Moxifloxacin

When ATH:
J01MA14

Characteristic.

Fluoroquinolone antibacterial agent Generation IV. Moxifloxacin hydrochloride is yellowish or yellow crystalline substance. It differs from other fluoroquinolones presence in the molecular structure methoxy group at position 8 and bitsikloamina position 7.

Pharmacological action.
Broad-spectrum antibacterial, bactericide.

Application.

According to Physicians Desk Reference (2009), moxifloxacin indicated for treatment of infections, caused by susceptible strains of microorganisms, adult patients (senior 18 years).

Ostryi baktyerialinyi sinusitis, caused Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis.

Exacerbation of chronic bronchitis, associated with bacterial infection (Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin Staphylococcus aureus or Moraxella catarrhalis).

Community-acquired pneumonia, caused Streptococcus pneumoniae (incl. caused by strains of microorganisms with multiple antibiotic resistance *), Haemophilus influenzae, Moraxella catarrhalis, methicillin Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae or Chlamydia pneumoniae.

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

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

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

* — strains with multiple antibiotic resistance (Multi-drug resistant Streptococcus pneumoniae - MDRSP), including strains, previously known as PRSP (Penicillin-resistant S. pneumoniae) strains and, resistant to two or more of the following antibiotics: penicillin (BMD at ≥2 mg / ml), II generation cephalosporins (eg cefuroxime), makrolidы, tetracyclines and trimethoprim / sulfamethoxazole.

Contraindications.

Hypersensitivity (incl. to other quinolones), Age to 18 years (Safety and efficacy have not been determined; it should be understood, that moxifloxacin is arthropathy in young growing animals).

Restrictions apply.

Long QT syndrome; uncorrected hypokalemia; the simultaneous use of antiarrhythmics class IA (quinidine, prokaynamyd) or Class III (Amiodarone, sotalol); CNS disorders, predisposing to seizures; epilepsy; severe hepatic insufficiency (Child Pugh Class C).

Pregnancy and breast-feeding.

Application during pregnancy is possible, if the effect of therapy outweighs the potential risk to the fetus (adequate and well-controlled studies of the safety of use in pregnant women were not conducted).

Teratogenic effects. Moxifloxacin had no teratogenicity when a pregnant rats during organogenesis at doses greater than 500 mg / kg / day, which corresponds to approximately 0,24 MRDC (based on AUC values), but the observed decrease in body weight of fruit and a slight delay the formation of the skeleton, indicating fetotoxicity.

When in/with the introduction of pregnant rats at the dose of moxifloxacin 80 mg / kg / day (about 2 MRDC times based on the body surface (mg / m²) toxicity was observed for females and a minimal effect on the fetus, the weight and appearance of the placenta. The on/in a dose of more than 80 mg/kg/day there was no teratogenic effects. In/in a krol′čiham during pregnancy during organogeneza dose 20 mg / kg / day (roughly identical MRDC ingestion) It resulted in reduced body weight and delayed ossification fruit skeleton. The signs of toxicity in female rabbits at these doses were mortality, Abortions, a marked reduction in food intake, reduction in water consumption, gipoaktivnostь. Evidence of teratogenicity when using Cynomolgus monkeys administered dose 100 mg / kg / day (2,5 MRDC) orally missing. Body weight reducing frequency of newborn pups increased dose 100 mg / kg / day. Rats were detected, that when administered dose 500 mg/kg/day were observed the following effects: a slight increase in the duration of pregnancy, prenatal loss, reduced weight in newborn babies, decrease in neonatal survival. Toxic effect of moxifloxacin on the mother's body was manifested with the rats doses during pregnancy 500 mg / kg / day.

Category actions result in FDA - C

Moxifloxacin is excreted in the breast milk of rats. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.) Since moxifloxacin can penetrate into the breast milk of nursing women, and cause serious side effects in children, breastfed, nursing mothers should stop breast-feeding or, or the use of moxifloxacin (Considering the importance of the drug to the mother).

Side effects.

During clinical trials to include more than 9200 patients, receiving moxifloxacin inside and / in (above 8600 patients received at a dose 400 mg), most noted side effects were mild or moderate intensity and did not require discontinuation of treatment. Therapy was discontinued due to the occurrence associated with taking the drug side effects in 2,9% patients with ingestion and 6,3% patients, treated it consistently (w / w and inwardly).

The following adverse effects were assessed as at least possibly related to the drug administration and observed in patients ≥2%: nausea (6%), diarrhea (5%), dizziness (2%).

