Probis^®

Probis is a preparation of Bisoprolol Fumarate. Bisoprolol is a potent highly [31-selective adrenoceptor blocking agent. As with
other Ph-blocking agents, the method of acting in hypertension is unclear. However, it is known that Bisoprolol reduces plasma
renin activity markedly. Bisoprolol by inhibiting the cardiac beta-receptors inhibits the response given to sympathetic activation.
That results in the decrease of heart rate and contractility this way decreasing the oxygen demand of the cardiac muscle.

No Data

Probis is indicated for-
• Treatment of hypertension
• Treatment of stable chronic angina
• Treatment of stable chronic heart failure with reduced systolic left ventricular function in addition to ACE inhibitors,
diuretics and optionally cardiac glycosides

Adults
The dose should be individually adjusted. It is recommended to start with 5 mg per day. The usual dose is 10 mg once daily
with a maximum recommended dose of 20 mg per day. Treatment should not be stopped abruptly. The dose should be
diminished slowly by a weekly halving of the dose.

Renal impairment
In patients with severe renal impairment (creatinine clearance < 20 ml/min) the dose should not exceed 10 mg once daily.
This dose may eventually be divided into halves.

Stable chronic heart failure
Patients should be stable (without acute failure) when bisoprolol treatment is initiated. The treatment of stable chronic heart
failure with bisoprolol requires a titration phase. The treatment with bisoprolol is to be started with a gradual uptitration
according to the following steps:
• 1.25 mg once daily for 1 week, if well tolerated increase to
• 2.5 mg once daily for a further week, if well tolerated increase to
• 3.75 mg once daily for a further week, if well tolerated increase to
• 5 mg once daily for the 4 following weeks, if well tolerated increase to
• 7.5 mg once daily for the 4 following weeks, if well tolerated increase to
• IO mg once daily for the maintenance therapy.
The maximum recommended dose is IO mg once daily. If the maximum recommended dose is not well tolerated, gradual
dose reduction may be considered. If discontinuation is considered, gradual dose decrease is recommended, since abrupt
withdrawal may lead to acute deterioration of the patient's condition.

Renal or hepatic impairment
There is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired
hepatic or renal function. Uptitration of the dose in these populations should therefore be made with additional caution.

Pregnancy:

Bisoprolol is not recommended during pregnancy unless clearly necessary.

Lactation:

There are no data on the excretion of bisoprolol in human milk. Therefore, breastfeeding is not recommended
during administration of bisoprolol.

Use in children and adolescents
Safety and effectiveness in pediatric patients have not been established.

In patients with ischemic heart disease the cessation of therapy with bisoprolol must not be done abruptly unless clearly
indicated, because this may lead to transition worsening of heart condition. Bisoprolol must be used with caution in-
• Bronchospasm (bronchial asthma, obstructive airways diseases)
• Diabetes mellitus with large fluctuations in blood glucose values
• Strict fasting
• Ongoing desensitisation therapy
• First degree AV block
• Prinzmetal's angina
• Peripheral arterial occlusive disease
• General anaesthesia.
Patients with psoriasis or with a history of psoriasis should only be given beta-blockers after carefully balancing the benefits
against the risks. In patients with phaeochromocytoma, bisoprolol must not be administered until after alpha-receptor
blockade.

The most common side effects are dizziness, headache, bradycardia (in patients with chronic heart failure), worsening of pre-existing heart failure (in patients with chronic heart failure), feeling of coldness or numbness in the extremities, hypotension especially in patient with heart failure, nausea, vomiting, diarrhea, constipation, asthenia (in patients with chronic heart failure and fati ue.

Bisoprolol is contraindicated in patients with known hypersensitivity to bisoprolol or any other components of this product.
Bisoprolol is also contraindicated in Chronic heart failure patients with:
• Acute heart failure or during episodes of heart failure decompensation requiring IV 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
• Late stages of peripheral arterial occlusive disease and Raynaud's syndrome
• Untreated phaeochromocytoma
• Metabolic acidosis

Drug interaction with medication: Bisoprolol should not be combined with other beta-blocking agents. Coadministration of
catecholamine depleting drugs, such as reserpine or guanethidine and bisoprolol may produce excessive reduction of
sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested
that bisoprolol be discontinued for several days before the withdrawal of clonidine. Bisoprolol should be used with care when
myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the
phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes) or antiarrhythmic agents, such as disopyramide, are
used concurrently. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate.
Concomitant use can increase the risk of bradycardia. Concurrent use of rifampin increases the metabolic clearance of
bisoprolol, resulting in a shortened elimination half-life of bisoprolol. While taking beta-blockers, patients with a history of
severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental,
diagnostic or therapeutic.

Drug interaction with food and others: Not applicable.

The most common signs expected with overdose of a beta-blocker are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency and hypoglycemia. If overdose occurs, discontinuation of bisoprolol treatment and supportive and symptomatic treatment is recommended.

No Data

Store in a cool & dry place protected from light. Keep away from the reach of children.

Probis@ 1.25 tablet: Each coated tablet contains Bisoprolol Fumarate USP 1.25 mg.
Probis@ 2.5 tablet: Each coated tablet contains Bisoprolol Fumarate USP 2.5 mg.
Probis@ 5 tablet: Each coated tablet contains Bisoprolol Fumarate USP 5 mg.