Diutensat Comp.

What are the side effects you encounter while taking this medicine?
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Diutensat Comp. uses

Diutensat Comp. consists of Hydrochlorothiazide, Propranolol Hydrochloride, Triamterene.

Hydrochlorothiazide:


Diutensat Comp. information

Diutensat Comp. (Hydrochlorothiazide) is an antihypertensive, diuretic drug that acts on the electrolyte reabsorption in the renal tubular mechanism increasing the excretion of chloride and sodium in equivalent amounts. The exact mechanism of its antihypertensive action is not known at this time.

Diutensat Comp. indications

Diutensat Comp. (Hydrochlorothiazide) is typically employed for the treatment of patients suffering from hypertension, either as monotherapy or in combination with other antihypertensive medication. It is also employed in some cases as a diuretic agent. Diutensat Comp. (Hydrochlorothiazide) therapy may also be prescribed for the treatment of hepatic cirrhosis, edema (in patients suffering from congestive heart failure), nephrotic syndrome, drug induced edema, chronic renal failure or acute glomerulonephritis. Health care professionals may prescribe this drug in order to treat other medical conditions as well; if you would like to know more about the reasons you have been prescribed this drug, it is advised to ask your personal physician.

Diutensat Comp. warnings

Diutensat Comp. (Hydrochlorothiazide) may not be used in the treatment of patients who are allergic to this drug, any of its components or other sulfonamide-derived medication. Also, this drug may not be suitable for use in patients that are suffering from anuria, azotemia or impaired renal functions. Caution should be employed if the patient is suffering from hepatic disease. Other medical conditions may also influence the examining health care provider's decision of prescribing Diutensat Comp. (Hydrochlorothiazide); it is strongly recommended to make sure that the health care professional is fully aware of your health condition and medical history before starting a treatment with this drug.

Use of Diutensat Comp. (Hydrochlorothiazide) during pregnancy or breast-feeding is also not recommended. This medicine may affect an unborn baby and it also passes into breast milk. As such, use of this drug in pregnant women or breast-feeding mothers should not be employed.

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Diutensat Comp. intake guidelines

You should always take Diutensat Comp. (Hydrochlorothiazide) as you have been directed by the prescribing health care specialist. While in some cases daily administration of the drug is recommended, other patients may be prescribed an intermittent therapy. Also, the number of daily doses may vary. As such, it is best that you do not follow another patient's intake schedule. If you have difficulties understanding the intake guidelines that your prescribing health care professional has provided, you should ask for further explanations from an authorized health care specialist - such as a pharmacist, a doctor or a nurse.

Diutensat Comp. dosage

The exact Diutensat Comp. (Hydrochlorothiazide) dosage may vary greatly from one case to another, depending on the condition being treated, on the patient's medical history and general health condition, on his or her age as well as on a number of other factors. As such you are advised to use the exact Diutensat Comp. (Hydrochlorothiazide) dosage that has been prescribed to you and never use the dosage prescribed to another patient or a dosage that you have been prescribed in the past. Taking a different Diutensat Comp. (Hydrochlorothiazide) dose may cause the treatment to not have the desired effect, and if you take this drug in larger doses you may have a higher risk of developing side effects, or you may suffer from an overdose.

Diutensat Comp. overdose

You should never exceed the Diutensat Comp. (Hydrochlorothiazide) prescribed dosage, in order to avoid an overdose with this medication. However, if you consider that you are affected by an overdose with this drug it is advised to immediately consult your personal health care provider, the local poisons center or to go to the nearest medical facility to seek emergency medical attention. The common symptoms of an overdose with Diutensat Comp. (Hydrochlorothiazide) are dehydration and cardiac arrhythmia. The patient may also suffer from electrolyte depletion and thus may present the relevant signs and symptoms.

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Diutensat Comp. missed dose

In case you have missed a dose of Diutensat Comp. (Hydrochlorothiazide), it is advised that you take the dose as soon as you remember. If the moment when you remember is too close to another intake of the medication, you should completely skip the missed Diutensat Comp. (Hydrochlorothiazide) dose and take the next scheduled dose on time. You should never take a larger dose of the drug in order to make up for a missed dose, unless your prescribing health care provider directs you to do so.

Diutensat Comp. side effects

In some patients Diutensat Comp. (Hydrochlorothiazide) may cause side effects. While they are not very common, it is recommended to let your personal health care provider know if you begin experiencing any side effects. Several types of symptoms are possible: dizziness, headache, paresthesias, gastric irritation, anorexia, nausea and vomiting, diarrhea or constipation, pancreatitis, jaundice, hypotension. Metabolic side effects may include glycosuria, hyperglycemia, hyperuricemia, hypokalemia or hyponatremia. Renal failure or dysfunction may develop, as well as interstitial nephritis. Some patients reported experiencing muscle spasms, restlessness, unusual weakness and blurred vision. In some cases photosensitivity, anaphylactic reactions, respiratory distress, fever, rashes, vasculitis or toxic epidermal necrolysis have occurred.

Diutensat Comp. drug reactions

Diutensat Comp. (Hydrochlorothiazide) may interact with barbiturates and narcotics, as well as with alcohol. If you are also following a treatment course with antidiabetic drugs, their dosage may need to be adjusted before starting to take Diutensat Comp. (Hydrochlorothiazide). This drug may have an additive effect with other antihypertensive medication. ACE inhibitors, ACTH, corticosteroids and skeletal muscle relaxants may also interact with this drug causing unwanted effects. This drug may not be properly absorbed if the patient is also taking Colestipol resins or Cholestyramine. NSAIDs, lithium and Pressor amines may affect or be affected by Diutensat Comp. (Hydrochlorothiazide), and as such it is strongly recommended to let the prescribing health care provider know if you are taking these or any other drugs before starting a therapy course with this medicine. Other drug interactions that are not listed here are also possible.

Propranolol Hydrochloride:


DESCRIPTION

Diutensat Comp. (Propranolol Hydrochloride) Hydrochloride, USP is a synthetic beta-adrenergic receptor blocking agent chemically described as (+)-1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol hydrochloride. Its structural formula is:

Diutensat Comp. (Propranolol Hydrochloride) Hydrochloride, USP is a stable, white, crystalline solid which is readily soluble in water and ethanol. Its molecular weight is 295.80.

Diutensat Comp. (Propranolol Hydrochloride) Hydrochloride Injection, USP is available as a sterile injectable solution for intravenous administration. Each mL contains 1 mg of Diutensat Comp. (Propranolol Hydrochloride) Hydrochloride, USP in Water for Injection, USP. The pH is adjusted with anhydrous Citric Acid, USP.