Clinically significant side effects, that have been assessed as at least possibly related to the drug administration and observed in <2% and ≥0,1% of patients included:

From the nervous system and sensory organs: ≥0,1% <2% - Headache, asthenia, malaise, insomnia / drowsiness, nervousness, alarm, tremor, vertigo, dysgeusia; <0,1% -unusual dreams, blurred vision, ažitaciâ, amblyopia, amnesia, afazija, convulsions, confusion, depersonalization, depression, emotional lability, hallucinations, uncoordinated movement, paraesthesia, parosmija, sleep disturbance, speech disorder, ageusia, violation of the thinking process, tynnyt.

Cardio-vascular system and blood (hematopoiesis, hemostasis): ≥0,1% <2% - Tachycardia, heartbeat, vasodilation, QT prolongation, leukopenia, decrease of prothrombin (increased prothrombin time / INR increase), eozinofilija, thrombocythemia; <0,1% - Anemia, Atrial fibrillation, ECG abnormalities, hypertension, gipotenziya, peripheral edema, increase in prothrombin (decrease of prothrombin time / INR reduction), thrombocytopenia, supraventricular tachycardia, reduction thromboplastin, ventricular tachycardia.

From the digestive tract: ≥0,1% <2% - Vomiting, dry mouth, dyspepsia, flatulence, constipation, oral candidiasis, anorexia, stomatitis, glossitis, violation of indicators of liver function tests, increase the level of gamma-glutamyl; <0,1% - Psevdomembranoznыy colitis, dysphagia, gastritis, gastrointestinal disorders, jaundice (mostly cholestatic ), color change language.

With the genitourinary system: ≥0,1% <2% - Vaginal candidiasis, vaginitis; <0,1% — hyperuricemia, impairment of renal function.

For the skin: ≥0,1% <2% - Rashes (macular-papular, purpura, pustular), itch.

Other: ≥0,1% <2% - Allergic reactions, abdominal pain, reactions at the injection site (including phlebitis), arthralgia, myalgia, changes in laboratory parameters (nonspecific), an increase in blood levels of amylase, increase the level of lactate dehydrogenase, dyspnoea, Sweating, hives, candidiasis; <0,1% - Arthritis, pain syndrome, incl. chest pain, back, in the legs, pelvic pain; asthma, swelling of the face, giperglikemiâ, hyperlipidemia, hypertension, gipesteziya, photosensitivity reaction / phototoxicity, syncope, tendopatii.

IN post-marketing studies It reported the following side effects: anaphylactic reactions, angioedema (including laryngeal edema), hepatic failure (including fatal cases), hepatitis (mostly cholestatic), photosensitivity reaction / phototoxicity, psychotic reactions, Stevens-Johnson syndrome, tendon rupture, toxic epidermal necrolysis, and ventricular tachyarrhythmia (including very rare cases of cardiac arrest and twist of points usually in patients with severe concomitant symptoms proarrhythmic).

Cooperation.

There were no clinically significant effect on the pharmacokinetics of moxifloxacin following medicines: itraconazole, theophylline, warfarin, Digoxin, oral contraceptives. Had no significant effect on the pharmacokinetics of moxifloxacin itraconazole, theophylline, warfarin, Digoxin, probenecid, morphine, ranitidine, calcium (as a supplement to the diet). Antacids and iron tools significantly reduce the bioavailability of moxifloxacin (as well as other quinolones).

In clinical studies involving 24 healthy volunteers found no significant drug interaction between moxifloxacin and R- or S-isomers of warfarin (in the presence of moxifloxacin were observed changes in prothrombin time). However, as reported, that certain quinolones increased anticoagulant effect of warfarin or its derivatives, patients, taking both warfarin and quinolones should be monitored prothrombin time and other coagulation parameters.

According to pharmacokinetic research data, and, received in vitro, moxifloxacin does not inhibit cytochrome P450 isozyme CYP3A4 is, CYP2D6, CYP2C9, CYP2C19, CYP1A2, It is indicating a low probability of change of the metabolic clearance of drugs, metabolized with the participation of these isoenzymes (eg midazolam, cyclosporine, warfarin, theophylline).

While the use of corticosteroids increases the risk of developing tenosynovitis or tendon rupture.

Antacids, sucralfate, metal cations, multivitamins, etc.. may reduce the absorption of quinolones due to the formation of chelate complexes, It resulted in significantly reduced plasma concentration quinolones. In pharmacokinetic studies 12 healthy volunteers it was shown, that single dose of moxifloxacin inside the dose 400 mg for 2 h to, at the same time or through 4 h after administration magnisoderjath aluminum antacids (900 mg aluminum hydroxide and 600 mg magnesium hydroxide once inside) It led to lower values ​​for AUC moxifloxacin 26%, 60% and 23%, respectively. At the same time taking moxifloxacin and iron sulphate (100 mg 1 once a day for two days) значения AUC и C_max moxifloxacin were down 39% and 59%, respectively. Moxifloxacin, taken orally at least 4 hours before or after 8 h after administration of magnesium- or aluminum-containing antacids, sucralfate, metal cations, eg, gland, multivitamins, containing zinc.

