Avelox, 400 mg, 5 pcs.

Pharmacological group Quinolones/fluoroquinolones

Characteristics

Antibacterial agent of IV generation fluoroquinolones. Moxifloxacin hydrochloride is a yellowish or yellow crystalline substance. It differs from other fluoroquinolones by the presence of a methoxy group in position 8 and bicycloamine in position 7 of the molecule. Molecular weight is 437.9.

Indications

According to rxlist.com (2020), moxifloxacin for oral and IV administration is indicated for treatment of infections caused by susceptible strains of microorganisms in adult patients (over 18 years).

Pulmonary pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains [MDRSP]), Haemophilus influenzae, Moraxella catarrhalis, methicillin-sensitive Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae or Chlamydia pneumoniae.

Uncomplicated infections of the skin and its appendages caused by methicillin-sensitive Staphylococcus aureus or Streptococcus pyogenes.

Complicated infectious diseases of the skin and its appendages caused by methicillin-sensitive Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Enterobacter cloacae.

Complicated intra-abdominal infections, including polymicrobial infections such as abscesses caused by Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron or Peptostreptococcus spp.

Plague, including pneumonic and septic plague caused by Yersinia pestis, and plague prevention. A study of the efficacy of moxifloxacin could not be conducted in plague patients. This indication is based on efficacy studies conducted only on animals.

Acute bacterial sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis.

Because the use of fluoroquinolones, including moxifloxacin, is associated with the development of serious adverse reactions (see “Precautions”) and acute bacterial sinusitis is a self-resolving condition in some patients, use to treat acute bacterial sinusitis is only possible in patients who have no alternative therapy options (see “Precautions”).

The exacerbation of chronic bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-sensitive Staphylococcus aureus or Moraxella catarrhalis.

Because the use of fluoroquinolones, including moxifloxacin, is associated with the development of serious adverse reactions (see Precautions), and exacerbations of chronic bronchitis in some patients are self-limited, use in the treatment of exacerbations of chronic bronchitis is only possible for patients who have no alternative therapy options.

Active ingredient

Composition

How to take, the dosage

Ingestion.

The recommended dosing regimen for moxifloxacin is 400 mg (1 tablet) once daily for the infections listed above. The recommended dose should not be exceeded.

The tablets should be swallowed whole, without chewing, with plenty of water, regardless of meals.

The duration of treatment
The duration of treatment is determined by the localization and severity of the infection, as well as the clinical effect:

Do not exceed the recommended duration of treatment.

Avelox® tablets have been studied in clinical studies for up to 21 days.

If a dose of the drug is missed, it should be taken as soon as the patient remembers it that day. Double doses should not be taken to make up for a missed dose.

Patients in the elderly
No change in dosing regimen is necessary in elderly patients.

Children
Efficacy and safety of moxifloxacin in children and adolescents has not been established.

Hepatic impairment
Due to the limited clinical data the use of moxifloxacin is contraindicated in patients with severe hepatic impairment (class C according to the Child-Pugh classification) and patients with transaminases elevated more than five times the upper limit of normal. Patients with mild to moderate hepatic impairment (Child-Pugh class A or B) do not require a change in dosing regimen.

Renal failure
In patients with impaired renal function (including patients with severe renal failure with creatinine clearance ≤30 ml/min/1.73 m2) as well as in patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis, dosing changes are not required.

Application in patients of different ethnic groups
No change in dosing regimen is required.

Interaction

Antacids, sucralfate, multivitamins and other drugs containing polyvalent cations. Moxifloxacin forms chelate complexes with cations of alkaline earth and transition metals. Oral administration of moxifloxacin with antacids containing aluminum or magnesium, sucralfate, metal cations such as iron or multivitamins containing iron or zinc, or with LS containing divalent and trivalent cations, such as didanosine buffered tablets for oral suspension or infant powder for oral solution, can significantly affect the absorption of moxifloxacin, resulting in systemic concentrations significantly lower than desired.

