Baxfendy (baxdrostat)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

*Consider the patient's risk of hyperkalemia and hyponatremia before initiating baxdrostat.

*Recommended dosage is 2 mg orally once daily.

*For patients at increased risk of hyperkalemia or hyponatremia, the recommended dosage is 1 mg once daily.

*Take with or without food.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Baxdrostat; Potassium-Spar Diuretics/Cyclosporine;Tacrolimus

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use of cyclosporine(1) or tacrolimus(2) with baxdrostat(3) or a potassium-sparing diuretic may result in additive or synergistic effects on potassium levels.

CLINICAL EFFECTS: Concurrent use of cyclosporine(1) or tacrolimus(2) with baxdrostat(3) or a potassium-sparing diuretic may result in severe hyperkalemia.

PREDISPOSING FACTORS: Renal impairment increases the risk for hyperkalemia.

PATIENT MANAGEMENT: The US manufacturers of cyclosporine(1) and tacrolimus(2) state that potassium-sparing diuretics should not be used during therapy with these agents.

DISCUSSION: Hyperkalemia has been reported with cyclosporine, therefore, the US manufacturer states that potassium-sparing diuretics should not be used with cyclosporine.(1) In tacrolimus clinical trials, mild to severe hyperkalemia was reported in 31% of kidney transplant patients, 45% of US liver transplant patients, and 13% of European liver transplant patients. The manufacturer of tacrolimus states that potassium levels should be closely monitored in all patients maintained on tacrolimus and that potassium-sparing diuretics should be avoided during tacrolimus therapy.(2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Aldosterone Receptor Antag; Baxdrostat/Nsaids; Salicylates

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow baxdrostat, eplerenone, finerenone, or spironolactone-induced nephrotoxicity or hyperkalemia to occur in some patients.(1-4) In some patients, NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of baxdrostat, eplerenone, finerenone, or spironolactone.(1-4)

CLINICAL EFFECTS: Concurrent use of baxdrostat, eplerenone, finerenone, or spironolactone with NSAIDs may result in renal failure or hyperkalemia. The effects of the diuretic, natriuretic, or antihypertensive effects of baxdrostat, eplerenone, finerenone, or spironolactone may be decreased.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: When possible, avoid concurrent therapy with baxdrostat, eplerenone, finerenone, or spironolactone with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. The manufacturer of eplerenone recommends checking serum potassium and serum creatinine within 3-7 days of concurrent therapy with NSAIDs.(1) The manufacturer of spironolactone states concurrent use with NSAIDs may lead to severe hyperkalemia and extreme caution should be used during concurrent therapy.(2)

DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction with all potassium-sparing diuretics. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure.

Aldosterone Receptor Antagonists; Baxdrostat/Lithium

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aldosterone receptor antagonists, including eplerenone, finerenone and spironolactone, bind to mineralocorticoid receptors, blocking the action of aldosterone. Baxdrostat inhibits aldosterone synthesis. The subsequent increase in sodium and water excretion may lead to reduced renal clearance of lithium.(1-4)

CLINICAL EFFECTS: Lithium has a narrow therapeutic range. Unintended increases in lithium concentrations may lead to lithium toxicity. Early symptoms of lithium toxicity may include: lethargy, muscle weakness or stiffness, new onset or coarsening of hand tremor, vomiting, diarrhea, confusion, ataxia, blurred vision, tinnitus and nystagmus. Severe toxicity may produce multiple organ dysfunction (e.g. seizures, coma, renal failure, cardiac arrhythmias, cardiovascular collapse) and may be fatal.(5)

PREDISPOSING FACTORS: Risk factors for lithium toxicity include: renal impairment or worsening of existing renal disease, dehydration, low sodium diet, and concomitant use of multiple medications which may impair renal elimination of lithium (e.g. ARBs, ACE Inhibitors, NSAIDs, diuretics).(5) Patients who require higher therapeutic lithium levels to maintain symptom control are particularly susceptible to these factors.

PATIENT MANAGEMENT: Evaluate renal function and most recent lithium levels. If renal function is not stable or if the lithium level is in the high therapeutic range, then consider lowering the lithium dose when an aldosterone antagonist is started, or consider withholding the aldosterone antagonist until renal function is stable. If renal function is stable and baseline lithium concentrations are in the therapeutic range, recheck lithium levels 5 to 7 days after initiation of baxdrostat, eplerenone, finerenone, or spironolactone. Adjust the lithium dose as necessary based on lithium serum levels and patient response. If an interacting drug is discontinued, the lithium level may fall. Monitor lithium concentration and adjust dose if needed.(5) Counsel patient to assure they know signs and symptoms of lithium toxicity and understand the importance of follow-up laboratory testing.

