Nitroglycerin - Proper storage can save lives

Author: Zhang Qingxia, Deputy Chief Pharmacist, Xuanwu Hospital, Capital Medical University

Reviewer: Liu Zhijun, Chief Pharmacist, Beijing Anzhen Hospital, Capital Medical University

Figure 1 Copyright image, no permission to reprint

Once, Mr. Li, 57, went to the hospital for angina pectoris. The doctor prescribed nitroglycerin tablets and other secondary prevention drugs for coronary heart disease. It was the first time Mr. Li took nitroglycerin tablets sublingually. At that time, he felt a strong tingling sensation under his tongue, and the angina pectoris was quickly relieved. After that, Mr. Li carried nitroglycerin tablets close to his body (placed in his trouser pocket) for a long time.

A year later, when Mr. Li's angina pectoris attacked again, he took out the nitroglycerin tablets he carried with him and placed them under his tongue as usual. However, this time Mr. Li did not feel a strong tingling sensation, but a sweet taste, and the symptoms were relieved after taking two tablets at an interval.

Mr. Li was very puzzled: What on earth is going on? Last time, I took one nitroglycerin tablet and it was relieved. This time, I took two tablets and it was better. I took the same medicine, so why didn't it work this time?

With a lot of doubts, Mr. Li came to the hospital's "Coronary Intervention + Drug Therapy Management Joint Clinic" to consult a doctor and pharmacist. The pharmacist learned about Mr. Li's medical history, looked at the medicine he brought with him, which was also the medicine he took during his most recent angina attack, and told Mr. Li that he could no longer take the nitroglycerin tablets he was taking because they had gone bad.

"Ah? I just opened this bottle not long ago, how come it has gone bad?" Mr. Li was even more confused. The pharmacist explained: "Nitroglycerin needs to be stored properly after opening. If it is not stored properly, it will easily go bad."

So what kind of medicine is nitroglycerin? How to store it correctly after opening? How long is the shelf life? For this reason, the author has conducted a nationwide survey on the storage knowledge and status of nitroglycerin tablets after opening for medical staff and patients who are using nitroglycerin. The survey found that medical staff and patients have a serious lack of knowledge about the storage of nitroglycerin after opening. Especially in the hot summer, nitroglycerin is more likely to lose its effectiveness. Today we will learn about the storage and shelf life of nitroglycerin.

1.What disease is nitroglycerin mainly used to treat?

Let's first understand the indications of the drug nitroglycerin. Nitroglycerin is mainly used to relieve acute attacks of angina pectoris. Its main pharmacological effect is to relax vascular smooth muscle, thereby dilating blood vessels and reducing the preload and postload of the heart. At therapeutic doses, this drug can lower systolic blood pressure, diastolic blood pressure and mean arterial pressure. Nitroglycerin is absorbed quickly and completely when taken sublingually, with a bioavailability of up to 80%. It takes effect in 2 to 3 minutes, reaches the maximum effect in 5 minutes, and lasts for 20 to 30 minutes. In the case of acute ischemic attacks of chronic stable angina pectoris, nitroglycerin should be used first to terminate the attack. When taking it sublingually, you should sit up as much as possible to avoid aggravating the hypotensive reaction. For those with frequent attacks of angina pectoris, it can be taken prophylactically 5 to 10 minutes before straining to defecate or working.

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2. How to store nitroglycerin correctly?

(1) Storage method and expiration date of nitroglycerin before opening

Nitroglycerin is available in tablets, aerosols, sprays and other dosage forms. Each dosage form should be protected from light, sealed and stored in a cool place (not exceeding 20°C) before opening. The shelf life is generally 24 months. The storage instructions of different manufacturers vary slightly, as follows.

Figure 3 Copyright image, no permission to reprint

(2) Storage method and expiration date of nitroglycerin after opening

Take nitroglycerin tablets as an example. Since the active ingredients contained in nitroglycerin tablets can easily evaporate from the tablets, users should follow the following conditions after opening to ensure the continued efficacy of the tablets.

