Ridaq-12,5 Tablets 12.5 mg Tablets

RIDAQ-12,5 is indicated for:

• mild to moderate hypertension, alone or in combination with other anti-hypertensives.

Posology

Adults

If a single dose is indicated, RIDAQ-12,5 should preferably be taken in the morning in order to minimise the effect of increased frequency of urination during sleep. RIDAQ-12,5 should be taken with or after meals to minimise stomach upset.

Hypertension

For the treatment of mild to moderate hypertension

Take one tablet (12,5 mg) daily.

As an adjunct in the treatment of hypertension

Take one to two tablets (12,5 mg to 25 mg) daily in conjunction with an anti-hypertensive medicine.

The dosage should not be higher than necessary to achieve the desired effect. Prolonged treatment may result in potassium ion loss. Potassium supplements may be necessary.

Paediatric population

No data are available.

Method of administration

For oral administration.

RIDAQ-12,5 is contraindicated in:

• Patients with hypersensitivity to hydrochlorothiazide, other sulphonamide-derived medicines or to any of the excipients in RIDAQ-12,5 (see section 6.1).
• Patients with anuria or severe renal (creatinine clearance <30 mL/min) impairment.
• Patients with severe hepatic impairment.
• Patients with Addisonu2019s disease.
• Patients with pre-existing hypercalcaemia.
• Patients with a history of previous and/or current basal cell carcinomas and/or squamous cell carcinomas of the skin and lip.
• The second and third trimesters of pregnancy and during lactation (see section 4.6).

Hepatobiliary disorders

RIDAQ-12,5 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 and increases the risk of hepatic encephalopathy. Patients with hepatic cirrhosis are particularly at risk of hypokalaemia.

Renal and urinary disorders

RIDAQ-12,5 should be given with caution in renal function impairment since it can further reduce renal function (see section 4.3). In patients with renal disease, RIDAQ-12,5 may precipitate azotaemia and oliguria. Cumulative effects of the medicine may develop in patients with impaired renal function. RIDAQ-12,5 is ineffective at creatinine clearance values of 30 mL/min or below (i.e. moderate or severe renal insufficiency). If progressive renal impairment becomes evident, as indicated by rising non-protein nitrogen, careful reappraisal of therapy is necessary, with consideration given to discontinuing diuretic therapy.

Diabetes mellitus

RIDAQ-12,5 may cause hyperglycaemia and aggravate or unmask diabetes mellitus. Blood-glucose concentrations should be monitored in patients taking antidiabetic medicines, including insulin and oral hypoglycaemic medicines, since requirements may change.

Electrolyte imbalance

All patients should be carefully observed for signs of fluid and electrolyte imbalance namely, hyponatremia, hyperchloremic alkalosis, and hypokalaemia; serum and urine electrolyte determinations are particularly important especially in the presence of vomiting or during parenteral fluid therapy. Elderly patients are particularly susceptible to electrolyte imbalance.

Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at appropriate intervals.

Hypokalaemia

Hypokalaemia may develop, especially with brisk diuresis, in patients receiving concomitant therapy with corticosteroids or adrenocorticotropic hormone (ACTH) also known as corticotropin, or after prolonged therapy. Interference with adequate oral electrolyte intake will also contribute to hypokalaemia. Hypokalaemia may cause cardiac dysrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g. increased ventricular irritability). Hypokalaemia may be avoided or treated by use of potassium sparing diuretics or potassium supplements such as foods with a high potassium content.

Chloride deficit

Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.

Hyponatremia

Dilutional hyponatremia may occur in oedematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Hyperuricaemia

Hyperuricaemia may occur, or acute gout may be precipitated in certain patients receiving RIDAQ-12,5.

Hypomagnesaemia

RIDAQ-12,5 have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesaemia.

Hypercalcaemia

RIDAQ-12,5 may decrease urinary calcium excretion. RIDAQ-12,5 may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. RIDAQ-12,5 should be discontinued before carrying out tests for parathyroid function.

Cholesterol and triglyceride levels

Increases in cholesterol and triglyceride levels may be associated with RIDAQ-12,5 therapy.

Systemic lupus erythematosus (SLE)

There is a possibility that RIDAQ-12,5 may exacerbate or activate systemic lupus erythematosus in susceptible patients.

Antihypertensive medicines

RIDAQ-12,5 may add to or potentiate the action of other antihypertensive medicines.

History of allergy or bronchial asthma

Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.

Lithium

Lithium generally should not be given with diuretics (see section 4.5).

