Pritor® / KINZAL® Product Information
Pharmacology
Telmisartan the active component of Pritor®/Kinzalmono® is a highly selective nonpeptide angiotensin II receptor (type AT1) blocker (ARB) [1]. Angiotensin II receptor blockers bind to the angiotensin II type 1 (AT1) receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, which ultimately leads to a reduction in arterial blood pressure. PritorPlus®/Kinzalkomb® is a combination of an angiotensin II receptor antagonist, telmisartan, and a thiazide diuretic, HCTZ. The combination of these ingredients has an additive antihypertensive effect, reducing blood pressure to a greater degree than either component alone. PritorPlus®/Kinzalkomb® once daily produces effective and smooth reductions in blood pressure across the therapeutic dose range. HCTZ (hydrochlorothiazide) is a thiazide diuretic with antihypertensive effect. Thiazides effect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. The diuretic action of HCTZ reduces plasma volume, increases plasma renin activity, increases aldosterone secretion, with consequent increases in urinary potassium and bicarbonate loss, and decreases in serum potassium.
Pharmacokinetic properties
Telmisartan Tmax is 0.5 to 1 hr after dosing. Food slightly reduces bioavailability of telmisartan, with an AUC reduction of about 6% with a 40 mg tablet and 19% with a 160 mg dose. At 40 and 160 mg, the bioavailability was 42% and 58%. Telmisartan is greater than 99.5% protein bound. It is metabolized by conjugation to form a pharmacologically inactive acylglucuronide. The glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. Telmisartan t½ is approximately 24 hr and total plasma clearance is greater than 800 mL/min. After IV or oral administration, more than 97% is eliminated unchanged in faeces via biliary excretion. Concomitant administration of hydrochlorothiazide and telmisartan does not appear to affect the pharmacokinetics of either drug in healthy subjects. HCTZ (Hydrochlorothiazide): Following oral administration of PritorPlus®/Kinzalkomb® peak concentrations of HCTZ are reached in approximately 1.0 ? 3.0 hours after dosing. Based on cumulative renal excretion of HCTZ the absolute bioavailability was about 60 %. HCTZ is 68 % protein bound in the plasma and its apparent volume of distribution is 0.83 ? 1.14 l/kg. HCTZ is not metabolised in man and is excreted almost entirely as unchanged drug in urine. About 60 % of the oral dose are eliminated as unchanged drug within 48 hours. Renal clearance is about 250 ? 300 ml/min. The terminal elimination half-life of HCTZ is 10 ? 15 hours.
Indication
Pritor®/Kinzalmono® is indicated for the treatment of essential hypertension. PritorPlus®/Kinzalkomb® is indicated in patients whose blood pressure is not adequately controlled on telmisartan alone.
Dosage Monotherapy: Pritor®/Kinzalmono® may be used alone as a monotherapy. It is available as tablets for oral administration, containing 20 mg, 40 mg and 80 mg of telmisartan. In most patients with mild or moderate hypertension, maximum blood pressure reduction is achieved with 40 mg or 80 mg once daily.
Fixed Combination: PritorPlus®/Kinzalkomb® is available as tablets for oral administration, containing 40 mg/12.5 mg or 80 mg/12.5 mg of telmisartan and HCTZ.
In patients whose blood pressure is not adequately controlled on Pritor®/Kinzalmono® monotherapy the fixed-dose combination of telmisartan and thiazide-type diuretic (HCTZ) PritorPlus®/Kinzalkomb® may be used. HCTZ has been shown to have an additive blood pressure lowering effect when co-administered with telmisartan.
Contraindications
PritorPlus®/Kinzalkomb® additionally:
Adverse Effects
Back pain (e. g. sciatica), chest pain, influenza-like illness, symptoms of infection (e. g. urinary tract infection including cystitis), Visual disturbance, hyperhidrosis, vertigo, abdominal pain, diarrhoea, dyspepsia, dry mouth, flatulence, stomach discomfort, arthralgia, muscle spasms or pain in extremity, myalgia, tendonitis, anxiety, upper respiratory tract infection including pharyngitis and sinusitis, eczema, erythema, pruritus, syncope, insomnia, depression, vomiting, hypotension (including orthostatic hypotension), bradycardia, tachycardia, hepatic function abnormal, liver disorder, renal impairment including acute renal failure, hyperkalaemia, dyspnoea, anaemia, eosinophilia, thrombocytopenia, asthenia and lack of efficacy. Isolated cases of angioneurotic oedema, urticaria and other related events. PritorPlus/Kinzalkomb additionally: erectile dyfunction, pain, hypersensitivity, dizziness, gastritis, hypercholesterolaemia, hypokalaemia, diabetes mellitus inadequate control, hyperuricaemia, osteoarthritis, bronchitis. Laboratory findings (Pritor®/Kinzalmono®): Haemoglobin decrease or blood uric acid increase. In addition cases with blood creatinine phosphokinase increased.
Use in Pregnancy
There are no adequate data from the use of Pritor®/Kinzalmono®/PritorPlus®/Kinzalkomb® in pregnant women. Therefore, it should preferably not be used during the first trimester of pregnancy. A switch to a suitable alternative treatment should be carried out in advance of a planned pregnancy. In the second and third trimesters, substances that act directly on the renin-angiotensin-system can cause injury and even death in the developing foetus, therefore, Pritor®/Kinzalmono®/PritorPlus®/Kinzalkomb® is contraindicated in the second and third trimesters of pregnancy. If pregnancy is diagnosed Pritor®/Kinzalmono®/PritorPlus®/Kinzalkomb® should be discontinued as soon as possible.
