英文药名: XIFAXANTA(Rifaximin film-coated tablets)

中文药名: 利福昔明膜包衣片

生产厂家: 英国Norgine制药
药品介绍
药理作用
药理作用：利福昔明是广谱肠道抗生素。它是利福霉素SV的半合成衍生物。利福昔明和其它利福霉素类抗生素一样，通过与细菌DNA-依赖RNA聚合酶的B-亚单位不可逆转地结合而抑制细菌RNA的合成，最终抑制细菌蛋白质的合成。由于其与酶的结合是不可逆的，所以其活性为对敏感菌的杀菌活性。对利福昔明抗菌活性的研究资料显示，本品与利福霉素具有同样广泛的抗菌谱，对多数革兰氏阳性菌和革兰氏阴性菌，包括需氧菌和厌氧菌的感染具有杀菌作用。由于利福昔明口服时不被胃肠道吸收，所以它是通过杀灭肠道的病原体而在局部发挥抗菌作用。毒理作用：重复给药毒性：大鼠每天口服本品25,50及100mg/kg，连续180天后，耐受性好，除雌鼠血清总胆固醇呈剂量相关性增加外(可能为对肠道菌群产生作用的结果)，未见其他异常改变。遗传毒性：体内外研究未见本品有致突变作用。生殖毒性：大鼠及家兔给予本品50及100mg/kg未见致畸作用及其他生殖毒性。
药代动力学
在鼠，家狗和人体药代动力学的研究证明，本品经口服不被吸收(吸收小于1%)。
适应症
对利福昔明敏感的病原菌引起的肠道感染，包括急性和慢性肠道感染，腹泻综合症，夏季腹泻，旅行者腹泻和小肠结肠炎等。
用法用量
成人口服。每次0.2g(1片)，每日3-4次。
6-12岁儿童口服。每次0.1-0.2g(0.5-1片)，每日4次。
12岁以上儿童，剂量同成人。
可根据医嘱调节剂量和服用次数。除非是遵照医嘱的情况下，每一疗程不应超过7天。
不良反应
部分患者用药后可出现恶心（通常出现在第一次服药后），但症状可迅速消退。大剂量长期用药，极少数患者可能出现蕈麻疹样皮肤反应。
1，中枢神经系统有出现头痛的报道。
2，代谢/分泌系统肝性脑病患者服用本药后可出现体重下降，血清钾和血清钠浓度轻度升高。
3，胃肠道系统常见的症状为腹涨，腹痛，恶心和呕吐。以上症状发生率者均低于1%。
4，皮肤大剂量长期用药，极少数患者可能出现蕈麻疹样皮肤反应。
5，其他有用药后可能引起足水肿的报道。
禁 忌
以下患者禁用：
1.对本药或利福霉素过敏者；
2.肠梗阻者；
3.严重的肠道溃疡性病变者。
注意事项
1.儿童连续服用本药不能超过7日。
2.对6岁以下儿童建议不要服用本药片剂。
3.长期大剂量用药或肠黏膜受损时，会有极少量（少于1%）被吸收，导致尿液呈粉红色。
4.请置于儿童触及不到的地方。
5.如果出现对抗生素不敏赶的微生物，应中断治疗并采取其他适当治疗措施。
6.对驾驶和操纵机器的影响，未知。
孕妇及哺乳期妇女用药
1.药物对妊娠的影响：动物实验本药无致畸作用。但妊娠期妇女用药的安全性和有效性尚不明确。因此，妊娠期妇女需权衡利弊后用药。
2.药物对哺乳的影响：本药口服后只有极少量被吸收，在乳汁中的浓度也极低，哺乳期妇女可在有适当医疗监测的情况下服用本药。
儿童用药
建议6岁以下儿童不要服用，6岁及6岁以上儿童服用方法请参见[用法用量]。
药物相互作用
口服利福昔明只有少于1%口服剂量经胃肠道吸收，所以利福昔明不会引起因药物的相互作用而导致的全身问题。
药物过量
试验证明服用本品剂量达1.6g/日，既没有局部也没有全身的不良事件发生。一旦过量服用应洗胃，并配合其他适当治疗。
包装规格
200mg片* 27片/盒 
生产商：
英国 Norgine Pharmaceuticals 生产

