azilsartan medoxomil
Regulatory sources consulted
Approved indications
- Treatment of essential hypertension in adults.
Contraindications
Absolute
- Hypersensitivity to the active substance or its excipients.
- Second or third trimester of pregnancy.
- Concomitant aliskiren in patients with diabetes or GFR below 60 mL/min/1.73 m².
Clinical warnings
- Boxed warning · Fetal toxicity: discontinue as soon as pregnancy is detected. — DailyMed set ID b1c8de43-3b26-408f-8c7e-6c7d76348199
- Major warning · RAAS blockade may cause hypotension, hyperkalemia, and renal impairment, including acute renal failure; correct volume depletion and monitor blood pressure, creatinine, and potassium. — CIMA registro 11734002
Drug interactions
- HighLithium
Mechanism: May reversibly increase serum lithium concentration and toxicity.
Recommendation: Avoid if possible; if essential, closely monitor serum lithium.
https://cima.aemps.es/cima/dochtml/ft/11734002/FT_11734002.html
- ModerateNSAIDs, including COX-2 inhibitors
Mechanism: May reduce the antihypertensive effect and increase the risk of renal impairment and hyperkalemia.
Recommendation: Maintain adequate hydration and monitor renal function and potassium.
https://cima.aemps.es/cima/dochtml/ft/11734002/FT_11734002.html
- ModeratePotassium supplements or potassium-sparing diuretics
Mechanism: They increase the risk of hyperkalemia.
Recommendation: Use cautiously and monitor serum potassium.
https://cima.aemps.es/cima/dochtml/ft/11734002/FT_11734002.html
Adverse events
Common (≥1%)
Dizziness · Diarrhea · Increased blood creatine phosphokinase
Rare but serious
Angioedema · Acute renal failure · Fetal toxicity
Pregnancy and lactation
Use is not recommended in the first trimester and is contraindicated in the second and third; discontinue when pregnancy is diagnosed. Breastfeeding use is not recommended, and an alternative with better-established safety is preferred.
Recent literature (PubMed)
A systematic literature review and network meta-analysis was conducted on azilsartan medoxomil (AZL-M) versus other antihypertensive drugs' efficacy in hypertensive patients. The search utilized English platforms, from January 2000 until December 2023, resulting in 10,380 articles being screened. Screening criteria included hypertension (mild or moderate); first-line treatment and washout periods; studies (monotherapy) with AZL-M, angiotensin type II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitor (ARNIs), beta-blockers, calcium channel blockers (CCBs), and diuretics, either as intervention or comparator; and antihypertension efficacy as an outcome measure. Study design was randomized clinical trials. Efficacy variables included absolute office systolic and diastolic blood pressure (BP) reductions. A total of 21 publications provided adequate data for analysis, of which 20 studies reported both systolic and diastolic BP and one study reported only the diastolic BP. In 21 studies on systolic BP, against the common comparator placebo, the differences in systolic BP were significantly in favor of AZL-M, amlodipine, candesartan, irbesartan, nebivolol, nifedipine, olmesartan, sacubitril valsartan, telmisartan, and valsartan. The surface under the cumulative ranking curve (SUCRA) ranking shows that AZL-M 80 mg had the highest ranking, with a possibility of 93% being the best in all other included treatments. In 20 studies on diastolic BP, against the common comparator placebo, the differences in diastolic BP were significantly in favor of AZL-M, amlodipine, bisoprolol, nebivolol, olmesartan, sacubitril valsartan, telmisartan, and valsartan. The SUCRA ranking shows that AZL-M 80 mg had the highest ranking, with a possibility of 90% being the best in all other included treatments. AZL-M at 40 mg and 80 mg shows favorable efficacy compared to other anti-hypertensives, and the 80 mg dosage seemed to be the
Drug discovery campaigns often face biopharmaceutical challenges, some of which can be solved by a prodrug approach. Prodrugs are enzymatically or chemically transformed in vivo to produce active drugs. Among these, medoxomil promoieties have been judiciously employed in multiple drug discovery campaigns, leading to three prodrugs gaining FDA approval: azilsartan medoxomil (6), olmesartan medoxomil (20), and ceftobiprole medocaril (29), and one approval in Japan: prulifloxacin (35). The promoiety can be easily appended to mask carboxylic acids, amines, zwitterionic compounds, and other polar groups, imparting lipophilicity to the parent compound. The promoiety has the added advantage of rapid and complete conversion to the parent drug by multiple enzymatic pathways across different tissues. The approach has been used for drugs spanning multiple classes to improve oral bioavailability, solubility, tissue localization, efflux, and side effect profiles. This Perspective analyzes the history and application of medoxomil prodrugs and discusses their potential for drug development.
