Generic
Aliskiren Hemifumarate + Hydrochlorothiazide
1 brands available in the market
At a glance
Aliskiren Hemifumarate + Hydrochlorothiazide is a fixed-dose combination medicine used for the treatment of essential hypertension in adults. Aliskiren is a direct renin inhibitor, and hydrochlorothiazide is a thiazide diuretic.
Description
Aliskiren Hemifumarate + Hydrochlorothiazide is a fixed-dose combination product containing two antihypertensive agents: aliskiren (a direct renin inhibitor) and hydrochlorothiazide (a thiazide diuretic) [citation:1][citation:5]. Aliskiren inhibits the renin-angiotensin system (RAS) at the point of activation by blocking the enzyme renin, preventing the conversion of angiotensinogen to angiotensin I and decreasing angiotensin II levels [citation:1][citation:2][citation:3]. Hydrochlorothiazide acts on the distal convoluted tubule to increase sodium and chloride excretion, reducing plasma volume [citation:1][citation:3][citation:6]. The combination provides greater blood pressure reduction than either component alone and is indicated for patients not adequately controlled on monotherapy [citation:1][citation:4][citation:5].
Indications
Essential hypertension in adults, particularly in patients whose blood pressure is not adequately controlled on aliskiren or hydrochlorothiazide alone [citation:1][citation:4][citation:5].
Therapeutic class
Direct Renin Inhibitor + Thiazide Diuretic
Pharmacological class
Antihypertensive (Renin Inhibitor + Diuretic)
Pharmacology
Aliskiren is a potent, selective, orally active direct renin inhibitor that inhibits the enzyme renin, preventing the conversion of angiotensinogen to angiotensin I [citation:2][citation:3]. This reduces angiotensin II (a potent vasoconstrictor) and aldosterone levels, lowering blood pressure [citation:1][citation:2][citation:5]. Unlike ACE inhibitors or ARBs, aliskiren decreases plasma renin activity (PRA) [citation:2][citation:3][citation:6]. Hydrochlorothiazide is a thiazide diuretic that inhibits the Na+-Cl- symporter in the distal convoluted tubule, increasing sodium and chloride excretion [citation:2][citation:3][citation:6]. This reduces plasma volume and lowers blood pressure [citation:1][citation:3][citation:5].
Mechanism of action
Aliskiren directly inhibits renin at the origin of the RAS, preventing angiotensin II production, leading to vasodilation and decreased blood pressure. Hydrochlorothiazide reduces blood volume by increasing sodium and water excretion. The combination of these two different mechanisms provides synergistic blood pressure reduction [citation:2][citation:6].
Dosage
Adults:
- Usual starting dose: 150/12.5 mg once daily [citation:4]
- May be titrated up to maximum 300/25 mg once daily as needed [citation:4]
Administration
- May be taken with or without food, but establish a consistent routine [citation:3][citation:4]
- High-fat meals substantially decrease aliskiren absorption (AUC and Cmax reduced by 60-82%) – avoid taking with high-fat meals [citation:3][citation:4]
- Swallow tablet whole
Missed dose
If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.
Side effects
Common side effects:
- Diarrhea – most common side effect of aliskiren [citation:1][citation:5]
- Dizziness
- Joint pain
- Cough [citation:1][citation:5]
- Fatigue
- Increased blood potassium levels
- Gastrointestinal irritation, weakness, headache (from hydrochlorothiazide) [citation:1][citation:5]
Serious (rare): Angioedema (rare with aliskiren) [citation:1][citation:5]
Precautions & warnings
- Pregnancy: Highly unsafe (Category D). Discontinue immediately if pregnancy is detected [citation:3][citation:4][citation:6]
- Severe renal impairment: Not recommended [citation:3]
- Diabetes with renal impairment (GFR <60 mL/min): Avoid concomitant use with ACE inhibitors or ARBs
- History of angioedema: Caution required
- Volume depletion/dehydration: Not recommended as initial therapy [citation:4]
- Electrolyte imbalance: Regular monitoring required
Contraindications
- Hypersensitivity to aliskiren or hydrochlorothiazide
- Pregnancy [citation:3][citation:4][citation:6]
- Severe renal impairment [citation:3]
- Anuria
- History of angioedema [citation:1][citation:5]
- Concomitant use with ACE inhibitors or ARBs in patients with diabetes and renal impairment
Drug interactions
- Cyclosporine, itraconazole, quinidine: Avoid concomitant use
- ACE inhibitors or ARBs: Avoid concomitant use in patients with diabetes and renal impairment
- Potassium supplements or potassium-sparing diuretics: Risk of hyperkalemia
- NSAIDs: May reduce renal function
- Lithium: May increase toxicity (hydrochlorothiazide reduces lithium clearance)
Food interactions
- Alcohol: May cause excessive drowsiness and dizziness; avoid
- High-fat meals: Substantially decrease aliskiren absorption [citation:3][citation:4]
- Food intake: Taking with food reduces aliskiren AUC and Cmax by 60-82% [citation:3]
Use in pregnancy
Pregnancy Category: D
Aliskiren + Hydrochlorothiazide is highly unsafe during pregnancy. Drugs acting on the renin-angiotensin system can cause fetal and neonatal morbidity and death [citation:6]. Discontinue immediately if pregnancy is detected [citation:3][citation:4][citation:6].
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Hydrochlorothiazide is excreted in breast milk [citation:3]. It is not known whether aliskiren is excreted in human milk. Use with caution.
Pediatric use
Safety and efficacy have not been established in pediatric patients under 18 years of age [citation:3].
Geriatric use
Elderly patients (≥65 years) have increased aliskiren exposure (AUC); however, no starting dose adjustment is required [citation:3].
Renal / hepatic impairment
- Renal impairment: No dose adjustment required in mild-moderate impairment; not recommended in severe renal impairment [citation:3]. Monitor creatinine and potassium regularly.
- Hepatic impairment: No dose adjustment required in mild-severe liver disease [citation:3].
Overdose effects
Overdose symptoms: electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration from excessive diuresis [citation:6]. Treatment: symptomatic and supportive measures.
Storage conditions
Store below 30°C in a cool and dry place, protected from light. Keep out of reach of children.
Chemical structure
C₃₀H₅₃N₃O₆·C₇H₅ClN₂O₄S₂ (Aliskiren Hemifumarate + Hydrochlorothiazide)