Converide Special Precautions

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 exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitizing actions of hydrochlorothiazide could act as a possible mechanism for NMSC.
Patients taking hydrochlorothiazide 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 in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. The use of hydrochlorothiazide may also need to be reconsidered in patients who have experienced previous NMSC.
Hypotension - Volume-depleted patients: Converide has been rarely associated with symptomatic hypotension in hypertensive patients without other risk factors for hypotension. Symptomatic hypotension may be expected to occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before initiating therapy with Converide.
Renal artery stenosis - Renovascular hypertension: There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with angiotensin converting enzyme inhibitors or angiotensin-II receptor antagonists. While this is not documented with Converide, a similar effect should be anticipated.
Renal impairment and kidney transplantation: When Converide is used in patients with impaired renal function, a periodic monitoring of potassium, creatinine and uric acid serum levels is recommended. There is no experience regarding the administration of Converide in patients with a recent kidney transplantation. Converide should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) (see Contraindications). Thiazide diuretic-associated azotemia may occur in patients with impaired renal function. No dosage adjustment is necessary in patients with renal impairment whose creatinine clearance is ≥30 ml/min. However, in patients with mild to moderate renal impairment (creatinine clearance ≥30 ml/min but <60 ml/min) this fixed dose combination should be administered with caution.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS): Dual blockade of the RAAS by combining Converide with an angiotensin-converting enzyme inhibitor (ACEI) or with aliskiren is not recommended since there is an increased risk of hypotension, hyperkalaemia, and changes in renal function. The use of Converide in combination with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m²) (see Interactions). The use of Converide in combination with an ACEI is contraindicated in patients with diabetic nephropathy (see Interactions).
Hepatic impairment: 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. There is no clinical experience with Converide in patients with hepatic impairment.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Primary aldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of Converide is not recommended.
Metabolic and endocrine effects: Thiazide therapy may impair glucose tolerance. In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Latent diabetes mellitus may become manifest during thiazide therapy.
Increases in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy; however at the 12.5 mg dose contained in Converide, minimal or no effects were reported. Hyperuricaemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
Electrolyte imbalance: As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals.
Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance (hypokalaemia, hyponatraemia, and hypochloremic alkalosis). Warning signs of fluid or electrolyte imbalance are dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting. Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with irbesartan may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greatest in patients with cirrhosis of the liver, in patients experiencing brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes and in patients receiving concomitant therapy with corticosteroids or ACTH. Conversely, due to the irbesartan component of Converide, hyperkalaemia might occur, especially in the presence of renal impairment and/or heart failure, and diabetes mellitus. Adequate monitoring of serum potassium in patients at risk is recommended. Potassium-sparing diuretics, potassium supplements or potassium-containing salts substitutes should be co-administered cautiously with Converide (see Interactions).
There is no evidence that irbesartan would reduce or prevent diuretic-induced hyponatraemia. Chloride deficit is generally mild and usually does not require treatment.
Thiazides may decrease urinary calcium excretion and cause an intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
Thiazides have been shown to increase the urinary excretion of magnesium, which may result in hypomagnaesemia.
Lithium: The combination of lithium and Converide is not recommended (see Interactions).
Anti-doping test: Hydrochlorothiazide contained in this medication could produce a positive analytic result in an anti-doping test.
General: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with angiotensin converting enzyme inhibitors or angiotensin-II receptor antagonists that affect this system has been associated with acute hypotension, azotemia, oliguria, or rarely acute renal failure. As with any antihypertensive agent, excessive blood pressure decrease in patients with ischemic cardiopathy or ischemic cardiovascular disease could result in a myocardial infarction or stroke.
Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.
Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazide diuretics.
Cases of photosensitivity reactions have been reported with thiazides diuretics (see Adverse Reactions). If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration of diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.
Acute myopia and secondary acute angle-closure glaucoma: Sulfonamide drugs or sulfonamide derivative drugs can cause an idiosyncratic reaction, resulting in transient myopia and acute angle-closure glaucoma. While hydrochlorothiazide is a sulfonamide, only isolated cases of acute angle-closure glaucoma have been reported so far with hydrochlorothiazide. 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 drug 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 (see Adverse Reactions).
Lactose: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. Based on its pharmacodynamic properties, Converide is unlikely to affect this ability. When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or weariness may occur during treatment of hypertension.
Use in Pregnancy: Angiotensin II receptor antagonists including Converide should not be initiated during pregnancy. Unless continued therapy with angiotensin-II receptor antagonists is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin-II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started (see Contraindications and Use in Pregnancy & Lactation).