- Zestopril®-H  contains two active ingredients, lisinopril and hydrochlorothiazide. 
- Lisinopril is a peptidyl dipeptidase inhibitor. It inhibits the angiotensin converting
  enzyme (ACE) that catalyses the conversion of angiotensin I to the vasoconstrictor
  peptide, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the
  adrenal cortex. Inhibition of ACE results in decreased concentrations of angiotensin 
  II which results in decreased vasopressor activity and reduced aldosterone secretion. 
  The latter decrease may result in an increase in serum potassium concentration.
- Hydrochlorothiazide is a diuretic and an antihypertensive agent. It affects the distal
  renal tubular mechanism of electrolytes 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.
- Concomitant administration of lisinopril and hydrochlorothiazide has little or no 
  effect on the bioavailability of either drug. The combination tablet is bioequivalent 
  to concomitant administration of the separate entities.
- After oral administration of  lisinopril peak serum concentration occurs within about 
  7 hours. Absorption is  not affected by the presence of food. 
- Lisinopril does not appear to be bound to serum proteins, studies in rats indicate that 
  lisinopril crosses the blood-brain barrier poorly.
- Lisinopril does not metabolize and is excreted entirely unchanged into the urine.
  Lisinopril crosses the placental barrier and appears in cord blood. It is not known 
  whether lisinopril is secreted in human milk or not.

- Each tablet of Zestopril®-H 20 mg/12.5 mg contains: 
       Lisinopril                                       20 mg (as Lisinopril  dihydrate)
       Hydrochlorothiazide                   12.5 mg
- Each tablet of Zestopril®-H 5 mg/12.5 mg contains: 
       Lisinopril                                        5 mg (as Lisinopril  dihydrate)
       Hydrochlorothiazide                  12.5 mg

- Zestopril®-H  is contraindicated in patients with anuria, hypersensitivity to lisinopril,
  hypersensitivity to other derivatives of sulphonamide or excipients of this product, in 
  patients with a history of angioedema relating to previous treatment with an ACE
  inhibitors and in patients with hereditary or idiopathic angioedema.
- Zestopril®-H  is contraindicated in second and third trimesters of pregnancy.

- Potassium: 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. Therefore, frequent 
  control of serum potassium is recommended.
- Lithium: Administration of diuretics and ACE inhibitors increases the risk of lithium 
  toxicity due to reduction of the renal clearance of lithium with administration of these 
  agents, so lithium should not be given with diuretics or ACE inhibitors.   
- Indomethacin: Indomethacin may reduce the antihypertensive efficacy of
  concomitantly administered hydrochlorothiazide and lisinopril.
- Antidiabetics: Concurrent administered with ACE inhibitors: increases the risk of 
  hypoglycaemia, especially in frist weeks of the treatment.
- Nondepolarizing muscle relaxants: Thiazides may increase therapeutical response 
  to tubocurarine.
- Allopurinol, cytostatics or immunosuppressive drugs, systemic corticosteroids 
  or procainamide: Concurrent administration with ACE inhibitors may lead to 
  increased risk of  leukopenia.
- Antacids: They stimulate decrease of bioavailability of ACE inhibitors.
- Sympathomimetic: They may reduce antihypertensive effects of ACE inhibitors.
- Cyclosporine: Administration of cyclosporine with ACE inhibitors may increase risk
   of  hyperkalemia.
- Alcohol, barbituratates or narcotics: They may enhance orthostatic hypotension if 
  concurrently administered with  Zestopril®-H  .

- Zestopril®-H is contraindicated in the second and third trimesters of pregnancy . The
  use of Zestopril®-H  is not recommended during the first trimester of pregnancy.
- It is not known whether lisinopril is secreted in human milk; however, thiazides do
  appear in human milk. Because of the potential for serious reactions from 
  hydrochlorothiazide in breast-fed infants, a decision should be made whether to 
  discontinue breast feeding or to discontinue Zestopril®-H , taking into account the
  importance of the drug to the mother.

Effects on ability to drive and use machines:-
- When driving vehicles or operating machines it should be taken into account that 
  dizziness or tiredness may occur.

- Zestopril®-H  is mostly well tolerated. 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, dry cough, 
  fatigue and hypotension including orthostatic hypotension.
- Rare adverse effects are: diarrhoea , nausea, vomiting, pancreatitis, dry mouth, rash, 
  gout, palpitations, feeling of uneasiness in chest, muscle spasms and muscular  
  weakness, paresthesia, general weakness and impotence.
- Angioneurotic oedema of face, extremities, lips, tongue and/or larynx can rarely occur 
  with administration of Zestopril®-H . Fever, vasculitis, myalgia, arthritis, eosinophilia
  and leucocytosis, rash, photosensitivity or other dermatological manifestations may  

- Hypotension and electrolytes/fluids imbalance, more likely in the presence of fluids or 
  electrolytes imbalance, e.g. volume depletion, hyponatraemia, hypochloraemic 
  alkalosis, hypomagnesaemia or hypokalaemia which may occur from prior diuretic
  therapy, dietary salt restriction, dialysis, or during intercurrent diarrhoea or vomiting.
- As with other vasodilators, Zestopril®-H  should be given with caution to patients 
  with aortic stenosis or hypertrophic cardiomyopathy.
- Zestopril®-H  should not be administered to patients with renal insufficiency
  (creatinine clearance less than or equal to 30 ml/min) until titration of the individual
  components has shown the need for the doses present in the combination tablet.
- Zestopril®-H  should be used with caution in patients with impaired hepatic function 
  or progressive liver disease, since minor alterations of fluids and electrolytes balance 
  may precipitate hepatic coma.
- In patients undergoing major surgery or during anaesthesia with agents that produce
  hypotension, lisinopril may block angiotensin II formation secondary to compensatory
  renin release. If hypotension occurs and is considered to be due to this mechanism, it 
  can be corrected by volume expansion.
- Thiazide therapy may affect glucose tolerance. Dosage adjustment of antidiabetic
  agents, including insulin, may be required.
- Thiazides may decrease urinary calcium excretion and may cause intermittent and 
  slight elevation of serum calcium. Marked hypercalcaemia may be evidence of hidden
  hyperparathyroidism. Thiazides should be discontinued before carrying out tests for
  parathyroid function.
- Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic
- Thiazide therapy may precipitate hyperuricaemia and/or gout in certain patients. 
  However, lisinopril may increase urinary uric acid and thus may attenuate the
  hyperuricaemic effect of hydrochlorothiazide.
- Zestopril®-H  should be discontinued in case angioedema of the face, extremities,
  lips, tongue, glottis and/or larynx .
- The use of Zestopril®-H is not indicated in patients requiring dialysis for renal
- Cough has been reported with the use of ACE inhibitors. Characteristically, the 
  cough is non-productive, persistent and resolves after discontinuation of therapy. 
- In patients receiving thiazides, sensitivity reactions may occur with or without a
  history of allergy or bronchial asthma.
- Patients receiving ACE inhibitors during desensitisation treatment (e.g. 
  hymenoptera venom) have sustained anaphylactoid reactions, these reactions 
  have been avoided when ACE inhibitors were temporarily withheld but they have 
  reappeared upon inadvertent re-administration of the medicinal product.

- Zestopril®-H 20mg/12.5mg  Tablets (Blister of 10 tablets, pack of 2 blisters.)
- Zestopril®-H 5 mg/12.5mg  Tablets (Blister of 10 tablets, pack of 2 blisters.)

- keep the  product in a dry place at temprature below 30°C.