Dicyclomine And Ranitidine: Are They Safe To Take Together?

In our latest question and answer, the pharmacist discusses the use of dicyclomine and ranitidine together.

Aug 06, 2019

Jim asked

Can I take dicyclomine and ranitidine together?

At a glance

  • While some 'drug interaction checkers' will list an interaction between ranitidine and dicyclomine, it isn't considered to be clinically significant. In most cases, they are safe to take together.


Yellow Pills In Blister Pack With Text - Taking Ranitidine And Dicyclomine Together

Most drug interaction resources (e.g. Drugs.com; RxList.com) do not list an interaction between ranitidine (brand name Zantac) and dicyclomine (Bentyl).

However, some (including our own, which utilizes information from DrugBank.ca) does list an interaction between them.

This discrepancy is likely for a few reasons.

Large-scale studies and published case reports have not reported a clinically significant interaction between dicyclomine and ranitidine.

They are not known to interfere with each other in a way that would necessitate an alteration in therapy. In the vast majority of cases, they can be taken together and their individual effects shouldn't be altered in a negative way.

The reason DrugBank (and therefore our own interaction checker) lists an interaction between the two drugs is that DrugBank looks for interactions and conflicts between drugs based solely on their mechanism of action and their overall classification.

Ranitidine and dicyclomine do in fact have conflicting effects based on their mechanism of action, which I discuss more in the next section.

It is important to point out though, that overall, this interaction isn't considered to be one that needs to have any special attention in terms of therapy adjustment.

The Interaction

Ranitidine is a commonly used drug to treat heartburn, GERD (gastroesophageal reflux disease), gastric ulcers and other stomach-acid associated disorders.

It is classified as an 'H2-blocker' since it works by inhibiting the binding of histamine to receptors (H2-receptors) on parietal cells, which are found in the stomach. This results in a reduction of acid secretion.

In addition to ranitidine's effects on H2-receptors, studies show that it also inhibits an enzyme known as 'acetylcholinesterase'.

Acetylcholinesterase is an enzyme that breaks down acetylcholine. Therefore, inhibition of acetylcholinesterase would decrease the breakdown of acetylcholine, increasing concentrations of it overall.

Acetylcholine is a neurotransmitter that is responsible for countless functions and effects in the body.

As it concerns the gastrointestinal tract, it affects how it contracts and the overall movement of food through it.

Dicyclomine, the other drug in question here, is an antispasmodic. It works on muscles in the GI tract, decreasing contractions, and spasms. It does this by blocking the effects of acetylcholine. In fact, it is classified as an anticholinergic.

So, we can see simply based on how ranitidine and dicyclomine work, they appear to be at odds with one another.

Ranitidine can increase acetylcholine concentrations while dicyclomine works by blocking its effects.

This is all summed up by what our interaction checker says about this drug combination:

"Cholinesterase inhibitors [like ranitidine] increase the amount of acetylcholine available in synapses, allowing competition with anticholinergic agents [like dicyclomine] for receptor binding. This can potentially reduce the therapeutic efficacy of anticholinergics when used concomitantly."

Even though this interaction exists theoretically (based on the mechanisms of both drugs), in actuality, it doesn't appear to be overly significant.

While ranitidine does appear to have some activity in increasing acetylcholine, it is a very weak effect overall.

Most studies report that it doesn't increase contractibility in the GI tract or alter how quickly food moves through it, which is what would be expected with an increase in acetylcholine.

So, the interaction that DrugBank shows is accurate if you base it simply on the known effects of the drugs, but not so much when you consider how strongly those effects occur.

You can feel comfortable knowing that ranitidine and dicyclomine don't interfere with one another in a significant manner.

  1. ClinicalKey: Ranitidine Monograph. ClinicalKey
  2. ClinicalKey: Dicyclomine Monograph. ClinicalKey
  4. Inhibition of cholinesterases by histamine 2 receptor antagonist drugs. Europe PMC
  5. The inhibition of acetylcholinesterase by ranitidine: a study on the guinea pig ileum. PubMed
  6. Effects of ranitidine on the enzyme cholinesterase and the rat anococcygeus muscle. PubMed
  7. Cholinergic effects of histamine-H2 receptor antagonists partly through inhibition of acetylcholinesterase. Springer Link

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