Pharmaceutical interaction. Given the limited information about the compatibility of moxifloxacin in the form of a solution for / in with other medications for the on / in the, there should be no simultaneous infusion. Moxifloxacin solution is compatible with the following solutions: 0,9% sodium chloride, 1M sodium chloride, 5% dextrose, Water for Injection, 10% dextrose, simply entails Ringer Lactate.

Overdose.

Single dose to 2,8 g was not associated with any serious adverse reactions.

Treatment Acute overdose: gastric lavage and use of activated charcoal is recommended only in case of an overdose ingestion, adequate hydration, ECG monitoring (in connection with the possibility of long QT), simptomaticheskaya therapy. About 3 and 9% dose moxifloxacin, and 2 and 4,5% its glucuronide are removed with long-term ambulatory peritoneal dialysis and hemodialysis.

Dosing and Administration.

Inside, I / (infusion over 60 m), 400 mg 1 once a day. The duration of therapy depends on indication for use.

Elderly patients, patients with impaired liver light (Child Pugh Class A) and secondary (Child Pugh Class B) severity, as well as in patients with impaired renal function (incl. In severe renal failure with creatinine Cl ≤30 mL / min / 1.73 m²), incl. are on hemodialysis and continuous ambulatory peritoneal dialysis prolonged, Changing the dosage is not required.

Precautions.

Against the background of moxifloxacin may increase the QT interval, It should therefore be used with caution in his patients, simultaneously receiving other drugs, also lengthen the QT interval (cisapride, Erythromycin, neuroleptics, tricyclic antidepressants), tk. additive effect can not be excluded.

Be wary appointed in the background antiarrhythmics class IA (quinidine, prokaynamyd) or Class III (Amiodarone, sotalol).

Due to limited clinical data, the use of moxifloxacin in patients with clinically significant bradycardia and signs of acute myocardial ischemia, should be used with caution in these patients it. The degree of prolongation of the QT interval can be increased with increasing concentration of the substance and an increase in infusion rate / introduction, so you should not exceed the recommended dose and time of administration. QT prolongation may lead to an increased risk of ventricular arrhythmias, including twist of points. There were no reported cases of morbidity or mortality, associated with QT prolongation in controlled clinical trials when using more than moxifloxacin 9200 patients (including 223 patients with hypokalemia in early treatment), and no increase in mortality 18 th. patients, taking into moxifloxacin, during post-marketing studies without control of ECG.

The use of quinolones due to the potential risk of seizures, as well as other disorders of the nervous system (dizziness, confusion, tremor, hallucinations, depression and rarely, suicidal thoughts or actions). These reactions may be observed after the first dose. In case of such reactions, moxifloxacin should be discontinued. As with other quinolones, moxifloxacin should be used with caution in the presence or suspected CNS disorders (incl. pronounced cerebral arteriosclerosis, epilepsy) or when there are other factors, predisposing to seizures or decrease seizure threshold.

It reported cases of serious anaphylactic reactions when taking medications for patients, taking quinolones, including moxifloxacin. In some cases, these reactions are accompanied by cardiac collapse, loss of consciousness, swoon, swelling of the face or throat, dyspnoea, krapivnicej, zudom. In the case of anaphylactic reactions require immediate administration of epinephrine. When a skin rash or other signs of hypersensitivity reactions therapy with moxifloxacin should be discontinued and hold (if necessary) appropriate resuscitation.

It is important to take into account the possibility of pseudomembranous colitis, If the intake of antibiotics in patients appear diarrhea. Treatment antibacterial agents leads to modification of the normal colonic flora, and can lead to increased growth of clostridia. If the diagnosis "pseudomembranous colitis" should start appropriate therapy.

The therapy fluoroquinolones, incl. moxifloxacin, possible development of tendinitis and tendon rupture (Achilles and other). In postmarketing surveillance reported an increased risk in patients, receiving concomitant corticosteroids, especially over the age of 60 years. Therefore, the appearance of pain, inflammation, or rupture of a tendon receiving moxifloxacin should be discontinued. It will be appreciated, that tendon rupture can occur during or after therapy with quinolones (including as moxifloxacin).

Cautions.

Before treatment should be carried out appropriate tests to identify microorganisms, cause disease, and evaluation of sensitivity to moxifloxacin. Moxifloxacin therapy may be initiated before the results of these tests. When the test results will be known, adequate therapy should be continued.

Cooperation