Acute myopia and secondary angle-closure glaucoma

RIDAQ-12,5, a sulphonamide, can cause an idiosyncratic reaction, resulting in acute 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 medicine initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue RIDAQ-12,5 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.

Choroidal effusion

Sulfonamide or sulfonamide derivative medicines, such as hydrochlorothiazide, as in RIDAQ-12,5, 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 medicine initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue medicines 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 sulfonamide or penicillin allergy.

Non-melanoma skin cancer

An increased risk of non-melanoma skin cancer (NMSC) (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) with increasing cumulative dose of hydrochlorothiazide (HCTZ), as in RIDAQ-12,5, exposure has been observed in two epidemiological studies. Photosensitising actions of RIDAQ-12,5 could act as a possible mechanism for NMSC. Patients taking RIDAQ-12,5 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 case of exposure, adequate protection should be advised to the patients to minimise the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. RIDAQ-12,5 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).

Post-sympathectomy

The antihypertensive effects of the medicine may be enhanced in the post-sympathectomy patient.

Anti-doping test

RIDAQ-12,5 could produce a positive analytical result in an anti-doping test.

Excipients:

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicine.

Amphotericin B (parenteral), carbenoxolone or stimulant laxatives:

RIDAQ-12,5 may intensify electrolyte imbalance, particularly hypokalaemia.

Antidiabetic medicines (insulin and oral antidiabetics):

Dosage adjustment of the antidiabetic medicines may be necessary.

Calcium salts:

Increased serum calcium levels due to decreased excretion may occur when administered concurrently with RIDAQ-12,5.

Colestyramine resin and colestipol:

The presence of anionic exchange resins may delay or decrease absorption of RIDAQ-12,5. Sulphonamide diuretics should be taken at least one hour before or four to six hours after these medicines.

Digitalis glycosides:

RIDAQ-12,5 may enhance the toxicity of digitalis glycosides by depleting serum-potassium concentrations.

Nondepolarising skeletal muscle relaxants (e.g. tubocurarine):

RIDAQ-12,5 may enhance the neuromuscular blocking action of competitive muscle relaxants, such as tubocurarine.

Antihypertensive medicines, alcohol, barbiturates and opioids:

RIDAQ-12,5 may enhance or potentiate the effect of other antihypertensive medicines, while postural hypotension associated with this therapy may be enhanced by concomitant ingestion of alcohol, barbiturates, or opioids.

Corticosteroids, ACTH, corticotropin, beta 2 -agonists:

The potassium-depleting effect of RIDAQ-12,5 may be enhanced by corticosteroids, ACTH or corticotropin and beta 2 -agonists such as salbutamol.

Pressor amines:

RIDAQ-12,5 has been reported to diminish the response to pressor amines, such as noradrenaline, but the clinical significance of this effect is uncertain.

Lithium:

Concomitant administration of RIDAQ-12,5 and lithium is not generally recommended since RIDAQ-12,5 may reduce the renal clearance of lithium and may lead to toxic blood concentrations of lithium (see section 4.4).

Non-steroidal anti-inflammatory drugs (NSAIDs):

In some patients, the administration of NSAIDs can reduce the diuretic, natriuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when RIDAQ-12,5 and NSAIDs are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Medicines associated with Torsades de pointes:

Due to the risk of hypokalaemia, caution should be used when RIDAQ-12,5 is co-administered with medicines associated with torsades de pointes, e.g. anti-dysrhythmics, antipsychotics and other medicines known to induce Torsades de pointes.

Laboratory tests:

RIDAQ-12,5 should be discontinued before carrying out tests for parathyroid function (see section 4.3). RIDAQ-12,5 may cause diagnostic interference of the bentiromide test. RIDAQ-12,5 may decrease serum Protein Bound Iodine (PBI) levels without signs of thyroid disturbance.

The safety of RIDAQ-12,5 in pregnancy and lactation has not been established (see section 4.3).

Pregnancy

There is limited experience with RIDAQ-12,5 during pregnancy, especially during the first trimester. RIDAQ-12,5 crosses the placenta and there have been reports of neonatal jaundice, thrombocytopenia, icterus and electrolyte imbalances following maternal treatment and is not recommended for use in pregnancy. Reductions in maternal blood volume could also adversely affect placental perfusion.

RIDAQ-12,5 should not be used for gestational oedema, gestational hypertension or pre-eclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease.

RIDAQ-12,5 should not be used for essential hypertension in pregnant women.

