XII. 参考資料
1. 主な外国での発売状況
レボフロキサシン製剤は1993年の日本での承認以降、海外では経口及び注射剤が同時に開発され、米国ではジ ョンソン＆ジョンソン、欧州ではサノフィ・アベンティスにより承認が取得された。主な販売国及び地域を以下 の通り示す。
米国、英国、中国、香港、韓国、台湾、アイルランド、アラブ首長国連邦、アルゼンチン、イスラエル、イタリ ア、インド、インドネシア、エジプト、オーストリア、オランダ、ギリシャ、シンガポール、スイス、スペイン、
タイ、チリ、ドイツ、トルコ、、パキスタン、ハンガリー、ポルトガル、フィリピン、フィンランド、フランス、
ベトナム、ベネズエラ、ベルギー、ロシア連邦等 （2016年9月現在）
主な外国での効能・効果、用法・用量は以下のとおりである。
出典 記載内容
米国の添付文書
（LEVAQUIN, Janssen
Pharmaceuticals, Inc., 2018年7月）
1 INDICATIONS AND USAGE 1.1 Nosocomial Pneumonia
LEVAQUIN® is indicated in adult patients for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae,
Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal
-lactam is recommended [see Clinical Studies (14.1)].
1.2 Community-Acquired Pneumonia: 7–14 day Treatment Regimen LEVAQUIN® is indicated in adult patients for the treatment of
community-acquired pneumonia due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.2)].
MDRSP isolates are isolates resistant to two or more of the following
antibacterials: penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.
1.3 Community-Acquired Pneumonia: 5-day Treatment Regimen LEVAQUIN® is indicated in adult patients for the treatment of
community-acquired pneumonia due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.3)].
Clinical Studies (14.5)].
1.5 Uncomplicated Skin and Skin Structure Infections
LEVAQUIN® is indicated in adult patients for the treatment of uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to
methicillin-susceptible Staphylococcus aureus, or Streptococcus pyogenes.
1.6 Chronic Bacterial Prostatitis
LEVAQUIN® is indicated in adult patients for the treatment of chronic bacterial prostatitis due to Escherichia coli, Enterococcus faecalis, or methicillin-susceptible Staphylococcus epidermidis [see Clinical Studies (14.6)].
1.7 Inhalational Anthrax (Post-Exposure)
LEVAQUIN® is indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis in adults and pediatric patients, 6 months of age and older [see Dosage and Administration (2.2)]. The effectiveness of LEVAQUIN® is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit.
LEVAQUIN® has not been tested in humans for the post-exposure prevention of inhalation anthrax. The safety of LEVAQUIN® in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. Prolonged LEVAQUIN® therapy should only be used when the benefit outweighs the risk [see Clinical Studies (14.9)].
1.8 Plague
LEVAQUIN® is indicated for treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis (Y. pestis) and prophylaxis for plague in adults and pediatric patients, 6 months of age and older [see Dosage and
Administration (2.2)].
Efficacy studies of LEVAQUIN® could not be conducted in humans with plague for ethical and feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in animals [see Clinical Studies (14.10)].
1.9 Complicated Urinary Tract Infections: 5-day Treatment Regimen
LEVAQUIN® is indicated in adult patients for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis [see Clinical Studies (14.7)].
1.10 Complicated Urinary Tract Infections: 10-day Treatment Regimen LEVAQUIN® is indicated in adult patients for the treatment of complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis,
Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa [see Clinical Studies (14.8)].
1.11 Acute Pyelonephritis: 5 or 10-day Treatment Regimen
LEVAQUIN® is indicated in adult patients for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia [see Clinical Studies (14.7, 14.8)].
1.12 Uncomplicated Urinary Tract Infections
LEVAQUIN® is indicated in adult patients for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.
Because fluoroquinolones, including LEVAQUIN®, have been associated with serious adverse reactions [see Warnings and Precautions (5.1–5.14)] and for some patients uncomplicated urinary tract infection is self-limiting, reserve
LEVAQUIN® for treatment of uncomplicated urinary tract infections in patients who have no alternative treatment options.
1.13 Acute Bacterial Exacerbation of Chronic Bronchitis
LEVAQUIN® is indicated in adult patients for the treatment of acute bacterial exacerbation of chronic bronchitis (ABECB) due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.
Because fluoroquinolones, including LEVAQUIN®, have been associated with serious adverse reactions [see Warnings and Precautions (5.1–5.14)] and for some patients ABECB is self-limiting, reserve LEVAQUIN® for treatment of ABECB in patients who have no alternative treatment options.