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CLINICAL PHARMACOLOGY

General

Diutensat Comp. (Propranolol Hydrochloride) is a nonselective beta-adrenergic receptor blocking agent possessing no other autonomic nervous system activity. It specifically competes with beta-adrenergic receptor stimulating agents for available receptor sites. When access to beta-recceptor sites is blocked by Diutensat Comp. (Propranolol Hydrochloride), chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are decreased proportionately. At doses greater than required for beta blockade, Diutensat Comp. (Propranolol Hydrochloride) also exerts a quinidine-like or anesthetic-like membrane action, which affects the cardiac action potential. The significance of the membrane action in the treatment of arrhythmias is uncertain.

Mechanism of Action

The effects of Diutensat Comp. (Propranolol Hydrochloride) are due to selective blockade of beta-adrenergic receptors, leaving alpha-adrenergic responses intact. There are two well-characterized subtypes of beta receptors (beta1 and beta2); Diutensat Comp. (Propranolol Hydrochloride) interacts with both subtypes equally. Beta1-adrenergic receptors leads to a decrease in the activity of both normal and ectopic pacemaker cells and a decrease in A-V nodal conduction velocity. All of these actions can contribute to antiarrhythmic activity and control of ventricular rate during arrhythmias. Blockade of cardiac beta1-adrenergic receptors also decreases the myocardial force of contraction and may provoke cardiac decompensation in patients with minimal cardiac reserve.

Beta2-adrenergic receptors are found predominantly in smooth muscle-vascular, bronchial, gastrointestinal and genitourinary. Blockade of these receptors results in constriction. Clinically, Diutensat Comp. (Propranolol Hydrochloride) may exacerbate respiratory symptoms in patients with obstructive pulmonary diseases such as asthma and emphysema.

Propranolol's beta blocking effects are attributable to its S(-) enantiomer.

Pharmacokinetics and Drug Metabolism

Distribution

Diutensat Comp. (Propranolol Hydrochloride) has a distribution half-life (T1/2 alpha) of 5-10 minutes and a volume of distribution of about 4 to 5 L/kg. Approximately 90% of circulating Diutensat Comp. (Propranolol Hydrochloride) is bound to plasma proteins. The binding is enantiomer-selective. The S-isomer is preferentially bound to alpha1 glycoprotein and the R-isomer is preferentially bound to albumin.

Metabolism and Elimination

The elimination half-life (T½ beta) is between 2 and 5.5 hours. Diutensat Comp. (Propranolol Hydrochloride) is extensively metabolized with most metabolites appearing in the urine. The major metabolites include Diutensat Comp. (Propranolol Hydrochloride) glucuronide, naphthyloxylactic acid, and glucuronic acid and sulfate conjugates of 4-hydroxy Diutensat Comp. (Propranolol Hydrochloride). Following single-dose intravenous administration, side-chain oxidative products account for approximately 40% of the metabolites, direct conjugation products account for approximately 45-50% of metabolites, and ring oxidative products account for approximately 10-15% of metabolites. Of these, only the primary ring oxidative product (4-hydroxypropranolol) possesses beta-adrenergic receptor blocking activity.

In vitro studies have indicated that the aromatic hydroxylation of Diutensat Comp. (Propranolol Hydrochloride) is catalyzed mainly by polymorphic CYP2D6. Side‑chain oxidation is mediated mainly by CYP1A2 and to some extent by CYP2D6. 4-hydroxy Diutensat Comp. (Propranolol Hydrochloride) is a weak inhibitor of CYP2D6.

Pharmacodynamics

As Diutensat Comp. (Propranolol Hydrochloride) concentration increases, so does its beta-blocking effect, as evidenced by a reduction in exercise-induced tachycardia (n = 6 normal volunteers).

Special Populations

Pediatric

The pharmacokinetics of Diutensat Comp. (Propranolol Hydrochloride) have not been investigated in patients under 18 years of age. Diutensat Comp. (Propranolol Hydrochloride) injection is not recommended for treatment of cardiac arrhythmias in pediatric patients.

Geriatric

Elevated Diutensat Comp. (Propranolol Hydrochloride) plasma concentrations, a longer mean elimination half-life (254 vs. 152 minutes), and decreased systemic clearance (8 vs. 13 mL/kg/min) have been observed in elderly subjects when compared to young subjects. However, the apparent volume of distribution seems to be similar in elderly and young subjects. These findings suggest that dose adjustment of Diutensat Comp. (Propranolol Hydrochloride) injection may be required for elderly patients.

Gender

Intravenously administered Diutensat Comp. (Propranolol Hydrochloride) was evaluated in 5 women and 6 men. When adjusted for weight, there were no gender-related differences in elimination half-life, volume of distribution, protein binding, or systemic clearance.

Obesity

In a study of intravenously administered Diutensat Comp. (Propranolol Hydrochloride), obese subjects had a higher AUC (161 versus 109 hr·mcg/L) and lower total clearance than did non-obese subjects. Diutensat Comp. (Propranolol Hydrochloride) plasma protein binding was similar in both groups.

Renal Insufficiency

The pharmacokinetics of Diutensat Comp. (Propranolol Hydrochloride) and its metabolites were evaluated in 15 subjects with varying degrees of renal function after Diutensat Comp. (Propranolol Hydrochloride) administration via the intravenous and oral routes. When compared with normal subjects, an increase in fecal excretion of Diutensat Comp. (Propranolol Hydrochloride) conjugates was observed in patients with increased renal impairment. Diutensat Comp. (Propranolol Hydrochloride) was also evaluated in 5 patients with chronic renal failure, 6 patients on regular dialysis, and 5 healthy subjects, following a single oral dose of 40 mg of Diutensat Comp. (Propranolol Hydrochloride). The peak plasma concentrations (Cmax) of Diutensat Comp. (Propranolol Hydrochloride) in the chronic renal failure group were 2- to 3-fold higher (161 ng/mL) than those observed in the dialysis patients (47 ng/‌mL) and in the healthy subjects (26 ng/mL). Diutensat Comp. (Propranolol Hydrochloride) plasma clearance was also reduced in the patients with chronic renal failure.

Chronic renal failure has been associated with a decrease in drug metabolism via downregulation of hepatic cytochrome P-450 activity.

