Adco Retic 5mg/50mg Tablets

ADCO RETIC is indicated in the treatment of patients with:

• oedema of cardiac decompensation or associated with hepatic cirrhosis and corticosteroid therapy.
• essential hypertension. ADCO RETIC may be used alone or as an adjunct to other antihypertensive medicines.

Posology

Potassium supplements should not be given with ADCO RETIC tablets.

Oedema

The usual dosage is one or two tablets a day. The optimal dosage is determined by the diuretic response and the serum potassium level. Once an initial diuresis has been achieved, reduction in dosage should be attempted for maintenance therapy.

Hypertension

The usual dosage is one ADCO RETIC tablet daily. Some patients may require half a tablet daily. ADCO RETIC may be used alone or as an adjunct to other antihypertensive medicines. ADCO RETIC may add to or potentiate the action of other antihypertensive medicines. If ADCO RETIC is added to therapy with other antihypertensive medicines, dosage reduction of such medicines may be necessary in order to reduce the risk of an excessive drop in blood pressure.

Special populations

Paediatric population

The safety of the use of amiloride hydrochloride (as in ADCO RETIC) in children has not been established (see section 4.3).

Method of administration

For oral administration.

• Hypersensitivity to amiloride hydrochloride and hydrochlorothiazide or to any of the excipients listed in section 6.1.
• Concomitant use with spironolactone or triamterene.
• Severe hepatic failure.
• Addisonu2019s disease.
• Hypercalcaemia.
• Concurrent lithium therapy.
• Hyperkalaemia: ADCO RETIC should not be used in the presence of elevated plasma potassium levels (interpreted as over 5,5 mmol/L).
• Antikaliuretic therapy, potassium supplementation or potassium-rich food (except in severe and/or refractory cases of hypokalaemia under careful monitoring): Other antikaliuretic medicines and potassium supplements are contraindicated in patients receiving ADCO RETIC due to the potassium-sparing effect of amiloride hydrochloride (such combination therapy is commonly associated with rapid increases in plasma potassium levels).
• Impaired renal function: Anuria, acute renal failure, severe progressive renal disease and diabetic nephropathy are contraindications to the use of ADCO RETIC. Patients with increases in blood urea nitrogen (BUN) over 5 mmol/L, in serum creatinine levels over 130 u03bcmol/L, or in whole blood urea values over 10 mmol/L should not receive ADCO RETIC without careful, frequent monitoring of serum electrolytes and BUN levels. Potassium retention in the presence of renal impairment is accentuated by the addition of an antikaliuretic medicine and may result in the rapid development of hyperkalaemia.
• Patients with a history of previous and/or current basal cell carcinomas and/or squamous cell carcinomas of the skin and lip.
• In children: The safety of the use of amiloride hydrochloride in children has not been established; therefore, ADCO RETIC is not recommended in children under 18 years of age.
• Contraindicated in pregnancy and lactation (see section 4.6).

An increased risk of nonmelanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies. Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC. Patients taking ADCO RETIC should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Possible preventive measures such as limited exposure to sunlight and UV rays and, in the case of exposure, adequate protection should be advised to the patients to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. ADCO RETIC should not be used by patients who have had previous and/or current basal cell carcinomas and/or squamous cell carcinomas of the skin and/or lip (see section 4.3).

Patients with partial heart block may develop complete heart block. Rises in blood urea nitrogen concentrations may occur, as well as abnormalities in liver function tests. Amiloride hydrochloride (as in ADCO RETIC) may cause hepatic encephalopathy manifested by tremors, confusion and coma. Patients with liver disease should be observed for this complication when ADCO RETIC is administered. In cirrhotic patients, jaundice associated with the underlying disease process may deepen. In diabetic patients, hyperkalaemia may occur with amiloride hydrochloride (as in ADCO RETIC) administration, particularly if chronic renal disease or pre-renal azotaemia is present. Before initiating therapy in diabetic or suspected diabetic patients, the renal function status should be known. Therapy with ADCO RETIC should be discontinued at least three days before giving a glucose tolerance test. Amiloride hydrochloride (as in ADCO RETIC) should be given with care to patients likely to develop acidosis, such as severely ill patients with cardiopulmonary disease and with decompensated diabetes. Pathological changes in the parathyroid gland with hypercalcaemia and hypophosphatemia may occur with prolonged treatment with hydrochlorothiazide (as in ADCO RETIC). Hydrochlorothiazide (as in ADCO RETIC) should be used with caution in patients with impaired hepatic or renal function, or with diabetes mellitus or adrenal disease. Insulin requirements in diabetic patients may be increased, decreased, or unchanged due to hydrochlorothiazide. Diabetes mellitus which has been latent may become manifest during thiazide administration. Blood-glucose concentrations should be monitored in patients taking antidiabetic medicines since their requirements of these medicines may change. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy. Electrolyte imbalance and reversible BUN increases: Hydrochlorothiazide (as in ADCO RETIC) may produce hypomagnesaemia, hyponatraemia, hypochloraemia and hypokalaemia. Hyponatraemia may occur in patients with congestive heart failure who are very oedematous, particularly with large doses in conjunction with restricted salt in the diet. Hypokalaemia intensifies the effect of digoxin on cardiac muscle and administration of digoxin or its glycosides may have to be temporarily suspended. Urinary calcium excretion may be decreased in patients receiving hydrochlorothiazide (as in ADCO RETIC). All patients should be carefully observed for signs of fluid and electrolyte imbalance, especially in the presence of vomiting or during parenteral fluid therapy. If increasing azotaemia and oliguria occur during treatment ADCO RETIC tablets should be discontinued. Hydrochlorothiazide (as in ADCO RETIC) may interfere with a number of diagnostic tests, including tests for parathyroid function; serum concentrations of protein-bound iodine may increase without signs of thyroid disturbance. ADCO RETIC should be discontinued before carrying out tests for parathyroid function.

