Bisotrak T Tablets 2.5mg

Bisoprolol Fumarate and Telmisartan Tablets

Each film coated tablet contains: Bisoprolol Fumarate IP 2.5/5 mg Telmisaratan IP 40 mg

Film Coated Tablet Bisoprolol Fumarate (2.5/5) mg and Telmisartan 40 mg

4.1 Therapeutic indications

For the treatment of mild to moderate hypertension.

4.2 Posology and method of administration

1 tablet once daily.

FDC of Telmisartan and Bisoprolol Fumarate Tablets dosage should be adjusted according to each patient´s need, preferably starting with lower dose and titrate to higher dose in cases where the target blood pressure is not achieved, the dose of Telmisartan can be increased to a maximum of 80 mg and accordingly Bisoprolol Fumarate10 mg once daily.

4.3 Contraindications

• Hypersensitivity to the bisoprolol, telmisartan or to any of the excipients listed in the formulation
• Acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy
• Cardiogenic shock
• Second or third degree AV block (without a pacemaker)
• Sick sinus syndrome
• Sinoatrial block
• Symptomatic bradycardia
• Symptomatic hypotension
• Severe bronchial asthma or severe chronic obstructive pulmonary disease
• Severe forms of peripheral arterial occlusive disease or severe forms of Raynaud's syndrome
• Untreated phaeochromocytoma
• Metabolic acidosis
• Second and third trimester of pregnancy
• Biliary obstructive disorders since telmisartan can induce severe hypotension and renal insufficiency
• Severe hepatic impairment.
• The concomitant use of telmisartan with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²)

4.4 Special warnings and precautions for use

Bisoprolol Fumarate

The treatment of stable chronic heart failure with bisoprolol has to be initiated with a special titration phase.

In patients with ischaemic heart disease the cessation of therapy with bisoprolol must not be done abruptly unless clearly indicated, because this may lead to transitional worsening of heart condition.

Precautions

In hypertension or angina pectoris

Bisoprolol must be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.

In chronic heart failure

The initiation of treatment of stable chronic heart failure with bisoprolol necessitates regular monitoring.

There is no therapeutic experience of bisoprolol treatment of heart failure in patients with the following diseases and conditions:

• insulin dependent diabetes mellitus (type I)
• severely impaired renal function
• severely impaired hepatic function
• restrictive cardiomyopathy
• congenital heart disease
• haemodynamically significant organic valvular disease
• myocardial infarction within 3 months

Bisoprolol must be used with caution in:

• bronchospasm (bronchial asthma, obstructive airways diseases). In bronchial asthma or other chronic obstructive lung diseases, which may cause symptoms, bronchodilating therapy is recommended to be given concomitantly. Occasionally an increase of the airway resistance may occur in patients with asthma, therefore the dose of beta2-stimulants may have to be increased.
• diabetes mellitus with large fluctuations in blood glucose values; symptoms of hypoglycaemia (e.g. tachycardia, palpitations or sweating) can be masked
• strict fasting
• ongoing desensitisation therapy. As with other beta-blockers, bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Epinephrine treatment does not always yield the expected therapeutic effect.
• First degree AV block
• 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.
• peripheral arterial occlusive disease. Aggravation of symptoms may occur especially when starting therapy.
• general anesthesia

In patients undergoing general anaesthesia beta-blockade reduces the incidence of arrhythmias and myocardial ischemia during induction and intubation and the post-operative period. It is currently recommended that maintenance beta-blockade be continued peri-operatively. The anesthetist 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.

Combination of bisoprolol with calcium antagonists of the verapamil or diltiazem type, with Class I antiarrhythmic drugs and with centrally acting antihypertensive drugs is generally not recommended.

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, bisoprolol 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 dose of beta2-stimulants may have to be increased.

Patients with psoriasis or with a history of psoriasis should only be given beta-blockers (e.g. bisoprolol) after carefully balancing the benefits against the risks. In patients with phaeochromocytoma bisoprolol must not be administered until after alpha-receptor blockade. Under treatment with bisoprolol the symptoms of a thyrotoxicosis may be masked.

Telmisartan

Hepatic impairment

Telmisartan should be used only with caution in patients with mild to moderate hepatic impairment.

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 medicinal products that affect the renin-angiotensin-aldosterone system.

Renal impairment and kidney transplantation

When Telmisartan is used in patients with impaired renal function, periodic monitoring of potassium and creatinine serum levels is recommended. There is no experience regarding the administration of Telmisartan in patients with recent kidney transplantation

Intravascular hypovolemia

Symptomatic hypotension, especially after the first dose of Telmisartan, may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhea or vomiting. Such conditions should be corrected before the administration of Telmisartan. Volume and/or sodium depletion should be corrected prior to administration of Telmisartan.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended.