In a study in 12 healthy volunteers it was shown that a single oral administration of moxifloxacin at a dose of 400 mg 2 hours before, simultaneously or 4 hours after taking aluminum/magnesium antacid (900 mg aluminum hydroxide and 600 mg magnesium hydroxide once orally) resulted in reduction of moxifloxacin AUC values by 26, 60 and 23% respectively.

Moxifloxacin and iron sulfate tablets (100 mg once daily for two days) when administered simultaneously had average AUC and Cmax values of moxifloxacin decreased by 39 and 59% respectively.

Moxifloxacin should be taken orally at least 4 hours before or 8 hours after taking magnesium or aluminum-containing antacids, sucralfate, metal cations such as iron, multivitamins containing zinc.

Warfarin. In a study involving 24 healthy volunteers, no significant effect of moxifloxacin (400 mg once daily for 8 days) on the pharmacokinetics of R- or S-isomers of warfarin (warfarin in a single dose of 25 mg on day 5), no significant change in PV was observed in the presence of moxifloxacin. However, fluoroquinolones, including moxifloxacin, have been reported to increase the anticoagulant effect of warfarin or its derivatives. In addition, infectious disease and accompanying inflammatory process, age and general condition of the patient are risk factors for increased anticoagulant activity. Therefore, in patients taking warfarin and moxifloxacin concomitantly, PV, INR and other coagulation parameters should be closely monitored.

Antidiabetic agents. Changes in blood glucose levels, including hyperglycemia and hypoglycemia, have been reported in patients simultaneously receiving fluoroquinolones, including moxifloxacin, and antidiabetic agents. Therefore, close monitoring of blood glucose levels is recommended during concomitant use. In case of hypoglycemia the use of moxifloxacin should be stopped and a corresponding therapy should be started immediately.

The NSAIDs. Concomitant use of NSAIDs with fluoroquinolones, including moxifloxacin, may increase the risk of CNS stimulation and seizures.

The drugs prolonging the QT interval. There is limited information on the potential PDV of moxifloxacin and other drugs that prolong the QTc interval on ECG in humans. Sotalol, a class III antiarrhythmic agent, further prolongs the QTc interval in combination with high doses of IV infused moxifloxacin in dogs. Therefore, the use of moxifloxacin with antiarrhythmic agents of class IA and class III should be avoided.

Calcium, digoxin, itraconazole, morphine, probenecid, ranitidine, theophylline, cyclosporine and warfarin did not significantly affect the pharmacokinetics of moxifloxacin. These results and the data of in vitro studies suggest that it is unlikely to have a significant impact on moxifloxacin metabolic clearance of drugs metabolized with the participation of CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2 isoenzymes.

Moxifloxacin had no clinically significant effect on the pharmacokinetics of atenololol, digoxin, glyburide, itraconazole, oral contraceptives, theophylline, cyclosporine and warfarin.

Athenololol. In a cross-sectional study involving 24 healthy volunteers (12 men, 12 women), the mean AUC of atenolol after a single oral dose of 50 mg and placebo was similar to that observed when atenolol was taken simultaneously with a single oral dose of moxifloxacin 400 mg. The mean Cmax of single-dose atenolol was reduced by approximately 10% after concomitant administration with single-dose moxifloxacin.

Calcium. Twelve healthy volunteers received moxifloxacin (single dose of 400 mg) and calcium (single dose of 500 mg as a Ca++ supplement) simultaneously, followed by 2 additional doses of calcium 12 and 24 hours after moxifloxacin administration. Calcium had no significant effect on the AUC of moxifloxacin. Mean Cmax was slightly decreased and Tmax in plasma was increased when moxifloxacin was used with calcium compared to when moxifloxacin was used alone (2.5 h versus 0.9 h). These differences are not considered clinically significant.

Digoxin. In a study involving 12 healthy volunteers, there was no significant effect of moxifloxacin (400 mg once daily for 2 days) on the AUC of digoxin (0.6 mg as a single dose). Mean Cmax was increased by approximately 50% during the distribution phase of digoxin. This temporary increase in Cmax of digoxin is not considered clinically significant. The pharmacokinetics of moxifloxacin were similar in the presence or absence of digoxin. No dose adjustment of moxifloxacin or digoxin is required when used concomitantly.

