Kompozisyon:
Tedavide kullanılır:
Fedorchenko Olga Valeryevna tarafından tıbbi olarak gözden geçirilmiştir, Eczane Son güncelleme: 01.04.2022
Dikkat! Sayfadaki bilgiler sadece sağlık profesyonelleri içindir! Bilgi kamu kaynaklarında toplanır ve anlamlı hatalar içerebilir! Dikkatli olun ve bu sayfadaki tüm bilgileri tekrar kontrol edin!
Aynı bileşenlere sahip en iyi 20 ilaç:
EG1, aşağıda listelenen koşullarda belirtilen mikroorganizmaların duyarlı suşlarının neden olduğu enfeksiyonların tedavisi için endikedir. (Görmek DOZAJ VE YÖNETİM ve Klinik çalışmalar).
Kronik bronşitin akut bakteriyel alevlenmesi (ABECB) neden oldu Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, veya Moraxella catarrhalis.
Çünkü EG1 dahil florokinolonlar ciddi advers reaksiyonlarla ilişkilendirilmiştir (bkz UYARILAR) ve bazı hastalar için ABECB kendi kendini sınırlar, alternatif tedavi seçeneği olmayan hastalarda ABECB tedavisi için EG1 ayırın.
Toplum kökenli pnömoni (hafif ila orta şiddette) neden olur Streptococcus pneumoniae (çok ilaca dirençli suşlar [MDRSP] dahil) *, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, veya Klebsiella pneumoniae.
*MDRSP: çoklu ilaca dayanıklı Streptococcus pneumoniae, daha önce PRSP (penisiline dirençli) olarak bilinen izolatları içerir Streptococcus pneumoniae)ve aşağıdaki antibiyotiklerden ikisine veya daha fazlasına dirençli suşlar: penisilin (MIC ≥2 ug / mL), 2. nesil sefalosporinler (ör., sefuroksim), makrolidler, tetrasiklinler ve trimetoprim / sülfametoksazol.
İlaca dirençli bakterilerin gelişimini azaltmak ve EG1 ve diğer antibakteriyel ilaçların etkinliğini korumak için EG1 sadece duyarlı bakterilerin neden olduğu kanıtlanmış veya şüphelenilen enfeksiyonları tedavi etmek için kullanılmalıdır. Kültür ve duyarlılık bilgileri mevcut olduğunda, antibakteriyel tedavinin seçilmesinde veya değiştirilmesinde dikkate alınmalıdır. Bu tür verilerin yokluğunda, lokal epidemiyoloji ve duyarlılık paternleri ampirik tedavi seçimine katkıda bulunabilir.
EG1, yiyecekle birlikte veya yiyeceksiz alınabilir ve liberal miktarda sıvı ile tamamen yutulmalıdır. Aşağıdaki tabloya göre önerilen EG1 dozu günde 320 mg'dır (Tablo 4).
Tablo 4. EG1'in Önerilen Dozaj Rejimi
5 günlük veya 7 günlük bir rejimin kullanımına ilişkin klinik karar, ilk balgam kültürünün sonuçları ile yönlendirilmelidir.
GÖSTERGE | DOZ / SÜRE |
Kronik bronşitin akut bakteriyel alevlenmesi | 5 gün boyunca günde bir 320 mg tablet |
Toplum kökenli pnömoni (hafif ila orta şiddette) | |
bilinen veya şüphelenilen S. pneumoniae, H. influenzae, M. pneumoniae veya C. pneumoniae enfeksiyonu nedeniyle | 5 gün boyunca günde bir 320 mg tablet |
bilinen veya şüphelenilen MDRSP *, K. pneumoniae veya M. catarrhalis enfeksiyonu nedeniyle | 7 gün boyunca günde bir 320 mg tablet |
* MDRSP: çoklu ilaca dayanıklı Streptococcus pneumoniae, daha önce PRSP (penisiline dirençli) olarak bilinen izolatları içerir Streptococcus pneumoniae)ve aşağıdaki antibiyotiklerden ikisine veya daha fazlasına dirençli suşlar: penisilin (MIC ≥2 ug / mL), 2. nesil sefalosporinler (ör., sefuroksim), makrolidler, tetrasiklinler ve trimetoprim / sülfametoksazol.