1) If the tablet is not used within 8 weeks after opening the bottle, please buy a new one. The validity period of nitroglycerin tablets after opening is up to 8 weeks, so the remaining medicine should be stopped after 8 weeks of opening, and the old tablets should be returned to the pharmacist; the new tablet will produce a slight burning sensation when placed under the tongue. If there is no slight burning sensation when taking it, it means that the drug effect has disappeared and a new drug needs to be obtained; in any case, do not use the tablet after the expiration date displayed.

2) Nitroglycerin tablets should be placed in a sealed glass container with a foil-lined lid, as other materials will absorb nitroglycerin.

3) After each use, close the bottle cap tightly. Studies have found that under the same conditions, the sealing degree of the medicine bottle is closely related to the content of nitroglycerin tablets. Therefore, repeated opening and improper sealing are one of the important reasons for the decrease in the content of nitroglycerin tablets.

4) Do not put cotton, other medicines or anything else in the bottle of tablets, because many materials including cotton can easily absorb nitroglycerin and cause its content to decrease.

5) The tablets should be stored in a dry place below 20°C (refer to the drug instructions for details) and away from light. Therefore, if you want to carry it with you, please do not hold it close to your skin.

Note: Please keep this medicine out of sight and reach of children.

3.Why can’t nitroglycerin tablets be carried on the body?

Nitroglycerin needs to be carried with you, but it cannot be carried close to your body (such as in a coat pocket or trouser pocket), because studies have found that the temperature of a trouser pocket is 7°C higher than the temperature of a wallet and 9°C higher than the ambient temperature. The higher the temperature, the faster the nitroglycerin content decreases, and the shelf life will be significantly shortened. For example, the storage conditions of nitroglycerin tablets produced by a certain company on the instructions for December 1, 2015 are "shaded, sealed, and stored in a cool place (not exceeding 20°C)", and the unopened shelf life is 36 months. However, the storage conditions of the instructions for December 1, 2020 increase the storage temperature from "a cool place (not exceeding 20°C)" to "stored below 25°C", and the unopened shelf life is reduced to 24 months. Based on this, we can infer that if the temperature rises by 5°C, the shelf life of the unopened nitroglycerin tablets will be shortened by 12 months. Therefore, if you need to carry nitroglycerin with you, do not carry it close to your body, but put it in a wallet, purse or handbag that you carry with you.

4. How to identify whether nitroglycerin is ineffective by taste?

Normal nitroglycerin tablets will produce a slight burning sensation when placed under the tongue; if there is no such feeling, it means that the active ingredient has evaporated and a fresh tablet should be obtained. In the opening case, Mr. Li only tasted sweetness when he took nitroglycerin sublingually for the second time because the active ingredient nitroglycerin had evaporated, leaving only the sweetness of the auxiliary material. At this time, the nitroglycerin had lost its efficacy. Once again, we remind all patients with angina pectoris that if there is no burning sensation when taking nitroglycerin tablets sublingually, do not take them again and replace them with new tablets.

References

[1] Ding Qian, Li Boyu, Zhang Qingxia. Investigation and prevention of storage risks of nitroglycerin after opening[J]. Chinese Journal of Pharmacovigilance, 2023, 20(3): 326-330.

[2] Chinese Society of Cardiology, Editorial Board of Chinese Journal of Cardiology. Expert consensus on the standardized use of nitrates in cardiovascular disease[J]. Chinese Journal of Cardiology, 2010, 38(9): 770-774.

[3] Chen Yuzhen, Liang Cunxian, Wang Xiaohua, et al. Study on the stability of nitroglycerin tablets under different conditions [J]. Chinese Journal of Pharmaceutical Sciences, 1993, 28(3): 150-151+189.

[4] FELTON LA, LAUBER DA, KOURY J, et al. Readers' Comments an explanation for the effect of different storage conditions on sublingual nitroglycerin tablet stability[J]. Am J Cardiol. 2019, 124(6): 990-991.