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Other conditions with stimulation of the renin-angiotensin-aldosterone system

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 medicinal products that affect this system such as telmisartan has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure.

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 telmisartan is not recommended.

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.

Diabetic patients treated with insulin or antidiabetics

In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics may be required, when indicated.

Hyperkalaemia

The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause hyperkalaemia.

In the elderly, in patients with renal insufficiency, in diabetic patients, in patients concomitantly treated with other medicinal products that may increase potassium levels, and/or in patients with intercurrent events, hyperkalaemia may be fatal. Before considering the concomitant use of medicinal products that affect the renin-angiotensin-aldosterone system, the benefit risk ratio should be evaluated.

The main risk factors for hyperkalaemia to be considered are:

• Diabetes mellitus, renal impairment, age (> 70 years)
• Combination with one or more other medicinal products that affect the renin-angiotensin-aldosterone system and/or potassium supplements. Medicinal products or therapeutic classes of medicinal products that may provoke hyperkalaemia are salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressives (cyclosporin or tacrolimus), and trimethoprim.
• Intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis, worsening of renal function, sudden worsening of the renal condition (e.g. infectious diseases), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis, extend trauma).

Close-monitoring of serum potassium in at risk patients is recommended.

Other

As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke.

4.5 Drug interactions

Bisoprolol Fumarate

Combinations not recommended

Applies only to chronic heart failure

Class-I antiarrhythmic drugs (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.

Applies to all indications

Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: negative effect on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients on beta-blocker treatment may lead to profound hypotension and atrio-ventricular block.

Centrally-acting antihypertensive drugs (e.g. clonidine, methyldopa, moxonidine, rilmenidine): concomitant use of centrally-acting antihypertensive drugs may further decrease the central sympathetic tonus and may thus lead to reduction of heart rate and cardiac output and to vasodilatation. Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase the risk of “rebound hypertension”.

Combinations to be used with caution

Applies only to hypertension or angina pectoris

Class-I antiarrhythmic drugs (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide propafenone): Effect on atrioventricular conduction time may be potentiated and negative inotropic effect increased.

Applies to all indications

Calcium antagonists of the dihydropyridine type such as felodipine and amlodipine: Concomitant use may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.

Class-III antiarrhythmic drugs (e.g. amiodarone): Effect on atrio-ventricular conduction time may be potentiated. Parasympathomimetic drugs: Concomitant use may increase atrio-ventricular conduction time and the risk of bradycardia.

Topical beta-blocking agents (e.g. eye drops for glaucoma treatment) may add to the systemic effects of bisoprolol.

Insulin and oral antidiabetic drugs: Increase of blood sugar lowering effect. Blockade of beta-adrenoreceptors may mask symptoms of hypoglycaemia.

Anaesthetic agents: Attenuation of the reflex tachycardia and increase of the risk of hypotension.

Digitalis glycosides: Increase of atrio-ventricular conduction time, reduction in heart rate. Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs may reduce the hypotensive effect of bisoprolol.

β-Sympathomimetic agents (e.g. isoprenaline, dobutamine): Combination with bisoprolol may reduce the effect of both agents.

Sympathomimetics that activate both β- and α-adrenoceptors (e.g. norepinephrine, epinephrine): Combination with bisoprolol may unmask the α-adrenoceptor-mediated vasoconstrictor effects of these agents leading to blood pressure increase and exacerbated intermittent claudication. Such interactions are considered to be more likely with nonselective β-blockers.

Concomitant use with antihypertensive agents as well as with other drugs with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotension.

Combinations to be considered

Mefloquine: increased risk of bradycardia

Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blocking agents but also risk for hypertensive crisis.

Rifampicin: Slight reduction of the half-life of bisoprolol possible due to the induction of hepatic drug metabolising enzymes. Normally no dosage adjustment is necessary. Ergotamine derivatives: Exacerbation of peripheral circulatory disturbances.

Telmisartan

Digoxin

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. When initiating, adjusting, and discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.

As with other medicinal products acting on the renin-angiotensin-aldosterone system, telmisartan may provoke hyperkalaemia. The risk may increase in case of treatment combination with other medicinal products that may also provoke hyperkalaemia (salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressives (cyclosporin or tacrolimus), and trimethoprim).