Önerilen EG1 dozu ve süresi aşılmamalıdır (bakınız Tablo 2).
Böbrek yetmezliği olan hastalarda kullanın
Kreatinin klerensi> 40 mL / dak olan hastalarda doz ayarlaması gerekli değildir. Kreatinin klerensi olan hastalar için dozajın değiştirilmesi önerilir ?40 mL / dk. Tablo 5, böbrek yetmezliği olan hastalarda kullanım için dozaj kılavuzları sunmaktadır.
Tablo 5. Böbrek yetmezliği olan hastalar için önerilen dozlar
Kreatinin Açıklığı (mL / dak) | Doz |
> 40 | Bkz. Genel Dozaj |
≥ 40 | 24 saatte bir 160 mg |
Rutin hemodiyaliz veya sürekli ayaktan periton diyalizi (CAPD) gerektiren hastalar 24 saatte bir 160 mg almalıdır.
Sadece serum kreatinin konsantrasyonu bilindiğinde, kreatinin klerensini tahmin etmek için aşağıdaki formül kullanılabilir.
Erkekler: | (kg cinsinden ağırlık) x (140 - yaş) |
(72) x serum kreatinin (mg / 100 mL) | |
Dişiler: | (0.85) x (değerin üstünde) |
Hepatik Bozulmuş Hastalarda Kullanım
Hafif (Child-Pugh Sınıf A), orta (Child-Pugh Sınıf B) veya şiddetli (Child-Pugh Sınıf C) karaciğer yetmezliği olan hastalarda doz ayarlaması önerilmez.
Yaşlılarda kullanın
Doz ayarlaması önerilmez.
EG1, gemifloksasin, florokinolon antibiyotik ajanları veya ürün bileşenlerinden herhangi birine karşı aşırı duyarlılık öyküsü olan hastalarda kontrendikedir.
WARNINGS
Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects
Fluoroquinolones, including EG1 have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting EG1. Patients of any age or without pre-existing risk factors have experienced these adverse reactions (See WARNINGS, Tendinitis and Tendon Rupture, Peripheral Neuropathy and Central Nervous System Effects)
Discontinue EG1 immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including EG1, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.
Tendinitis and Tendon Rupture
Fluoroquinolones, including EG1, have been associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur within hours or days after starting EG1, or as long as several months after completion of therapy. Tendinitis and tendon rupture can occur bilaterally.
The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Other factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Discontinue EG1 if the patient experiences pain, swelling, inflammation or rupture of a tendon. Avoid fluoroquinolones, including EG1, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug.
Peripheral Neuropathy
Fluoroquinolones, including EG1, have been associated with an increased risk of peripheral neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones, including EG1. Symptoms may occur soon after initiation of EG1 and may be irreversible in some patients. Discontinue EG1 immediately if the patient experiences symptoms of peripheral neuropathy, including pain, burning, tingling, numbness, and/or weakness or other alterations in sensations including light touch, pain, temperature, position sense, and vibratory sensation.
CNS Effects
Fluoroquinolones, including EG1, have been associated with an increased risk of central nervous system (CNS) effects, including convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis. In clinical studies with EG1, central nervous system (CNS) effects have been reported infrequently. As with other fluoroquinolones, EG1 should be used with caution in patients with CNS diseases such as epilepsy or patients predisposed to convulsions. CNS stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, insomnia, and rarely suicidal thoughts or acts may also be caused by other fluoroquinolones. If these reactions occur in patients receiving EG1, discontinue EG1 immediately and institute appropriate measures.
Exacerbation of Myasthenia Gravis
Fluoroquinolones, including EG1, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Avoid EG1 in patients with known history of myasthenia gravis. (See PATIENT INFORMATION and ADVERSE REACTIONS/Post-Marketing Adverse Reactions.)
