ZESTORETIC Tablet

គុណភាពព្យាបាល៖

- ប្រើសម្រាប់ព្យាបាលជំងឺសម្ពាធឡើង ដែលតម្រូវឱ្យប្រើឱសថដែលមានសមាសធាតុចម្រុះ 2មុខ (Lisinopril និង Hydrochlorothiazide) ។

កម្រិត និងរបៀបប្រើ៖

ត្រូវប្រើតាមវេជ្ជបញ្ជា

- កម្រិតប្រើជាទូទៅគឺ 1ថ្ងៃ 1គ្រាប់ ក្នុងពេលព្រឹក ឬពេលណាមួយដូចគ្នាជារៀងរាល់ថ្ងៃ

- បើក្នុងរយៈពេល 1-2សប្តាហ៍ កម្រិតប្រើ 1ថ្ងៃ 1គ្រាប់ គ្មានប្រសិទ្ធភាពទេ (សម្ពាធឈាមមិនចុះទេ) អាចបង្កើនកម្រិតប្រើលេបម្តង 2គ្រាប់ក្នុង 1ថ្ងៃ។

- ចំពោះអ្នកជំងឺតម្រងនោមខ្សោយ មិនអាចប្រើឱសថនេះភ្លាមទេ ត្រូវត្រួតពិនិត្យ Creatinine clearance ប្រសិនបើ Creatinine clearance ស្ថិតក្នុងកម្រិត > 30 និង < 80ម.ល/នាទី នោះអាចប្រើបាន តែចាប់ផ្តើមប្រើក្នុងកម្រិត 5-10ម.ក្រ នៃ Lisinopril ។

The treatment of essential hypertension for patients in whom combination therapy is appropriate.

Posology and method of administration

Essential hypertension

1 tablet, administered once daily.

Zestoretic should be taken at approximately the same time each day.

In general, if the desired therapeutic effect cannot be achieved in a period of 2-4 weeks at this dose level, the dose can be increased to 2 tablets administered once daily.

Dosage in renal insufficiency: see the package insert.

Prior diuretic therapy

Symptomatic hypotension may occur following the initial dose of Zestoretic; this is more likely in patients who are volume and/or salt depleted as a result of prior diuretic therapy. The diuretic therapy should be discontinued for 2-3 days prior to initiation of therapy with Zestoretic. If this is not possible, treatment should be started with lisinopril alone, in a 5mg dose.

Paediatric use

Safety and effectiveness in children have not been established.

Use in the elderly

In clinical studies the efficacy and tolerability of lisinopril and hydrochlorothiazide, administered concomitantly, were similar in both elderly and younger hypertensive patients.

Lisinopril, within a daily dosage range of 20-80mg, was equally effective in elderly (65 years or older) and non-elderly hypertensive patients. In elderly hypertensive patients, monotherapy with lisinopril was as effective in reducing diastolic blood pressure as monotherapy with either hydrochlorothiazide or atenolol. In clinical studies, age did not affect the tolerability of lisinopril.

- អ្នកមានជំងឺ Anuria ជំងឺ Angioedema ជំងឺខ្សោយតម្រងនោមខ្លាំង​

- អ្នកធ្លាប់មានប្រតិកម្មជាមួយសារធាតុផ្សំណាមួយនៃឱសថនេះ ឬជាមួយឱសថដែលមានប្រភពពី Sulphonamide

- ស្ត្រីមានផ្ទៃពោះក្នុងត្រីមាសទី2 ឬទី3

In patients with anuria.

In patients who are hypersensitive to ay component of this product, in patients with a history of angioedema relating to previous treatment with an angiotensin-converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema.

In patients who are hypersensitive to other sulphonamide-derived drugs.

In second and third trimesters of pregnancy.

អាចមានផលវិបាកខ្លះដូចជា៖ វិលមុខ ឈឺក្បាល ក្អក អស់កម្លាំង សម្ពាធឈាមចុះ។

One of the most common clinical side effects was dizziness, which generally responded to dosage reduction and seldom required discontinuation of therapy.