The occurrence of hyperkalaemia depends on associated risk factors. The risk is increased in case of the above-mentioned treatment combinations. The risk is particularly high in combination with potassium sparing-diuretics, and when combined with salt substitutes containing potassium. A combination with ACE inhibitors or NSAIDs, for example, presents a lesser risk provided that precautions for use are strictly followed. Concomitant use not recommended

Potassium sparing diuretics or potassium supplements

Angiotensin II receptor antagonists such as telmisartan, attenuate diuretic induced potassium loss. Potassium sparing diuretics e.g. spirinolactone, eplerenone, triamterene, or amiloride, potassium supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium. If concomitant use is indicated because of documented hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors, and with angiotensin II receptor antagonists, including telmisartan. If use of the combination proves necessary, careful monitoring of serum lithium levels is recommended. Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the co-administration of angiotensin II receptor antagonists and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter.

Diuretics (thiazide or loop diuretics)

Prior treatment with high dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may result in volume depletion, and in a risk of hypotension when initiating therapy with telmisartan.

To be taken into account with concomitant use

Based on their pharmacological properties it can be expected that the following medicinal products may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, amifostine. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics, or antidepressants.

Corticosteroids (systemic use)

Reduction of the antihypertensive effect.

4.6 Use in special populations

Pregnancy

When pregnancy is diagnosed, treatment with Bisotrak^TM T should be stopped immediately, and, if appropriate, alternative therapy should be started.

Breast-feeding

There are no data on the excretion of Bisotrak^TM T in human breast milk or the safety of Bisotrak^TM T exposure in infants. Therefore, breastfeeding is not recommended during administration of Bisotrak^TM T.

4.7 Effects on ability to drive and use machines

In a study with coronary heart disease patients, Bisotrak^TM T did not impair driving performance. However, depending on the individual patient’s response to treatment an effect on the ability to drive a vehicle or to use machines cannot be excluded. This needs to be considered particularly at start of treatment, upon change of medication, or in conjunction with alcohol.

4.8 Undesirable effects

Infections and infestations

Uncommon: upper respiratory tract infection including pharyngitis and sinusitis, urinary tract infection including cystitis

Rare: sepsis including fatal outcome

Blood and the lymphatic system disorders

Uncommon: anaemia

Rare: eosinophilia, thrombocytopenia

Immune system disorders

Rare: anaphylactic reaction, hypersensitivity

Metabolism and nutrition disorders

Uncommon: hyperkalaemia

Rare: hypoglycaemia (in diabetic patients)

Psychiatric disorders

Uncommon: depression, insomnia, sleep disorders

Rare: anxiety, nightmares, hallucinations

Nervous system disorders

Common: dizziness, headache

Uncommon: syncope

Rare: somnolence

Eye disorders

Rare: visual disturbance, reduced tear flow (to be considered if the patient uses lenses)

Very rare: conjunctivitis.

Ear and labyrinth disorders

Uncommon: vertigo

Rare: hearing disorders

Cardiac disorders

Very common: bradycardia (in patients with chronic heart failure).

Common: worsening of pre-existing heart failure (in patients with chronic heart failure).

Uncommon: AV-conduction disturbances, worsening of pre-existing heart failure (in patients with hypertension or angina pectoris) ; bradycardia (in patients with hypertension or angina pectoris).

Rare: tachycardia

Vascular disorders

Common: feeling of coldness or numbness in the extremities, hypotension especially in patient with heart failure.

Uncommon: hypotension, orthostatic hypotension

Respiratory, thoracic and mediastinal disorders

Uncommon: dyspnoea, cough, bronchospasm in patients with bronchial asthma or a history of obstructive airways disease.

Rare: allergic rhinitis Very rare: Interstitial lung disease

Gastrointestinal disorders

Common: gastrointestinal complaints such as nausea, vomiting, diarrhoea, constipation.

Uncommon: Abdominal pain, dyspepsia, flatulence,

Rare: Stomach discomfort, dry mouth, dysgeusia

Hepato-biliary disorders

Rare: hepatic function abnormal/liver disorder, hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: hyperhidrosis, pruritus, rash

Rare: Angioedema (also with fatal outcome), eczema, erythema, urticaria, drug eruption, toxic skin eruption

Rare: hypersensitivity reactions (flush and angioedema).

Very rare: beta blockers may provoke or worsen psoriasis or induce psoriasis like rash, alopecia.

Musculoskeletal and connective tissue disorders

Uncommon: myalgia, back pain (e.g. sciatica), muscle spasms, muscular weakness and cramps.