THE SAFETY AND EFFECTIVENESS OF EG1 IN CHILDREN, ADOLESCENTS (LESS THAN 18 YEARS OF AGE), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED. (See PRECAUTIONS: Pediatric Use, Pregnancy and Nursing Mothers subsections.)
QT Effects
Fluoroquinolones may prolong the QT interval in some patients. EG1 should be avoided in patients with a history of prolongation of the QTc interval, patients with uncorrected electrolyte disorders (hypokalemia or hypomagnesemia), and patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents.
Pharmacokinetic studies between gemifloxacin and drugs that prolong the QTc interval such as erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. EG1 should be used with caution when given concurrently with these drugs, as well as in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia or acute myocardial ischemia. No cardiovascular morbidity or mortality attributable to QTc prolongation occurred with EG1 treatment in over 8119 patients, including 707 patients concurrently receiving drugs known to prolong the QTc interval and 7 patients with hypokalemia.
The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. QTc prolongation may lead to an increased risk for ventricular arrhythmias including torsades de pointes. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin.
Hypersensitivity Reactions
Serious hypersensitivity and/or anaphylactic reactions have been reported in patients receiving fluoroquinolone therapy, including EG1. Hypersensitivity reactions reported in patients receiving fluoroquinolone therapy have occasionally been fatal. These reactions may occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath and acute respiratory distress), dyspnea, urticaria, itching and other serious skin reactions.
EG1 should be discontinued immediately at the appearance of any sign of an immediate type I hypersensitivity skin rash or any other manifestation of a hypersensitivity reaction; the need for continued fluoroquinolone therapy should be evaluated. As with other drugs, serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines and airway management as clinically indicated. (See PRECAUTIONS and ADVERSE REACTIONS.) Other serious and sometimes fatal adverse reactions, some due to hypersensitivity and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including EG1. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:
- fever, rash or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson Syndrome);
- vasculitis; arthralgia; myalgia; serum sickness;
- allergic pneumonitis;
- interstitial nephritis; acute renal insufficiency or failure;
- hepatitis; jaundice; acute hepatic necrosis or failure;
- anemia, including hemolytic and aplastic;
- thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia agranulocytosis; pancytopenia; and/or other hematologic abnormalities.
Discontinue EG1 immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and institute supportive measures (See PATIENT INFORMATION and ADVERSE REACTIONS).
Clostridium Difficile Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including EG1, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
PRECAUTIONS
General
Prescribing EG1 in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drugresistant bacteria.
Rash
In clinical studies, rash occurred more often with EG1 than with therapy with comparator agents (2.7% vs. 0.6%). Increasing incidence of rash was associated with younger age (especially below 40), female gender, use of hormone replacement therapy and longer durations of therapy (see Table 2). Urticarial reactions, some of which were not classified as rash, were more common in EG1 patients than in comparator patients (0.6% vs. 0.2%). EG1 should be discontinued in patients developing a rash or urticaria while on treatment. (See ADVERSE REACTIONS and Clinical Studies.)
Table 2. Rash Incidence in EG1 Treated Patients from the Clinical Studies Population* by Gender, Age, and Duration of Therapy
Duration of EG1 Therapy | ||||
Gender & Age (yr) Category | 5 days | 7 days | 10 days** | 14 days** |
Female < 40 | 10/399 (2.5%) | 49/407 (12.0%) | 20/131 (15.3%) | 7/31 (22.6%) |
Female ≥ 40 | 30/1438 (2.1%) | 34/887 (3.8%) | 19/308 (6.2%) | 10/126 (7.9%) |
Male < 40 | 6/356 (1.7%) | 26/453 (5.7%) | 7/74 (9.5%) | 3/39 (7.7%) |
Male ≥ 40 | 10/1503 (0.7%) | 26/984 (2.6%) | 9/345 (2.6%) | 3/116 (2.6%) |
Totals | 56/3696 (1.5%) | 135/2732 (4.9%) | 55/858 (6.4%) | 23/312 (7.4%) |
*includes patients from studies of community-acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, and other indications **exceeds the recommended duration of therapy (see DOSAGE AND ADMINISTRATION)
The most common form of rash associated with EG1 was described as maculopapular and mild to moderate in severity. Eighty percent of rashes resolved within 14 days. Approximately 10% of the rashes (0.5% of all patients) were described as of severe intensity and approximately 10% of those with rash were treated with systemic steroids. There were no documented cases in the clinical trials of more serious skin reactions known to be associated with significant morbidity or mortality.
Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V†area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with use of quinolones after sun or UV light exposure. Therefore excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs. (See ADVERSE REACTIONS and ADVERSE REACTIONS: Post-Marketing Adverse Reactions.)
Hepatic Effects
Liver enzyme elevations (increased ALT and/or AST) occurred at similar rates in patients receiving EG1 320 mg daily relative to comparator antimicrobial agents (ciprofloxacin, levofloxacin, clarithromycin/cefuroxime axetil, amoxicillin/clavulanate potassium, and ofloxacin). In patients who received gemifloxacin at doses of 480 mg per day or greater there was an increased incidence of elevations in liver enzymes. (See ADVERSE REACTIONS.)
There were no clinical symptoms associated with these liver enzyme elevations. The liver enzyme elevations resolved following cessation of therapy. The recommended dose of EG1 320 mg daily should not be exceeded and the recommended length of therapy should not be exceeded. (See DOSAGE AND ADMINISTRATION.)
Renal Effects
Alteration of the dosage regimen is necessary for patientswith impairment of renal function (creatinine clearance ?40 mL/min). (See DOSAGE AND ADMINISTRATION.) Adequate hydration of patients receiving EG1 should be maintained to prevent the formation of a highly concentrated urine.
Information for Patients
Advise the patient to read the FDA-approved patient labeling (Medication Guide)
Serious Adverse Reactions
Advise patients to stop taking EG1 if they experience an adverse reaction and to call their healthcare provider for advice on completing the full course of treatment with another antibacterial drug.
Inform patients of the following serious adverse reactions that have been associated with EG1 or other fluoroquinolone use:
- Disabling and potentially irreversible serious adverse reactions that may occur together, including tendinitis and tendon rupture, peripheral neuropathies, and central nervous system effects, have been associated with use of EG1 and may occur together in the same patient. Inform patients to stop taking EG1 immediately if they experience an adverse reaction and to call their healthcare provider;
- Tendinitis and tendon rupture: instruct patients to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue EG1 treatment. The risk of severe tendon disorders with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants;
- Peripheral neuropathies: Inform patients that peripheral neuropathies have been associated with the use of EG1, that symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, patients should immediately discontinue EG1 and contact their physician;
- Central nervous system effects (for example, convulsions, dizziness, lightheadedness, increased intracranial pressure): Inform patients that convulsions have been reported in patients receiving fluoroquinolones, including EG1. Patients should notify their physician before taking EG1 if they have a history of convulsions, seizures, or epilepsy; Inform patients that other central nervous system problems such as tremors, restlessness, lightheadedness, confusion and hallucinations may occur rarely;
- Exacerbation of Myasthenia Gravis: Inform patients that fluoroquinolones like EG1 may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if they have any worsening muscle weakness or breathing problems;
- Hypersensitivity Reactions: Inform patients that EG1 may be associated with hypersensitivity reactions, including anaphylactic reactions, even following a single dose; patients should immediately discontinue the drug at the sign of a rash or other allergic reaction and seek medical care; Inform patients that EG1 has been associated with rash and hives. Rash occurs more commonly in those under 40, especially women and in women on hormone replacement therapy. The incidence of rash increases with duration more than 5 days and particularly longer than 7 days. Patients should discontinue EG1 and call their healthcare provider if they develop a rash;
- Diarrhea: Inform patients that diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible;
- Prolongation of the QT interval: inform patients of the following:
- that EG1 may cause changes in the electrocardiogram (QTc interval prolongation);
- that EG1 should be avoided in patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents;
- that EG1 should be used with caution in patients receiving drugs that affect the QTc interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants;
- to inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia;
- to contact their physician if they experience palpitations or fainting spells while taking EG1;
- that EG1 may cause dizziness; if this occurs, patients should not operate an automobile or machinery or engage in activities requiring mental alertness or coordination;
- Photosensitivity/Phototoxicity: Inform patients that photosensitivity/phototoxicity has been reported in patients receiving quinolones. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician; (See CLINICAL PHARMACOLOGY: Photosensitivity Potential).
