(25mg/Tablet)
COMPOSITION:
Each tablet contains 25mg Hydrochlorothiazide.
CLINICAL PHARMACOLOGY:
Pharmacodynamic:
Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.
The precise mechanism of action of thiazides diuretics as antihypertensive agents is unknown, although the beneficial effects appear to result from an altered sodium balance. Upon initiation of treatment with a thiazide, cardiac output is decreased and blood volume is diminished during chronic therapy, the cardiac 
output returns to normal, peripheral vascular resistance falls, and there is a persistent, small reduction in extracellular water and plasma volume. The decreased peripheral vascular resistance caused by the administration of a thiazide appears to be the result of sodium depletion, and such depletion may have secondary effects on the vasculature.
Pharmacokinetics:
Thiazides are absorbed from the gastro-intestinal tract, principally in the upper part of the small intestine. The absorption of Hydrochlorothiazide is dependent on intestinal transit time, being increased when the intestinal transit time is slow. The thiazides are widely distributed in body fluids and are extensively (92%) bound to plasma proteins, particularly so to albumin, the substituted molecules being the most highly bound. Plasma levels decline according to a two compartmental model. Most of the thiazide is excreted in the urine unchanged and more than 96% of hydrochlorothiazide appears unchanged in the urine within 3-6 hours after an oral dose.
INDICATIONS:
- Management of mild to moderate hypertension.
- Treatment of oedema associated with congestive heart failure, hepatic cirrhosis, premenstrual tension and oedema due to various forms of renal dysfunction (i.e. nephritic syndrome, acute glomerular nephritis, chronic renal failure).
Hydrochlorothiazide can be used as an adjunct to other antihypertensive drugs.
CONTRAINDICATIONS:
Hypersensitivity to hydrochlorothiazide or any component of the formulation, thiazides or sulfonamide-derived drugs; anuria, and severe renal and hepatic failure. Addison’s disease, hypercalcaemia, current lithium therapy.
DRUG INTERACTION AND OTHER FORM OF INTERACTION
– Alcohol, barbiturates or narcotics: Co-administration may potentiate orthostatic hypotension.
– Oral and parenteral antidiabetic drugs may require adjustment of dosage with concurrent use.
– Food: Hydrochlorothiazide peak serum levels may be decreased if taken with food. The product may deplete potassium, sodium and magnesium.
– Herb/Nutraceutical: Avoid dong qua if using for hypertension (has estrogenic activity). Dong qua may also cause photosensitization. Avoid Ephedra, ginseng, yohimbe (may worsen hyponatraemia). Avoid garlic (may have increased antihypertensive effect).
WARNINGS/PRECAUTIONS
– Patients should be carefully monitored for signs of fluid and electrolyte imbalance (hyponutraemia, hypochloraemic, alkalosis, hypokalaemia and hypomagnesaemia).
– Hypokalaemia may be avoided or treated in the adult by concurrent use of amiloride HCl, a potassium-conserving agent. Hypokalaemia may be avoided by giving potassium chloride or foods with a high potassium content.
– Thiazides should be discontinued before carrying out tests for parathyroid function.
– Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
KEEP OUT OF THE REACH OF CHILDREN!
ADVERSE REACTIONS/SIDE EFFECTS
–Gastro-intestinal system: anorexia, gastric irritation, nausea, vomiting, cramps, constipation and jaundice.
– Central nervous system: Dizziness, vertigo, paraesthesiae, headache and yellow vision.
– Haematological: Leucopenia, agranulocytosis, thrombocytopenia, a plastic anaemia and haemolytic anaemia.
– Cardiovascular: Hypotension, including orthostatic hypotension.
Use in the elderly particular caution is needed in the elderly because of their susceptibility to electrolyte imbalances; the dosage should be carefully adjusted according to renal function should be carefully adjusted and clinical response, if lower dosage is required 25mg/tablet are available.
– Hypersensitivity: Purpura, photosensitivity, rash, urticaria, fever, respiratory distress and anaphylactic reactions.
– Metabolic: Hyperglycemia, glycosuria, hyperuricaemia, electrolyte imbalance including hyponatraemia and hypokalaemia.
SYMPTOMS OF OVERDOSAGE AND ANTIDOTE
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalaemia hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis. In the event of over dosage, symptomatic and supportive measures should be employed. If ingestion is recent, emesis should be induced or gastric lavage performed, Dehydration, electrolyte imbalance, hepatic coma and hypotension should be corrected by established procedures. If required give oxygen or artificial respiration for respiratory impairment.
PREGNANCY AND LACTATION
Thiazides cross the placental barrier and appear in cord blood. The use of hydrochlorothiazide requires that the benefits of the drug be weighed against possible hazards to the foetus. These hazards include foetal or neonatal jaundice, thrombocytopenia and possibly other adverse reactions which have occurred in the adult. The routine use of diuretics in otherwise healthy pregnant women with or without mild oedema is not recommended because their use may be associated with hypovolaemia, increased blood viscosity and decreased placental perfusion. Thiazides appear in breast milk. If use of the drug is deemed essential, the patient should stop breast-feeding.
DOSAGE AND ADMINISTRATION
Dosage should be determined on an individual basis and the lowest dosage necessary to achieve the desired result should be used.
ADULT
– For oedema: the usual initial dose is 25-100mg a day given in a single dose or in two divided doses. The maximum recommended daily dose is 100mg.
– In oedema accompanying pre-menstrual tension; 25-50mg once or twice a day from the first morning of symptoms until the onset of the menses.
– For control of hypertension: usual starting dosage is 25mg a day as a single or divided dose. In some patients a starting dose of 12.5mg alone or with another antihypertensive may be sufficient. Dosage should be adjusted to response but should not exceed 50mg a day. Thiazides may add to the action of other antihypertensives. If Hydrochlorothiazide is used with other antihypertensive agents, it may be necessary to reduce the dosage of such agents so as to prevent an excessive drop in blood pressure.
INFANT AND CHILDREN
– A suggested initial dose for children is 2.5mg/kg body-weight daily in 2 divided doses.
– Infants under 6 months may need doses of up to 3.5mg/kg a day in two doses.
– Infants up to 2 years of age may be given 12.5-37.5mg of hydrochlorothiazide a day in two doses.
– Children from 2 to 12 years of age may be given 37.5-100mg a day in two doses. Dosage should be based on body weight.
STORAGE
Store in a cool dry place below 30OC
PRESENTATION
Hydrochlorothiazide is a 25mg tablet presented in a blister pack of 3 x10’s and 10 x 10’s