Rare: arthralgia, pain in extremity, tendon pain (tendonitis like symptoms)

Reproductive system and breast disorders

Rare: erectile dysfunction.

Renal and urinary disorders

Common: asthenia (in patients with chronic heart failure), fatigue.

Uncommon: renal impairment including acute renal failure, asthenia (in patients with hypertension or angina pectoris)

General disorders and administration site conditions

Uncommon: chest pain, asthenia (weakness)

Rare: influenza-like illness

Investigations

Uncommon: blood creatinine increased

Rare: blood uric acid increased, hepatic enzyme increased, blood creatine phosphokinase increased, haemoglobin decreased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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 email to: medico@zuventus.com Website: https://www.zuventus.com/drug-safety-reporting By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

The most common signs expected with overdose are bradycardia, tachycardia, hypotension, bronchospasm, acute cardiac insufficiency, hypoglycemia, dizziness, increase in serum creatinine, and acute renal failure. The patient should be closely monitored, and the treatment should be symptomatic and supportive. Management depends on the time since ingestion and the severity of the symptoms. Suggested measures include induction of emesis and / or gastric lavage. Activated charcoal may be useful in the treatment of overdose.

5.1 Mechanism of action/ Pharmacodynamic properties

Bisoprolol is a potent highly beta1-selective-adrenoceptor blocking agent, lacking intrinsic sympathomimetic and relevant membrane stabilizing activity. It only shows low affinity to the beta2-receptor of the smooth muscles of bronchi and vessels as well as to the beta2-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence the airway resistance and beta2-mediated metabolic effects. Its beta1-selectivity extends beyond the therapeutic dose range.

Telmisartan is an orally active and specific angiotensin II receptor (type AT1) antagonist. Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT1 receptor subtype, which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is long-lasting. Telmisartan does not show affinity for other receptors, including AT2 and other less characterized AT receptors. The functional role of these receptors is not known, nor is the effect of their possible overstimulation by angiotensin II, whose levels are increased by telmisartan. Plasma aldosterone levels are decreased by telmisartan. Telmisartan does not inhibit human plasma renin or block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the enzyme which also degrades bradykinin. Therefore, it is not expected to potentiate bradykinin-mediated adverse events.

In human, an 80 mg dose of telmisartan almost completely inhibits the angiotensin II evoked blood pressure increase. The inhibitory effect is maintained over 24 hours and still measurable up to 48 hours.

5.2 Pharmacokinetic Properties

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data.

Bisoprolol Fumarate is a synthetic, beta1-selective (cardioselective) adrenoceptor blocking agent. It possesses an asymmetric carbon atom in its structure and is provided as a racemic mixture.

Chemical name: (±)-1-[4-[[2-(1-Methylethoxy)ethoxy]methyl]phenoxy]-3-[(1- methylethyl)amino]-2-propanol (E)-2-butenedioate (2:1) (salt)

Molecular formula: (C18H31NO4)2•C4H4O4

Molecular weight: 766.97

Telmisartan Tablets are a non-peptide angiotensin II receptor (type AT1) antagonist.

Chemical name: 4'-[(1,4'-dimethyl-2'-propyl [2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid.

Molecular formula: C33H30N4O2

Molecular weight: 514.63

8.1 Incompatibilities

Not applicable

8.2 Shelf Life

Refer on the pack

8.3 Packaging Information

Bisotrak^TM T 2.5 mg: Alu-Alu blister strip of 10 tablets.

Bisotrak^TM T 5 mg: Alu-Alu blister strip of 10 tablets.

8.4 Storage and handing Instructions

Store protected from light & moisture at a temperature not exceeding 30°C. Keep out of reach of children.

Patients, especially those with coronary artery disease, should be warned about discontinuing use of BisotrakTM T without a physician's supervision. Patients should also be advised to consult a physician if any difficulty in breathing occurs, or if they develop signs or symptoms of congestive heart failure or excessive bradycardia. Patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned that beta-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia, and Bisotrak^TMT should be used with caution.

Patients should know how they react to this medicine before they operate automobiles and machinery or engage in other tasks requiring alertness.

Pregnancy

Advise female patients of childbearing age about the consequences of exposure to Bisotrak^TM T during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible.

Lactation

Advise nursing women not to breastfeed during treatment with Bisotrak^TM T.

Symptomatic Hypotension and Syncope

Advise patients that light headedness can occur, especially during the first days of therapy, and to report it to their healthcare provider. Inform patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of light headedness and possible syncope. Advise patients to contact their healthcare provider if syncope occurs.

12.06.2024