (the interval between single doses should be at least 2 hours);
• other drugs eliminated by renal tubular secretion, including cimetidine, probenecid, methotrexate, furosemide: increased serum concentrations of ofloxacin;
• glibenclamide: a slight increase in its serum concentration;
• nonsteroidal anti-inflammatory drugs, methylxanthine and nitroimidazole derivatives: increased likelihood of neurotoxic effects;
• theophylline, fenbufen or other non-steroidal anti-inflammatory drugs, as well as other drugs that can lower the threshold for seizure activity: a noticeable decrease in the threshold for seizure activity;
• vitamin K antagonists: development of interaction (control of the blood coagulation system is required);
• drugs that prolong the QT interval (macrolides, tricyclic antidepressants, class IA and III antiarrhythmic drugs): increased likelihood of prolongation of the QT interval;
• glucocorticosteroids: increased likelihood of tendon rupture, especially in elderly patients;
• drugs that alkalinize urine, including citrates, carbonic anhydrase inhibitors, sodium bicarbonate: increased likelihood of nephrotoxic effects and crystalluria.

Indications for use

According to the instructions, Tarivid is prescribed for the treatment of infectious and inflammatory diseases caused by microorganisms that are sensitive to the action of the active substance of the drug (ofloxacin), including infections of the following organs/systems:

• respiratory tract (except pneumococcal infection);
• ear, throat, nose (except acute tonsillitis);
• abdominal cavity and bile ducts;
• kidneys, urinary tract, prostate gland, urethra (including infections of gonococcal etiology);
• pelvic organs;
• bones and joints;
• leather and soft tissues.

Tarivid is also used in patients with impaired immune status, including patients with neutropenia, for prophylactic purposes.

Pharmacological properties

Pharmacodynamics

Tarivid is an antimicrobial drug belonging to the group of fluoroquinolones with a broad spectrum of action. It has a bactericidal effect associated with the blockade of the DNA gyrase enzyme in bacterial cells.

Ofloxacin, the active component of Tarivid, is characterized by high activity against most gram-negative and some gram-positive organisms: Staphylococcus coagulase negative, Staphylococcus aureus methi-S, Aeromonas hydrophila, Chlamydia trachomatis, Branhamella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Brucella spp., Gardnerella vaginalis, Clostridium perfringens, Escherichia coli, Vibrio spp., Salmonella spp., Mycoplasma spp., Enterobacter spp., Helicobacter pylori, Serratia spp., Klebsiella spp., including Klebsiella pneumoniae, Citrobacter spp., Moraxella morganii, Yersinia spp., Proteus vulgaris (indole + and indole –), Proteus spp., including Proteus mirabilis, Providencia spp., Shigella spp., Haemophilus ducreyi, Haemophilus influenzae and parainfluenzae, Legionella, Plesiomonas.

Streptococcus spp. are moderately sensitive to ofloxacin. (especially β-hemolytic type), Acinetobacter spp., Pseudomonas spp., Ureaplasma urealyticum, Streptococcus pneumoniae, Bacteroides fragilis, Enterococcus faecalis, Mycobacterium tuberculosis, Anaerobic Gram positive cocci, Chlamydia psittaci, Mycobacterium leprae.

The drug has no effect on the following microorganisms: Treponema pallidum, Acinetobacter baumannii, Nocardia spp., Clostridium difficile, Staphylococci methi-R, Listeria monocytogenes, Enterococcus.

Pharmacokinetics

After oral administration, ofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract. Its bioavailability reaches 100%. The maximum concentration of this substance in the blood plasma after a single dose of 200 mg is 2.5–3 mcg/ml and is achieved after approximately 1 hour. Ofloxacin is bound to plasma proteins by 25% and is metabolized by approximately 5%. The half-life is 6-7 hours. The distribution volume is approximately 120 l. Up to 90% of ofloxacin is excreted unchanged through the kidneys, approximately 4% is excreted in the bile.

Instructions for use of Tarivid: method and dosage

The dosage regimen and course duration are determined by the general condition, severity and type of infection, as well as the functional state of the kidneys.

Pills

Tarivid is taken orally, whole, with water. Reception is possible before and during meals. Combined use with antacids should be avoided.

The average adult daily dose can vary between 200–600 mg, course duration is 7–10 days.

Recommended frequency of administration (depending on the daily dose):

• up to 400 mg: in 1 dose (preferably in the morning);
• from 400 mg: in 2 doses with equal intervals between them.

Special applications:

• uncomplicated lower urinary tract infections: 200 mg per day for 3–5 days;
• severe infections or therapy for overweight patients: the daily dose may be increased to 800 mg;
• gonorrhea: 400 mg once.