1.14 Acute Bacterial Sinusitis: 5 -day and 10–14 day Treatment Regimens LEVAQUIN® is indicated in adult patients for the treatment of acute bacterial sinusitis (ABS) due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies (14.4)].
Because fluoroquinolones, including LEVAQUIN®, have been associated with serious adverse reactions [see Warnings and Precautions (5.1–5.14)] and for some patients ABS is self-limiting, reserve LEVAQUIN® for treatment of ABS in patients who have no alternative treatment options.
1.15 Usage
To reduce the development of drug-resistant bacteria and maintain the
effectiveness of LEVAQUIN® and other antibacterial drugs, LEVAQUIN® should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Culture and susceptibility testing
Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see Microbiology (12.4)]. Therapy with
LEVAQUIN® may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected.
As with other drugs in this class, some isolates of Pseudomonas aeruginosa may
2 DOSAGE AND ADMINISTRATION
2.1 Dosage of LEVAQUIN® Tablets in Adult Patients with Creatinine Clearance ≥ 50 mL/minute
The usual dose of LEVAQUIN® Tablets is 250 mg, 500 mg, or 750 mg
administered orally every 24 hours, as indicated by infection and described in Table 1.
These recommendations apply to patients with creatinine clearance ≥ 50 mL/minute. For patients with creatinine clearance less than 50 mL/min,
adjustments to the dosing regimen are required [see Dosage and Administration (2.3)].
Table 1: Dosage of LEVAQUIN® Tablets in Adult Patients with Creatinine Clearance greater than or equal to 50 mL /minute
Type of infection* Dosed Every 24 hours Duration (days)†
Nosocomial Pneumonia 750mg 7 to 14
Commnity Acquired
Pneumonia‡ 500mg‡ 7 to 14
Commnity Acquired
Pneumonia§ 750mg§ 5§
Complicated Skin and Skin
Structure Infections (SSSI) 750mg 7 to 14
Uncomplicated SSSI 500mg 7 to 10
Chronic Bacterial Prostatitis 500mg 28
Inhalational Anthrax (Post-Exposure), adult and pediatric patients weighing 50kg¶,# or greater
Pediatric patients weighing 30 kg to less than 50 kg¶,#
500mg
see Table 2 below (2.2)
60#
60#
Plague, adult and pediatric patients weighing 50kgÞ or greater
Pediatric patients weighing 30 kg to less than 50 kg
500mg
see Table 2 below(2.2)
10 to 14 10 to 14
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)ß
750mg 5
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)à
250mg 10
Uncomplicated Urinary Tract
Infection 250mg 3
Acute Bacterial Exacerbation
of Chronic Bronchitis (ABECB) 500mg 7
Acute Bacterial Sinusitis
(ABS) 750mg 5
500mg 10 to 14
* Due to the designated pathogens [see Indications and Usage (1)].
† Sequential therapy (intravenous levofloxacin to oral LEVAQUIN® tablets) may be instituted at the discretion of the healthcare provider.
‡ Due to methicillin-susceptible Staphylococcus aureus, Streptococcus
pneumoniae (including multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)].
§ Due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage (1.3)].
¶ This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia.
# This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis,
Pseudomonas aeruginosa; and for AP due to E. coli.
Þ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)].
ß The safety of LEVAQUIN® in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged
LEVAQUIN® therapy should only be used when the benefit outweighs the risk.
à Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Higher doses of LEVAQUIN® typically used for treatment of pneumonia can be used for treatment of plague, if clinically indicated.
2.2 Dosage in Pediatric Patients with Inhalational Anthrax or Plague
The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.
Table 2: Dosage in Pediatric Patients ≥ 6 months of age
Type of infection* Dose Frequency Duration† Inhalational Anthrax
(post-exposure)‡,§
Pediatric patients weighing
50kg or greater 500mg every 24
hours 60days§ Pediatric patients weighing
30 kg to less than 50 kg 250 mg every 12
hours 60days§ Plague¶
Pediatric patients weighing
50kg or greater 500mg every 24
hours 10 to 14days Pediatric patients weighing
30 kg to less than 50 kg 250 mg every 12
hours 10 to 14days
* Due to Bacillus anthracis [see Indications and Usage (1.13) ] and Yersinia pestis
exposure to aerosolized B. anthracis.
§ The safety of LEVAQUIN® in pediatric patients for durations of therapy beyond 14 days has not been studied. [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9) ]. Begin LEVAQUIN® Tablets as soon as possible after suspected or confirmed exposure to Yersinia pestis.
2.3 Dosage Adjustment in Adults with Renal Impairment
Administer LEVAQUIN® with caution in the presence of renal insufficiency.
Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.
No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.