Glibenclamide. In diabetic patients, the mean AUC and Cmax values of glibenclamide (2.5 mg once daily for 2 weeks before treatment and for 5 days at concomitant use) were 12 and 21% lower, respectively, when used with moxifloxacin (400 mg once daily for 5 days) compared to placebo. However, blood glucose levels were slightly reduced in patients taking glibenclamide and moxifloxacin compared with those taking glibenclamide alone, indicating no effect of moxifloxacin on glibenclamide activity. These interaction results are not considered clinically significant.

Itraconazole. In a study involving 11 healthy volunteers, there was no significant effect of itraconazole (200 mg once daily for 9 days), a strong CYP3A4 isoenzyme inhibitor, on the pharmacokinetics of moxifloxacin (a single dose of 400 mg on day 7 of itraconazole). In addition, moxifloxacin has not been shown to affect the pharmacokinetics of itraconazole.

Morphine. In a study involving 20 healthy male and female volunteers there was no significant effect of morphine sulfate (single dose of 10 mg w/v) on the average AUC and Cmax of moxifloxacin (single dose of 400 mg).

The oral contraceptives. A placebo-controlled study involving 29 healthy women showed that moxifloxacin taken at a dose of 400 mg/day for 7 days had no effect on the hormonal suppression caused by an oral contraceptive containing 0.15 mg levonorgestrel/0.03 mg ethinylestradiol (as measured by serum progesterone, FSH, estradiol and LH ) and on the pharmacokinetics of the active ingredients of the contraceptive taken.

Probenecid. In a study involving 12 healthy volunteers, probenecid (500 mg twice daily for 2 days) was shown to have no effect on renal clearance and total amount of moxifloxacin (single dose of 400 mg) excreted through the kidneys.

Ranitidine. In a study involving 10 healthy volunteers there was no significant effect of ranitidine (150 mg 2 times daily for 3 days prior to moxifloxacin administration) on pharmacokinetics of moxifloxacin (single dose of 400 mg).

Theophylline. In a study involving 12 healthy volunteers, no significant effect of moxifloxacin (200 mg every 12 hours for 3 days) on the pharmacokinetics of theophylline (400 mg every 12 hours for 3 days) was found. In addition, it has been shown that theophylline does not affect the pharmacokinetics of moxifloxacin. The effect of concomitant use of moxifloxacin 400 mg once daily with theophylline has not been studied.

Pharmaceutical interaction. Due to the limited data on compatibility of moxifloxacin in a form of solution for intravenous administration with other drugs for intravenous administration, a simultaneous infusion should not be conducted. The solution of moxifloxacin is compatible with the following solutions in a ratio from 1:10 to 10:1: 0.9% sodium chloride, 1M sodium chloride, 5% dextrose, water for injection, 10% dextrose, Ringer-lactate solution.

Special Instructions

Contraindications

Side effects

The following serious and important adverse reactions are detailed in the precautions section:

– incapacitating and potentially irreversible serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects (see “Precautions”);

– tendinitis and tendon rupture (see Precautions);

– peripheral neuropathy (see “Precautions”);

– effects on the CNS (see “Precautions”). “Precautions);

– aggravation of myasthenia gravis (see Precautions);

– prolongation of the QT interval (see Precautions).

– other serious and sometimes fatal reactions (see “Precautions”);

– hypersensitivity reactions (see “Precautions”);

– diarrhea associated with Clostridium difficile (see “Precautions”). Precautions);

– changes in blood glucose levels (see “Precautions”);

– photosensitivity/phototototoxicity (see “Precautions”). “

– development of drug-resistant bacteria (see “Precautions”).

The results of clinical trials

Because clinical trials are conducted with a different set of conditions, the frequency of adverse reactions observed in these clinical trials may not be the same as those obtained in other clinical trials and observed in clinical practice.

