Tekturna

Uses

Treatment of essential hypertension in adults. Indicated in patients whose blood pressure is not adequately controlled on aliskiren or hydrochlorothiazide used alone. Indicated as substitution therapy in patients adequately controlled with aliskiren and hydrochlorothiazide, given concurrently, at the same dose level as in the combination.

Tekturna is also used to associated treatment for these conditions: Acidosis, Renal Tubular, Calcium Nephrolithiasis, Cirrhosis of the Liver, Congestive Heart Failure (CHF), Diabetes Insipidus, Edema, High Blood Pressure (Hypertension), Hypertension,Essential, Hypokalemia caused by diuretics, Nephrotic Syndrome, Premenstrual tension with edema, Sodium retention, Stroke, Prophylaxis of preeclampsia

How Tekturna works

Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).

Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.

Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

Dosage

Tekturna dosage

The recommended dose is one tablet per day. The antihypertensive effect is largely manifested within 1 week and the maximum effect is generallyseen within 4 weeks

• 150 mg/12.5 mg may be administered in patients whose blood pressure is not adequatelycontrolled with Aliskiren 150 mg or Hydrochlorothiazide 12.5 mg alone.
• 150 mg/25 mg may be administered in patients whose blood pressure is not adequately controlled with Aliskiren 150 mg or Hydrochlorothiazide 25 mg alone or by Aliskiren + Hydrochlorothiazide 150 mg/12.5 mg.
• 300 mg/12.5 mg may be administered in patients whose blood pressure is not adequately controlled with Aliskiren 300 mg or Hydrochlorothiazide 12.5 mg alone or by Aliskiren + Hydrochlorothiazide150 mg/12.5 mg.
• 300 mg/25 mg may be administered in patients whose blood pressure is not adequately controlled with Aliskiren 300 mg or Hydrochlorothiazide 25 mg alone or by Aliskiren + Hydrochlorothiazide 300 mg/12.5 mg or 150 mg/25 mg.
• If blood pressure remains uncontrolled after 2-4 weeks of therapy, the dose may be titrated up to a maximum of Aliskiren + Hydrochlorothiazide 300 mg/25 mg daily. Dosing should be individualised and adjusted according to the patient’s clinical response.

Side Effects

Dizziness,Vertigo,Hypokalemia,Increased uric acid level ,Hyperkalemia, Diarrhea, Increased ALT , Flu-like syndrome, Cough, Weakness, Arthralgia, Diarrhea, Cough, Rash, Increased creatinine kinase, Increased BUN, Hyperkalemia, Decreased hematocrit, Decreased hemoglobin Aliskiren, Gastroesophageal reflux, Periorbital edema, Toxic epiderma necrolysis, Increased uric acid, Severe hypotension, Stevens Johnson syndrome.

Toxicity

The oral LD₅₀ of hydrochlorothiazide is >10g/kg in mice and rats.

Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment.

Precaution

Serious CHF, sodium or volume depletion. Discontinue if diarrhoea is severe and persistent. Lactation. Monitoring Parameters Periodically monitor serum potassium concentration and renal function.

Discontinue as soon as possible when pregnancy is detected; affects renin- angiotensin system causing oligohydramnios, which may result in fetal injury and/ or death.

Interaction

Aliskiren increased risk of hypotension with other antihypertensives. Increased risk of acute renal failure with ACE inhibitors, angiotensin II receptor antagonists or NSAIDs. Antihypertensive effect may be reduced with NSAIDs. Increased serum levels with atorvastatin, itraconazole, ketoconazole, verapamil. Significant decrease in furosemide concentrations with aliskiren. Increased risk of hyperkalaemia with potassium-sparing diuretics, potassium supplements or any substances that may increase serum potassium levels.

Potentially Fatal: Increased risk of renal impairment, hypotension and hyperkalaemia with ACE inhibitors or angiotensin II receptor antagonists. Markedly increased plasma concentration with ciclosporin, itraconazole and quinidine.

Hydrochlorothiazide increases toxicity of lithium. May potentiate orthostatic hypotension with barbiturates and narcotics. Enhanced neuromuscular blocking action of competitive neuromuscular blockers (e.g. atracurium). Increased hypokalaemic effect with corticosteroids, corticotropin, beta 2 agonists (e.g. salbutamol). Additive effect with other antihypertensives. Potentiation of orthostatic hypotension with barbiturates or opioids. Reduced antihypertensive effect by drugs that cause fluid retention (e.g. corticosteroids, NSAIDs, carbenoxolone). Enhanced nephrotoxicity of NSAIDs. Reduced therapeutic effect of antidiabetics.

Volume of Distribution

The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg.

Elimination Route

An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a T_max of 1-5 hours, and a C_max of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, C_max is 20% lower, and T_max increases from 1.6 to 2.9 hours.

Half Life

The plasma half life of hydrochlorothiazide is 5.6-14.8h.

Clearance

The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min.

Elimination Route

Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide.

Pregnancy & Breastfeeding use

Pregnancy Category-D. Enters in breast milk; Not recommended

Contraindication

• Hypersensitivity to the active substances
• History of angioedema with aliskiren.
• Hereditary or idiopathic angioedema.
• Second and third trimesters of pregnancy
• Anuria.
• Hyponatraemia, hypercalcaemia, symptomatic hyperuricaemia and refractory hypokalaemia.
• Severe hepatic & renal impairment.
• The concomitant use of Aliskiren & Hydrochlorothiazide with an ACEI or an ARB is contraindicated in patients with diabetes mellitus or renal impairment

Special Warning

Elderly people (over 65 years): The recommended starting dose in elderly patients is 150 mg. No clinically meaningful additional blood pressure reduction is observed by increasing the dose to 300 mg in the majority of elderly patients.

Paediatric population: The safety and efficacy in children below 18 years have not yet been established. No data are available.

Children <2 years: Contraindicated in children from birth to less than 2 years and should not be used in children aged 2 to less than 6 years because of safety concerns due to potential aliskiren overexposure

Renal impairment: Due to the hydrochlorothiazide component, this is contraindicated for use in patients with anuria and in patients with severe renal impairment glomerular filtration rate <30 ml/min/1.73 m2 ). No adjustment of the initial dose is required for patients with mild to moderate renal impairment

Hepatic impairment: Contraindicated in patients with severe hepatic impairment and should be used with caution in patients with mild to moderate hepatic impairment or progressive liver disease. No adjustment of the initial dose is required for patients with mild to moderate hepatic impairment

Acute Overdose

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. Rarely, autoimmune hemolytic anemia and other hypersensitivity reactions may complicate the picture.

In the event of over dosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. Hemodialysis can be used successfully to treat severe intoxication.

Storage Condition

Store between 15-30°C. Protect from light, moisture and freezing.

Innovators Monograph

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