Hepatic Insufficiency

Diutensat Comp. (Propranolol Hydrochloride) is extensively metabolized by the liver. In a study conducted in 6 normal subjects and 20 patients with chronic liver disease, including hepatic cirrhosis, 40 mg of R-propranolol was administered intravenously. Compared to normal subjects, patients with chronic liver disease had decreased clearance of Diutensat Comp. (Propranolol Hydrochloride), increased volume of distribution, decreased protein-binding, and considerable variation in half-life. Caution should be exercised when Diutensat Comp. (Propranolol Hydrochloride) is used in this population. Consideration should be given to lowering the dose of intravenous Diutensat Comp. (Propranolol Hydrochloride) in patients with hepatic insufficiency.

Thyroid Dysfunction

No pharmacokinetic changes were observed in hyperthyroid or hypothyroid patients when compared to their corresponding euthyroid state. Dosage adjustment does not seem necessary in either patient population based on pharmacokinetic findings.

Drug Interactions

Interactions with Substrates, Inhibitors or Inducers of Cytochrome P-450 Enzymes

Because propranolol’s metabolism involves multiple pathways in the cytochrome P-450 system (CYP2D6, 1A2, 2C19), administration of Diutensat Comp. (Propranolol Hydrochloride) with drugs that are metabolized by, or affect the activity (induction or inhibition) of one or more of these pathways may lead to clinically relevant drug interactions.

Substrates or Inhibitors of CYP2D6

Blood levels of Diutensat Comp. (Propranolol Hydrochloride) may be increased by administration of Diutensat Comp. (Propranolol Hydrochloride) with substrates or inhibitors of CYP2D6, such as amiodarone, cimetidine, delavirdine, fluoxetine, paroxetine, quinidine, and ritonavir. No interactions were observed with either ranitidine or lansoprazole.

Substrates or Inhibitors of CYP1A2

Blood levels of Diutensat Comp. (Propranolol Hydrochloride) may be increased by administration of Diutensat Comp. (Propranolol Hydrochloride) with substrates or inhibitors of CYP1A2, such as imipramine, cimetidine, ciprofloxacin, fluvoxamine, isoniazid, ritonavir, theophylline, zileuton, zolmitriptan, and rizatriptan.

Substrates or Inhibitors of CYP2C19

Blood levels of Diutensat Comp. (Propranolol Hydrochloride) may be increased by administration of Diutensat Comp. (Propranolol Hydrochloride) with substrates or inhibitors of CYP2C19, such as fluconazole, cimetidine, fluoxetine, fluvoxamine, teniposide, and tolbutamide. No interaction was observed with omeprazole.

Inducers of Hepatic Drug Metabolism

Blood levels of Diutensat Comp. (Propranolol Hydrochloride) may be decreased by administration of Diutensat Comp. (Propranolol Hydrochloride) with inducers such as rifampin and ethanol. Cigarette smoking also induces hepatic metabolism and has been shown to increase up to 100% the clearance of Diutensat Comp. (Propranolol Hydrochloride), resulting in decreased plasma concentrations.

Cardiovascular Drugs

Antiarrhythmics

The AUC of propafenone is increased by more than 200% with co-administration of Diutensat Comp. (Propranolol Hydrochloride).

The metabolism of Diutensat Comp. (Propranolol Hydrochloride) is reduced by co-administration of quinidine, leading to a 2- to 3-fold increased blood concentrations and greater beta-blockade.

The metabolism of lidocaine is inhibited by co-administration of Diutensat Comp. (Propranolol Hydrochloride), resulting in a 25% increase in lidocaine concentrations.

Calcium Channel Blockers

The mean Cmax and AUC of Diutensat Comp. (Propranolol Hydrochloride) are increased respectively, by 50% and 30% by co-administration of nisoldipine and by 80% and 47%, by co-administration of nicardipine.

The mean values of Cmax and AUC of nifedipine are increased by 64% and 79%, respectively, by co-administration of Diutensat Comp. (Propranolol Hydrochloride).

Diutensat Comp. (Propranolol Hydrochloride) does not affect the pharmacokinetics of verapamil and norverapamil. Verapamil does not affect the pharmacokinetics of Diutensat Comp. (Propranolol Hydrochloride).

Non-Cardiovascular Drugs

Migraine Drugs

Administration of zolmitriptan or rizatriptan with Diutensat Comp. (Propranolol Hydrochloride) resulted in increased concentrations of zolmitriptan (AUC increased by 56% and Cmax by 37%) or rizatriptan (the AUC and Cmax were increased by 67% and 75%, respectively).

Theophylline

Co-administration of theophylline with Diutensat Comp. (Propranolol Hydrochloride) decreases theophylline clearance by 33% to 52%.

Benzodiazepines

Diutensat Comp. (Propranolol Hydrochloride) can inhibit the metabolism of diazepam, resulting in increased concentrations of diazepam and its metabolites. Diazepam does not alter the pharmacokinetics of Diutensat Comp. (Propranolol Hydrochloride).

The pharmacokinetics of oxazepam, triazolam, lorazepam, and alprazolam are not affected by co-administration of Diutensat Comp. (Propranolol Hydrochloride).

Neuroleptic Drugs

Co-administration of Diutensat Comp. (Propranolol Hydrochloride) at doses greater than or equal to 160 mg/day resulted in increased thioridazine plasma concentrations ranging from 50% to 370% and increased thioridazine metabolites concentrations ranging from 33% to 210%.

Co-administration of chlorpromazine with Diutensat Comp. (Propranolol Hydrochloride) resulted in increased plasma levels of both drugs (70% increase in Diutensat Comp. (Propranolol Hydrochloride) concentrations).

Anti-Ulcer Drugs

Co-administration of Diutensat Comp. (Propranolol Hydrochloride) with cimetidine, a non-specific CYP450 inhibitor, increased Diutensat Comp. (Propranolol Hydrochloride) concentrations by about 40%. Co‑administration with aluminum hydroxide gel (1200 mg) resulted in a 50% decrease in Diutensat Comp. (Propranolol Hydrochloride) concentrations.

Co-administration of metoclopramide with Diutensat Comp. (Propranolol Hydrochloride) did not have a significant effect on propranolol’s pharmacokinetics.

Lipid Lowering Drugs

Co-administration of cholesteramine or colestipol with Diutensat Comp. (Propranolol Hydrochloride) resulted in up to 50% decrease in Diutensat Comp. (Propranolol Hydrochloride) concentrations.

