Biocar 80

Each uncoated tablet contains:

Telmisartan BP …..  80 mg

Excipients: Sorbitol, Meglumine, Povidone, Microcrystalline Cellulose, Crospovidone, Magnesium Stearate.

PHARMACEUTICAL DOSAGE FORM: Uncoated  tablet.

PHARMACO-DYNAMICS

Mechanism of action:

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 characterised 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 effects.

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.

PHARMACOKINETICS:

Absorption:

Absorption of telmisartan is rapid although the amount absorbed varies. The mean absolute bioavailability for telmisartan is about 50 %. When telmisartan is taken with food, the reduction in the area under the plasma concentration-time curve (AUCo-∞) of telmisartan varies from approximately 6 % (40 mg dose) to approximately 19 % (160 mg dose). By 3 hours after administration, plasma concentrations are similar whether telmisartan is taken fasting or with food.

Linearity/non-linearity:

The small reduction in AUC is not expected to cause a reduction in the therapeutic efficacy. There is no linear relationship between doses and plasma levels. Cmax and to a lesser extent AUC increase disproportionately at doses above 40 mg.

Distribution:

Telmisartan is largely bound to plasma protein (>99.5 %), mainly albumin and alpha-1 acid glycoprotein. The mean steady state apparent volume of distribution (Vdss) is approximately 500 I.

Metabolism:

Telmisartan is metabolised by conjugation to the glucuronide of the parent compound. No pharmacological activity has been shown for the conjugate.

Elimination:

Telmisartan is characterised by biexponential decay pharmacokinetics with a terminal elimination half-life of >20 hours. The maximum plasma concentration (Cmax) and, to a smaller extent, the area under the plasma concentration-time curve (AUC), increase disproportionately with dose. There is no evidence of clinically relevant accumulation of telmisartan taken at the recommended dose. Plasma concentrations were higher in females than in males, without relevant influence on efficacy.

After oral (and intravenous) administration, telmisartan is nearly exclusively excreted with the faeces, mainly as unchanged compound. Cumulative urinary excretion is <1 % of dose. Total plasma clearance (Cltot) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about 1,500 ml/min).

INDICATIONS

Hypertension

Treatment of essential hypertension in adults.

Cardiovascular prevention

Reduction of cardiovascular morbidity in patients with:

– Manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or peripheral arterial disease) or

-Type 2 diabetes mellitus with documented target organ damage

DOSAGE AND ADMINISTRATION

Treatment of essential hypertension:

The usually effective dose is 40 mg once daily. Some patients may already benefit at a daily dose of 20 mg. In cases where the target blood pressure is not achieved, the dose of telmisartan can be increased to a maximum of 80 mg once daily. Alternatively, telmisartan may be used in combination with thiazide-type diuretics such as hydrochlorothiazide, which has been shown to have an additive blood pressure lowering effect with telmisartan. When considering raising the dose, it must be borne in mind that the maximum antihypertensive effect is generally attained four to eight weeks after the start of treatment.

Cardiovascular prevention:

The recommended dose is 80 mg once daily. It is not known whether doses lower than 80 mg of telmisartan are effective in reducing cardiovascular morbidity.

When initiating telmisartan therapy for the reduction of cardiovascular morbidity, close monitoring of blood pressure is recommended, and if appropriate adjustment of medications that lower blood pressure may be necessary.

Telmisartan may be taken with or without food.

Special patient populations:

Renal impairment: No posology adjustment is required for patients with mild to moderate renal impairment. Limited experience is available in patients with severe renal impairment or haemodialysis. A lower starting dose of 20 mg is recommended in these patients.

Hepatic impairment: In patients with mild to moderate hepatic impairment, the posology should not exceed 40 mg once daily.

Elderly

No dose adjustment is necessary for elderly patients.

Paediatric patients

Telmisartan is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.

CONTRA-INDICATIONS

• Hypersensitivity to the active substance or to any of the excipients
• Second and third trimesters of pregnancy
• Biliary obstructive disorders
• Severe hepatic impairment

SPECIAL WARNING AND PRECAUTIONS FOR USE

Pregnancy:

Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued angiotensin II receptor antagonist therapy 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.

Hepatic impairment:

Telmisartan is not to be given to patients with cholestasis, biliary obstructive disorders or severe hepatic impairment since Telmisartan is mostly eliminated with the bile. These patients can be expected to have reduced hepatic clearance for telmisartan. Telmisartan should be used only with caution in patients with mild to moderate hepatic impairment.

Reno vascular 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 hypovolemic:

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, diarrhoea, 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: As a consequence of inhibiting the renin-angiotensin-aldosterone system, hypotension, syncope, hyperkalaemia, and changes in renal function (including acute renal failure) have been reported in susceptible individuals, especially if combining medicinal products that affect this system. Dual blockade of the renin-angiotensin-aldosterone system (e.g. by adding an ACE-inhibitor to an angiotensin II receptor antagonist) is therefore not recommended in patients with already controlled blood pressure and should be limited to individually defined cases with close monitoring of renal function.

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.