Other Information
Advise Patients:
- that increases of the International Normalized Ratio (INR), or prothrombin time (PT), and/or clinical episodes of bleeding have been noted with concurrent administration of warfarin or its derivatives, and EG1. Patients should notify their physicians if they are taking warfarin or its derivatives;
- to inform their physician of any other medications when taken concurrently with EG1, including over-the-counter medications and dietary supplements; • that EG1 may be taken with or without meals;
- to drink fluids liberally;
- not to take antacids containing magnesium and/or aluminum or products containing ferrous sulfate (iron), multivitamin preparations containing zinc or other metal cations, or Videx? (didanosine) chewable/buffered tablets or the pediatric powder for oral solution within 3 hours before or 2 hours after taking EG1 tablets;
- that EG1 should be taken at least 2 hours before sucralfate;
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long term studies in animals to determine the carcinogenic potential of gemifloxacin have not been conducted.
Photocarcinogenesis
Gemifloxacin did not shorten the time to development of UVR-induced skin tumors in hairless albino (Skh-1) mice; thus, it was not photocarcinogenic in this model. These mice received oral gemifloxacin and concurrent irradiation with simulated sunlight 5 days per week for 40 weeks followed by a 12-week treatment-free observation period. The daily dose of UV radiation used in this study was approximately 1/3 of the minimal dose of UV radiation that would induce erythema in Caucasian humans. The median time to the development of skin tumors in the hairless mice was similar in the vehicle control group (36 weeks) and those given up to 100 mg/kg gemifloxacin daily (39 weeks). Following repeat doses of 100 mg/kg gemifloxacin per day, the mice had skin gemifloxacin concentrations of approximately 7.4 µg/g. Plasma levels following this dose were approximately 1.4 µg/mL in the mice around the time of irradiation. There are no data on gemifloxacin skin levels in humans, but the mouse plasma gemifloxacin levels are in the expected range of human plasma Cmax levels (0.7-2.6 µg/mL, with an overall mean of about 1.6 µg/mL) following multiple 320 mg oral doses.
Mutagenesis
Gemifloxacin was not mutagenic in 4 bacterial strains (TA 98, TA 100, TA 1535, TA 1537) used in an Ames Salmonella reversion assay. It did not induce micronuclei in the bone marrow of mice following intraperitoneal doses of up to 40 mg/kg and it did not induce unscheduled DNA synthesis in hepatocytes from rats which received oral doses of up to 1600 mg/kg. Gemifloxacin was clastogenic in vitro in the mouse lymphoma and human lymphocyte chromosome aberration assays. It was clastogenic in vivo in the rat micronucleus assay at oral and intravenous dose levels (?800 mg/kg and ?40 mg/kg, respectively) that producedbone marrow toxicity. Fluoroquinolone clastogenicity is apparently due to inhibition of mammalian topoisomerase activity which has threshold implications.
Impairment of Fertility
Gemifloxacin did not affect the fertility of male or female rats at AUC levels following oral administration (216 and 600 mg/kg/day) that were approximately 3- to 4-fold higher than the AUC levels at the clinically recommended dose.