XIFAXANTA 200 mg Film-coated Tablets
1. Name of the medicinal product
▼ Xifaxanta 200 mg film-coated tablets
2. Qualitative and quantitative composition
One film-coated tablet contains:
Rifaximin 200 mg
Excipients:
For a full list of excipients, see section 6.1.
3. Pharmaceutical form
Film-coated tablet
Pink circular biconvex film-coated tablets, with “AW” printed on both sides.
4. Clinical particulars
4.1 Therapeutic indications
Xifaxanta 200mg film-coated tablets are indicated for the treatment of travellers' diarrhoea that is not associated with any of:
Fever
Bloody diarrhoea
Eight or more unformed stools in the previous 24 h
Occult blood or leucocytes in the stool.
Xifaxanta 200mg film-coated tablets may shorten the duration of diarrhoea when this is associated with non-invasive strains of E.coli (see sections 4.4 and 5.1).
4.2 Posology and method of administration
Posology
200 mg every 8 hours for three days (total 9 doses).
Rifaximin must not be used for more than 3 days even if symptoms continue and a second course of treatment must not be taken (see section 4.4).
Rifaximin can be administered with or without food.
Paediatric population
The safety and efficacy of Xifaxanta 200 mg film-coated tablets in children (aged less than 18 years) have not been established.
A dosage adjustment for patients with hepatic or renal insufficiency is not necessary.
Method of administration
Orally with a glass of water.
4.3 Contraindications
Hypersensitivity to the active substance, to any rifamycin (e.g. rifampicin or rifabutin) or to any of the excipients.
4.4 Special warnings and precautions for use
Clinical data have shown that Rifaximin is not effective in the treatment of travellers' diarrhoea caused by invasive enteric pathogens such as Campylobacter, Salmonella and Shighella, which typically produce dysentery-like diarrhoea characterised by fever, blood in the stool and high stool frequency.
If symptoms worsen treatment with Rifaximin should be interrupted.
If symptoms have not resolved after 3 days of treatment, or recur shortly afterwards, a second course of Rifaximin should not be administered.
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including Rifaximin. The potential association of Rifaximin treatment with CDAD and pseudomembranous colitis (PMC) cannot be ruled out.
Paediatric population
Xifaxanta 200 mg film-coated tablets are not recommended for use in children (<18 years old).
4.5 Interaction with other medicinal products and other forms of interaction
There is no experience regarding administration of rifaximin to subjects who are taking another rifamycin antibacterial agent to treat a systemic bacterial infection. Due to the lack of data and the potential for severe disruption of gut flora with unknown consequences rifaximin should not be administered concomitantly with other rifamycins.
Due to the negligible gastrointestinal absorption of orally administered Rifaximin (less than 1%), the systemic drug interaction potential is low.
In vitro data show that Rifaximin is a weak inducer of the CYP3A4 isoenzyme of the P450 cytochrome. Drug-drug interaction studies investigating the clinical interaction between Rifaximin and drugs metabolised by the human cytochrome P450 isoenzymes demonstrated that Rifaximin did not significantly affect the pharmacokinetics of midazolam or an oral contraceptive containing ethinyl estradiol and norgestimate. Therefore, clinical interactions with drugs metabolised by these isoenzymes are not expected.
The potential for drug-drug interactions to occur at the level of gut transporter systems has not been evaluated and cannot be ruled out.
No drug interaction studies investigating the concomitant intake of Rifaximin and other drugs that might be used during an episode of travellers' diarrhoea (e.g. loperamide, charcoal) are available. Patients should take Rifaximin at least 2 hours after the administration of charcoal.
4.6 Fertility, pregnancy and lactation
For Rifaximin no clinical data on exposed pregnancies are available.
Animal studies have shown reproductive toxicity (see 5.3).
Rifaximin is not recommended during pregnancy and in women of childbearing potential not using contraception (see Section 5.3).
It is not known whether rifaximin is excreted in human milk. A decision should be taken whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
In clinical controlled trials dizziness has been reported but rifaximin has negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
In clinical studies in subjects who received Rifaximin for treatment of travellers' diarrhoea Adverse Reactions considered as being at least possibly related to Rifaximin have been categorised by organ system and frequency.