Co-administration of Diutensat Comp. (Propranolol Hydrochloride) with lovastatin or pravastatin decreased 20% to 25% the AUC of both, but did not alter their pharmacodynamics. Diutensat Comp. (Propranolol Hydrochloride) did not have an effect on the pharmacokinetics of fluvastatin.

Warfarin

Concomitant administration of Diutensat Comp. (Propranolol Hydrochloride) and warfarin has been shown to increase warfarin bioavailability and increase prothrombin time.

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CLINICAL STUDIES

In a series of 225 patients with supraventricular (n = 145), ventricular (n = 69), or both (n = 11) arrythmias resistant to digitalis, intravenous Diutensat Comp. (Propranolol Hydrochloride) hydrochloride was administered in single doses, averaging 1 to 5 mg. Approximately one-quarter of the patients with supraventricular arrhythmias (generally those with sinus or atrial tachycardia) reverted to normal sinus rhythm. About one-half had symptoms ameliorated either by a decrease in ventricular rate or an attenuation of frequency or severity of paroxysmal attacks.

Approximately one-half of patients with ventricular arrhythmias (generally those with frequent PVCs) reverted to normal sinus rhythm or responded with a reduction in ventricular rate.

Similar findings were seen in a series of 25 Bantu patients with atrial fibrillation (n = 16), sinus tachycardia (n = 5), and multifocal ventricular extrasystoles (n = 9).

In another series, 7 of 8 patients with digitalis-related tachyarrhythmia had ventricular rate decreases after intravenous Diutensat Comp. (Propranolol Hydrochloride). Similarly limited clinical experience has shown that intravenous Diutensat Comp. (Propranolol Hydrochloride) will slow the ventricular rate in patients with Wolff-Parkinson-White syndrome or with tachycardia associated with thyrotoxicosis.

Onset of activity is usually within five minutes.

INDICATIONS & USAGE

Cardiac Arrhythmias

Intravenous administration is usually reserved for life-threatening arrhythmias or those occurring under anesthesia.

1. Supraventricular arrhythmias

Intravenous Diutensat Comp. (Propranolol Hydrochloride) is indicated for the short-term treatment of supraventricular tachycardia, including Wolff‑Parkinson‑White syndrome and thyrotoxicosis, to decrease ventricular rate. Use in patients with atrial flutter or atrial fibrillation should be reserved for arrythmias unresponsive to standard therapy or when more prolonged control is required. Reversion to normal sinus rhythm has occasionally been observed, predominantly in patients with sinus or atrial tachycardia.

2. Ventricular tachycardias

With the exception of those induced by catecholamines or digitalis, Diutensat Comp. (Propranolol Hydrochloride) is not the drug of first choice. In critical situations when cardioversion techniques or other drugs are not indicated or are not effective, Diutensat Comp. (Propranolol Hydrochloride) may be considered. If, after consideration of the risks involved, Diutensat Comp. (Propranolol Hydrochloride) is used, it should be given intravenously in low dosage and very slowly, as the failing heart requires some sympathetic drive for maintenance of myocardial tone. Some patients may respond with complete reversion to normal sinus rhythm, but reduction in ventricular rate is more likely. Ventricular arrhythmias do not respond to Diutensat Comp. (Propranolol Hydrochloride) as predictably as do the supraventricular arrhythmias.

Intravenous Diutensat Comp. (Propranolol Hydrochloride) is indicated for the treatment of persistent premature ventricular extrasystoles that impair the well‑being of the patient and do not respond to conventional measures.

3. Tachyarrhythmias of digitalis intoxication

Intravenous Diutensat Comp. (Propranolol Hydrochloride) is indicated to control ventricular rate in life-threatening digitalis-induced arrhythmias. Severe bradycardia may occur.

4. Resistant tachyarrhythmias due to excessive catecholamine action during anesthesia

Intravenous Diutensat Comp. (Propranolol Hydrochloride) is indicated to abolish tachyarrhythmias due to excessive catecholamine action during anesthesia when other measures fail. These arrhythmias may arise because of release of endogenous catecholamines or administration of catecholamines. All general inhalation anesthetics produce some degree of myocardial depression. Therefore, when Diutensat Comp. (Propranolol Hydrochloride) is used to treat arrhythmias during anesthesia, it should be used with extreme caution, usually with constant monitoring of the ECG and central venous pressure.

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CONTRAINDICATIONS

Diutensat Comp. (Propranolol Hydrochloride) is contraindicated in 1) cardiogenic shock; 2) sinus bradycardia and greater than first-degree block; 3) bronchial asthma; and 4) in patients with known hypersensitivity to Diutensat Comp. (Propranolol Hydrochloride) hydrochloride.

WARNINGS

Cardiac Failure

Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, some have been shown to be highly beneficial when used with close follow-up in patients with a history of failure who are well compensazted and are receiving additional therapies, including diiuretics as needed. Beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle.

Nonallergic Bronchospasm (e.g., Chronic Bronchitis, Emphysema)

In general, patients with bronchospastic lung disease should not receive beta blockers. Diutensat Comp. (Propranolol Hydrochloride) should be administered with caution in this setting since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta-receptors.

Major Surgery

The necessity or desirability of withdrawal of beta-blocking therapy prior to major surgery is controversial. It should be noted, however, that the impaired ability of the heart to respond to reflex adrenergic stimuli in propranolol-treated patients might augment the risks of general anesthesia and surgical procedures.

Diutensat Comp. (Propranolol Hydrochloride) is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension.

Diabetes and Hypoglycemia

Beta-adrenergic blockade may prevent the appearance of certain premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycemia, especially in labile insulin-dependent diabetics. In these patients, it may be more difficult to adjust the dosage of insulin.

Diutensat Comp. (Propranolol Hydrochloride) therapy, particularly in infants and children, diabetic or not, has been associated with hypoglycemia especially during fasting, as in preparation for surgery. Hypoglycemia has been reported after prolonged physical exertion and in patients with renal insufficiency.

Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism. Therefore, abrupt withdrawal of Diutensat Comp. (Propranolol Hydrochloride) may be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. Diutensat Comp. (Propranolol Hydrochloride) may change thyroid-function tests, increasing T4 and reverse T3, and decreasing T3.

Wolff-Parkinson-White Syndrome

Beta-adrenergic blockade in patients with Wolff-Parkinson-White syndrome and tachycardia has been associated with severe bradycardia requiring treatment with a pacemaker. In one case this resulted after an initial 5 mg dose of intravenous Diutensat Comp. (Propranolol Hydrochloride).

