Lisinopril + Hydrochlorothiazide

Oral
Hypertension

CrCl (mL/min)	Dosage
<30	Contraindicated.

Severe: Contraindicated.

May be taken with or without food.

Hypersensitivity to lisinopril, hydrochlorothiazide or sulfonamide-derived drugs. History of angioedema with previous ACE inhibitor therapy; idiopathic or hereditary angioedema, anuria. Severe renal (CrCl <30 mL/min) and hepatic impairment. Pregnancy. Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²); neprilysin inhibitor (e.g. sacubitril); avoid use with or within 36 hours of switching from or to sacubitril/valsartan combination.

Patient with unstented unilateral/bilateral renal artery stenosis, volume depletion (e.g. dietary salt restriction, receiving diuretic therapy or dialysis, has diarrhoea or vomiting), ischaemic heart disease, cerebrovascular disease, mitral valve stenosis, left ventricular outflow tract obstruction (e.g. aortic stenosis, hypertrophic cardiomyopathy), heart failure, prediabetes or diabetes mellitus, history of angioedema unrelated to ACE inhibitor use, collagen vascular disease (e.g. SLE), history of gout or familial predisposition to gout, moderate or high cholesterol concentrations. Patient undergoing major surgery or desensitising treatment. Not recommended in patients receiving certain haemodialysis procedures (e.g. with high-flux membranes such as AN 69) or low-density lipoproteins apheresis with dextran sulfate. Black patients. Not intended for initial therapy of hypertension. Renal (CrCl 30-80 mL/min) and hepatic impairment. Lactation.

Significant: Symptomatic hypotension with or without syncope (particularly in volume-depleted patients), renal function deterioration, transient increase in BUN and serum creatinine; anaphylactoid reactions; impaired glucose tolerance, fluid or electrolyte imbalance (e.g. hypokalaemia, hyponatraemia, hypochloraemic alkalosis, hyperkalaemia); exacerbation or activation of SLE, neutropenia with myeloid hypoplasia, agranulocytosis, thrombocytopenia, anaemia; persistent non-productive cough, choroidal effusion with visual field defect, acute transient myopia, acute angle-closure glaucoma, increased risk of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma), gout, photosensitivity. Rarely, cholestatic jaundice or hepatitis progressing to fulminant necrosis; angioedema of the face, extremities, lips, tongue, glottis and/or larynx.
Cardiac disorders: MI, palpitations, tachycardia.
Ear and labyrinth disorders: Vertigo.
Eye disorders: Xanthopsia, transient blurred vision.
Gastrointestinal disorders: Diarrhoea, vomiting, nausea, abdominal pain, indigestion, taste disturbance, pancreatitis.
General disorders and administration site conditions: Asthenia, fatigue, fever.
Investigations: Increased liver enzymes, bilirubin, cholesterol and triglycerides levels.
Metabolism and nutrition disorders: Anorexia, hyperuricaemia.
Musculoskeletal and connective tissue disorders: Muscle weakness and spasm.
Nervous system disorders: Dizziness, headache, syncope, paraesthesia.
Psychiatric disorders: Restlessness, depression, mood alterations, sleep disturbances.
Renal and urinary disorders: Renal dysfunction, glycosuria, interstitial nephritis.
Reproductive system and breast disorders: Impotence.
Respiratory, thoracic and mediastinal disorders: Respiratory distress (including pulmonary oedema and pneumonitis), rhinitis.
Skin and subcutaneous tissue disorders: Rash, pruritus, toxic epidermal necrolysis.
Vascular disorders: CVA, Raynaud's syndrome, necrotising angiitis.
Potentially Fatal: Very rarely, angioedema associated with laryngeal or tongue oedema.

PO: D

Avoid prolonged exposure to sunlight and UV rays, wear sunscreen or protective clothing when going outdoors.

Monitor blood pressure, serum creatinine, BUN, electrolytes; CBC with differential (periodically or more frequently if with collagen vascular disease and/or renal impairment).

Symptoms: Hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough; diuresis, convulsions, paresis, cardiac arrhythmias, depression of consciousness (including coma). Management: Supportive and symptomatic treatment. Administer IV infusion of 0.9% NaCl solution. In case of hypotension, place the patient in a supine position. May also consider treatment with angiotensin II infusion and/or IV catecholamines. Use measures such as gastric lavage, emesis, or administration of absorbents or Na sulfate if ingestion is recent. Lisinopril may be removed by haemodialysis. For therapy-resistant bradycardia, pacemaker therapy may be used. Monitor vital signs, serum electrolytes and creatinine concentrations frequently. Administer atropine in case of bradycardia or extensive vagal reactions.