In patients with impaired renal function (creatinine clearance <50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations (8.6)].
Table 3 shows how to adjust dose based on creatinine clearance.
Table 3: Dosage Adjustment in Adult Patients with Renal Impairment (creatinine clearance <50 mL/min)
Dosage in Normal Renal Function Every 24 hours
Creatinine Clearance 20 to 49 mL/min
Creatinine Clearance
10 to 19 mL/min Hemodialysis or Chronic
Ambulatory Peritoneal Dialysis (CAPD) 750 mg 750 mg every 48
hours 750 mg initial dose, then 500 mg every 48 hours
750 mg initial dose, then 500 mg every 48 hours 500 mg 500 mg initial
dose, then 250 mg every 24 hours
500 mg initial dose, then 250 mg every 48 hours
500 mg initial dose, then 250 mg every 48 hours 250 mg No dosage
adjustment required
250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required
No information on dosing adjustment is available
2.4 Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins
LEVAQUIN® Tablets and Oral Solution
LEVAQUIN® Tablets and Oral Solution should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions (7.1) and Patient Counseling Information (17)].
2.5 Administration Instructions
Food and LEVAQUIN® Tablets and Oral Solution
LEVAQUIN® Tablets can be administered without regard to food. It is
recommended that LEVAQUIN® Oral Solution be taken 1 hour before or 2 hours after eating.
Hydration for Patients Receiving LEVAQUIN® Tablets, Oral Solution, and Injection
Adequate hydration of patients receiving oral or intravenous LEVAQUIN® should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions (6.1) and Patient Counseling Information (17)].
英国のSPC
（Levofloxacin 500mg Film-coated Tablets, Accord Healthcare
Limited, 2014年10 月）
4. Clinical particulars 4.1 Therapeutic indications
Levofloxacin Tablets is indicated in adults for the treatment of the following infections (see sections 4.4 and 5.1):
• Acute bacterial sinusitis
• Acute exacerbations of chronic bronchitis
• Community-acquired pneumonia
• Complicated skin and soft tissue infections
For the above-mentioned infections Levofloxacin Tablets should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of these infections.
• Pyelonephritis and complicated urinary tract infections (see section 4.4)
• Chronic bacterial prostatitis
• Uncomplicated cystitis (see section 4.4)
• Inhalation Anthrax: post exposure prophylaxis and curative treatment (see section 4.4)
Levofloxacin Tablets may also be used to complete a course of therapy in patients who have shown improvement during initial treatment with intravenous
levofloxacin.
Consideration should be given to official guidance on the appropriate use of antibacterial agents
4.2 Posology and method of administration
Levofloxacin Tablets are administered once or twice daily. The dosage depends on the type and severity of the infection and the sensitivity of the presumed causative pathogen.
Treatment time
The duration of therapy varies according to the course of the disease (see table below). As with antibiotic therapy in general, administration of Levofloxacin Tablets should be continued for a minimum of 48 to 72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.
Indication Daily dose regimen
(according to severity) Duration of treatment (according to severity) Acute bacterial sinusitis 500 mg once daily 10 - 14 days
Acute bacterial
exacerbations of chronic bronchitis
500 mg once daily 7 - 10 days
Community-acquired
pneumonia 500 mg once or twice daily 7 - 14 days Pyelonephritis 500 mg once daily 7 - 10 days Complicated urinary tract
infections 500mg once daily 7 - 14 days Uncomplicated cystitis 250 mg once daily 3 days Chronic bacterial
prostatitis 500 mg once daily 28 days Complicated Skin and soft
tissue infections 500 mg once or twice daily 7 - 14 days Inhalation Anthrax 500mg once daily 8 weeks Special populations
Impaired renal function (creatinine clearance ≤ 50 ml/min) Dosage regimen
250 mg/24 h 500 mg/24 h 500 mg/12 h Creatinine clearance First dose: 250 mg First dose: 500 mg First dose: 500 mg 50-20 ml/min Then: 125 mg/24 h Then: 250 mg/24 h Then: 250 mg/12 h 19-10 ml/min Then: 125 mg/48 h Then: 125 mg/24 h Then: 125 mg/12 h
< 10 ml/min (including haemodialysis and CAPD) 1
Then: 125 mg/48 h Then: 125 mg/24 h Then: 125 mg/24 h
1 No additional doses are required after haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
Impaired liver function
No adjustment of dosage is required since levofloxacin is not metabolised to any relevant extent by the liver and is mainly excreted by the kidneys.
Elderly population
No adjustment of dosage is required in the elderly, other than that imposed by consideration of renal function (see section 4.4 “Tendinitis and tendon rupture” and
“QT interval prolongation”).
