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Warnings: Hydrochlorothiazide: Lodoz must be used with caution in patients with impaired liver function.
In patients with liver disease, thiazide diuretics and related drugs may trigger hepatic encephalopathy.
Should this happen, diuretic therapy must be stopped immediately. This medication should not be taken in lactating women.
Precautions for Use: Bisoprolol: Asthma and Chronic Obstructive Pulmonary Disease: Although cardioselective (beta1) beta-blockers may have less effect on lung function than non-selective beta-blockers, as with all beta-blockers, these should be avoided in patients with obstructive airways diseases, unless there are compelling clinical reasons for their use. Where such reasons exist, Lodoz may be used with caution. In patients with obstructive airways diseases the treatment with bisoprolol should be started at the lowest possible dose and patients should be carefully monitored for new symptoms (e.g. dyspnea, exercise intolerance, cough). In bronchial asthma or other chronic obstructive lung diseases, which may cause symptoms, bronchodilating therapy should be given concomitantly. Occasionally an increase of the airway resistance may occur in patients with asthma, therefore the treatment of beta2-stimulants may have to be adapted.
Cardiac Failure: Patients with compensated cardiac failure who require beta-blocker therapy may be administered with bisoprolol using a very low starting dose, to be increased gradually with close medical monitoring.
First Degree AV Block: Having negative dromotropic activity, beta-blockers should be used cautiously in patients with first degree AV block.
Prinzmetal's Angina: Beta-blockers may increase the frequency and length of vasospastic episodes in patients with Prinzmetal's angina. Cases of coronary vasospasm have been observed. Despite its high beta1-selectivity, angina attacks cannot be completely excluded when bisoprolol is administered to patients with Prinzmetal's angina. A β1-selective beta-blocker may be used in minor or mixed clinical presentations of Prinzmetal's angina if a vasodilator is used concurrently.
Peripheral Arterial Occlusive Disease: Beta-blockers may aggravate the symptoms of peripheral arterial occlusive disease (PAOD) or Raynaud's syndrome. Such patients should preferably be prescribed a β1-selective beta-blocker.
Pheochromocytoma: In patients with pheochromocytoma, Lodoz must not be administered until after alpha-receptor blockade. Blood pressure response should be closely monitored.
Diabetics: Diabetic patients should be aware of the risk of hypoglycemic episodes and of the increased need for careful home glucose monitoring in the initial phase of therapy. The warning signs of hypoglycemia, particularly tachycardia, palpitations, and sweating, may be masked.
Psoriasis: There have been reports of beta-blockers being associated with worsening of psoriasis, thus patients with psoriasis should receive bisoprolol only if clearly needed.
Hypersensitivity Reactions: In patients at risk of severe anaphylactic reaction to whatever allergen, particularly when using iodine-containing contrast materials or during specific immunotherapy (desensitisation), beta-blockers may aggravate the anaphylactic reaction and cause unresponsiveness to the usual doses of epinephrine used to treat hypersensitivity reactions.
General Anesthesia: In patients undergoing general anaesthesia, beta-blockade reduces the incidence of arrhythmias and myocardial ischaemia during induction and intubation, and the post-operative period. It is currently recommended that maintenance beta-blockade be continued perioperatively.
The anaesthetist must be aware of beta-blockade because of the potential for interactions with other drugs, resulting in bradyarrhythmias, attenuation of the reflex tachycardia and the decreased reflex ability to compensate for blood loss. If it is thought necessary to withdraw beta-blocker therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia.
Thyrotoxicosis: Beta-blockers may mask the cardiovascular signs of hyperthyroidism.
Competitive athletes: Competitive athletes should be aware that this medicinal product contains an agent that may give a positive reaction in doping tests.
Strict fasting: Lodoz must be used with caution in patients under strict fasting.
Combination with verapamil, diltiazem or bepridil: Such combinations require a close clinical and ECG monitoring, notably in the elderly and at the beginning of the treatment.
Hydrochlorothiazide: 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) 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 Adverse Reactions).