Pregnancy
Teratogenic Effects
Pregnancy Category C. Gemifloxacin treatment during organogenesis caused fetal growth retardation in mice (oral dosing at 450 mg/kg/day), rats (oral dosing at 600 mg/kg/day) and rabbits (IV dosing at 40 mg/kg/day) at AUC levels which were 2-, 4- and 3-fold those in women given oral doses of 320 mg. In rats, this growth retardation appeared to be reversible in a pre- and postnatal development study (mice and rabbits were not studied for the reversibility of this effect). Treatment of pregnant rats at 8-fold clinical exposure (based upon AUC comparisons) caused fetal brain and ocular malformations in the presence of maternal toxicity. The overall no-effect exposure level in pregnant animals was approximately 0.8 to 3-fold clinical exposure.
The safety of EG1 in pregnant women has not been established. EG1 should not be used in pregnant women unless the potential benefit to the mother outweighs the risk to the fetus. There are no adequate and well-controlled studies in pregnant women.
Nursing Mothers
Gemifloxacin is excreted in the breast milk of rats. There is no information on excretion of gemifloxacin into human milk. Therefore, EG1 should not be used in lactating women unless the potential benefit to the mother outweighs the risk.
Pediatric Use
Safety and effectiveness in children and adolescents less than 18 years of age have not been established. Fluoroquinolones, including gemifloxacin, cause arthropathy and osteochondrosis in immature animals. (See WARNINGS.)
Geriatric Use
Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as EG1. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. Caution should be used when prescribing EG1 to elderly patients especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue EG1 and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur (See BOXED WARNING, WARNINGS, and ADVERSE REACTIONS/Post-Marketing Adverse Event Reports).
Of the total number of subjects in clinical studies of EG1, 29% (2314) were 65 and over, while 11% (865) were 75 and over. No overall difference in effectiveness was observed between these subjects and younger subjects; the adverse event rate for this group was similar to or lower than that for younger subjects with the exception that the incidence of rash was lower in geriatric patients compared to patients less than 40 years of age.
Elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, EG1 should be avoided in patients taking drugs that can result in prolongation of the QT interval (e.g., Class IA or Class III antiarrhythmics) or in patients with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).
Klinik çalışmalarda 8119 hastaya günlük 320 mg EG1 oral doz verildi. Ek olarak, 1797 sağlıklı gönüllü ve böbrek veya karaciğer yetmezliği olan 81 hasta klinik farmakoloji çalışmalarında tek veya tekrarlı gemifloksasin dozları aldı. Klinik çalışmalarda hastaların yaşadığı advers reaksiyonların çoğunun hafif ila orta şiddette olduğu düşünülmüştür.
EG1, öncelikle döküntü (% 0.8), bulantı (% 0.3), ishal (% 0.3) nedeniyle hastaların% 2.0'ında olumsuz bir olay (araştırmacı tarafından muhtemelen veya muhtemelen ilaçla ilişkili olduğu tespit edilmiştir) nedeniyle kesilmiştir. ürtiker (% 0.2) ve kusma (% 0.2). Karşılaştırıcı antibiyotikler, esas olarak ishal (% 0.5), bulantı (% 0.4), kusma (% 0.3), döküntü (% 0.3), karın ağrısı (% 0.2) nedeniyle genel olarak karşılaştırılabilir bir oranda advers bir olay nedeniyle kesildi. ) ve baş dönmesi (% 0.2). Sıklıkla bildirilen en yaygın advers olaylar ?Karşılaştırıcı ilaca (beta-laktam antibiyotikler, makrolidler veya diğer florokinolonlar) karşı 320 mg EG1 alan hastalar% 2 aşağıdaki gibidir: ishal% 5.0 vs. % 6.2; döküntü% 3.5'e karşı. % 1.1; mide bulantısı% 3.7'ye karşı. % 4.5; baş ağrısı% 4.2'ye karşı. % 5.2; karın ağrısı% 2.2'ye karşı. % 2.2; kusma% 1.6 vs. % 2.0; ve baş dönmesi% 1.7'ye karşı. % 2.6.