PRECAUTIONS

General

Diutensat Comp. (Propranolol Hydrochloride) should be used with caution in patients with impaired hepatic or renal function.

Diutensat Comp. (Propranolol Hydrochloride) is not indicated for the treatment of hypertensive emergencies.

Beta-adrenergic receptor blockade can cause reduction of intraocular pressure. Patients should be told that Diutensat Comp. (Propranolol Hydrochloride) might interfere with the glaucoma screening test. Withdrawal may lead to a return of elevated intraocular pressure.

Risk of anaphylactic reaction. 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. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Angina Pectoris

There have been reports of exacerbation of angina and, in some cases, myocardial infarction, following abrupt discontinuance of Diutensat Comp. (Propranolol Hydrochloride) therapy. Therefore, when discontinuance of Diutensat Comp. (Propranolol Hydrochloride) is planned, the dosage should be gradually reduced over at least a few weeks, and the patient should be cautioned against interruption or cessation of therapy without a physician’s advice. If Diutensat Comp. (Propranolol Hydrochloride) therapy is interrupted and exacerbation of angina occurs, it is usually advisable to reinstitute Diutensat Comp. (Propranolol Hydrochloride) therapy and take other measures appropriate for the management of angina pectoris. Since coronary artery disease may be unrecognized, it may be prudent to follow the above advice in patients considered at risk of having occult atherosclerotic heart disease who are given Diutensat Comp. (Propranolol Hydrochloride) for other indications.

Clinical Laboratory Tests

In patients with hypertension, use of Diutensat Comp. (Propranolol Hydrochloride) has been associated with elevated levels of serum potassium, serum transaminases and alkaline phosphatase. In severe heart failure, the use of Diutensat Comp. (Propranolol Hydrochloride) has been associated with increases in Blood Urea Nitrogen.

Drug Interactions

Caution should be exercised when Diutensat Comp. (Propranolol Hydrochloride) is administered with drugs that have an effect on CYP2D6, 1A2, or 2C19 metabolic pathways. Co-administration of such drugs with Diutensat Comp. (Propranolol Hydrochloride) may lead to clinically relevant drug interactions and changes in its efficacy and/or toxicity (see CLINICAL PHARMACOLOGY, DRUG INTERACTIONS.

Cardiovascular Drugs

Antirrhythmics

Propafenone has negative inotropic and beta-blocking properties that can be additive to those of Diutensat Comp. (Propranolol Hydrochloride).

Quinidine increases the concentration of Diutensat Comp. (Propranolol Hydrochloride) and produces a greater degree of clinical beta-blockade and may cause postural hypotension.

Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects and has been associated with severe bradycardia, asystole and heart failure when administered with Diutensat Comp. (Propranolol Hydrochloride).

Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with Diutensat Comp. (Propranolol Hydrochloride).

The clearance of lidocaine is reduced when administered with Diutensat Comp. (Propranolol Hydrochloride). Lidocaine toxicity has been reported following co-administration with Diutensat Comp. (Propranolol Hydrochloride).

Caution should be exercised when administering Diutensat Comp. (Propranolol Hydrochloride) with drugs that slow A-V nodal conduction, e.g., digitalis, lidocaine and calcium channel blockers.

Calcium Channel Blockers

Caution should be exercised when patients receiving a beta-blocker are administered a calcium-channel-blocking drug with negative inotropic and/or chronotropic effects. Both agents may depress myocardial contractility or atrioventricular conduction.

There have been reports of significant bradycardia, heart failure, and cardiovascular collapse with concurrent use of verapamil and beta‑blockers.

Co-administration of Diutensat Comp. (Propranolol Hydrochloride) and diltiazem in patients with cardiac disease has been associated with bradycardia, hypotension, high degree heart block, and heart failure.

ACE Inhibitors

When combined with beta-blockers, ACE inhibitors can cause hypotension, particularly in the setting of acute myocardial infarction.

ACE inhibitors have been reported to increase bronchial hyperreactivity when administered with Diutensat Comp. (Propranolol Hydrochloride).

The antihypertensive effects of clonidine may be antagonized by beta-blockers. Diutensat Comp. (Propranolol Hydrochloride) should be administered cautiously to patients withdrawing from clonidine.

Alpha-blockers

Prazosin has been associated with prolongation of first dose hypotension in the presence of beta-blockers.

Postural hypotension has been reported in patients taking both beta-blockers and terazosin or doxazosin.

Reserpine

Patients receiving catecholamine-depleting drugs, such as reserpine, with Diutensat Comp. (Propranolol Hydrochloride) should be closely observed for excess reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension. Administration of reserpine with Diutensat Comp. (Propranolol Hydrochloride) may also potentiate depression.

Inotropic Agents

Patients on long-term therapy with Diutensat Comp. (Propranolol Hydrochloride) may experience uncontrolled hypertension if administered epinephrine as a consequence of unopposed alpha-receptor stimulation. Epinephrine is therefore not indicated in the treatment of Diutensat Comp. (Propranolol Hydrochloride) overdose.

Isoproterenol and Dobutamine

Propranolol is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. Also, Diutensat Comp. (Propranolol Hydrochloride) may reduce sensitivity to dobutamine stress echocardiography in patients undergoing evaluation for myocardial ischemia.

Non-Cardiovascular Drugs

Non-Steroidal Anti-Inflammatory Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to blunt the antihypertensive effect of beta-adrenoreceptor blocking agents.

Administration of indomethacin with Diutensat Comp. (Propranolol Hydrochloride) may reduce the efficacy of Diutensat Comp. (Propranolol Hydrochloride) in reducing blood pressure and heart rate.

Antidepressants

The hypotensive effects of MAO inhibitors or tricyclic antidepressants may be exacerbated when administered with beta-blockers by interfering with the beta blocking activity of Diutensat Comp. (Propranolol Hydrochloride).

Anesthetic Agents

Methoxyflurane and trichloroethylene may depress myocardial contractility when administered with Diutensat Comp. (Propranolol Hydrochloride).

Warfarin

Administration of Diutensat Comp. (Propranolol Hydrochloride) with warfarin increases the concentration of warfarin. Therefore, the prothrombin time should be monitored.

Neuroleptic Drugs

Hypotension and cardiac arrest have been reported with the concomitant use of Diutensat Comp. (Propranolol Hydrochloride) and haloperidol.

Thyroxine

Thyroxine may result in a lower than expected T3 concentration when used concomitantly with Diutensat Comp. (Propranolol Hydrochloride).