To assess the antihypertensive efficacy and safety of azilsartan medoxomil (AZM) and amlodipine (AML) combination therapy in patients with mild-to-moderate hypertension inadequately controlled by AZM or AML monotherapy. In this multicenter, randomized, double-blind Phase III study (NCT05385770), patients with mild-to-moderate hypertension inadequately controlled with AZM 40/80 mg or AML 5/10 mg were randomized (1:1:1) to receive low-dose or high-dose AZM/AML combination therapy or continued monotherapy as control. Eligible patients completed a 4-week active run-in period before randomization. The primary endpoint was change from baseline in mean sitting systolic blood pressure (SBP) after 8 weeks of treatment. A total of 890 patients were randomized. AZM/AML combination therapy resulted in significantly greater reductions in mean sitting SBP compared with AZM or AML monotherapy across all dose groups. Least-squares mean reductions in mean sitting SBP at week 8 ranged from 5.2 to 9.0 mm Hg across all monotherapy nonresponder groups, with all comparisons showing statistical significance (P < 0.05). Reductions in mean sitting diastolic blood pressure also favored combination therapy. Safety profiles were comparable across all treatment arms, with most adverse events mild or moderate in severity. No additional safety concerns were identified compared with monotherapy. AZM/AML combination therapy was more effective than monotherapy in patients with mild-to-moderate hypertension inadequately controlled with either agent alone, even at maximum doses. Both low-dose and high-dose combinations were well tolerated. AZM/AML combination therapy may offer enhanced BP-lowering efficacy compared with other angiotensin II receptor blocker-based regimens.
This study aims to assess the effectiveness and safety of azilsartan-medoxomil/chlorthalidone (AZI-M/CT) compared to olmesartan-medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with hypertension. Systematic searches were conducted on PubMed, Google Scholar, and ClinicalTrials.gov, starting from their establishment until March 15, 2023. The purpose of these searches was to locate original reports that compare the effectiveness of AZI-M/CT and OLM/HCTZ in treating hypertension. Data on various characteristics at the beginning and end of the studies were gathered. The analyses were carried out using Review Manager 5.4.1 (The Nordic Cochrane Center, The Cochrane Collaboration, 2014, Odense, Denmark) and STATA 16.0 software (Stata Corp. LP, College Station, TX, USA). Risk ratios (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated as part of the study. A total of 3,146 individuals from four separate investigations were included in the study, with 1,931 individuals receiving AZI-M/CT and 1,215 individuals receiving OLM/HCTZ. The combined analysis revealed that the average diastolic blood pressure (DBP) was significantly lower in the AZI-M/CT group compared to the OLM/HCTZ group (WMD -2.64 [-2.78, -2.51]; P = 0.00001; I2 = 1%). However, there were no significant differences in mean systolic blood pressure (SBP; WMD -2.95 [-6.64, 0.73]; P = 0). Furthermore, the AZI-M/CT group had a notably higher incidence of major adverse events (RR 1.58 [1.20, 2.08]; P = 0.001; I2 = 11%) and any treatment-emergent adverse events (RR 1.11 [1.03, 1.20]; P = 0.007; I2 = 51%). However, there was no significant difference in the mortality risk between the two groups (RR 0.74 [0.14, 3.91]; P = 0.72; I2 = 0%). Based on the results of our meta-analysis, AZI-M/CT is more effective than OLM/HCTZ at reducing blood pressure in elderly hypertensive patients. However, because of the small sample size, favorable results must be carefully reevaluated, and mor
Angiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes. We performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software. A total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: -2.85 mmHg), clinic SBP (MD: -3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: -1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: -3.59 mmHg), 24-h ABPM mean DBP (MD: -2.62 mmHg), clinic SBP (MD: -4.42 mmHg), clinic DBP (MD: -3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in th