Other side effects were headache, cough, fatigue and hypotension including orthostatic hypotension.

Blood and the lymphatic system disorders

Rare: anaemia

Very rare: bone marrow depression thrombocytopenia, leucopenia, agranulocytosis, haemolytic anaemia.

Endocrine disorders

Rare: Inappropriate antidiuretic hormone secretion.

Metabolism and nutrition disorders

Uncommon: gout

Rare: hyperglycaemia, hypokalaemia, hyperuricemia, hyperkalaemia

Nervous system and psychiatric disorders

Common: dizziness, headache, paraesthesia

Uncommon: depressive symptoms

Rare: olfactory disturbance

Cardiac and vascular disorders

Common: orthostatic effects (including hypotension), syncope

Uncommon: palpitations.

Respiratory, thoracic and mediastinal disorders

Common: cough.

Gastrointestinal disorders

Common: diarrhoea, nausea, vomiting

Uncommon: dry mouth

Rare: pancreatitis

Very rare: intestinal angioedema.

Hepato-biliary disorders

Very rare: hepatitis-either hepatocellular or cholestatic, jaundice hepatic failure. Very rarely, it has been reported that in some patients the undesirable development of hepatitis has progressed to hepatic failure. Patients receiving Zestoretic who develop jaundice or marked elevation of hepatic enzymes should discontinue Zestoretic and receive appropriate medical follow up.

Skin and subcutaneous tissue disorders

Common: rash

Uncommon: hypersensitivity/angioneurotic oedema: angioneurotic oedema of the face, extremities, lips, tongue, glottis, and/or larynx

Very rare: cutaneous pseudolymphoma.

A symptom complex has been reported which may include one or more of the following: fever, vasculitis, myalgia, arthralgia/arthritis, a positive antinuclear antibodies (ANA), elevated red blood cell sedimentation rate (ESR), eosinophilia and leucocytosis, rash, photosensitivity or other dermatological manifestations may occur.

Musculoskeletal, connective tissue and bone disorders

Common: muscle cramps

Rare: muscle weakness.

Reproductive system and breast disorders

Common: impotence

General disorders and administration site conditions

Common: fatigue, asthenia

Uncommon: chest discomfort

Investigations

Common: increases in blood urea, increases in serum creatinine, increases in liver enzymes, decreases in haemoglobin

Uncommon: decreases in haematocrit

Rare: increases in serum bilirubin.

Other side effects reported with the individual components alone, and which may be potential side effects with Zestoretic, are:

Hydrochlorothiazide: anorexia, gastric irritation, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialoadenitis, vertigo, xanthopsia, leucopenia, agranulocytosis, thrombocytopenia, aplastic anaemia, haemolytic anaemia, purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis) (cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary oedema, anaphylactic reactions, hyperglycaemia, glycosuria, hyperuricaemia, electrolyte imbalance including hyponatraemia, muscle spasm, restlessness, transient blurred vision, renal failure, renal dysfunction and interstitial nephritis, acute myopia and acute angle-closure glaucoma.

Lisinopril: myocardial infarction or cerebrovascular accident possibly secondary to excessive hypotension in high risk patients, tachycardia, abdominal pain and indigestion, mood alterations, mental confusion and vertigo have occurred; as with other angiotensin converting enzyme inhibitors, taste disturbance and sleep disturbance have been reported; bronchospasm, rhinitis, sinusitis, alopecia, urticaria, diaphoresis, pruritus, psoriasis and severe skin disorders, (including pemphigus, toxic epidermal necrolysis, Stevens-Johnson Syndrome and erythema multiforme), have been reported; hyponatraemia, uraemia, oliguria/anuria, renal dysfunction, acute renal failure, pancreatitis. Rarely, haemolytic anaemia has been reported.

