Source: Υπουργείο Υγείας (CY) Revision Year: 2021 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
In patients with anuria.
Hypersensitivity to hydrochlorothiazide or to any of the other excipients listed in section 6.1.
History of sensitivity to sulphonamides.
Severe renal or hepatic failure.
In patients with Addison’s disease or hypercalcaemia.
Pregnancy and breast feeding.
Patients under lithium treatment should not receive hydrochlorothiazide.
Very rare severe 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 If diagnosis of ARDS is suspected, hydrochlorothiazide should be withdrawn and appropriate treatment given. Hydrochlorothiazide should not be administered to patients who previously experienced ARDS following hydrochlorothiazide intake.
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) exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC.
Patients taking HCTZ 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 HCTZ may also need to be reconsidered in patients who have experienced previous NMSC (see also section 4.8).
Sulfonamide drugs or sulfonamide derivative drugs 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 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.
Patients should be carefully monitored for signs or fluid and electrolyte imbalance (like hyponatraemia, hypochloraemic alkalosis, hypokalaemia, and hypomagnesaemia). It is particularly important to make serum and urine electrolyte determinations when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance include: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, seizures, confusion, muscle pains or cramps, muscle fatigue, hypotension, oliguria, tachycardia, gastrointestinal disturbances (like nausea and vomiting).
Hypokalaemia may develop, especially with brisk diuresis, when severe cirrhosis is present or after prolonged therapy. Hypokalaemia can sensitise or exaggerate the response of the heart to the toxic effects of digitalis (such as increased ventricular irritability).
Sensitivity reactions may occur in patients with or without history of allergic or bronchial asthma.
Hypokalaemia may be avoided or treated in the adult by the concurrent use of amiloride hydrochloride (a potassium converting agent). It may also be avoided by giving potassium chloride or foods with high potassium content. In case symptoms and signs which might indicate ulceration or obstruction of the small bowel in patients taking potassium supplements are indications of stopping treatment with such preparations immediately.
Diuretic induced hyponatraemia is usually mild and asymptomatic. It may occur in oedematous patients in hot weather. It is life threatening in rare cases. Appropriate therapy is water restriction rather than the administration of salt.
Thiazides may decrease serum protein bound Iodine levels without signs of thyroid disturbances.
Thiazides may decrease urinary calcium excretion and may also cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Thiazides should be discontinued before carrying out test of parathyroid function.
When creatinine clearance is below 30 ml/min thiazide diuretics are not effective.
Uraemia may be precipitated or increased by chlorothiazide. Cumulative effects of the drug may develop in patients with impaired renal function. If increasing uraemia and oliguria occur during treatment of renal disease, hydrochlorothiazide should be discontinued.
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.
Hyperuricaemia may occur, or gout may be precipitated in certain patients receiving thiazide therapy.
Thiazide therapy may impair glucose tolerance.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.
Latent diabetes may become manifest during thiazide administration.
Thiazides diuretics, including hydrochlorothiazide should be used with caution in patients with sulfonamide hypersensitivity or carbonic anhydrase inhibitor hypersensitivity because of the risk of cross sensitivity.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Alcohol, barbiturates or narcotics: Co-administration may potentiate orthostatic hypotension.
Oral and parenteral antidiabetic drugs: May require adjustment of dosage with concurrent use.
Other antihypertensive drugs: May have an additive effect. Discontinuation of diuretic therapy 2 to 3 days before the initiation of treatment with an ACE inhibitor may reduce the likelihood of first dose-hypotension. The antihypertensive effect of the drug may be enhanced in the post-sympathectomy patient.
Cholestyramine and colestipol resin: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43% respectively.
Corticosteroids or ACTH may intensify any thiazide-reduced electrolyte depletion, particularly hypokalaemia.
Pressor amines (like adrenaline) may show decreased arterial responsiveness when used with Didralin, but this reaction is not enough to prelude their therapeutic usefulness.
Non-depolarising muscle relaxants such as tubocurarine may possible interact with hydrochlorothiazide to increase muscle relaxation.
NSAIDs may attenuate the diuretic and antihypertensive effect of diuretics.
Drug / Laboratory tests: Since thiazides may affect calcium metabolism, hydrochlorothiazide may interfere with test for parathyroid action.
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 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.
Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit the milk production. The use of Didralin during breast feeding is not recommended. If Didralin is used during breast feeding, doses should be kept as low as possible.
Infrequently, 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.
The adverse reactions are displayed by frequency using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (adverse reactions from post-marketing experience; frequency cannot be estimated from the available data).
Not known: Non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma)
Not known: Anorexia, gastric irritation, nausea, vomiting, cramps, diarrhoea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, salivary gland inflammation.
Not known: Dizziness, vertigo, paraesthesiae, headache, yellow vision.
Not known: choroidal effusion, acute myopia and secondary acute angle-closure glaucoma.
Not known: Leucopenia, agranulocytosis, thrombocytopenia, aplastic anemia, haemolytic anaemia.
Not known: Hypotension, including orthostatic hypotension (may be potentiated by alcohol, barbiturates or narcotics).
Very rare: Acute respiratory distress syndrome (ARDS) (see section 4.4).
Not known: Purpura, photosensitivity, rash, urticaria, necrotising angiitis, fever, respiratory distress including pneumonitis and pulmonary oedema, anaphylactic reaction, toxic epidermal necrolysis.
Not known: Hyperglycaemia, glycosuria, hyperuricaemia, electrolyte imbalance including hyponatraemia and hypokalaemia.
Not known: Renal dysfunction, interstitial nephritis, renal failure.
Not known: Muscle pain, weakness, restlessness, transient blurred vision, impotence.
In case side effects are moderate to severe dosage reduction or even discontinuation of treatment should be considered.
Non-melanoma skin cancer: Based on available data from epidemiological studies, cumulative dose-dependent association between HCTZ and NMSC has been observed (see also sections 4.4 and 5.1).
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via national reporting system.
None.
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