N-亞硝基二甲胺（英語：N-Nitrosodimethylamine, NDMA）又稱二甲基亞硝胺，是一種半揮發性有機化學品，氣味很弱，易溶於水及醇、醚等有機溶劑，極易光解。NDMA具有強肝臟毒性，屬IARC第2A類致癌物質。主要用於火箭燃料、抗氧劑等製造。
N-亞硝基二甲胺由二甲胺與亞硝酸鹽在酸性條件下反應而生成，微量存在於多種食物中，例如：醃製食品、魚、啤酒和菸草煙霧中等，但是它不會在生物體中累積。
N-亞硝基二甲胺還是以氯或二氧化氯消毒自來水時的可能副產物，而用臭氧作消毒劑則不會生成。
NDMA不易降解或揮發，且不能被活性炭吸附，因此不容易從飲用水中去除。
美國環保署已規定飲用水中的N-亞硝基二甲胺最大容許濃度為每升中7奈克，尚未設置飲用水監管的最大污染物水平（MCL）。
N-亞硝基二甲胺急性中毒可引起肝臟損傷、血液血小板計數下降、轉氨酶濃度升高，還包括頭痛，發燒，嘔吐，腹痛，分散性皮下出血，嗜睡，噁心，腹瀉等症狀。
較小劑量的長期暴露也可能增加肝癌風險。N-亞硝基二甲胺小鼠口服半數致死量（LD50）為37.0mg/kg。
比起降血壓藥中的N-亞硝基二甲胺(NDMA)，民眾在日常更容易接觸的是亞硝酸鹽，存在蔬菜、菸、酒、檳榔與醃漬的魚或肉，例如：火腿、培根、熱狗等。
它若在體內和胺作用就會形成致癌物亞硝胺(煙、酒、檳榔中，是直接以亞硝胺形態存在)，會引發肝炎、肝癌、口腔癌、胃癌、食道癌、鼻咽癌、胰臟癌、氣管炎等。當亞硝酸鹽會與腸道或蔬菜、醃漬物等食物中的次級胺結合，會形成亞硝胺，就會對人體產生影響，長期下來就會導致罹癌的風險大增。
因此，平日少吃這些食物，或在食用這些東西先水煮，可降低體內亞硝胺含量。此外，多吃五穀雜糧等高纖維類食物，可促進腸胃蠕動，抑制腸道壞菌生長，減少亞硝酸的合成；而多補充維生素C和益生菌，也可幫助代謝腸道中的亞硝酸鹽，保持腸道平衡。
台灣衛生福利部食品藥物管理署於
2018/7/8
食藥署調查使用中國大陸浙江華海製藥公司valsartan原料藥之異常事件說明
2018/7/9
食藥署調查使用中國大陸浙江華海製藥公司valsartan原料藥之異常事件接續說明
2018/8/2
食藥署全面調查valsartan原料藥異常事件說明
2018/8/3
輸入valsartan原料藥已完成清查，未有新增其他市售藥品受影響
Update on review of recalled valsartan medicines
Update on review of recalled valsartan medicines
Preliminary assessment of possible risk to patients
EMA is conducting a review of the possible health effects in patients who may have taken valsartan medicines containing N-nitrosodimethylamine (NDMA) – an impurity found in the active substance manufactured by Zhejiang Huahai Pharmaceuticals.
NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on animal tests. It is present in some foods and water supplies but is not expected to cause harm when ingested in very low levels.
Following a preliminary evaluation, EMA estimates that there could be one extra case of cancer for every 5,000 patients taking the affected medicines at the highest valsartan dose (320 mg) every day for 7 years. This is based on average levels of this impurity detected in the active substance from Zhejiang Huahai Pharmaceuticals (60 parts per million).
The possible cancer risk has been extrapolated from animal studies and should be considered in the context of the lifetime risk of cancer in the EU (1 in 3) and NDMA exposure from other sources.
This preliminary estimate is based on the assumption that the NDMA present in the active substance is carried over in the final product in the same amount.
Companies that had used the active substance from Zhejiang Huahai in their valsartan medicines are required to test samples they hold to determine the actual NDMA levels in the final products. Additional checks are being carried out by EU official control laboratories. Once data from all these tests are available, EMA will be able to provide more information on the risk that the impurity may have posed for patients in the EU.
It is important to note that there is no immediate risk to patients. Patients taking the affected medicines who have not yet switched to an alternative should not stop taking their medicines without consulting their doctor or pharmacist.
Valsartan medicines are used for patients with serious or potentially serious conditions of the circulatory system (high blood pressure, a recent heart attack and heart failure). It is therefore not advisable to go without treatment if a treatment has been prescribed.
All valsartan medicines containing the active substance from Zhejiang Huahai Pharmaceuticals have been recalled from pharmacies in the EU but several other valsartan medicines not affected by the impurity are available. Patients who want more information about their treatments should contact their doctor or pharmacist. Further information is provided by national medicines authorities.
NDMA was an unexpected impurity believed to have formed as a side product after Zhejiang Huahai introduced changes to its manufacturing process in 2012. No other active substances produced by the company are affected.
EMA is working closely with international partners and will provide further information on its website as the review progresses.
More about the medicine
Valsartan is an angiotensin-II-receptor antagonist used to treat hypertension (high blood pressure), recent heart attack and heart failure. It is available on its own or in combination with other active substances.
The review covers all medicines that contain valsartan supplied by Zhejiang Huahai Pharmaceuticals. As a precaution, the review will also consider whether other valsartan medicines may be affected.
More about the procedure
The review of valsartan medicines in relation to NDMA found in the active substance from Zhejiang Huahai Pharmaceuticals was triggered by the European Commission on 5 July 2018 Article 31 of Directive 2001/83/EC.
The review is being carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt the Agency’s opinion. The CHMP opinion will then be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.
EMA Updates on Recalled Valsartan Medicines
Posted 02 August 2018 | By Ana Mulero
EMA Updates on Recalled Valsartan Medicines
An initial health risk assessment conducted by the European Medicines Agency (EMA) projects a hypothetical increase in cancer cases among patients who took certain medicines with a Chinese company’s active substance that was previously found to contain an impurity.
“There could be one extra case of cancer for every 5,000 patients” who took valsartan supplied by Zhejiang Huahai Pharmaceuticals at its highest dosage each day for seven years, EMA reported on Thursday. The estimates are based on the average levels of the chemical impurity N-nitrosodimethylamine (NDMA) that the company detected in the valsartan medicines.
NDMA had been classified as a probable human carcinogen prior to the investigation that resulted in an international recall of the affected blood pressure and heart medicines.
“The possible cancer risk has been extrapolated from animal studies and should be considered in the context of the lifetime risk of cancer in the EU (1 in 3) and NDMA exposure from other sources,” EMA clarified. “This preliminary estimate is based on the assumption that the NDMA present in the active substance is carried over in the final product in the same amount.”
The recall was initiated throughout Europe in early July, followed by the US Food and Drug Administration (FDA). FDA concluded in its analysis, released last week, that “some levels of the impurity may have been in the valsartan-containing products for as long as four years.”
EMA’s ongoing investigation also requires all drug manufacturers that have used Zhejiang Huahai Pharmaceuticals’ valsartan to test samples to determine NDMA levels in finished medicines. The agency intends to provide another update once these data area available.