The data below reflect exposure to moxifloxacin in 14981 patients in 71 controlled phase II-IV active-drug clinical trials for various indications. The mean age of patients was 50 years (approximately 73% were younger than 65), 50% were male, 63% were white, 12% were Asian, and 9% were African American. Patients received moxifloxacin at a dose of 400 mg once daily orally, intravenously, or sequentially (intravenously, then orally). The duration of treatment was usually 6 to 10 days; the average number of days of therapy was 9 days.

Therapy was discontinued because of adverse effects in 5% of patients overall, 4% of patients when given orally, 4% when given by injection, and 8% when given sequentially (oral and IV). The most common adverse reactions (>0.3%) that led to withdrawal of therapy when taking moxifloxacin orally were nausea, diarrhea, dizziness and vomiting. The most common adverse effect that led to withdrawal when administered by injection was rash. The most common adverse reactions leading to withdrawal with sequential therapy (IV, oral) were diarrhea, hyperthermia.

The side effects observed in controlled clinical trials with the active drug in patients receiving moxifloxacin (N=14981), with a frequency of >0.1%, are presented below. The most common adverse reactions (≥3%) were nausea, diarrhea, headache, and dizziness.

Nervous system and sensory organs: Headache (4%), dizziness (3%), insomnia (2%); ≥0.1% < 1% were fatigue, malaise, asthenia, somnolence, tremor, lethargy, paresthesia, hypoesthesia, syncope, anxiety, confusion, agitation, depression, nervousness, anxiety, hallucinations, disorientation, vertigo, visual disturbance, perversion of taste, tinnitus.

System and blood (hematopoiesis, hemostasis): Anemia (1%); ≥0.1% < 1% – atrial fibrillation, palpitations, tachycardia, angina pectoris, heart failure, cardiac arrest, bradycardia, hypertension, hypotension, thrombocythemia, eosinophilia, neutropenia, thrombocytopenia, leukopenia, leukocytosis.

Respiratory system: ≥0.1% < 1% – shortness of breath, asthma, wheezing, bronchospasm.

Gastrointestinal organs: nausea (7%), diarrhea (6%), vomiting (2%), constipation (2%), abdominal pain (2%), dyspepsia (1%); ≥0.1% < 1% – dry mouth, abdominal discomfort, flatulence, bloating, gastritis, GERD, gastroenteritis, liver function disorder.

Metabolic disorders: hypokalemia (1%); ≥0.1% < 1% – hyperglycemia, anorexia, hyperlipidemia, decreased appetite, dehydration.

Urogenital system disorders: ≥0.1% < 1% – renal failure, dysuria, vaginal candidiasis, vulvovaginal pruritus.

Musculoskeletal and connective tissue disorders: ≥0.1% < 1% – back pain, extremities, arthralgia, muscle spasm, musculoskeletal pain.

Skin disorders: ≥0.1% < 1% – rash, itching, hyperhidrosis, erythema, urticaria, allergic dermatitis, night sweats.

Laboratory and instrumental parameters: increased ALT (1%); ≥0.1% < 1% – increased AST, increased GGT, increased alkaline phosphate in blood, prolonged QT interval on ECT, increased LDH in blood, increased blood amylase, increased lipase, increased blood creatinine, increased blood urea, increased hematocrit, increased PV, increased eosinophil count, increased ACTV, increased blood triglyceride levels, increased blood uric acid.

Others: pyrexia (1%), ≥0.1% < 1% – chills, extravasation at the IV site including phlebitis, edema, urticaria, fungal infection, pain syndrome including chest pain, facial pain.

Changes in laboratory parameters

Changes in laboratory parameters not listed above, which were reported in ≥2% of patients and with a frequency higher than that of controls, included increases in mean corpuscular hemoglobin (MCH), neutrophils, leukocytes, PV ratio, ionized calcium, chloride, albumin, globulin, bilirubin; decreased Hb, red blood cell count, neutrophils, eosinophils, basophils, glucose, partial pressure of oxygen (PO2), bilirubin, and amylase. It is not possible to determine whether any of the above laboratory abnormalities were caused by the drug or the underlying disease.