Sıklığı% 1'den az olan Olumsuz Olaylar
8119 hastada ilaca bağlı ek advers olaylar (muhtemelen veya muhtemelen ilişkili), sıklığı>% 0.1'dir ?% 1 dahil: karın ağrısı, anoreksiya, kabızlık, dermatit, baş dönmesi, ağız kuruluğu, dispepsi, yorgunluk, şişkinlik, mantar enfeksiyonu, gastrit, genital moniliaz, genital kaşıntı, hiperglisemi, artmış alkalin fosfataz, artmış ALT, artmış kreatin fosfokinaz, uykusuzluk, lökopeni, kaşıntı.
Klinik çalışmalarda bildirilen ve potansiyel klinik öneme sahip olan ve ilaçla şüpheli bir ilişkisi olduğu düşünülen diğer advers olaylar meydana gelmiştir ?Hastaların% 0.1'i: anormal idrar, anormal görme, anemi, artralji, asteni, sırt ağrısı, bilirubinemi, dispne, egzama, eozinofili, yüz ödemi, kızarma, gastroenterit, granülositopeni, sıcak basmaları, artmış GGT, artmış protein olmayan azot, bacak krampları, moniliaz, miyalji. (Görmek ÖNLEMLER.)
Kronik bronşitin (ABECB) ve toplum kaynaklı pnömoninin (CAP) akut bakteriyel alevlenmesinin klinik çalışmalarında, döküntü insidansı aşağıdaki gibidir (Tablo 3):
Tablo 3. EG1 ile Tedavi Edilen Hastalarda Klinik Endikasyonla Döküntü İnsidansı
ABECB (5 gün) N = 2284 | CAP (5 gün) N = 256 | CAP (7 gün) N = 643 | ||||
n / N | % | n / N | % | n / N | % | |
Toplamlar | 27/2284 | 1.2 | 1/256 | 0.4 | 26/643 | 4.0 |
Dişiler, <40 yıl | NA * | 1/37 | 2.7 | 8/88 | 9.1 | |
Dişiler, ≥ 40 yıl | 16/1040 | 1.5 | 0/73 | 0 | 5/214 | 2.3 |
Erkekler, <40 yıl | NA * | 0/65 | 0 | 5/101 | 5.0 | |
Erkekler, ≥ 40 yıl | 11/1203 | 0.9 | 0/81 | 0 | 8/240 | 3.3 |
* anlamlı bir analiz için bu kategorideki yetersiz hasta sayısı (Bkz ÖNLEMLER).
Laboratuvar Değişiklikleri
Birden fazla doz EG1 alan ve laboratuvar anormalliği olan hastaların yüzdeleri aşağıda listelenmiştir. Bu anormalliklerin EG1 veya altta yatan bir durumla ilişkili olup olmadığı bilinmemektedir.
Klinik Kimya: artan ALT (% 1.7) AST arttı (% 1.3) artan kreatin fosfokinaz (% 0.7) artmış alkalin fosfataz (% 0.4) toplam bilirubin arttı (% 0.4) artan potasyum (% 0.3) azaltılmış sodyum (% 0.2) artan kan üre azotu (% 0.3) azalmış albümin (% 0.3) artmış serum kreatinin (% 0.2) azalmış kalsiyum (% 0.1) azalmış toplam protein (% 0.1) potasyum azaldı (% 0.1) artan sodyum (% 0.1) artmış laktat dehidrojenaz (<% 0.1) ve artmış kalsiyum (<% 0.1).
CPK yükselmeleri seyrek olarak kaydedildi: EG1 hastalarında% 0.7'ye karşı. Karşılaştırıcı hastalarda% 0.7.
Hematoloji: artmış trombositler (% 1.0), azalmış nötrofiller (% 0.5), artmış nötrofiller (% 0.5), azalmış hematokrit (% 0.3), azalmış hemoglobin (% 0.2), azalmış kırmızı kan hücreleri (% 0.1), artmış hemoglo.