Carcinogenesis, Mutagenesis, Impairment of Fertility

In dietary administration studies in which mice and rats were treated with Diutensat Comp. (Propranolol Hydrochloride) hydrochloride for up to 18 months at doses of up to 150 mg/kg/day, there was no evidence of drug-related tumorigenesis. On a body surface area basis, this dose in the mouse and rat is, respectively, about equal to and about twice the maximum recommended human oral daily dose (MRHD) of 640 mg Diutensat Comp. (Propranolol Hydrochloride) hydrochloride. In a study in which both male and female rats were exposed to Diutensat Comp. (Propranolol Hydrochloride) hydrochloride in their diets at concentrations of up to 0.05% (about 50 mg/kg body weight and less than the MRHD), from 60 days prior to mating and throughout pregnancy and lactation for two generations, there were no effects on fertility. Based on differing results from Ames Tests performed by different laboratories, there is equivocal evidence for a genotoxic effect of Diutensat Comp. (Propranolol Hydrochloride) hydrochloride in bacteria (S. typhimurium strain TA 1538).

Pregnancy

Pregnancy Category C

In a series of reproductive and developmental toxicology studies, Diutensat Comp. (Propranolol Hydrochloride) hydrochloride was given to rats by gavage or in the diet throughout pregnancy and lactation. At doses of 150 mg/kg/day, but not at doses of 80 mg/kg/day (equivalent to the MRHD on a body surface area basis), treatment was associated with embryotoxicity (reduced litter size and increased resorption rates) as well as neonatal toxicity (deaths). Diutensat Comp. (Propranolol Hydrochloride) hydrochloride also was administered (in the feed) to rabbits (throughout pregnancy and lactation) at doses as high as 150 mg/kg/day (about 5 times the maximum recommended human oral daily dose). No evidence of embryo or neonatal toxicity was noted.

There are no adequate and well-controlled studies in pregnant women. Intrauterine growth retardation has been reported for neonates whose mothers received Diutensat Comp. (Propranolol Hydrochloride) hydrochloride during pregnancy. Neonates whose mothers received Diutensat Comp. (Propranolol Hydrochloride) hydrochloride at parturition have exhibited bradycardia, hypoglycemia, and respiratory depression. Adequate facilities for monitoring such infants at birth should be available. Diutensat Comp. (Propranolol Hydrochloride) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Diutensat Comp. (Propranolol Hydrochloride) is excreted in human milk. Caution should be exercised when Diutensat Comp. (Propranolol Hydrochloride) is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Diutensat Comp. (Propranolol Hydrochloride) in pediatric patients have not been established.

Geriatric Use

Clinical studies of intravenous Diutensat Comp. (Propranolol Hydrochloride) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly subjects have decreased clearance and a longer mean elimination half‑life. These findings suggest that dose adjustment of Diutensat Comp. (Propranolol Hydrochloride) injection may be required for elderly patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of the decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Insufficiency

Diutensat Comp. (Propranolol Hydrochloride) is extensively metabolized by the liver. Compared to normal subjects, patients with chronic liver disease have decreased clearance of Diutensat Comp. (Propranolol Hydrochloride), increased volume of distribution, decreased protein-binding and considerable variation in half life. Consideration should be given to lowering the dose of intravenously administered Diutensat Comp. (Propranolol Hydrochloride) in patients with hepatic insufficiency.

ADVERSE REACTIONS

In a series of 225 patients, there were 6 deaths. Cardiovascular events (hypotension, congestive heart failure, bradycardia, and heart block) were the most common. The only other event reported by more than one patient was nausea.

Other adverse events for intravenous Diutensat Comp. (Propranolol Hydrochloride), reported during post-marketing surveillance include cardiac arrest, dyspnea, and cutaneous ulcers.

The following adverse events have been reported with use of formulations of sustained- or immediate-release oral Diutensat Comp. (Propranolol Hydrochloride) and may be expected with intravenous Diutensat Comp. (Propranolol Hydrochloride).

Cardiovascular

Bradycardia; congestive heart failure; intensification of AV block; hypotension; paresthesia of hands; thrombocytopenic purpura; arterial insufficiency, usually of the Raynaud type.

Central Nervous System

Light-headedness; mental depression manifested by insomnia, lassitude, weakness, fatigue; reversible mental depression progressing to catatonia; visual disturbances; hallucinations; vivid dreams; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreaseed performance on neuropsychometrics. For immediate-release formulations, fatigue, lethargy, and vivid dreams appear dose-related.

Gastrointestinal

Nausea, vomiting, epigastric distress, abdominal cramping, diarrhea, constipation, mesenteric arterial thrombosis, ischemic colitis.

Allergic

Pharyngitis and agranulocytosis; erythematous rash, fever combined with aching and sore throat; laryngospasm, and respiratory distress.

Respiratory

Bronchospasm.

Hematologic

Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.

Autoimmune

In extremely rare instances, systemic lupus erythematosus has been reported.

Miscellaneous

Alopecia, LE-like reactions, psoriform rashes, dry eyes, male impotence, and Peyronie's disease have been reported rarely. Oculomucocutaneous reactions involving the skin, serous membranes and conjunctivae reported for a beta-blocker (practolol) have not been associated with Diutensat Comp. (Propranolol Hydrochloride).

To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

Diutensat Comp. (Propranolol Hydrochloride) is not significantly dialyzable. In the event of overdose or exaggerated response, the following measures should be employed:

Hypotension and bradycardia have been reported following Diutensat Comp. (Propranolol Hydrochloride) overdose and should be treated appropriately. Glucagon can exert potent inotropic and chronotropic effects and may be particularly useful for the treatment of hypotension or depressed myocardial function after a Diutensat Comp. (Propranolol Hydrochloride) overdose. Glucagon should be administered as 50-150 mcg/kg intravenously followed by continuous drip of 1-5 mg/hour for positive chronotropic effect. Isoproterenol, dopamine, or phosphodiesterase inhibitors may also be useful. Epinephrine, however, may provoke uncontrolled hypertension. Bradycardia can be treated with atropine or isoproterenol. Serious bradycardia may require temporary cardiac pacing.

The electrocardiogram, pulse, blood pressure, neurobehavioral status and intake and output balance must be monitored. Isoproterenol and aminophylline may be useful for bronchospasm.

