Niclosamide

السلام عليكم ..
معلومات مفيدة وقيمة بارك الله فيكم ..شكر للاخ المراقب العام و د. مهند .

SAFETY REVIEW OF NICLOSAMIDE

Prepared for Quality Assurance & Safety: Medicines, WHO/PSM for the Expert Committee on the Selection and Use of Essential Medicines meeting, 7-11 March 2005

February 2004


SAFETY REVIEW OF NICLOSAMIDE,
Executive Summary
The WHO Model List of Essential Medicines (2003) includes intestinal anthelminthics (pyrantel and niclosamide) and antischistosomal and antitrematodes (oxamniquine and triclabendazole). The continued inclusion of oxamniquine, triclabendazole, pyrantel and niclosamide on the EML has been questioned on the basis of their public health relevance and/or efficacy and/or safety. These four medicines among others will be reviewed at the next meeting of the Expert Committee (March 2005).

Introduction
Parasitic infections are a major cause of disease burden, particularly in many countries in the tropics and sub-tropics. Several millions of people suffer because of diseases caused by schistosomes and other trematodes, and soil transmitted helminths. The importance of schistosomiasis and soil-transmitted helminthsic infections have been recognised as priority health problems and through guidelines and technical assistance WHO has encouraged member

In the 2003 review of the Model List of Essential Medicines several drugs were flagged for consideration, by the Expert Committee at its next meting, of their continued inclusion on the

This report examines the safety of niclosamide as used in humans. It must be noted that these drugs have been used extensively in veterinary practice.

Main Outcome
The safety profile of niclosamide in humans.

Results
The safety assessment of niclosamide is presented below. Very few studies were found that provided detailed information on safety of the medicines.


NICLOSAMIDE
Niclosamide (2', 5-Dichloro-4'-nitrosalicylanilide; 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide) is a nitrosalicylanilide introduced in early 1960s as an anticestodal drug. The drug has been used extensively since then and is listed on the WHO Model List of Essential Medicines 2003 and the WHO Model Formulary 2004.


Indication
An anthelmintic which is active against most tapeworms, including the beef tapeworm (Taenia saginata), the pork tapeworm (T. solium), the fish tapeworm (Diphyllobothrium latum), the dwarf tapeworm (Hymenolepis nana), and the dog tapeworm (Dipylidium caninum).

Adverse Effects
The WHO Model Formulary 2004 lists the adverse effects of niclosamide as follows: nausea, retching, abdominal pain; light-headedness, pruritus. Although there were several publications on the use of niclosamide in taeniasis, few provided enough information about adverse effects.


Since 1975, there have been 84 reports of suspected adverse drug reactions to niclosamide in the WHO database. These 84 reports involve 173 reactions from 16 countries (figures 1 and 2). The most common adverse reactions are those involving the skin and appendages (41), gastrointestinal tract (37) and cardiovascular system (28). There were 9 reports of anaphylactic shock and anaphylactoid reactions.

A recent review of adverse events to anthelmintics in the French national pharmacovigilance database revealed that adverse drug reactions in 9 subjects were reported between 1985 and 1999 (Bagheri et al., 2004). The majority of the reports related to the use of the drug in tapeworm infection. The ADRs occurring during treatment for taeniasis were abdominal pain and vomiting – 3; dizziness – 2 and one each of polymorph erythema, sweating and anaphylactoid reaction (requiring hospitalization).

Safety in children and pregnancy
According to Martindale, The Extra Pharmacopoeia, there is no contra-indication for the use of niclosamide in both small children and pregnant women.
Pregnancy
FDA Pregnancy Category B. According to Martindale, The Extra Pharmacopoeia, there is no contra-indication for the use of niclosamide in pregnant women.
Breast Feeding
No data on distribution into milk. No effects in humans documented.
Paediatrics: No paediatric specific problems documented and niclosamide is not contra-indicated in small children.
Geriatrics: No information available
Carcinogenicity: No human studies and animal data to suggest carcinogenicity
Mutagenicity: No studies available
Medical considerations: None known except hypersensitivity to niclosamide

Drug Interactions
Niclosamide is soluble in alcohol which enhances its absorption raising the possibility of dose related adverse effects. Alcohol intake is therefore restricted during treatment with niclosamide.
Discussion
Niclosamide is a well established drug which has been used in several countries since 1960. Whilst the absence of formal pharmacovigilance systems in most of the countries where the drug has been widely deployed limits the safety data available for analysis, anecdotal evidence and the published literature points to a dearth of adverse events in its usage. If there are substantial safety concerns associated with the use of niclosamide, these will have been noted during its 40 years of usage.
Conclusions
The current review supports the continuous use of niclosamide as no major safety concerns have been raised. Its safety in children and pregnant women and efficacy and safety in treating T. solium carriers even in the presence of (neuro)cysticercosis is an advantage over praziquantel.



