Patient Case: Identifying and Managing a Prescribing Cascade

Laura is a 102-year-old PACE participant.

A review of her medication list reveals 12 active medications for several conditions including depression, high blood pressure, and hypothyroidism. Laura is taking a common over-the-counter acid-reducing medication that not only interacts with her other medications, but may be contributing to a prescribing cascade.

What is a Prescribing Cascade?

A prescribing cascade is when a patient takes a medication that causes side effects, and then is prescribed another medication to treat those side effects. The cascade can compounded by the new medication causing additional side effects, and more prescribed medications, and so on. While in some cases a prescribing cascade may be intentional for additive effects, in many cases it is unintentional.

Dreischulte et al.¹  suggest asking a series of questions when deciding how to address a prescribing cascade:

1. Did the medication cause or increase the risk of an adverse drug reaction?
2. Is the medication still needed?
3. Will changing the medication in question help to avoid an adverse drug reaction?
4. Is the medication being used to treat the adverse drug reaction beneficial?
5. Do the benefits of the prescribing cascade outweigh the risks?

One example of an inappropriate cascade is a patient taking a non-steroidal anti-inflammatory drug (NSAID) for pain, which also increases the patient’s blood pressure. The patient is then prescribed blood pressure medication.

Another potentially more concerning example is a patient taking amitriptyline to help with sleep. Due to its anticholinergic properties, amitriptyline increases the risk of cognitive impairment and dementia. A patient may then be prescribed medications to treat dementia.

Identifying a Prescribing Cascade

While reviewing her medication regimen, I noticed Laura is taking omeprazole, magnesium chloride, and ondansetron. I identified this prescribing cascade based on common side effects.

• Omeprazole is a proton-pump inhibitor used to treat symptoms of excess stomach acid. For Laura, it is being used for gastroesophageal reflux disease (GERD). In general, this class of medications is not recommended in older adults for long periods of time. Omeprazole is only approved for GERD for a period of 4-8 weeks.²
  
  
• Magnesium chloride is a supplement to replace magnesium.
  
  
• Ondansetron is commonly used to treat nausea and vomiting, although it is specifically approved for patients undergoing chemotherapy or radiation therapy, as well as for post-operative nausea and vomiting.³

The prescribing information for omeprazole² includes a warning for low magnesium levels. The risk of low magnesium increases with longer use, specifically in those taking omeprazole for more than three months. This low magnesium typically requires magnesium supplementation, which Laura was also prescribed. In addition, nausea and vomiting may occur in up to 4% of patients taking omeprazole. This may account for the need for ondansetron to treat nausea.

Additional Risks

Laura is being treated for depression with citalopram. In addition to the prescribing cascade, I identified an interaction between omeprazole and citalopram. This interaction could significantly increase the levels of citalopram and thus increase the risk of side effects. Perhaps most concerning, when these medications are taken together, there is a rare but serious change to the heart rhythm known as QT prolongation. Citalopram carries a risk of QT prolongation⁴, and the higher levels of citalopram as a result of this interaction may further increase this risk.

As mentioned above, the use of ondansetron may be a result of side effects caused by omeprazole. Ondansetron prescribing information also warns of an increased risk in QT prolongation³. For a review on QT prolongation and the associated risks, please revisit our blog on high-risk dosing in older adults.

Due to the risks of side effects and interactions associated with omeprazole and the general recommendation to avoid long-term use, I recommended to discontinue omeprazole. To revisit the discontinuation recommendation for omeprazole, please refer to our previous blog on deprescribing.

Summary

Part of managing a patient’s medication list should involve a comprehensive review of the entire regimen. While each of these medications on their own may be warranted, when looked at as a whole using medication safety analytics, I was able to identify a prescribing cascade and risks of side effects and interactions.

Discontinuing omeprazole will not only avoid a significant drug-drug interaction but will also reduce the need for magnesium and ondansetron. These changes will help to reduce Laura’s overall risk of side effects and improve outcomes while simplifying her regimen and improving her satisfaction.

References

[1] Dreischulte T, Shahid F, Muth C, et al. Prescribing Cascades: How to Detect Them, Prevent Them, and Use Them Appropriately. Dtsch Arztebl Int. 2022 Nov 4;119(44):745-752.

[2] U.S. Food and Drug Administration. PRILOSEC (omeprazole) delayed-release capsules and PRILOSEC (omeprazole magnesium) for delayed-release oral suspension: Prescribing information. NDA 019810/S-096. Silver Spring, MD: FDA; 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019810s096lbl.pdf. Accessed December 31, 2025.

[3] U.S. Food and Drug Administration. ZOFRAN (ondansetron hydrochloride) tablets, orally disintegrating tablets, and oral solution: Prescribing information NDA 020103/S-035, 020605/S-019, 020781/S-019. Silver Spring, MD: FDA; 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020103s035_020605s019_020781s019lbl.pdf. Accessed December 31, 2025

[4] U.S. Food and Drug Administration. Celexa (citalopram hydrobromide) tablets/oral solution: Prescribing information (Proposed labeling). NDA 020822/S-037, 021046/S-015. Silver Spring, MD: FDA; 2009. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020822s037,021046s015lbl.pdf. Accessed December 31, 2025.