Aliskiren + Hydrochlorothiazide

Oral
Hypertension

Severe (GFR <30 mL/min/1.73m²): Contraindicated.

Severe: Contraindicated.

May be taken with or without food. Take w/ a light meal, preferably at the same time each day. Swallow whole w/ water. Avoid taking w/ fruit juices.

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.

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.

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.

PO: D

This drug may cause dizziness or drowsiness, if affected, do not drive or operate machinery.

Correct hypovolaemia or salt depletion prior to initiation of therapy. Monitor blood pressure, serum electrolytes, BUN, serum creatinine, fluid status; parathyroid and renal function.

Symptoms: Hypotension, electrolyte depletion (e.g. hypokalaemia, hypochloraemia, hyponatraemia), dehydration. Management: Symptomatic and supportive treatment.

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.

Aliskiren: Reduced bioavailability with high fat meals. Reduced serum concentration with grapefruit juice.
Hydrochlorothiazide: Enhanced orthostatic hypotensive effect with alcohol.

Hydrochlorothiazide: May interfere with parathyroid function tests.

Description:
Mechanism of 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.
Pharmacokinetics:
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.

Source: National Center for Biotechnology Information. PubChem Database. Aliskiren, CID=5493444, https://pubchem.ncbi.nlm.nih.gov/compound/Aliskiren (accessed on Jan. 20, 2020)

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3639, Hydrochlorothiazide. https://pubchem.ncbi.nlm.nih.gov/compound/Hydrochlorothiazide. Accessed Oct. 24, 2023.

Store at 25°C. Protect from moisture.

ACE Inhibitors/Direct Renin Inhibitors / Diuretics

C09XA52 - aliskiren and hydrochlorothiazide ; Belongs to the class of renin-inhibitors. Used in the treatment of cardiovascular disease.

Anon. Aliskiren and Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/03/2018.

Anon. Aliskiren. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/03/2018.

Anon. Hydrochlorothiazide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/03/2018.

Buckingham R (ed). Aliskiren Fumarate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/03/2018.

Buckingham R (ed). Hydrochlorothiazide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/03/2018.

McEvoy GK, Snow EK, Miller J et al (eds). Aliskiren Hemifumarate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 02/03/2018.

Rasilez (Noden Pharma DAC). European Medicines Agency [online]. Accessed 02/03/2018.

Tekturna HCT Tablet, Film Coated (Noden Pharma USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/03/2018.