DISCUSSION: Although the magnitude and frequency of this specific diuretic interaction is not clear, manufacturer product information for spironolactone and lithium state that lithium patients should generally not receive diuretics.(2,3) The manufacturer of eplerenone recommends frequent monitoring of lithium levels in patients who receive concomitant therapy.(1)

Baxdrostat/Agents That Increase Potassium

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The combination of baxdrostat and agents that increase potassium such as aldosterone receptor antagonists, potassium-sparing diuretics, and potassium supplements can have an additive effect on serum potassium levels.

CLINICAL EFFECTS: Concurrent use of baxdrostat and agents that increase potassium may result in hyperkalemia, which may be severe.

PREDISPOSING FACTORS: More frequent monitoring is recommended for patients at increased risk of hyperkalemia (e.g., patients greater than or equal to 65 years or age, those with diabetes mellitus or chronic kidney disease).(1)

PATIENT MANAGEMENT: The manufacturer of baxdrostat states concurrent use with medications that may increase potassium warrants more frequent monitoring of serum potassium.(1) Assess serum potassium prior to initiation of baxdrostat and monitor periodically during treatment. Correct serum potassium abnormalities prior to initiation of baxdrostat.(1) If hyperkalemia occurs, treat hyperkalemia and consider interrupting or discontinuing baxdrostat. Consider more frequent monitoring of serum potassium in patients who restart baxdrostat after experiencing hyperkalemia. Permanently discontinue baxdrostat if clinically significant hyperkalemia recurs.(1)

DISCUSSION: Baxdrostat may increase potassium. Concurrent use with aldosterone receptor antagonists, potassium-sparing diuretics, and potassium supplements may have additive effects on serum potassium levels, resulting in hyperkalemia. The risk of hyperkalemia can be reduced by monitoring serum potassium more frequently when baxdrostat is administered concomitantly with these agents.

Selected Antihypertensives And Vasodilators/Apomorphine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Apomorphine causes dose-dependent decreases in blood pressure. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and apomorphine may result in orthostatic hypotension with or without dizziness, nausea, or syncope.(1)

PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in patients with renal or hepatic impairment.(1)

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Healthy volunteers who took sublingual nitroglycerin (0.4 mg) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.7 mm Hg and in supine diastolic blood pressure (DBP) of 9.3 mm Hg, and a mean largest decrease in standing SBP and DBP of 14.3 mm Hg and 13.5 mm Hg, respectively. The maximum decrease in SBP and DBP was 65 mm Hg and 43 mm Hg, respectively. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively.(1)

Selected Antihypertensives/Tizanidine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Tizanidine is an alpha-2 agonist. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and tizanidine may result in hypotension.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. The risk of hypotension may be decreased by careful titration of tizanidine dosages and monitoring for hypotension prior to dose advancement. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Severe hypotension has been reported following the addition of tizanidine to existing lisinopril therapy.(2-4)

None.

There are no contraindication contraindications for this drug.

• Hyperkalemia
• Hyponatremia

There are no moderate contraindications for this drug.

The most common adverse reaction (more frequent than placebo and >= 5% in baxdrostat-treated patients) was hyperkalemia.

More Frequent

• Hyperkalemia

Less Frequent

• Hyponatremia

Less Frequent

• Dizziness
• Hypotension
• Muscle spasm

No enhanced messaging available.

The safety and effectiveness of baxdrostat in pediatric patients under 18 years of age have not been established.

There are no available data on the use of baxdrostat during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcome. Hypertension during pregnancy poses a risk to the mother and fetus. Although studies in animals have shown embryo-fetal toxicity at baxdrostat exposures > 29 times the human exposure at the clinical dose of 2 mg, the clinical significance of these findings is unclear.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Report any pregnancies while treated with baxdrostat to AstraZeneca at 1-800-236-9933.

Hypertension in pregnancy increases the risk for adverse maternal outcomes including pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension also increases the risk of adverse fetal outcomes including intrauterine growth restriction and stillbirth. Pregnant women with hypertension should be carefully monitored and managed accordingly.

There are no data on the presence of baxdrostat in human milk, the effects on the breastfed infant, or the effects on milk production. Baxdrostat transfers to milk in lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for baxdrostat and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

No dose adjustment is required based on age. In the BaxHTN trial , 88 (33%) patients were 65 to 74 years of age, and 33 (12%) patients were >= 75 years of age in the baxdrostat 2 mg group; and 71 (27%) patients were 65 to 74 years of age, and 25 (10%) patients were >= 75 years of age in the baxdrostat 1 mg group. No overall differences in effectiveness were observed between these patients and younger adult patients. Hyperkalemia occurred at a higher incidence in patients >= 65 years of age. Among patients 65 to 74 years of age, hyperkalemia occurred in 12 (14%) patients treated with baxdrostat 2 mg, 7 (10%) patients treated with baxdrostat 1 mg, and 3 (3%) patients treated with placebo. Among patients >= 75 years of age, hyperkalemia occurred in 7 (21%) patients treated with baxdrostat 2 mg, none of the patients treated with baxdrostat 1 mg, and none of the patients treated with placebo.