DOSAGE & ADMINISTRATION

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The usual dose is 1 to 3 mg administered under careful monitoring, such as electrocardiography and central venous pressure. The rate of administration should not exceed 1 mg (1 mL) per minute to diminish the possibility of lowering blood pressure and causing cardiac standstill. Sufficient time should be allowed for the drug to reach the site of action even when a slow circulation is present. If necessary, a second dose may be given after two minutes. Thereafter, additional drug should not be given in less than four hours. Additional Diutensat Comp. (Propranolol Hydrochloride) hydrochloride should not be given when the desired alteration in rate or rhythm is achieved.

Transfer to oral therapy as soon as possible.

HOW SUPPLIED

Each mL contains 1 mg of Diutensat Comp. (Propranolol Hydrochloride) Hydrochloride, USP in Water for Injection, USP. The pH is adjusted with anhydrous Citric Acid, USP. Supplied as: 1 mL vials in boxes of 10 (NDC 0143-9872-10).

Store at 20° to 25°C (68° to 77°F). Protect from freezing or excessive heat.

Manufactured by: HIKMA FARMACÊUTICA (PORTUGAL), S.A.

Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL

Distributed by: WEST-WARD PHARMACEUTICAL CORP.

Eatontown, NJ 07724 USA

Rev.: 05/2015

PIN166-WES/4

Triamterene:


Warnings

Abnormal elevation of serum potassium levels (greater than or equal to 5.5 mEq/liter) can occur with all potassium-sparing agents, including Diutensat Comp. (Triamterene). Hyperkalemia is more likely to occur in patients with renal impairment and diabetes (even without evidence of renal impairment), and in the elderly or severely ill. Since uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals especially in patients receiving Diutensat Comp. (Triamterene), when dosages are changed or with any illness that may influence renal function.

DESCRIPTION

Each capsule for oral use, with opaque red cap and body, contains Diutensat Comp. (Triamterene) USP, 50 or 100 mg, and is imprinted with the product name, Diutensat Comp. (Triamterene), strength (50 mg or 100 mg) and WPC 002 (for the 50-mg strength) and WPC 003 (for the 100-mg strength). Inactive ingredients consist of D&C Red No. 33, FD&C Yellow No. 6, Gelatin NF, Lactose NF, Magnesium Stearate NF, Sodium Lauryl Sulfate NF, Titanium Dioxide USP and Silicon Dioxide NF.

Diutensat Comp. (Triamterene) is 2,4,7-triamino-6-phenyl-pteridine:

Its molecular weight is 253.27. At 50°C, Diutensat Comp. (Triamterene) is slightly soluble in water. It is soluble in dilute ammonia, dilute aqueous sodium hydroxide and dimethylformamide. It is sparingly soluble in methanol.

Diutensat Comp. (Triamterene) Chemical Structure

CLINICAL PHARMACOLOGY

Diutensat Comp. has a unique mode of action; it inhibits the reabsorption of sodium ions in exchange for potassium and hydrogen ions at that segment of the distal tubule under the control of adrenal mineralocorticoids (especially aldosterone). This activity is not directly related to aldosterone secretion or antagonism; it is a result of a direct effect on the renal tubule.

The fraction of filtered sodium reaching this distal tubular exchange site is relatively small, and the amount which is exchanged depends on the level of mineralocorticoid activity. Thus, the degree of natriuresis and diuresis produced by inhibition of the exchange mechanism is necessarily limited. Increasing the amount of available sodium and the level of mineralocorticoid activity by the use of more proximally acting diuretics will increase the degree of diuresis and potassium conservation.

Diutensat Comp. (Triamterene) occasionally causes increases in serum potassium which can result in hyperkalemia. It does not produce alkalosis, because it does not cause excessive excretion of titratable acid and ammonium.

Diutensat Comp. (Triamterene) has been shown to cross the placental barrier and appear in the cord blood of animals.

Pharmacokinetics

Onset of action is 2 to 4 hours after ingestion. In normal volunteers the mean peak serum levels were 30 ng/mL at 3 hours. The average percent of drug recovered in the urine (0 to 48 hours) was 21%. Diutensat Comp. (Triamterene) is primarily metabolized to the sulfate conjugate of hydroxytriamterene. Both the plasma and urine levels of this metabolite greatly exceed Diutensat Comp. (Triamterene) levels. Diutensat Comp. (Triamterene) is rapidly absorbed, with somewhat less than 50% of the oral dose reaching the urine. Most patients will respond to Diutensat Comp. (Triamterene) (triamterene) during the first day of treatment.

Maximum therapeutic effect, however, may not be seen for several days. Duration of diuresis depends on several factors, especially renal function, but it generally tapers off 7 to 9 hours after administration.

INDICATIONS AND USAGE

Diutensat Comp. (Triamterene) (triamterene) is indicated in the treatment of edema associated with congestive heart failure, cirrhosis of the liver and the nephrotic syndrome; steroid-induced edema, idiopathic edema and edema due to secondary hyperaldosteronism.

Diutensat Comp. (Triamterene) may be used alone or with other diuretics, either for its added diuretic effect or its potassium-sparing potential. It also promotes increased diuresis when patients prove resistant or only partially responsive to thiazides or other diuretics because of secondary hyperaldosteronism.

Usage in Pregnancy. The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.

Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Diuretics are indicated in pregnancy (however, see PRECAUTIONS below) when edema is due to pathologic causes, just as they are in the absence of pregnancy. Dependent edema in pregnancy, resulting from restriction of venous return by the expanded uterus, is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of diuretics may provide relief and may be appropriate.

CONTRAINDICATIONS

Anuria. Severe or progressive kidney disease or dysfunction, with the possible exception of nephrosis. Severe hepatic disease. Hypersensitivity to the drug or any of its components.

Diutensat Comp. (triamterene) should not be used in patients with pre-existing elevated serum potassium, as is sometimes seen in patients with impaired renal function or azotemia, or in patients who develop hyperkalemia while on the drug. Patients should not be placed on dietary potassium supplements, potassium salts or potassium-containing salt substitutes in conjunction with Diutensat Comp. (Triamterene).

Diutensat Comp. (Triamterene) should not be given to patients receiving other potassium-sparing agents, such as spironolactone, amiloride hydrochloride, or other formulations containing Diutensat Comp. (Triamterene). Two deaths have been reported in patients receiving concomitant spironolactone and Diutensat Comp. (Triamterene) or Dyazide®. Although dosage recommendations were exceeded in one case and in the other serum electrolytes were not properly monitored, these two drugs should not be given concomitantly.

