Pharmacy/Extended release medication
QUESTION: Hello Doctor. My mother, age 89, has taken the medication Aggrenox for 10 years. (Generic name is dipyridamole, in combination with aspirin.) It is used every 12 hours as an antiplatelet to prevent stroke. It is a capsule that contains a small aspirin tablet, and also many tiny units of dipyridamole. My mother can no longer swallow the capsule. A pharmacist had told me that the capsule could be opened, the aspirin tablet could be crushed, but not to crush the dipyridamole units. Then add it all to something for her to drink. More recently I've read that the capsule should never be opened. Opening it can cause the release of too much medication at one time. I would like to know how the dipyridamole units are made, and how the medication is released over time. And in general, not just for this particular medication, I wonder how the extended release works. Since I have no education in this subject, I would assume that not all of the units of each medication are created equally, and that maybe some units have more protective coating than others so that they take longer to become active. But they are all within the same capsule. Is there a fairly simple way to explain it to those of us not trained in this subject? I wonder if the manufacturer of the Aggrenox capsules states that they should never be opened only as a precaution in case the medication might be crushed? Or is it safe to open the capsule but not crush the dipyridamole inside? Thank you very much.
ANSWER: Hi Vicki,
Sorry for the delay in replying. I was out of town and not carrying my laptop. The product you are asking about is Aggrenox which contains dipyridamole and aspirin. The capsule contains a tab of aspirin 25 mg and dipyridamole 200mg in a sustained release form. The yellow colored pellets contain dipyridamole in a sustained release (SR) form. The product is of Behringer Ingelheim, who have the best technology in this form of drugs.
SR formulations are of various types, the one used in Aggrenox uses the pellet technology. In this technology the following method is employed.
Pellets of the drug are prepared using wax like substances, and they are usually made in four or five lots. Each lot has a different dissolution pattern, so that one dissolves in 5 hours, another dissolves in 10 hours, one in 15 hours and one in 20 hours (this is an example).
Then the four lots are thoroughly mixed so that the mixture contains an equal number of the four types of pellets. These are packed in capsules with a tablet of aspirin.
Theoretically when a capsule is ingested, it breaks open in 30 min in the stomach. The fastest dissolving pellets start releasing the drug, and one after another each type of pellets continue to pour the drug into the system. Hopefully we get a slow release over a period of 20 hours
The effects of dipyridamole are short lived while those of aspirin are very long term. With this formulation the patients gets protection from platelet aggregation (which can cause strokes) for over 20 to 24 hours the capsule may be used once a day (or twice if the need be).
So what precautions should one take while taking this drug:
1. Take the capsule whole.
2. You may open the capsule, but do not crush the pellets, the sustained release technology goes waste if the pellets are crushed, you may also get side effects due to dumping of the drug.
3. If you open the capsule, do not dissolve the pellets before taking them, however you may pour the pellets over a porridge but again do not crush the pellets while chewing.
I do hope I have been able to explain in a simple way. But if you have doubts, please get back to me without hesitation.
All the best
---------- FOLLOW-UP ----------
QUESTION: Thank you so very much for your reply, which was very prompt. No delay at all! I am very grateful that you help people with your knowledge.
Since my mother cannot swallow the capsules, it does seem fairly safe to open the capsules, as long as the contents aren't crushed. The problem of dose dumping only happens with crushing, not merely opening the capsule, if I understand correctly. Again, many thanks for your help.
I am glad that I have been clear enough. Many experts will warn against opening a capsule, without realizing that the capsule itself plays no role in controlling the release of drugs. The age and difficulty of the patient has to be considered, in laying down ground rules.
Please convey my best wishes to your mother. My mother would have been of the same age had she survived till today.
All the best