Correction of the dosage regimen for patients with functional renal impairment (depending on creatinine clearance: single dose/break between doses):

• 50–20 ml/min: 100–200 mg/24 hours;
• up to 20 ml/min or hemodialysis: 100 mg/24 hours;
• up to 20 ml/min or peritoneal dialysis: 200 mg/48 hours.

The maximum permissible daily dose for liver failure is 400 mg.

After using the Tarivid infusion solution, if the patient's condition improves, therapy can be continued with oral administration of the drug.

Infusion solution

Tarivid solution is administered intravenously (slow drip).

Infusion time: for every 200 mg - at least 30 minutes. This is especially important to consider when combined with drugs with antihypertensive effects and drugs for anesthesia from the barbiturate group.

Standard dosage regimen: 2 times a day (with an interval of 12 hours) 200 mg. Daily doses of up to 400 mg per day can be used once a day (preferably in the morning), higher doses can be divided into 2 administrations, maintaining equal intervals between them.

When treating severe infections or overweight patients, the daily dose may be increased to 600 mg.

In the presence of functional kidney disorders, the drug is prescribed in the same way as for the tablet form.

If it is impossible to determine creatinine clearance in men, its value is calculated using one of two Cockroft formulas based on serum creatinine level (in ml/min):

• weight (kg) × (140 – age) / 72 × creatinine (mg%);
• weight (kg) × (140 – age) / 0.814 × creatinine (mmol/l).

To find out the creatinine clearance in women, the indicator in men is multiplied by 0.85.

The maximum permissible daily dose for liver failure is 400 mg.

Monitoring of serum concentrations of ofloxacin is recommended in severe renal failure and in patients on hemodialysis.

After the patient's condition improves, therapy can be continued with Tarivid taken orally.

The duration of the course is determined by the severity of the condition. After normalization of body temperature or if there is evidence of eradication of the bacterial agent, use of the drug should be continued for at least 2-3 days.

special instructions

Due to the high risk of photosensitivity, it is recommended to avoid exposure to ultraviolet rays/bright sunlight.

During therapy, especially during a long course, it is possible to develop a secondary infection associated with the growth of microorganisms that are resistant to the drug. It is necessary to re-evaluate the patient's condition. If a secondary infection develops during the course of therapy, appropriate measures should be taken.

When prescribing Tarivid, it is necessary to take into account the presence of the following risk factors for prolongation of the QT interval:

• diseases of the cardiovascular system, including heart failure, myocardial infarction, bradycardia;
• congenital prolongation of the QT interval;
• uncorrected electrolyte imbalance (eg, hypomagnesemia, hypokalemia);
• combined use with drugs that prolong the QT interval, including macrolides, tricyclic antidepressants, class IA and III antiarrhythmic drugs;
• elderly age.

The appearance of signs of tendinitis, especially in elderly patients, is the reason for discontinuation of therapy (immobilization of the Achilles tendon and consultation with an orthopedist are required).

If diarrhea develops during the period of use of the drug or after the end of the course (especially persistent or severe and/or mixed with blood), this may be a sign of the development of pseudomembranous colitis. If this disorder is suspected, Tarivid is immediately discontinued and specific antibacterial therapy is prescribed (for example, oral vancomycin, oral teicoplanin or metronidazole); the use of drugs that suppress intestinal motility is prohibited.

During therapy, the likelihood of the following conditions/disorders should be taken into account:

• increased frequency of attacks of porphyria;
• worsening of myasthenia gravis;
• the appearance of false positive results when determining porphyrins and opiates in urine, as well as during bacteriological diagnosis of tuberculosis.

Tarivid is not the drug of choice for the treatment of pneumonia caused by pneumococci. The drug is not prescribed for the treatment of acute tonsillitis.

During the period of use of Tarivid it is not recommended:

• Women's use of sanitary tampons (associated with an increased likelihood of thrush);
• ethanol consumption.

Since some adverse reactions, including visual disturbances, drowsiness and dizziness, can affect concentration and reaction, the risk increases in situations where the presence of these abilities is especially important (for example, while driving a vehicle or using other machinery).

Contraindications

Absolute:

• tendon lesions due to previous treatment with quinolones;
• epilepsy;
• lesions of the central nervous system with a reduced convulsive threshold - after a stroke, traumatic brain injury, inflammatory processes in the area of ​​the central nervous system (for tablets);
• age under 18 years;
• pregnancy and breastfeeding;
• hypersensitivity to the components of the drug, as well as other quinolones.

Relative (caution is required in the presence of the following diseases/conditions):

• organic lesions of the central nervous system, occurring with prolongation of the QT interval (for tablets);
• atherosclerosis of cerebral vessels (for tablets);
• chronic renal failure (for tablets);
• aggravated medical history of circulatory disorders (for tablets);
• lesions of the central nervous system with a reduced convulsive threshold - after a stroke, traumatic brain injury, inflammatory processes in the central nervous system (for infusion solution).