Paediatric population
Levofloxacin is contraindicated in children and growing adolescents (see section 4.3).
Method of administration
Levofloxacin Tablets should be swallowed without crushing and with sufficient amount of liquid. They may be divided at the score line to adapt the dose. The tablets may be taken during meals or between meals. Levofloxacin Tablets should be taken at least two hours before or after iron salts, zinc salts, magnesium- or aluminium-containing antacids, or didanosine (only didanosine formulations with aluminium or magnesium containing buffering agents), and sucralfate
administration since reduction of absorption can occur (see section 4.5).
なお、本邦におけるクラビット経口製剤の効能・効果、用法・用量は以下のとおりである。
【効能・効果】
＜適応菌種＞
本剤に感性のブドウ球菌属、レンサ球菌属、肺炎球菌、腸球菌属、淋菌、モラクセラ（ブランハメラ）・カタラ ーリス、炭疽菌、結核菌、大腸菌、赤痢菌、サルモネラ属、チフス菌、パラチフス菌、シトロバクター属、クレ ブシエラ属、エンテロバクター属、セラチア属、プロテウス属、モルガネラ・モルガニー、プロビデンシア属、
ペスト菌、コレラ菌、インフルエンザ菌、緑膿菌、アシネトバクター属、レジオネラ属、ブルセラ属、野兎病菌、
カンピロバクター属、ペプトストレプトコッカス属、アクネ菌、Q熱リケッチア（コクシエラ・ブルネティ）、
トラコーマクラミジア（クラミジア・トラコマティス）、肺炎クラミジア（クラミジア・ニューモニエ）、肺炎 マイコプラズマ（マイコプラズマ・ニューモニエ）
＜適応症＞
表在性皮膚感染症、深在性皮膚感染症、リンパ管・リンパ節炎、慢性膿皮症、ざ瘡（化膿性炎症を伴うもの）、外 傷・熱傷及び手術創等の二次感染、乳腺炎、肛門周囲膿痬、咽頭・喉頭炎、扁桃炎（扁桃周囲炎、扁桃周囲膿痬を 含む）、急性気管支炎、肺炎、慢性呼吸器病変の二次感染、膀胱炎、腎盂腎炎、前立腺炎（急性症、慢性症）、精 巣上体炎（副睾丸炎）、尿道炎、子宮頸管炎、胆嚢炎、胆管炎、感染性腸炎、腸チフス、パラチフス、コレラ、バ ルトリン腺炎、子宮内感染、子宮付属器炎、涙嚢炎、麦粒腫、瞼板腺炎、外耳炎、中耳炎、副鼻腔炎、化膿性唾液 腺炎、歯周組織炎、歯冠周囲炎、顎炎、炭疽、ブルセラ症、ペスト、野兎病、肺結核及びその他の結核症、Q熱
〈効能・効果に関連する使用上の注意〉
咽頭・喉頭炎、扁桃炎（扁桃周囲炎、扁桃周囲膿瘍を含む）、急性気管支炎、感染性腸炎、副鼻腔炎への使用に あたっては、「抗微生物薬適正使用の手引き」2)を参照し、抗菌薬投与の必要性を判断した上で、本剤の投与が 適切と判断される場合に投与すること。
【用法・用量】
通常、成人にはレボフロキサシンとして1回500mgを1日1回経口投与する。なお、疾患・症状に応じて適宜 減量する。
肺結核及びその他の結核症については、原則として他の抗結核薬と併用すること。
腸チフス、パラチフスについては、レボフロキサシンとして1回500mgを1日1回14日間経口投与する。
＜用法・用量に関連する使用上の注意＞
1. 本剤の使用にあたっては、耐性菌の発現等を防ぐため、原則として感受性を確認し、疾病の治療上必要な最 小限の期間の投与にとどめること。
2. 本剤の500mg 1日1回投与は、100mg 1日3回投与に比べ耐性菌の出現を抑制することが期待できる。本剤
の投与にあたり、用量調節時を含め錠250mg及び細粒10％を用いる場合も分割投与は避け、必ず1日量を1 回で投与すること（「薬効薬理」の項参照）。
3. 腸チフス、パラチフスについては、レボフロキサシンとして（注射剤より本剤に切り替えた場合には注射剤 の投与期間も含め）14日間投与すること。
4. 炭疽の発症及び進展の抑制には、欧州医薬品庁（EMA）が60日間の投与を推奨している。
5. 長期投与が必要となる場合には、経過観察を十分に行うこと。
6. 腎機能低下患者では高い血中濃度が持続するので、下記の用法・用量を目安として、必要に応じて投与量を