MedDRA System Organ Class (ver. 12.1)	Common (≥1/100 to <1/10)	Uncommon (≥ 1/1.000 to < 1/100)
Infections and infestations		Candidiasis, Herpes simplex, Nasopharyngitis, Pharyngitis, Upper respiratory tract infection
Blood and lymphatic system disorder		Lymphocytosis, Monocytosis, Neutropenia
Metabolism and nutrition disorders		Decreased appetite, Dehydration
Psychiatric Disorders		Abnormal dreams, Depressed mood, Insomnia, Nervousness
Nervous system disorders	Dizziness, Headache	Hypoesthesia, Migraine, Paraesthesia, Sinus headache, Somnolence
Eye disorders		Diplopia
Ear and labyrinth disorders		Ear pain, Vertigo
Cardiac disorders		Palpitations
Vascular disorders		Blood pressure increased Hot flush
Respiratory, thoracic, and mediastinal disorders		Cough, Dry throat, Dyspnoea, Nasal congestion, Oropharyngeal pain, Rhinorrhea
Gastrointestinal disorders	Abdominal pain, Constipation, Defecation urgency, Diarrhoea, Flatulence, bloating and distension, Nausea and vomiting symptoms, Rectal tenesmus	Abdominal pain upper, Dry lips, Dyspepsia, Gastrointestinal motility disorder, Faeces hard, Haematochezia, Mucous stools, Taste disorders
Hepatobiliary disorders		Aspartate aminotransferase increased
Skin and subcutaneous tissue disorders		Rashes, eruptions and exanthemas NEC Sunburn
Musculoskeletal and connective tissue disorders		Back pain, Muscle spasms, Muscular weakness, Myalgia Neck pain
Renal and urinary disorders		Blood in urine present Glycosuria, Pollakiuria, Polyuria Proteinuria
Reproductive system and breast disorders		Polymenorrhoea
General disorders and administration site conditions	Pyrexia	Asthenic conditions, Chills, Cold sweat, Hyperhidrosis, Influenza like illness, Oedema peripheral, Pain and discomfort NEC

Post-marketing experience
During post-approval use of Rifaximin further undesirable effects have been reported.
The frequency of these reactions is not known (cannot be estimated from the available data).

MedDRA System Organ Class (ver. 12.1)	Frequency not known
Infections and infestations	Clostridial infections
Blood and lymphatic system disorder	Thrombocytopenia
Immune system disorders	Anaphylactic responses, Angioedemas, Hypersensitivity
Vascular disorders	Presyncope
Hepatobiliary disorders	Liver function tests abnormalities
Skin and subcutaneous tissue disorders	Dermatitis Eczema Erythemas Pruritus NEC Urticarias
Investigations	International normalised ratio abnormalities

4.9 Overdose
No case of overdose has been reported.
In clinical trials with patients suffering from travellers' diarrhoea doses of up to 1800 mg/day have been tolerated without any severe clinical signs.
In case of overdose gastric emptying and administration of appropriate supportive treatment are recommended.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: intestinal anti-infective agents, antibiotics. ATC code: A07AA11
Mode of action
Rifaximin is an antibacterial agent of the rifamycin class that binds irreversibly to the beta sub-unit of the bacterial enzyme DNA-dependent RNA polymerase and consequently inhibits bacterial RNA synthesis.
Mechanism of resistance
The main mechanism of acquiring resistance to rifaximin appears to involve: a mutation in the rpoB gene encoding the bacterial RNA polymerase.
Susceptibility
Rifaximin is a non-absorbed antibacterial agent.In vitro susceptibility testing cannot be used to reliably establish susceptibility or resistance of bacteria to Rifaximin. There are currently insufficient data available to support the setting of a clinical breakpoint for susceptibility testing.
5.2 Pharmacokinetic properties
Absorption
Pharmacokinetic studies in rats, dogs and humans demonstrated that after oral administration Rifaximin in the polymorph α form is virtually not absorbed (less than 1%). Following the administration of therapeutic doses of Rifaximin in healthy volunteers and patients with damaged intestinal mucosa (Inflammatory Bowel Disease), plasma levels are negligible (less than 10 ng/ml). Systemic absorption of Rifaximin is increased but not by a clinically relevant extent by administration within 30 minutes of a high-fat breakfast.
Elimination
The urinary recovery of Rifaximin does not exceed 0.4% of the administered dose.
Special Populations
No clinical data are available on the use of Rifaximin in patients with impaired renal function.
In patients with hepatic encephalopathy mean peak plasma concentrations of 13.5 ng/mL Rifaximin were detected after administration of 800 mg Rifaximin three times daily for 7 days. Less than 0.1% of the administered dose was recovered after 7 days. Because of the limited systemic absorption of Rifaximin, no specific dosing adjustments are recommended for patients with hepatic insufficiency.
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity Morphological alterations have been observed in the foetuses of Rifaximin orally administered rats and rabbits.
6. Pharmaceutical particulars
6.1 List of excipients
Tablet core:
Sodium starch glycolate type A
glycerol distearate
colloidal anhydrous silica
talc
microcrystalline cellulose
Tablet coating:
hypromellose,
titanium dioxide
disodium edetate
propylene glycol
red iron oxide E172.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
Original packing: 3 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
PVC/PE/PVDC -Aluminium blister pack containing 9 tablets.
6.6 Special precautions for disposal and other handling
No special requirements.
7. Marketing authorisation holder
Norgine Pharmaceuticals Limited
Moorhall Road
Harefield
Uxbridge
UB9 6NS
8. Marketing authorisation number(s)
PL 20011/0021
9. Date of first authorisation/renewal of the authorisation
02/12/2010 / 01/12/2015
10. Date of revision of the text
01/06/2011