Fluid & Electrolyte Balance: During long-term therapy with Lodoz, periodic monitoring of serum electrolytes (especially potassium, sodium, calcium), creatinine and urea, the serum lipids (cholesterol and triglycerides), uric acid as well as blood glucose is recommended.
Long-term, continuous administration of hydrochlorothiazide may lead to fluid and electrolyte disturbances, in particular to hypokalaemia and hyponatraemia, also to hypomagnesaemia and hypochloraemia, and hypercalcaemia.
Plasma Sodium: Plasma sodium should be determined before and periodically during therapy. Any diuretic therapy may give rise to hyponatremia, with serious consequences in some cases.
As hyponatremia may initially be asymptomatic, periodic monitoring is indispensable and should be more frequent in high-risk populations, i.e., the elderly and patients with cirrhosis of the liver.
Plasma Potassium: Potassium loss resulting in hypokalemia is the greatest risk associated with thiazide diuretics and related drugs.
The risk of hypokalemia (< 3.5 mmol/L) should be anticipated in certain high-risk populations, i.e., elderly and/or malnourished and/or taking multiple drugs, and patients with coronary artery disease or heart failure, where hypokalemia increases the cardiotoxicity of digitalis glycosides and the risk of cardiac arrhythmia. Also at risk are patients with long QT syndrome, either congenital or iatrogenic. Hypokalemia (as well as bradycardia) facilitates the development of severe arrhythmias, particularly torsade de pointes, which maybe fatal. More frequent plasma potassium monitoring is indicated in all of the previously mentioned populations, starting within the week after initiation of therapy.
Plasma Calcium: Thiazide diuretics and related drugs may reduce urinary calcium excretion, resulting in mild, transient hypercalcemia. Significant hypercalcemia may be related to undiagnosed hyperparathyroidism. Therapy must be interrupted before performing parathyroid function tests.
Combination with lithium: Due to the diuretic, this combination should be avoided.
Blood Glucose: In diabetics, blood glucose must be monitored, especially in the presence of hypokalemia.
Uric Acid: In patients with hyperuricemia, the risk for attacks of gout may be increased. Dosage should be adjusted as a function of uric acid plasma concentrations.
Kidney Function & Diuretics: Full benefit from thiazide diuretics can be derived only if kidney function is normal or almost normal (serum creatinine < 25 mg/l, or 220 μmol/l, in adults).
Serum creatinine needs to be corrected for age, weight, and gender, using Crockroft's formula for instance: ClCr = (140 - Age) x Weight/0.814 x Serum Creatinine.
Where Age is indicated in years, Weight in kg, and Serum Creatinine in μmol/L.
The previously mentioned formula gives ClCr for elderly male subjects, and needs to be corrected for elderly female subjects by multiplying by 0.85.
Hypovolemia secondary to diuretic-induced water and sodium loss at the start of therapy reduces glomerular filtration, which may result in blood urea nitrogen and serum creatinine increases. This transient functional renal impairment is not relevant in patients with normal kidney function but may worsen pre-existing renal insufficiency.
Combination with other Antihypertensive Drugs: It is advisable to reduce the dosage when this medicinal product is combined with another antihypertensive, at least in the initial phase of therapy.
Photosensitivity: Photosensitivity reactions have been reported with thiazide diuretics in rare cases. If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration of treatment is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA-light.
Competitive athletes: Competitive athletes should be aware that this medicinal product contains an agent that may give a positive reaction in doping tests.
Choroidal effusion, acute myopia and secondary angle-closure glaucoma: Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in effusion with visual field defect, 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 drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide 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.
Acute respiratory toxicity: 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, Lodoz should be withdrawn and appropriate treatment given. Hydrochlorothiazide should not be administered to patients who previously experienced ARDS following hydrochlorothiazide intake.
Effects on ability to drive and use machines: Depending on the individual patient's response to LODOZ treatment the ability to drive and use machines may be impaired. This should be particularly considered at the start of treatment as well as in conjunction with alcohol.
Use in the Elderly: No dose adjustment is normally required. However, elderly patients should be closely monitored (see previous text under Fluid and electrolyte balance).