Hyperkalemia:

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

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, hyperkalemia 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 dehydratation, 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 re

commended.

Sorbitol:

This medicinal product contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take Telmisartan.

Ethnic differences:

As observed for angiotensin converting enzyme inhibitors, telmisartan and the other angiotensin II receptor antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.

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.

USE IN PREGNANCY AND LACTATION

Pregnancy:

The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy. The use of angiotensin II receptor antagonists is contraindicated during the second and third trimesters of pregnancy.

There are no adequate data from the use of Telmisartan in pregnant women. Studies in animals have shown reproductive toxicity.

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with angiotensin II receptor antagonists, similar risks may exist for this class of drugs. Unless continued angiotensin II receptor antagonist therapy 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.

Exposure to angiotensin II receptor antagonist therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).

Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension.

Lactation:

Because no information is available regarding the use of Telmisartan during breast-feeding, Telmisartan is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

EFFECTS ON ABILITY TO DRIVE AND OPERATE MACHINE

No studies on the effects on the ability to drive and use machines have been performed. However, when driving vehicles or operating machinery it should be taken into account that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy.

SIDE EFFECTS

The overall incidence of adverse events reported with telmisartan (41.4 %) was usually comparable to placebo (43.9 %) in controlled trials in patients treated for hypertension. The incidence of adverse events was not dose related and showed no correlation with gender, age or race of the patients. The safety profile of telmisartan in patients treated for the reduction of cardiovascular morbidity was consistent with that obtained in hypertensive patients.

Adverse reactions have been ranked under headings of 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), not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 

Infections and infestations

Uncommon: Upper respiratory tract infection including

Pharyngitis and sinusitis, urinary tract infect including cystitis

Not known:   Sepsis including fatal outcome

Blood and the lymphatic system disorders

Uncommon:   Anaemia

Rare:            Thrombocytopenia

Not known:    Eosinophilia

Immune system disorders

Rare:               Hypersensitivity

Not known:    Anaphylactic reaction

Metabolism and nutrition disorders

Uncommon:    Hyperkalaemia

Psychiatric disorders

Uncommon:  Depression, insomnia

Rare:            Anxiety

Nervous system disorders

Uncommon: Syncope

Eye disorders

Rare:    Visual disturbance

Ear and labyrinth disorders

Uncommon:     Vertigo

Cardiac disorders

Uncommon:     Bradycardia

Rare:              Tachycardia

Vascular disorders

Uncommon:   Hypotension, orthostatic hypotension

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnoea

Gastrointestinal disorders

Uncommon:  Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting

Rare:              Stomach discomfort, dry mouth

Hepato-biliary disorders

Rare:  Hepatic function abnormal/liver disorder

Skin and subcutaneous tissue disorders

Uncommon: Hyperhidrosis, pruritus, rash

Rare:            Erythema, angioedema, drug eruption, toxic skin eruption, eczema

Not known:   Urticaria

Muscoloskeletal and connective tissue disorders

Uncommon:  Myalgia, back pain (e.g. sciatica), muscle spasms

Rare:            Arthralgia, pain in extremity

Not known:   Tendon pain (tendinitis like symptoms)

Renal and urinary disorders

Uncommon: Renal impairment including acute renal failure

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

 

Inform your doctor in case of any adverse reactions related to drug use.

INTERACTIONS:

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription: Your doctor may need to change the dose of these other medicines or take other precautions. In some cases you may have to stop taking one of the medicines. This applies especially to the medicines listed below taken at the same time with Telmisartan:

–           Lithium containing medicines to treat some types of depression.

–           Medicines that may increase blood potassium levels such as salt

substitutes containing potassium, potassium-sparing diuretics (certain

‘water tablets’), ACE inhibitors, angiotensin II receptor antagonists,

NSAIDs (non steroidal anti-inflammatory medicines, e.g. aspirin or

ibuprofen), heparin, immunosuppressives (e.g. cyclosporin or

tacrolimus), and the antibiotic trimethoprim.

–         Diuretics (‘water tablets’), especially if taken in high doses together with

Telmisartan, may lead to excessive loss of body water and low blood

pressure (hypotension).

–           As with other blood pressure lowering medicines, the effect of

Telmisartan may be reduced when you take NSAIDs (non steroidal anti-

inflammatory medicines, e.g. aspirin or ibuprofen) or corticosteroids.

–        Telmisartan may increase the blood pressure lowering effect of other

medicines used to treat high blood pressure.

OVERDOSES

There is limited information available with regard to overdose in humans.

Symptoms: The most prominent manifestations of telmisartan overdose were hypotension and tachycardia; bradycardia dizziness, increase in serum creatinine, and acute renal failure have also been reported.

Treatment: Telmisartan is not removed by haemodialysis. 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 overdosage. Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a supine position, with salt and volume replacement given quickly.

STORAGE

Store at temperature not exceeding 300C in a dry place. Protect from light.

SHELF LIFE: 24 months from the date of manufacture.

PACKING SIZE: Packed in blister of 10 tablets, 3 blisters per box.