Breastfeeding

RIDAQ-12,5 is distributed into breast milk, and is not recommended for use in lactation. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue RIDAQ-12,5, considering the importance of the medicine to the mother. RIDAQ-12,5 in high doses causing intense diuresis can inhibit the milk production.

Fertility

There is no data available.

RIDAQ 12,5 mg has moderate influence on the ability to drive and use machines. Since adverse reactions such as somnolence, dizziness and blurred vision have been reported in patients receiving RIDAQ 12, 5 mg, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that RIDAQ 12,5 mg does not adversely affect their ability to do so (see section 4.8).

a) Tabulated list of adverse reactions

System organ class

Frequent

Less frequent

Frequency unknown (cannot be estimated from the available data)

Infections and infestations

Sialadenitis

Neoplasm benign, malignant and unspecified (including cysts and polyps)

Non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma)

Blood and the lymphatic system disorders

Blood dyscrasias, thrombocytopenia, granulocytopenia, leukopenia, aplastic anaemia, haemolytic anaemia

Agranulocytosis, neutropenia, bone marrow depression

Immune system disorders

Hypersensitivity reactions

Anaphylactic reactions, purpura

Metabolism and nutrition disorders

Electrolyte imbalances, hypochloraemic alkalosis, hyponatraemia (may occur in patients with severe heart failure who are very oedematous, particularly with large doses in conjunction with restricted salt in the diet), and hypokalaemia (intensifies the effect of digitalis on cardiac muscle and administration of digitalis or its glycosides may have to be temporarily suspended)

Metabolic disturbances especially at high doses, hyperglycaemia in diabetic and other susceptible patients, hyperuricaemia and precipitate attacks of gout in some patients, hypomagnesaemia, anorexia

Psychiatric disorders

Restlessness

Depression, sleep disturbances

Nervous system disorders

Lethargy, drowsiness, seizures

Headache, dizziness, paraesthesia

Light-headedness

Eye disorders

Yellow vision (xanthopsia)

Transient blurred vision, choroidal effusion

Ear and labyrinth disorders

Vertigo

Cardiac disorders

Cardiac dysrhythmias

Vascular disorders

Postural hypotension (aggravated by barbiturates, alcohol or narcotics)

Necrotising angiitis (vasculitis, cutaneous vasculitis)

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema, pneumonitis

Respiratory distress

Gastrointestinal disorders

Gastrointestinal disturbances, dry mouth

Gastric irritation, nausea, vomiting, constipation, diarrhoea, intestinal ulceration has occurred following the administration of tablets containing thiazides with an enteric-coated core of potassium chloride, pancreatitis, cramping

Hepato-biliary disorders

Cholestatic jaundice

Skin and subcutaneous tissue disorders

Photosensitivity reactions, skin rashes

Erythema multiforme including Stevens-Johnson Syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia, cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus erythematosus, urticaria

Musculoskeletal and connective tissue disorders

Muscle pain and cramps

Muscle spasm

Renal and urinary disorders

Oliguria

Glycosuria, urinary excretion of calcium is reduced

Renal failure, renal dysfunction, interstitial nephritis

Reproductive system and breast disorders

Impotence

General disorders and administrative site conditions

Thirst, weakness

Fever

Investigations

Adverse changes in plasma lipids have been noted but their clinical significance is unclear.

Increases in cholesterol and triglycerides

b) Description of selected adverse reactions :

Eye disorders : Cases of choroidal effusion with visual field defect have been reported after the use of thiazide and thiazide-like diuretics.

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. Healthcare providers are asked to report any suspected adverse reactions to: SAHPRA: https://www.sahpra.org.za/Publications/Index/8 Aspen Pharmacare: E-mail: [email protected] Tel: 0800 118 088

Symptoms

RIDAQ-12,5 can produce acute renal failure either from overdosage, producing saline depletion and hypovolaemia or, occasionally, as a result of a hypersensitivity reaction.

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalaemia may accentuate cardiac dysrhythmias.

Treatment

In massive overdosage, treatment is symptomatic and supportive. Recommended treatment for overdose includes immediate evacuation of the stomach (emesis or gastric lavage); supportive, symptomatic treatment; monitoring of serum electrolyte concentrations and renal function and immediate institution of appropriate treatment for hypokalaemia. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. If required, give oxygen or artificial respiration for respiratory impairment. The degree to which RIDAQ 12,5 is removed by haemodialysis has not been established.