Thiazide diuretics (thiazides) / K+-sparing diuretics (potassium- sparing diuretics).

Cyclopenthiazide, amiloride

6-Chloro-3-(cyclopentylmethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide1,1-dioxide (Cyclopenthiazide B.P.) 0.25mg. N-amindino-3,5-diamino-6-chloropyrazine-2-carboxamide hydrochloride dihydrate (Amiloride Hydrochloride Ph.Eur.) 2.5mg

Coated tablets

For the treatment of mild to moderate hypertension.

Adults: Usually 1 or 2 Navispare tablets taken once a day in the morning.

Navispare is not suitable for use in children.

Although no special dosage regime is necessary in the elderly, particular caution should be exercised in the elderly, since they are more susceptible to electrolyte imbalances.

Hypersensitivity to cyclopenthiazide or other sulphonamide derivatives;

Addison's disease;

Hyperkalaemia;

In the presence of other potassium conserving agents or potassium supplements;

Anuria;

Severe renal and hepatic failure;

Diabetic Nephropathy;

Concurrent lithium therapy;

Refractory hypokalaemia and hyponatraemia;

Hypercalcaemia;

Symptomatic hyperuricaemia.

Diabetes mellitus:

Hyperkalaemia has occurred in diabetic patients receiving amiloride hydrochloride, especially those with chronic renal disease or pre-renal azotaemia. The status of renal function should therefore be determine before use in a known or suspected diabetic patient. Navispare should be discontinued for at least three days before a glucose tolerance test.

Prolonged doses may bring about a decrease in glucose tolerance and precipitate a diabetic condition. In known diabetics the addition of a thiazide to the treatment regime may alter their antidiabetic requirement.

Metabolic or respiratory acidosis:

Potassium conserving therapy should be initiated with caution in patients in whom metabolic or respiratory acidosis may occur e.g. patients with cardiopulmonary disease or decompensated diabetes. Shifts in acid-base balance of extracellular potassium and the development of acidosis may be associated with rapid increase in plasma potassium.

Electrolyte considerations:

In patients with renal impairment, a rise in blood urea can occur. In such cases, either the dose should be reduced or the treatment interrupted temporarily. Thiazides may precipitate an attack of gout in patients predisposed to this condition.

The elderly, especially those suffering from chronic disease and patients with hepatic cirrhosis are more susceptible to a lack of electrolyte and fluid balance homeostatis. During treatment with thiazides hyponatraemia accompanied by neurological symptoms has been observed in isolated cases. In the elderly and patients with hepatic cirrhosis, the serum electrolytes should be monitored at more frequent intervals.

Patients receiving relatively high doses of thiazides may develop hypomagnesaemia accompanied by signs and symptoms such as nervousness, muscle spasms and cardiac arrhythmias.

Miscellaneous:

In patients with hyperlipidaemia, the serum lipids should be regularly monitored. In the event of a rise in serum lipids, withdrawal of the thiazide medication should be considered. Lupus erythematosus may possibly become activated under treatment with thiazides.

The concomitant administration of thiazides with other antihypertensive agents (e.g. beta-blockers, vasodilators, calcium antagonists) may necessitate adjustment of the dosage of those drugs.

The concomitant administration of potassium-sparing agents such as amiloride and ACE inhibitors may increase serum potassium levels and is not to be recommended. However, if the concomitant use of these agents is deemed appropriate, they should be used with caution and with frequent monitoring of plasma potassium.

NSAIDs may attenuate the antihypertensive effect of thiazide diuretics.

Thiazide containing drugs may increase the responsiveness to tubocurarine.

Orthostatic hypotension may occur and may be potentiated by alcohol, barbiturates and narcotics.

Navispare is generally well tolerated. Reported side-effects of the combination include rare cases of dizziness, headache, lightheadedness, tiredness, nausea and vomiting, discomfort/pain in the chest. However, the following side-effects of cyclopenthiazide and amiloride as single agents have been reported:

Cyclopenthiazide:

Skin:

Occasional: allergic urticaria (nettle rash) and other forms of skin rash.

Rare: photosensitisation. Isolated cases: necrotising vasculitis.

Gastro-intestintal tract:

Occasional: loss of appetite, mild nausea, vomiting.

Rare: gastrospasm, diarrhoea or possibly constipation. Isolated cases: pancreatitis.

Central nervous system:

Rare: headache, muzziness, dizziness, sleep disturbances, depression and paraesthesiae.

Blood:

Rare: thrombocytopenia sometimes with purpura. In isolated cases: leucopenia, agranulocytosis, anaemia and bone marrow depression.

Electrolytes:

Frequent: hypokalaemia.

Occasional: hyponatraemia, hypomagnesaemia.

Rare: hypercalcaemia. If hypercalcaemia occurs, further diagnostic clarification is necessary (e.g. possibility of hyperparathyroidism).

In isolated cases: hypochloraemic alkalosis.

Liver:

Rare: intrahepatic cholestasis or jaundice.

Miscellaneous:

Occasional: impotence.

Metabolic:

Occasional: hyperuricaemia. Rare: hyperglycaemia, glycosuria. Gout or diabetes may be precipitated or aggravated. Increased blood lipid levels in response to higher doses.

Cardiovascular system:

Occasional: postural hypotension, which may be aggravated by alcohol, anaesthetics or sedatives.

Rare: cardiac arrhythmias.

Amiloride:

Gastro-intestinal tract:

Rare: anorexia, nausea, vomiting, abdominal pain.

In isolated cases: diarrhoea, constipation, GI bleeding, jaundice, thirst, dyspepsia, heartburn, flatulence.

Central nervous system:

Rare: dizziness, paraesthesiae, tremors, mental confusion.

In isolated cases: encephalopathy, nervousness, insomnia, decreased libido, depression, somnolence, vertigo.

Cardiovascular system:

Rare: palpitation.

In isolated cases: angina pectoris, orthostatic hypotension, arrhythmias.

Respiratory:

Rare: cough, dyspnoea.

Urogenital:

Rare: frequency or micturition.

In isolated cases: impotence, polyuria, dysuria.

Musculoskeletal:

Rare: joint pain.

In isolated cases: muscle cramps.

Skin and appendages:

Rare: pruritus, rash, alopecia.

In isolated cases: dryness of mouth.

Goldshield

(POM)

27 September 2010