Comment: Even if one paper is published (not under publication) on the carcinogenecity or mutagenicity, that does not mean that the drug will be automatically banned. It has to go through a stringent chemical review.

The drug belongs to a group of chemicals which are the salicylanilides (closantel, niclosamide, oxyclozanide, rafoxanide), the phenylsulfonamide clorsulon, the biphenylsulfides bithionol and febantel, and nitroscanate and nitroxynil are structurally similar with all containing one or more phenyl groups with halide or phenolic hydroxyls and/or nitro group substitutions. They are among the older anthelmintics developed for veterinary medicine and are still used. If the carcinogenicity or mutogenicity has been established for any of the group , then the whole group of chemicals will be banned from use in vet medicines.

اخي العزيز الدكتور المراقب المحترم

بعد ان اقتنعت تماما بالادلة وكما وضحت بمساهمتي السابقة وهي دراسة حديثة وتعتبر هي الاحدث من نوعها لحد الان والبحث من جامعة برمنكهام/الولايات المتحدة الامريكية
ان مااضافه استاذي الدكتور عادل المحترم يصب بنفس الهدف ولاوجود لحد الان لراي يخالف استعمال الدواء لمعالجة الديدان وله مفعول تثبيطي لخلايا السرطان ؟

حيث توضيحا لمساهمتي السابقة التي توضح عدم استخدام الدواء Niclosamide حديثا في الولايات المتحدة حيث تم ايقاف تصنيعه منذ 2009 فهذا وحسب مناقشتي المستفيضة مع اخي د.عادل بانه لايدل بان السبب هو كون المادة مسرطنة بل ياتي بسبب خلو الولايات المتحدة من الامراض الديدان التي يستعمل هذا الدواء لمعالجتها !
اعيد الاقتباس

اقتباس :

Oral medications used to treat tapeworms - oral medication such as, praziquantel (Biltricide) or albendazole (Albenza) and niclosamide can be prescribed. Niclosamide is not currently available in the U.S. (November, 2009). In the United Kingdom, niclosamide and praziquantel are only available on a named-patient - because tapeworm infections in the UK are so rare, your doctor or pharmacist may have to make special arrangements to get the medicine.

اما الراي المقنع الان بان هذا الدواء يلعب دورا مهما لتاثيره بمنع نمو او تثبيط الاورام السرطانية هو يعتبر السائد واما الاراء الاخرى فنحتاج الى ادلة مثبتة كبحث منشور من مواقع معتمدة يوضح العكس لانني لم اجد طوال بحثي خلال الفترة السابقة عن هذا المرض اي شئ بخصوص ذلك... ولكنني وجدت اعداد من البحوث تثبت هذا الراي المقنع ولكنني اقتبست اخر دراسة فقط كونها بحث جديدويمكنني اضيف اعداد اخرى من المصادر ان تطلب الامر ذلك

فارجوا ان توفرت لديكم الدراسة التي ذكرتها بالمكسيك باعتبار هذا الدواء مسرطنا نرجوا ان يتم البحث عنها ونشرها لمزيد من المعرفة والاطلاع عليها كونها تعتبر الدراسة الاولى التي توضح عكس الاجماع

اما بخصوص ردود الفعل لزملائنا في المختبرات فيمكن لك الحق فيما طرحت لان مع الاسف لم يتواصلوا معنا الا بعد ان تم انتقاد ما... وعلما انه كان انتقادا بناءا ولم يقصد منه الاساءة او التشكيك بمهاراتهم او علميتهم ...لان كما تعرف نحن العراقيين لانقبل اي انتقاد من اي مصدر كان؟؟؟
فلذا اتمنى من جميع الزملاء المشاركة والتواجد الفعلي في المنتدى لكي يتحقق الهدف الرئيسي من انشاء المنتدى وهو تبادل المعلومات والاخبار والتواصل مع الاخرين ..
لذا اهيب باخي الدكتور باسم العضاض /مدير المختبرات ان يرشح احدا من الكادر العلمي والفني بالمختبر ليكون مخولا بالرد والتوضيح لما يتساءل عنه الزملاء..ويزودنا بشكل متعاقب الانجازات التي يقوم بها المختبر البيطري بكل اقسامه ..وان مالديهم ومايخزنوه كما هائلا حتما ونحن ماننتظره منهم كبير جدا لانني اثق تماما باخي د.باسم وبجميع الزملاء والكادر الفني في المختبر ..بانهم سيلبوا ندائنا سريعا..لانهم لم يقصروا بخدمة زملائهم...فالف تحية لهم جميعا

اخي العزيز
اتمنى ان تقبل مقترحي بتغيير عنوان المساهمة من دواء ممنوع ....الى Niclosamide لكي يتسنى لمن يبحث عن معلومات عن هذا الدواء الحصول عليها وبسرعة ....شنو رايك؟؟

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