Sacubitril; Valsartan with Yohimbine Interaction Details
Brand Names Associated with Sacubitril; Valsartan
- Entresto®
- Valsartan and Sacubitril
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 09, 2023
Interaction Effect
Reduced angiotensin II receptor antagonist effectiveness
Interaction Summary
Theoretically, yohimbine may directly counteract the hypotensive effect of angiotensin II receptor antagonists, resulting in inadequate blood pressure control in hypertensive patients. Yohimbine increased blood pressure in hypertensive and normotensive patients in several studies. Yohimbine is believed to increase norepinephrine release by at least one of three mechanisms: direct stimulation of sympathetic outflow from the brain; blockade of inhibitory alpha-2 adrenergic receptors on sympathetic nerve endings; blockade of alpha-2 adrenergic receptors on vascular smooth muscle with vasodilation eliciting reflexive increases in sympathetic outflow .
Severity
Moderate
Onset
Rapid
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of yohimbine and angiotensin II receptor antagonists. Yohimbine may counteract the hypotensive effect of angiotensin II receptor antagonists.
Mechanism Of Interaction
Increased norepinephrine release by yohimbine
Literature Reports
A) Yohimbine 10 mg taken orally induced a significant increase in diastolic blood pressure after 10 minutes of upright posture in hypertensive patients only in a placebo-controlled study of 25 healthy volunteers and 29 sex- and age-matched untreated mild to moderate hypertensive patients. Yohimbine produced a significant increase in plasma norepinephrine levels in both groups. Dopamine levels were significantly increased only in normotensive subjects after yohimbine administration (exact values not provided) .
B) Yohimbine 21.6 mg taken orally stimulated norepinephrine release, resulting in a pressor response in a study of 25 adult patients with uncomplicated essential hypertension. The systolic and diastolic blood pressures at baseline were 144 +/- 4 and 83 +/- 3 mmHg, respectively. Patients discontinued any antihypertensive medication 2 weeks prior to the study. At one hour after yohimbine administration, systolic pressure increased to 150 +/- 5 mmHg and diastolic pressure increased to 86 +/- 3 mmHg, both significant changes. Heart rate was not significantly changed by yohimbine. Norepinephrine levels increased from 293 +/- 29 picograms (pg)/mL (1.732 +/- 0.171 nanomol (nmol)/L) at baseline to 486 +/- 67 pg/mL (2.873 +/- 0.396 nmol/L) significantly one hour after yohimbine administration .
C) Yohimbine 0.2 mg/kg taken orally increased plasma concentrations of noradrenaline 67% in 9 hypertensive patients and 178% in 6 normotensive patients. Blood pressure increased significantly in response to yohimbine in hypertensive but not normotensive subjects. Patients did not take medications acting on blood pressure or the sympathetic nervous system; hypertensive patients averaged 68 years, normotensive patients averaged 63 years .
D) Yohimbine administered intravenously increased mean arterial pressure, norepinephrine, and epinephrine levels in all patients (p less than 0.001) in a study of 19 hypertensive patients and 19 normotensive patients. Yohimbine was administered as a 0.125 mg/kg IV bolus followed by 0.001 mg/kg/minute infusion for 15 minutes. Patients discontinued all medications 2 weeks prior to the study. Hypertensive patients averaged 35 years; normotensive patients averaged 30 years. Mean arterial pressure increased from 106 +/- 4 mmHg to 127 +/- 5 mmHg in the hypertensive group and from 88 +/- 2 mmHg to 101 +/- 3 mmHg in the normotensive group; in all patients, the increase was significant versus baseline .
E) In a randomized, double-blind study of 17 male volunteers, oral yohimbine 40 mg increased the rate of appearance of norepinephrine into the plasma (p less than 0.005) without a reduction in norepinephrine clearance. Plasma epinephrine was significantly increased. Diastolic blood pressure increased (p less than 0.01) as well as mean arterial blood pressure and pulse (p less than 0.025) .
Sacubitril; Valsartan Overview
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The combination of valsartan and sacubitril is usually used in combination with other medications to lower the risk of death and hospitalization in adults with certain types of heart failure. The combination of valsartan and sacubitril is also used to treat certain types of heart failure in children 1 year of age and older. Valsartan is in a class of medications called angiotensin II receptor antagonists. It works by blocking the action of certain natural substances that tighten the blood vessels, allowing the blood to flow more smoothly and the heart to pump more efficiently. Sacubitril is in a class of medications called neprilysin inhibitors. It works to help control blood volume.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.