Best Time To Take HCTZ And Lisinopril

In our latest question and answer, the pharmacist discusses the optimal time to take HCTZ and lisinopril.

Best Time To Take HCTZ And Lisinopril
Apr 24, 2019

HLT asked

I currently have a prescription for 25 mg HCTZ and 10 mg lisinopril to treat high blood pressure. When I take them together in the morning, my blood pressure goes too low (90/68) ….. if I take the HCTZ in the morning and the lisinopril at night it seems to maintain a healthy blood pressure. Is there a problem doing that?

Answer

Clock With Text Overlay - Time To Take HCTZ And Lisinopril

You can take HCTZ (hydrochlorothiazide) and lisinopril at any time during the day, but there are some recommendations to get the most benefit from them and reduce side effects.

The first thing you should do is discuss the issue with your doctor regarding your blood pressure dropping too low. This could be indicative that the dose of one or both may need adjusting.

However, if your blood pressure is well-controlled (and doesn't drop too low) when taking the HCTZ in the morning, and lisinopril at night, that is perfectly fine in most cases.

In fact, this may be the ideal way to take both medications.

HCTZ In The Morning

HCTZ (hydrochlorothiazide), a thiazide diuretic, can be taken anytime during the day but morning dosing is typically recommended.[1]

Since HCTZ is a diuretic, and causes fluid loss through urination, taking it in the evening can cause interruptions with sleep since you may need to go to the bathroom more often.[2]

Therefore, taking it in the morning may be wise to avoid disrupting your sleep.

Having said all of this, there have been some studies that suggest taking diuretics at nighttime lower blood pressure more effectively than taking them earlier in the day.[3]

While this certainly may conflict with the negative effects of having to use the bathroom in the middle of the night, most studies point out the diuretic (i.e. water loss) effect of thiazide diuretics only lasts a few weeks after starting therapy. After this time, your bathroom habits may go back to normal.[4]

The actual, long-term, blood pressure reducing mechanism of thiazide diuretics isn't well-understood and isn't necessarily only based on their diuretic effects. As one study puts it:[5]

How thiazides reduce total peripheral resistance is unclear. One hypothesis involves thiazides exerting a direct action on blood vessels.
Expert Rev Cardiovasc Ther. 2010 Jun; 8(6): 793–802.

More studies are needed to determine the ideal dosing time for HCTZ, but as a general rule of thumb, morning is best for most people since it still effectively lowers blood pressure at this time and eliminates the risk of needing to go to the bathroom in the middle of the night.

Lisinopril At Night

The evidence for lisinopril being more effective with nighttime dosing than morning dosing is fairly strong.

We know that blood pressure follows our circadian rhythm and generally decreases slightly while we are asleep and spikes in the morning.

This morning blood pressure spike has been associated with an increased risk of cardiovascular events like stroke and heart attack.[6]

It has been theorized that taking blood pressure medication (especially ACE-Inhibitors like lisinopril) at night would better control the early morning blood pressure spike since most medications may not be as effective at the end of their dosing interval (i.e. if you take a pill once every 24 hours, it may start to lose effect by the time you are scheduled to take your next dose).

Multiple studies have shown this to be accurate, that nighttime dosing of many different blood pressure medications do indeed lower blood pressure more effectively than when those same ones are taken in the morning.[7][8][9]

This effect doesn't appear to be the case for all medications, but lisinopril has specifically been noted as one that may be more effective if taken at night.[10][11]

Final Words

Taking HCTZ in the morning and lisinopril in the evening is certainly an acceptable way to take these medications, and may, in fact, be ideal to lower the risk of side effects (like waking up to go to the bathroom) and increase effectiveness.

You always want to make sure that you discuss how you take your medication with your doctor first, however, before making any changes.

References
  1. ^ Hydrochlorothiazide Prescribing Information. AccessFDA
  2. ^ Elsevier ClinicalKey: Hydrochlorothiazide Monograph. ClinicalKey
  3. ^ Diuretic drugs benefit patients with hypertension more with night-time dosing. PubMed
  4. ^ Thiazide diuretics. PubMed
  5. ^ Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics. PubMed
  6. ^ Vascular damage in exaggerated morning surge in blood pressure. PubMed
  7. ^ Chronotherapy improves blood pressure control and reverts the nondipper pattern in patients with resistant hypertension. PubMed
  8. ^ Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing. PubMed
  9. ^ Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension. PubMed
  10. ^ Time of administration important? Morning versus evening dosing of valsartan. PubMed
  11. ^ Management of antihypertensive treatment with Lisinopril: a chronotherapeutic approach. PubMed

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