Potassium supplements, potassium-sparing agents or potassium-containing salt substitutes

The potassium losing effect of thiazide diuretics is usually attenuated by the potassium conserving effect of lisinopril. The use of potassium supplements, potassium-sparing agents or potassium-containing salt substitutes, particularly in patients with impaired renal function, may lead to a significant increase in serum potassium. If concomitant use of Zestoretic and any of these agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium.

See the package insert about the details below:

- Lithium

- Gold

- Antihypertensive agents

- Other agents: Indomethacin, NSAIDs

- Tubocurarine

- ហាមប្រើចំពោះស្ត្រីមានផ្ទៃពោះក្នុងត្រីមាសទី2 ឬទី3។

- គួរជៀសវាងប្រើចំពោះស្ត្រីបំបៅកូន និងស្ត្រីមានផ្ទៃពោះក្នុងត្រីមាសទី1។ បើដឹងថាមានផ្ទៃពោះហើយ ត្រូវឈប់ប្រើជាប្រញាប់ព្រោះអាចប៉ះពាល់ដល់ទារកក្នុងផ្ទៃ។

See the package insert about the details below:

Pregnancy

Contraindicated in the second and third trimesters of pregnancy.

The use of Zestoretic is not recommended during the first trimester of pregnancy.

Lactation

A decision should be made whether to discontinue breast feeding or to discontinue Zestoretic, taking into account the importance of the drug to the mother.

- ការប្រើឱសថនេះអាចធ្វើឱ្យសម្ពាធឈាមចុះ និងអតុល្យភាពនៃជាតិ Electrolyte ហេតុនេះចាំបាច់ត្រូវធ្វើការត្រួតពិនិត្យកម្រិតប្រើ និងបរិមាណ Electrolyte ជាទៀងទាត់។

- ត្រូវប្រុងប្រយ័ត្នក្នុងការប្រើឱសថនេះចំពោះអ្នកធ្លាប់មានជំងឺ Ischaemic heart ឬ Cerebrovascular disease ឬ Aortic stenosis ឬ Hypertrophic Cardiomyopathy អ្នកមានជំងឺថ្លើមខ្សោយខ្លាំង។

- គួរជៀសវាងប្រើចំពោះស្ត្រីបំបៅកូន និងស្ត្រីមានផ្ទៃពោះក្នុងត្រីមាសទី1។ បើដឹងថាមានផ្ទៃពោះហើយ ត្រូវឈប់ប្រើជាប្រញាប់ព្រោះអាចប៉ះពាល់ដល់ទារកក្នុងផ្ទៃ។

- ជាការល្អត្រូវពិគ្រោះជាមួយគ្រូពេទ្យមុននឹងប្រើឱសថនេះ។

See the package insert about the details below:

- Hypotension and electrolyte/fluid imbalance

- Renal function impairment

- Hepatic disease

- Surgery/Anaesthesia

- Metabolic and endocrine effects

- Hypersensitivity/Angioedema

- Race

- Desensitisation

- Haemodialysis patients

- Cough

Zestoretic is a fixed dose combination product containing lisinopril, an inhibitor of angiotensin converting enzyme (ACE) and hydrochlorothiazide, a thiazide diuretic. Both components have complimentary modes of action and exert an additive antihypertensive effect.

Lisinopril is a peptidyl dipeptidase inhibitor. It inhibits the angiotensin converting enzyme (ACE) that catalyses the conversion of angiotensinⅠto the vasoconstrictor peptide, angiotensinⅡ. AngiotensinⅡalso stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased concentrations of angiotensinⅡwhich results in creased vasopressor activity and reduced aldosterone secretion. The latter decrease may result in an increase in serum potassium concentration.

While the mechanism through which lisinopril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, lisinopril is antihypertensive even in patients with low-renin hypertension. ACE is identical to kininaseⅡ, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodilatory peptide, play a role in the therapeutic effects of lisinopril remains to be elucidated.

Hydrochlorothiazide is a diuretic and an antihypertensive agent. It affects the distal renal tubular mechanism of electrolyte reabsorption and increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. The mechanism of the antihypertensive effect of the thiazides is unknown. Thiazides do not usually affect normal blood pressure.