Aliskiren + hydrochlorothiazide


Full Generic Medicine Info
Dosage/Direction for Use

Oral
Hypertension
Adult: Available preparations: Aliskiren 150 mg and Hydrochlorothiazide 12.5 mg Aliskiren 150 mg and Hydrochlorothiazide 25 mg Aliskiren 300 mg and Hydrochlorothiazide 12.5 mg Aliskiren 300 mg and Hydrochlorothiazide 25 mg 1 tab once daily. Dosage is individualised and may be increased after at least 2-4 weeks, according to response. Max: Aliskiren 300 mg and Hydrochlorothiazide 25 mg daily.
Renal impairment: Severe (GFR <30 mL/min/1.73m2): Contraindicated.
Hepatic impairment: Severe: Contraindicated.
Administration
May be taken with or without food. Take consistently w/ or w/o meals. Avoid taking w/ high fat meals.
Contraindications
Hypersensitivity to aliskiren and other sulfonamide-derived drugs. Anuria, volume depletion, history of angioedema, hereditary or idiopathic angioedema. Severe hepatic and renal impairment (GFR <30 mL/min/1.73m2). Concomitant use with ACE inhibitors or angiotensin II receptor antagonists in patient with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73m2). Concomitant use with potent P-glycoprotein (P-gp) inhibitors (e.g. ciclosporin, itraconazole and quinidine). Pregnancy.
Special Precautions
Patient with prediabetes or diabetes, history or risk for gout, history of allergy or bronchial asthma; volume or salt depletion, renal artery stenosis, CV disease, post MI, hypercalcaemia, moderate or high cholesterol levels, parathyroid disease, SLE. Mild to moderate renal and hepatic impairment. Lactation. Patient Counselling This drug may cause dizziness or drowsiness, if affected, do not drive or operate machinery. Monitoring Parameters Correct hypovolaemia or salt depletion prior to initiation of therapy. Monitor blood pressure, serum electrolytes, BUN, serum creatinine, fluid status; parathyroid and renal function.
Adverse Reactions
Significant: Electrolyte disturbances (e.g, hyper or hypokalaemia, hypochloraemic alkalosis, hypomagnesaemia, hypophosphataemia, hypercalcaemia, hyponatraemia), hypersensitivity reactions (e.g. urticaria), gout, hypotension, syncope, acute transient myopia, acute angle-closure glaucoma, photosensitivity, acute renal failure, metabolic disturbances (e.g. hypercholesterolaemia, hypertriglyceridaemia, altered glucose tolerance, hyperuricaemia), SLE exacerbation or activation. Cardiac disorders: Palpitations. Gastrointestinal disorders: Diarrhoea, decreased appetite, nausea, vomiting, oral mucosal reactions. Investigations: Increased liver enzymes. Metabolism and nutrition disorders: Peripheral oedema. Musculoskeletal and connective tissue disorders: Arthralgia. Nervous system disorders: Dizziness. Reproductive system and breast disorders Impotence. Respiratory, thoracic and mediastinal disorders: Cough. Skin and subcutaneous tissue disorders: Urticaria, rash, Stevens Johnson syndrome, toxic epidermal necrolysis, pruritus.
Potentially Fatal: Anaphylactic reactions, angioedema.
Overdosage
Symptoms: Hypotension, electrolyte depletion (e.g. hypokalaemia, hypochloraemia, hyponatraemia), dehydration. Management: Symptomatic and supportive treatment.
Drug Interactions
Aliskiren: Increased risk of hypotension with other antihypertensives. Increased risk of acute renal failure with ACE inhibitors, angiotensin II receptor antagonists or NSAIDs. Antihypertensive effect may be reduced with NSAIDs. Increased serum levels with atorvastatin, ketoconazole, verapamil. Decreases furosemide concentrations. Increased risk of hyperkalaemia with potassium-sparing diuretics, potassium supplements or any substances that may increase serum potassium levels. Hydrochlorothiazide: Increases toxicity of lithium. May potentiate orthostatic hypotension with barbiturates and narcotics. Increased hypokalaemic effect with corticosteroids or ACTH. Potentiation of orthostatic hypotension with barbiturates or opioids. Reduced antihypertensive effect by drugs that cause fluid retention (e.g. corticosteroids, NSAIDs, carbenoxolone). Enhanced nephrotoxicity of NSAIDs. May reduce the therapeutic effect of antidiabetics.
Potentially Fatal: Increased risk of renal impairment, stroke, hypotension and hyperkalaemia with ACE inhibitors or angiotensin II receptor antagonists. Markedly increased plasma concentration with ciclosporin, itraconazole and quinidine.
Food Interaction
Aliskiren: Reduced bioavailability with high fat meals. Reduced serum concentration with grapefruit juice. Hydrochlorothiazide: Enhanced orthostatic hypotensive effect with alcohol.
Lab Interference
Hydrochlorothiazide: May interfere with parathyroid function tests.
Action
Aliskiren is a direct inhibitor of renin, an enzyme essential for the conversion of angiotensinogen into angiotensin I. It decreases plasma renin activity therefore inhibiting the production of angiotensin II and aldosterone. Hydrochlorothiazide inhibits the reabsorption of Na in the distal tubules causing increased excretion of Na and water including K and hydrogen ions.
Onset: Aliskiren: Within 2 weeks. Hydrochlorothiazide: Approx 2 hours.
Duration: Hydrochlorothiazide: 6-12 hours.
Absorption: Aliskiren: Poorly absorbed from gastrointestinal tract. Food, particularly high fat meal, decreases rate and extent of absorption. Bioavailability: Approx 3%. Time to peak plasma concentration: 1-3 hours. Hydrochlorothiazide: Fairly rapid absorption from the gastrointestinal tract. Time to peak plasma concentration: Approx 1-5 hours. Bioavailability: Approx 65-70%.
Distribution: Aliskiren: Distributes extensively into extravascular space. Plasma protein binding: Approx 50%. Hydrochlorothiazide: Crosses the placenta and enters breast milk; distributes in erythrocytes. Volume of distribution: 3.6-7.8 L/kg. Plasma protein binding: Approx 40-68%.
Metabolism: Aliskiren: Minimal metabolism by CYP3A4 isoenzyme.
Excretion: Aliskiren: Mainly via faeces, as unchanged drug; urine (approx 25% as unchanged drug). Elimination half-life: Approx 24-40 hours. Hydrochlorothiazide: Via urine (≥61 % as unchanged drug). Elimination half-life: Approx 5-15 hours.
Storage
Oral: Store at 25°C. Protect from moisture.
ATC Classification
C09XA02 - aliskiren ; Belongs to the class of renin-inhibitors. Used in the treatment of cardiovascular disease.
C03AA03 - hydrochlorothiazide ; Belongs to the class of low-ceiling thiazide diuretics.
Disclaimer: This information is independently developed by CIMS based on aliskiren + hydrochlorothiazide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to CIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, CIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 CIMS. All rights reserved. Powered by CIMSAsia.com
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