Klinik çalışmalarda, EG1 ile tedavi edilen hastaların yaklaşık% 7'sinde çalışmaya başlamadan hemen önce ALT değerleri yükselmiştir. Bu hastaların yaklaşık% 15'i tedavi ziyaretinde ALT'larının daha da yükseldiğini ve% 9'u tedavi ziyaretinin sonunda daha fazla yükselme gösterdi. Bu hastaların hiçbiri hepatosellüler sarılık kanıtı göstermedi. Toplanan karşılaştırıcılar için, hastaların yaklaşık% 6'sı çalışmaya girmeden hemen önce ALT değerlerini yükseltmiştir. Bu hastaların yaklaşık% 7'si tedavi ziyaretinde ALT'larının daha da yükseldiğini ve% 4'ü tedavi ziyaretinin sonunda daha fazla yükselme gösterdiğini gösterdi.
638 hastanın 3 gün boyunca tek bir 640 mg doz gemifloksasin veya 250 mg BID siprofloksasin aldığı bir klinik çalışmada, gemifloksasin kolunda (% 3.9) ALT yükselme insidansı artmıştır. karşılaştırıcı kolu (% 1.0). Bu çalışmada, iki hasta normalin üst sınırının 8 ila 10 katı ALT yükselmeleri yaşamıştır. Bu yükselmeler asemptomatik ve geri dönüşümlüdür.
Pazarlama Sonrası Olumsuz Reaksiyonlar
Bildirilen pazarlama sonrası advers olayların çoğu kutanöz ve bunların çoğu döküntüdür. Bu kutanöz advers olayların bazıları ciddi kabul edildi. Döküntülerin çoğu kadınlarda ve 40 yaşın altındaki hastalarda meydana geldi.
Aşağıda, EG1'in pazarlama sonrası kullanımı sırasında bildirilen ek advers reaksiyonlar yer almaktadır. Bu reaksiyonlar, belirsiz büyüklükteki bir popülasyondan gönüllü olarak bildirildiğinden, sıklıklarını güvenilir bir şekilde tahmin etmek veya EG1 maruziyeti ile nedensel bir ilişki kurmak imkansızdır:
- geri döndürülemez olabilecek periferik nöropati;
- anafilaktik reaksiyon, eritema multiforme, cilt pul pul dökülme, yüz şişmesi ;
- miyastenia gravis alevlenmesi;
- kanama, artmış uluslararası normalleştirilmiş oran (INR), retina kanaması;
- periferik ödem;
- böbrek yetmezliği;
- uzun süreli QT, supraventriküler taşikardi, senkop, geçici iskemik atak ;
- ışığa duyarlılık / fototoksisite reaksiyonu (Bkz ÖNLEMLER);.
- antibiyotikle ilişkili kolit;
- tendon rüptürü.
Doz aşımı belirtileri veya semptomları semptomatik olarak tedavi edilmelidir. Spesifik bir antidot bilinmemektedir. Akut oral doz aşımı durumunda, mide kusma indüklenerek veya mide lavajı ile boşaltılmalıdır; hasta uygun hidrasyon korunarak semptomatik olarak gözlemlenmeli ve tedavi edilmelidir. Hemodiyaliz, oral bir gemifloksasin dozunun yaklaşık% 20 ila 30'unu plazmadan çıkarır.
Sıçanlarda 1600 mg / kg ve farelerde 320 mg / kg oral gemifloksasin dozlarında ölüm meydana geldi. Bu türlerde minimum ölümcül intravenöz dozlar sırasıyla 160 ve 80 mg / kg idi. Ataksi, uyuşukluk, piloereksiyon, titreme ve klonik konvülsiyonlar dahil kemirgenlere tek bir yüksek oral doz (400 mg / kg) gemifloksasin uygulandıktan sonra toksik belirtiler.
Gemifloksasinin farmakokinetiği, 40 mg ila 640 mg doz aralığında yaklaşık olarak doğrusaldır. 7 gün boyunca günde 640 mg'a kadar çoklu oral dozların ardından minimal gemifloksasin birikimi vardı (ortalama birikim <% 20). Günde bir kez 320 mg gemifloksasinin tekrar oral uygulamasını takiben, dozlamanın üçüncü günü ile kararlı duruma ulaşılır.
However, we will provide data for each active ingredient