Effects related to diuresis in cirrhotic patients: Oral diuretic therapy is more frequently accompanied by adverse reactions in patients with hepatic cirrhosis and ascites because these patients are intolerant of acute shifts in electrolyte balance, and because they often have pre-existing hypokalaemia as a result of associated aldosteronism.

Sensitivity reactions to ADCO RETIC tablets may occur in patients with or without a history of allergy or bronchial asthma. The possibility of exacerbation or activation of systemic lupus erythematosus may occur. Patients should be observed regularly for the possible occurrence of liver dysfunction, idiosyncratic reactions, or blood dyscrasias. Less frequent cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS) have been reported after taking hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours after hydrochlorothiazide intake. At the onset, symptoms include dyspnoea, fever, pulmonary deterioration and hypotension. If diagnosis of ARDS is suspected, ADCO RETIC should be withdrawn and appropriate treatment given. Hydrochlorothiazide should not be administered to patients who previously experienced ARDS following hydrochlorothiazide intake. Sulphonamide or sulphonamide derivative medicines can cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue the medicine intake as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulphonamide or penicillin allergy.

Excipients

ADCO RETIC contains lactose monohydrate. This should be taken into account in patients with diabetes mellitus. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take ADCO RETIC. ADCO RETIC contains the colourant Sunset yellow FCF lake which may cause allergic reactions.

Lithium

Lithium should generally not be given to patients receiving diuretics (such as ADCO RETIC) since the risk of lithium toxicity is very high in such patients due to the decrease in renal clearance of lithium.

Non-steroidal anti-inflammatory medicines including selective cyclooxygenase-2 (COX-2) inhibitors

Non-steroidal anti-inflammatory medicines (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effect of antihypertensive drugs, including the diuretic, natriuretic and antihypertensive effects of diuretics (such as ADCO RETIC). In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal anti-inflammatory medicines, including selective cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists or ACE inhibitors may result in a further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, the combination should be administered with caution in patients with compromised renal function.

Concomitant administration of NSAIDs and potassium-sparing medicines, including amiloride hydrochloride, may cause hyperkalaemia, particularly in elderly patients. Therefore, when amiloride hydrochloride is used concomitantly with NSAIDs, serum potassium levels should be carefully monitored.

Amiloride hydrochloride

When amiloride hydrochloride is administered concomitantly with an angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist, trilostane, ciclosporin or tacrolimus, the risk of hyperkalaemia may be increased. Therefore, if concomitant use of these medicines is indicated because of demonstrated hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.

Hydrochlorothiazide

When given concurrently, the following medicines may interact with thiazide diuretics (as in ADCO RETIC): The potassium depleting effects of hydrochlorothiazide (as in ADCO RETIC) may be enhanced by corticosteroids, corticotrophin and carbenoxalone. Hydrochlorothiazide (as in ADCO RETIC) potentiates the action of other antihypertensive medicines. Therefore, the dosage of these medicines, especially the ganglion blockers, may need to be reduced when ADCO RETIC tablets are added to the regimen. Diuretic therapy should be discontinued for 2-3 days prior to initiation of therapy with an ACE inhibitor to reduce the likelihood of first dose hypotension. Hydrochlorothiazide (as in ADCO RETIC) may increase the neuromuscular blocking action of non-depolarising muscle relaxants like tubocurarine. The antihypertensive effect of ADCO RETIC tablets may be enhanced in the post sympathectomy patient. Hydrochlorothiazide (as in ADCO RETIC) may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude the effectiveness of the pressor agent for therapeutic use. Orthostatic hypotension due to hydrochlorothiazide (as in ADCO RETIC) may be potentiated by alcohol, barbiturates or narcotics. Oral and parenteral antidiabetic medicines may require adjustment of dosage with concurrent use. ADCO RETIC can act synergistically with chlorpropamide to increase the risk of hyponatraemia. Cholestyramine and colestipol resins absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 %, respectively. When cholestyramine is given 4 hours after the hydrochlorothiazide, the absorption of hydrochlorothiazide is reduced by 30 to 35 %.

ADCO RETIC is contraindicated in pregnancy and lactation (see section 4.3).

Pregnancy

Diuretics

The routine use of diuretics in otherwise healthy pregnant women with or without mild oedema is not indicated, because they may be associated with hypovolaemia, increased blood viscosity, and decreased placental perfusion. Diuretics do not prevent the development of toxaemia of pregnancy and there is no satisfactory evidence that they are useful for its treatment.

Hydrochlorothiazide

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient. Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the second and third trimester may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance, bone marrow depression and thrombocytopenia. Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or preeclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease. Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other treatment could be used.

Breastfeeding

Although it is not known whether amiloride hydrochloride is excreted in human milk, it is known that hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit the milk production. The use of ADCO RETIC during breast feeding is not recommended. If ADCO RETIC is used during breastfeeding, doses should be kept as low as possible.

Fertility

No data available.

Patients may experience weakness, fatigue, dizziness, stupor and vertigo. Should any of these occur, the patient should be cautioned not to drive or operate machinery.

Tabulated list of adverse effects

Adverse effects of ADCO RETIC

Adverse effects of amiloride

Adverse effects of hydrochlorothiazide

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Symptoms

See section 4.8 and section 4.4.

Treatment

Treatment is symptomatic and supportive. Empty the stomach by emesis and give symptomatic treatment. Restore fluid and acid-base balance as indicated.