May increase serum lithium concentration and toxicity. May increase serum K with K-sparing diuretics (e.g. spironolactone, triamterene, amiloride), K supplements, K-containing salt substitutes. May increase hypotensive effect with other antihypertensive agents, nitrates (e.g. glyceryl trinitrate) or other vasodilators.
Lisinopril: May result in increased risk of angioedema with neutral endopeptidase (NEP) inhibitor (e.g. racecadotril), mammalian target of rapamycin (mTOR) inhibitors (e.g. sirolimus, everolimus, temsirolimus), vildagliptin, tissue plasminogen activator. May lead to further decrease of blood pressure with certain anaesthetic agents, TCA, antipyschotics. May reduce antihypertensive effect with NSAIDs (including cyclooxygenase-2 inhibitors). May result in nitritoid reactions (e.g. flushing, nausea, dizziness, hypotension) following injectable gold (e.g. Na aurothiomalate) use. Reduced antihypertensive effect with sympathomimetics. Increased risk of renal damage and leucopenia with allopurinol. Increased risk of hyperkalaemia with ciclosporin, lovastatin, and heparin. May lead to increased risk of leucopenia with cytostatics, immunosuppressive agents, and procainamide.
Hydrochlorothiazide: May increase risk of torsades de pointes with certain antiarrhythmics, antipsychotics and other drugs known to induce torsades de pointes. May aggravate hypotension with barbiturates, narcotics or anaesthetics. May reduce therapeutic effect of antidiabetic agents (e.g. insulin, oral hypoglycaemic drugs). May enhance hypokalaemic effect of other kaliuretic diuretics, carbenoxolone, corticosteroids, corticotropin, stimulant laxatives and parenteral amphotericin B. Increased serum Ca levels with calcium salts or vitamin D. May enhance adverse effects of cardiac glycosides. May reduce or delay absorption with colestyramine and colestipol. May enhance the hyperglycaemic effect of diazoxide. Risk of adverse effects of amantadine may be increased with hydrochlorothiazide. May increase the risk hyperuricaemia and gout-type complications with ciclosporin. May reduce the renal excretion and potentiate the myelosuppressive effects of cytotoxic drugs (e.g. methotrexate, cyclophosphamide).
Potentially Fatal:
Lisinopril: Increased risk of hypotension, syncope, hyperkalaemia, and changes in renal function with direct renin inhibitors (e.g. aliskiren). Increased risk of angioedema with neprilysin inhibitors (e.g. sacubitril).

Alcohol may aggravate the hypotensive effect of hydrochlorothiazide.

May give a positive analytic result in anti-doping test. May result in false-negative aldosterone/renin ratio. Hydrochlorothiazide may interfere with parathyroid functions tests by decreasing serum iodine (protein bound).

Description:
Mechanism of Action: Lisinopril and hydrochlorothiazide have complimentary mechanisms of action and exert an additive antihypertensive effect.
Lisinopril is a peptidyl dipeptidase inhibitor that competitively inhibits ACE from converting angiotensin I to angiotensin II, thereby resulting in decreased levels of angiotensin II causing an increased in plasma renin activity, decreased vasopressor activity, and reduced aldosterone secretion.
Hydrochlorothiazide, a thiazide diuretic, inhibits Na reabsorption in the distal tubules resulting in increased excretion of Na, water, K, and hydrogen ions.
Onset: Lisinopril: Hypotensive effect: 1-2 hours (Max: Approx 6 hours).
Hydrochlorothiazide: Diuresis: Within 2 hours.
Duration: Lisinopril: Blood pressure effect: 24 hours.
Hydrochlorothiazide: Diuresis: 6-12 hours.
Pharmacokinetics:
Absorption: Lisinopril: Incompletely and slowly absorbed. Bioavailability: Approx 25% (range: 6-60%). Time to peak plasma concentration: Approx 7 hours.
Hydrochlorothiazide: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 65-75%. Time to peak plasma concentration: Approx 1-5 hours.
Distribution: Hydrochlorothiazide: Crosses the placenta; enters the breast milk (small amounts). Plasma protein binding: Approx 40-68%.
Metabolism: Not metabolised.
Excretion: Lisinopril: Via urine (as unchanged drug). Elimination half-life: 12 hours.
Hydrochlorothiazide: Via urine (≥61% as unchanged drug). Elimination half-life: Approx 6-15 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5362119, Lisinopril. https://pubchem.ncbi.nlm.nih.gov/compound/Lisinopril. Accessed Apr. 27, 2022.

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 between 20-25°C. Protect from excessive humidity and light.

ACE Inhibitors/Direct Renin Inhibitors / Diuretics

C09BA03 - lisinopril and diuretics ; Belongs to the class of ACE inhibitors in combination with diuretics. Used in the treatment of cardiovascular disease.

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