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Drug Interactions between amlodipine / hydrochlorothiazide / valsartan and vericiguat

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

hydroCHLOROthiazide vericiguat

Applies to: amlodipine / hydrochlorothiazide / valsartan and vericiguat

MONITOR: Vericiguat may cause hypotension and coadministration with antihypertensives or organic nitrates may increase the potential for symptomatic hypotension, especially in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, or patients with a history of hypotension. Patients with heart failure receiving hemodynamically active substances have reported systolic blood pressure (SBP) reductions of approximately 1 to 2 mmHg with concomitant use. Co-administration of multiple doses of vericiguat up to 10 mg once daily did not significantly alter the seated blood pressure effects of short- and long-acting nitrates in patients with coronary artery disease and concomitant use of short-acting nitrates was well tolerated in patients with heart failure. However, there is limited experience with concomitant use of vericiguat and long-acting nitrates in patients with heart failure and no data on initiation of vericiguat in patients with systolic blood pressure (SBP) less than 100 mmHg or symptomatic hypotension at treatment initiation.

MANAGEMENT: If patients experience tolerability issues (symptomatic hypotension or SBP less than 90 mmHg), temporary down-titration or discontinuation of vericiguat is recommended.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2021) "Product Information. Verquvo (vericiguat)." Merck & Co., Inc

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Moderate

amLODIPine vericiguat

Applies to: amlodipine / hydrochlorothiazide / valsartan and vericiguat

MONITOR: Vericiguat may cause hypotension and coadministration with antihypertensives or organic nitrates may increase the potential for symptomatic hypotension, especially in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, or patients with a history of hypotension. Patients with heart failure receiving hemodynamically active substances have reported systolic blood pressure (SBP) reductions of approximately 1 to 2 mmHg with concomitant use. Co-administration of multiple doses of vericiguat up to 10 mg once daily did not significantly alter the seated blood pressure effects of short- and long-acting nitrates in patients with coronary artery disease and concomitant use of short-acting nitrates was well tolerated in patients with heart failure. However, there is limited experience with concomitant use of vericiguat and long-acting nitrates in patients with heart failure and no data on initiation of vericiguat in patients with systolic blood pressure (SBP) less than 100 mmHg or symptomatic hypotension at treatment initiation.

MANAGEMENT: If patients experience tolerability issues (symptomatic hypotension or SBP less than 90 mmHg), temporary down-titration or discontinuation of vericiguat is recommended.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2021) "Product Information. Verquvo (vericiguat)." Merck & Co., Inc

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Moderate

valsartan vericiguat

Applies to: amlodipine / hydrochlorothiazide / valsartan and vericiguat

MONITOR: Vericiguat may cause hypotension and coadministration with antihypertensives or organic nitrates may increase the potential for symptomatic hypotension, especially in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, or patients with a history of hypotension. Patients with heart failure receiving hemodynamically active substances have reported systolic blood pressure (SBP) reductions of approximately 1 to 2 mmHg with concomitant use. Co-administration of multiple doses of vericiguat up to 10 mg once daily did not significantly alter the seated blood pressure effects of short- and long-acting nitrates in patients with coronary artery disease and concomitant use of short-acting nitrates was well tolerated in patients with heart failure. However, there is limited experience with concomitant use of vericiguat and long-acting nitrates in patients with heart failure and no data on initiation of vericiguat in patients with systolic blood pressure (SBP) less than 100 mmHg or symptomatic hypotension at treatment initiation.

MANAGEMENT: If patients experience tolerability issues (symptomatic hypotension or SBP less than 90 mmHg), temporary down-titration or discontinuation of vericiguat is recommended.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2021) "Product Information. Verquvo (vericiguat)." Merck & Co., Inc

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Minor

hydroCHLOROthiazide amLODIPine

Applies to: amlodipine / hydrochlorothiazide / valsartan and amlodipine / hydrochlorothiazide / valsartan

The antihypertensive effect of amlodipine and thiazide diuretics may be additive. Management consists of monitoring blood pressure during coadministration, especially during the first 1 to 3 weeks of therapy.

References

  1. Kaplan NM (1991) "Amlodipine in the treatment of hypertension." Postgrad Med J, 67 Suppl 5, s15-9

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Drug and food interactions

Moderate

valsartan food

Applies to: amlodipine / hydrochlorothiazide / valsartan

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

References

  1. (2001) "Product Information. Cozaar (losartan)." Merck & Co., Inc
  2. (2001) "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals

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Moderate

vericiguat food

Applies to: vericiguat

ADJUST DOSING INTERVAL: Administration of vericiguat with food reduces its pharmacokinetic variability and increases its exposure. Vericiguat is less soluble at neutral pH than at acidic pH. Administration of vericiguat with a high-fat, high-calorie meal or low-fat, high-carbohydrate meal increased time to reach peak plasma concentration (Tmax) from about 1 hour (fasted) to about 4 hours (fed) and increased vericiguat systemic exposure (AUC) by 19% and peak plasma concentration (Cmax) by 9% for the 5 mg tablet and by 44% (AUC) and 41% (Cmax) for the 10 mg tablet as compared with the fasted state. Concurrent treatment with drugs that increase gastric pH, such as proton pump inhibitors or antacids, decrease vericiguat AUC by about 30%. Co-treatment with drugs that increase gastric pH did not affect vericiguat exposure in patients with heart failure when vericiguat was taken as directed with food.

MANAGEMENT: Administer vericiguat with food to ensure maximal exposure and decrease pharmacokinetic variability.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2021) "Product Information. Verquvo (vericiguat)." Merck & Co., Inc

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Moderate

hydroCHLOROthiazide food

Applies to: amlodipine / hydrochlorothiazide / valsartan

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

amLODIPine food

Applies to: amlodipine / hydrochlorothiazide / valsartan

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

amLODIPine food

Applies to: amlodipine / hydrochlorothiazide / valsartan

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

References

  1. Henry M, Kay MM, Viccellio P (1985) "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med, 3, p. 334-6
  2. Moller IW (1987) "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth, 59, p. 522-6
  3. Oszko MA, Klutman NE (1987) "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm, 6, p. 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. (1991) "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol, 67, p. 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF (1990) "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy, 10, p. 247
  6. Woie L, Storstein L (1981) "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J, 2, p. 239-42
  7. Morris DL, Goldschlager N (1983) "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA, 249, p. 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E (1987) "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol, 27, p. 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M (1994) "Calcium gluconate in severe verapamil intoxication." N Engl J Med, 330, p. 718-20
  10. Bar-Or D, Gasiel Y (1981) "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed), 282, p. 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L (1982) "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med, 8, p. 55-7
  12. McMillan R (1988) "Management of acute severe verapamil intoxication." J Emerg Med, 6, p. 193-6
  13. Perkins CM (1978) "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J, 2, p. 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M (1980) "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol, 17, p. 395-400
View all 14 references

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Minor

amLODIPine food

Applies to: amlodipine / hydrochlorothiazide / valsartan

The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Data have been conflicting and the clinical significance is unknown. Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

References

  1. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  2. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  3. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  4. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL (2000) "Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine." Br J Clin Pharmacol, 50, p. 455-63
  5. Josefsson M, Ahlner J (2002) "Amlodipine and grapefruit juice." Br J Clin Pharmacol, 53, 405; discussion 406
  6. Kane GC, Lipsky JJ (2000) "Drug-grapefruit juice interactions." Mayo Clin Proc, 75, p. 933-42
View all 6 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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