Postmarketing Experience

The following are adverse reactions that have been reported with moxifloxacin. Because reports of these cases are voluntary, from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous system and sense organs: movement coordination disorders, gait disturbances (see Precautions), myasthenia gravis (exacerbation) (see Precautions), muscle weakness, peripheral neuropathy (which may be irreversible), polyneuropathy (see Precautions). “Precautions”), psychotic reactions (very rarely ending in self-harming behavior such as suicidal thoughts/attempts) (see “Precautions”), hearing loss including deafness (most cases are reversible), vision loss (especially with CNS reactions, most cases are transient).

System and blood (hematopoiesis, hemostasis): ventricular tachyarrhythmia (including very rare cases of cardiac arrest and torsade de pointes, usually in patients with concomitant severe proarrhythmic symptoms), agranulocytosis, pancytopenia (see Precautions).

Respiratory system: allergic pneumonitis (see “Precautions”).

Gastrointestinal system disorders: hepatitis (predominantly cholestatic), liver failure (including fatal cases), jaundice, acute liver necrosis (see “Precautions”).

Urogenital system disorders: interstitial nephritis (see “Precautions”).

Musculoskeletal and connective tissue disorders: tendon rupture (see “Precautions”).

Skin disorders: photosensitivity/phototototoxicity reactions (see “Precautions”), Stevens-Johnson syndrome, toxic epidermal necrolysis.

Allergic reactions: anaphylactic reactions, anaphylactic shock, angioedema (including laryngeal edema).

Overdose

There are limited data on overdose of moxifloxacin. No adverse effects were observed when using moxifloxacin in doses up to 1200 mg once and 600 mg for 10 days or more. In case of overdose the clinical picture should be guided and symptomatic supportive therapy with ECG monitoring should be conducted.

The use of activated charcoal immediately after oral administration may help prevent excessive systemic exposure to moxifloxacin in cases of overdose.

Pregnancy use

Pregnant use is possible if the expected effects of therapy exceed the potential risk to the fetus (adequate and strictly controlled safety studies of use in pregnant women have not been conducted).

Teratogenic effects. Moxifloxacin had no teratogenic effect when administered orally to pregnant rats during organogenesis at doses above 500 mg/kg/day, which corresponds to approximately 0.24 MRHD (based on AUC values), but there was a reduction in fetal body weight and a slight delay in skeletal formation indicating fetotoxicity. When moxifloxacin was administered by IV to pregnant rats at a dose of 80 mg/kg/day (approximately 2 times the MRDH per body surface area (mg/m2)), toxicity to females and minimal effects on fetus, placental weight and appearance were observed.

No teratogenic effects were observed when doses above 80 mg/kg/day were administered by injection. IV administration to rabbits during pregnancy during organogenesis at a dose of 20 mg/kg/day (approximately identical to oral MRDH) resulted in decreased fetal body weight and delayed skeletal ossification. Signs of toxicity to female rabbits at these doses were lethality, miscarriage, markedly reduced food intake, reduced water intake, and hypoactivity. There was no evidence of teratogenicity when Cynomolgus was used in monkeys at an oral dose of 100 mg/kg/day (2.5 MRDH).

The incidence of weight loss in newborn calves was increased at the 100 mg/kg/day dose. In rats, the following effects were observed when the oral dose of 500 mg/kg/day was administered: a slight increase in pregnancy duration, prenatal losses, decreased weight in newborn calves, and decreased neonatal survival. Toxic effects of moxifloxacin on the maternal organism were manifested when administered to rats during pregnancy at a dose of 500 mg/kg/day.

The FDA fetal category of action is C.

Moxifloxacin is excreted into the breast milk of rats. Since moxifloxacin can penetrate into the breast milk of breastfeeding women and cause serious adverse reactions in breastfed children, breastfeeding women should stop either breastfeeding or using moxifloxacin (given the importance of the drug to the mother).

Similarities