Aliskiren
Contraindicated
Textbook
Increased risk of hypotension, hyperkalemia, and renal impairment.
Avoid concomitant use.
Source: G&G 14e · p603
Drug reference
Losartan + Hydrochlorothiazide
ARB · Antihypertensive
Also known as Losar-H, Cozaar-H, Rezil-H, Sartel-H
ARBAntihypertensiveATC C09DA01
CDSCO approvedSchedule HATC C09DA01
- ONSET
- 1.5h · Losartan: 1-2 hours. Hydrochlorothiazide: ~2 hours.
- PEAK
- 5h · Losartan: 6 hours (for active metabolite). Hydrochlorothiazide: 4-6 hours.
- t½
- 7.5h · Losartan: ~2 hours. E-3174 (active metabolite): 6-9 hours. Hydrochlorothiazide: 5.6-14.8 hours.
- DURATION
- 9h · Losartan: ~24 hours (due to active metabolite). Hydrochlorothiazide: 6-12 hours.
EXCRETION
—
not curated
INTERACTIONS
12 major
incl. contraindicated
PREGNANCY
D
FDA category + note
Top interactionssee all 12 →
- AliskirenContraindicatedTextbookG&G 14e · p603
- Sacubitril ValsartanContraindicatedTextbookG&G 14e · p602
- Angiotensin Converting Enzyme InhibitorsSevereTextbookHarrison 22e · p2396
- BenazeprilSevereTextbookG&G 14e
Mechanism
Losartan, an angiotensin II receptor blocker, selectively inhibits the binding of angiotensin II to the AT1 receptor, thereby reducing vasoconstriction and aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, leading to increased excretion of sodium, chloride, and water. This combination provides a synergistic antihypertensive effect through complementary mechanisms, improving blood pressure control. Combination rationale: Combining Losartan with Hydrochlorothiazide offers a more effective approach to blood pressure management than monotherapy. Losartan blocks the renin-angiotensin-aldosterone system, while hydrochlorothiazide enhances sodium and water excretion, leading to additive blood pressure lowering. This synergistic effect often allows for the use of lower doses of each component, potentially reducing individual drug-related side effects and improving patient adherence to therapy.
Indications
Essential hypertensionTo reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy
Dosing
- Adult
- Oral: Typically 50 mg losartan / 12.5 mg hydrochlorothiazide once daily. May be increased to 100 mg losartan / 12.5 mg or 100 mg losartan / 25 mg hydrochlorothiazide once daily, as needed.
- Pediatric
- Not recommended for use in children under 18 years of age due to lack of established safety and efficacy.
- Hepatic adjustment
- Use with caution in mild to moderate hepatic impairment. Contraindicated in severe hepatic impairment.
- Geriatric
- No specific dose adjustment for elderly patients based on age alone, but monitor renal function carefully. Initial doses may be lower for patients with volume depletion.
- Max dose
- 100 mg losartan / 25 mg hydrochlorothiazide once daily.
Pharmacokinetics
Onset
Losartan: 1-2 hours. Hydrochlorothiazide: ~2 hours.
Peak effect
Losartan: 6 hours (for active metabolite). Hydrochlorothiazide: 4-6 hours.
Duration
Losartan: ~24 hours (due to active metabolite). Hydrochlorothiazide: 6-12 hours.
Half-life
Losartan: ~2 hours. E-3174 (active metabolite): 6-9 hours. Hydrochlorothiazide: 5.6-14.8 hours.
Bioavailability
Losartan: Approximately 33%. Hydrochlorothiazide: Approximately 60-80%.
Protein binding
Losartan: >98%. Hydrochlorothiazide: 40-70%.
Metabolism
Losartan: Extensively metabolized by CYP2C9 and CYP3A4 to an active carboxylic acid metabolite (E-3174) and several inactive metabolites. Hydrochlorothiazide: Not metabolized.
Excretion
Losartan: Primarily via bile (approx. 60%) and urine (approx. 35%). Hydrochlorothiazide: Primarily renal (excreted unchanged).
Contraindications
- Anuria
- Hypersensitivity to losartan, hydrochlorothiazide, or sulfonamide-derived drugs
- Pregnancy
- Severe renal impairment (creatinine clearance < 30 mL/min)
- Severe hepatic impairment
- Concomitant use with aliskiren in patients with diabetes mellitus
Side effects
Common
DizzinessFatigueHeadacheUpper respiratory tract infectionNasal congestionNauseaDiarrheaMild electrolyte disturbances (e.g., hypokalemia, hyponatremia, hyperuricemia, hyperglycemia)Muscle crampsBack pain
Serious
- Angioedema
- Hypotension, especially in volume-depleted patients
- Renal dysfunction or acute renal failure
- Hyperkalemia (rarely)
- Acute myopia and secondary angle-closure glaucoma
- Stevens-Johnson syndrome
- Blood dyscrasias (e.g., thrombocytopenia, aplastic anemia)
- Contraindicated in pregnancy due to risk of fetal damage, growth retardation, fetal wastage, placental infarcts, miscarriage, and stillbirth.
Pregnancy & lactation
Pregnancy
D
Lactation
Both losartan and hydrochlorothiazide are excreted in breast milk. Due to the potential for serious adverse effects in the nursing infant, use is contraindicated during breastfeeding.
Drug interactions
Sacubitril Valsartan
Contraindicated
Textbook
Potentially excessive hypotension, increased risk of adverse effects.
Do not use in conjunction with other ARBs.
Source: G&G 14e · p602
Angiotensin Converting Enzyme Inhibitors
Severe
Textbook
Greater incidence of acute kidney injury (AKI) and adverse cardiac events.
The combination of these two classes should be avoided.
Source: Harrison 22e · p2396
Benazepril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Captopril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Enalapril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Enalaprilat
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Fosinopril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Imidapril
Severe
Textbook
Greater incidence of acute kidney injury (AKI) and adverse cardiac events.
The combination of these two classes should be avoided.
Source: Harrison 22e · p2396
Lisinopril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Moexipril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Perindopril
Severe
Textbook
Increased worsening of renal function, hypotension, syncope, and hyperkalemia without increased efficacy.
Not recommended for the treatment of hypertension. Previous studies indicate more harm than benefit.
Source: G&G 14e
Related guidelines
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