Telmisartan the active component of Pritor®/Kinzalmono® is a highly selective nonpeptide angiotensin II receptor (type AT1) blocker (ARB) [1]. Angiotensin II receptor blockers bind to the angiotensin II type 1 (AT1) receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, which ultimately leads to a reduction in arterial blood pressure. PritorPlus®/Kinzalkomb® is a combination of an angiotensin II receptor antagonist, telmisartan, and a thiazide diuretic, HCTZ. The combination of these ingredients has an additive antihypertensive effect, reducing blood pressure to a greater degree than either component alone. PritorPlus®/Kinzalkomb® once daily produces effective and smooth reductions in blood pressure across the therapeutic dose range. HCTZ (hydrochlorothiazide) is a thiazide diuretic with antihypertensive effect. Thiazides effect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. The diuretic action of HCTZ reduces plasma volume, increases plasma renin activity, increases aldosterone secretion, with consequent increases in urinary potassium and bicarbonate loss, and decreases in serum potassium.
Pharmacokinetic properties
Telmisartan Tmax is 0.5 to 1 hr after dosing. Food slightly reduces bioavailability of telmisartan, with an AUC reduction of about 6% with a 40 mg tablet and 19% with a 160 mg dose. At 40 and 160 mg, the bioavailability was 42% and 58%. Telmisartan is greater than 99.5% protein bound. It is metabolized by conjugation to form a pharmacologically inactive acylglucuronide. The glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. Telmisartan t½ is approximately 24 hr and total plasma clearance is greater than 800 mL/min. After IV or oral administration, more than 97% is eliminated unchanged in faeces via biliary excretion. Concomitant administration of hydrochlorothiazide and telmisartan does not appear to affect the pharmacokinetics of either drug in healthy subjects. HCTZ (Hydrochlorothiazide): Following oral administration of PritorPlus®/Kinzalkomb® peak concentrations of HCTZ are reached in approximately 1.0 ? 3.0 hours after dosing. Based on cumulative renal excretion of HCTZ the absolute bioavailability was about 60 %. HCTZ is 68 % protein bound in the plasma and its apparent volume of distribution is 0.83 ? 1.14 l/kg. HCTZ is not metabolised in man and is excreted almost entirely as unchanged drug in urine. About 60 % of the oral dose are eliminated as unchanged drug within 48 hours. Renal clearance is about 250 ? 300 ml/min. The terminal elimination half-life of HCTZ is 10 ? 15 hours.
Indication
Pritor®/Kinzalmono® is indicated for the treatment of essential hypertension. PritorPlus®/Kinzalkomb® is indicated in patients whose blood pressure is not adequately controlled on telmisartan alone.
Dosage Monotherapy: Pritor®/Kinzalmono® may be used alone as a monotherapy. It is available as tablets for oral administration, containing 20 mg, 40 mg and 80 mg of telmisartan. In most patients with mild or moderate hypertension, maximum blood pressure reduction is achieved with 40 mg or 80 mg once daily.
Fixed Combination: PritorPlus®/Kinzalkomb® is available as tablets for oral administration, containing 40 mg/12.5 mg or 80 mg/12.5 mg of telmisartan and HCTZ.
In patients whose blood pressure is not adequately controlled on Pritor®/Kinzalmono® monotherapy the fixed-dose combination of telmisartan and thiazide-type diuretic (HCTZ) PritorPlus®/Kinzalkomb® may be used. HCTZ has been shown to have an additive blood pressure lowering effect when co-administered with telmisartan.
Contraindications
- Hypersensivity to any of the active substances or to any of the excipients of the products
- Second and third trimesters of pregnancy and lactation
- Biliary obstructive disorders
- Severe hepatic impairment
PritorPlus®/Kinzalkomb® additionally:
- Hypersensivity to other sulphonamide-derived substances
- Cholestasis
- Severe renal impairment (cretainine clearance < 30 ml/min)
- Refractory hypokalaemia
- Hypercalcaemia
Adverse Effects
Back pain (e. g. sciatica), chest pain, influenza-like illness, symptoms of infection (e. g. urinary tract infection including cystitis), Visual disturbance, hyperhidrosis, vertigo, abdominal pain, diarrhoea, dyspepsia, dry mouth, flatulence, stomach discomfort, arthralgia, muscle spasms or pain in extremity, myalgia, tendonitis, anxiety, upper respiratory tract infection including pharyngitis and sinusitis, eczema, erythema, pruritus, syncope, insomnia, depression, vomiting, hypotension (including orthostatic hypotension), bradycardia, tachycardia, hepatic function abnormal, liver disorder, renal impairment including acute renal failure, hyperkalaemia, dyspnoea, anaemia, eosinophilia, thrombocytopenia, asthenia and lack of efficacy. Isolated cases of angioneurotic oedema, urticaria and other related events. PritorPlus/Kinzalkomb additionally: erectile dyfunction, pain, hypersensitivity, dizziness, gastritis, hypercholesterolaemia, hypokalaemia, diabetes mellitus inadequate control, hyperuricaemia, osteoarthritis, bronchitis. Laboratory findings (Pritor®/Kinzalmono®): Haemoglobin decrease or blood uric acid increase. In addition cases with blood creatinine phosphokinase increased.
Use in Pregnancy
There are no adequate data from the use of Pritor®/Kinzalmono®/PritorPlus®/Kinzalkomb® in pregnant women. Therefore, it should preferably not be used during the first trimester of pregnancy. A switch to a suitable alternative treatment should be carried out in advance of a planned pregnancy. In the second and third trimesters, substances that act directly on the renin-angiotensin-system can cause injury and even death in the developing foetus, therefore, Pritor®/Kinzalmono®/PritorPlus®/Kinzalkomb® is contraindicated in the second and third trimesters of pregnancy. If pregnancy is diagnosed Pritor®/Kinzalmono®/PritorPlus®/Kinzalkomb® should be discontinued as soon as possible.