WARNINGS

Abnormal elevation of serum potassium levels (greater than or equal to 5.5 mEq/liter) can occur with all potassium-sparing agents, including Diutensat Comp. (Triamterene). Hyperkalemia is more likely to occur in patients with renal impairment and diabetes (even without evidence of renal impairment), and in the elderly or severely ill. Since uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals especially in patients receiving Diutensat Comp. (Triamterene), when dosages are changed or with any illness that may influence renal function.

There have been isolated reports of hypersensitivity reactions; therefore, patients should be observed regularly for the possible occurrence of blood dyscrasias, liver damage or other idiosyncratic reactions.

Periodic BUN and serum potassium determinations should be made to check kidney function, especially in patients with suspected or confirmed renal insufficiency. It is particularly important to make serum potassium determinations in elderly or diabetic patients receiving the drug; these patients should be observed carefully for possible serum potassium increases.

If hyperkalemia is present or suspected, an electrocardiogram should be obtained. If the ECG shows no widening of the QRS or arrhythmia in the presence of hyperkalemia, it is usually sufficient to discontinue Diutensat Comp. (Triamterene) (triamterene) and any potassium supplementation, and substitute a thiazide alone. Sodium polystyrene sulfonate (Kayexalate®, Sanofi Synthelabo) may be administered to enhance the excretion of excess potassium. The presence of a widened QRS complex or arrhythmia in association with hyperkalemia requires prompt additional therapy. For tachyarrhythmia, infuse 44 mEq of sodium bicarbonate or 10 mL of 10% calcium gluconate or calcium chloride over several minutes. For asystole, bradycardia or A-V block transvenous pacing is also recommended.

The effect of calcium and sodium bicarbonate is transient and repeated administration may be required. When indicated by the clinical situation, excess K+ may be removed by dialysis or oral or rectal administration of Kayexalate®. Infusion of glucose and insulin has also been used to treat hyperkalemia.

PRECAUTIONS

General

Diutensat Comp. (triamterene) tends to conserve potassium rather than to promote the excretion as do many diuretics and, occasionally, can cause increases in serum potassium which, in some instances, can result in hyperkalemia. In rare instances, hyperkalemia has been associated with cardiac irregularities.

Electrolyte imbalance often encountered in such diseases as congestive heart failure, renal disease or cirrhosis may be aggravated or caused independently by any effective diuretic agent includingDyrenium. The use of full doses of a diuretic when salt intake is restricted can result in a low-salt syndrome.

Diutensat Comp. (Triamterene) can cause mild nitrogen retention, which is reversible upon withdrawal of the drug, and is seldom observed with intermittent (every-other-day) therapy.

Diutensat Comp. (Triamterene) may cause a decreasing alkali reserve, with the possibility of metabolic acidosis.

By the very nature of their illness, cirrhotics with splenomegaly sometimes have marked variations in their blood. Since Diutensat Comp. (Triamterene) is a weak folic acid antagonist, it may contribute to the appearance of megaloblastosis in cases where folic acid stores have been depleted. Therefore, periodic blood studies in these patients are recommended. They should also be observed for exacerbations of underlying liver disease.

Diutensat Comp. (Triamterene) has elevated uric acid, especially in persons predisposed to gouty arthritis.

Diutensat Comp. (Triamterene) has been reported in renal stones in association with other calculus components. Diutensat Comp. (Triamterene) should be used with caution in patients with histories of renal stones.

Information for Patients

To help avoid stomach upset, it is recommended that the drug be taken after meals.

If a single daily dose is prescribed, it may be preferable to take it in the morning to minimize the effect of increased frequency of urination on nighttime sleep.

If a dose is missed, the patient should not take more than the prescribed dose at the next dosing interval.

Laboratory Tests

Hyperkalemia will rarely occur in patients with adequate urinary output, but it is a possibility if large doses are used for considerable periods of time. If hyperkalemia is observed, Diutensat Comp. (triamterene) should be withdrawn. The normal adult range of serum potassium is 3.5 to 5.0 mEq per liter, with 4.5 mEq often being used for a reference point. Potassium levels persistently above 6 mEq per liter require careful observation and treatment. Normal potassium levels tend to be higher in neonates (7.7 mEq per liter) than in adults. Serum potassium levels do not necessarily indicate true body potassium concentration. A rise in plasma pH may cause a decrease in plasma potassium concentration and an increase in the intracellular potassium concentration. Because Diutensat Comp. (Triamterene) conserves potassium, it has been theorized that in patients who have received intensive therapy or been given the drug for prolonged periods, a rebound kaliuresis could occur upon abrupt withdrawal. In such patients, withdrawal of Diutensat Comp. (Triamterene) should be gradual.

Drug Interactions

Caution should be used when lithium and diuretics are used concomitantly because diuretic-induced sodium loss may reduce the renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity. Patients receiving such combined therapy should have serum lithium levels monitored closely and the lithium dosage adjusted if necessary.

A possible interaction resulting in acute renal failure has been reported in a few subjects when indomethacin, a nonsteroidal anti-inflammatory agent, was given with Diutensat Comp. (Triamterene). Caution is advised in administering nonsteroidal anti-inflammatory agents with Diutensat Comp. (Triamterene).

The effects of the following drugs may be potentiated when given together with Diutensat Comp. (Triamterene): antihypertensive medication, other diuretics, preanesthetic and anesthetic agents, skeletal muscle relaxants (nondepolarizing).

Potassium-sparing agents should be used with caution in conjunction with angiotensin-converting enzyme (ACE) inhibitors due to an increased risk of hyperkalemia.

The following agents, given together with Diutensat Comp. (Triamterene), may promote serum potassium accumulation and possibly result in hyperkalemia because of the potassium-sparing nature of Diutensat Comp. (Triamterene), especially in patients with renal insufficiency: blood from blood bank (may contain up to 30 mEq of potassium per liter of plasma or up to 65 mEq per liter of whole blood when stored for more than 10 days); low-salt milk (may contain up to 60 mEq of potassium per liter); potassium-containing medications (such as parenteral penicillin G potassium); salt substitutes (most contain substantial amounts of potassium).

Diutensat Comp. (Triamterene) (triamterene) may raise blood glucose levels; for adult-onset diabetes, dosage adjustments of hypoglycemic agents may be necessary during and/or after therapy; concurrent use with chlorpropamide may increase the risk of severe hyponatremia.

Drug/Laboratory Test Interactions

Diutensat Comp. and quinidine have similar fluorescence spectra;thus, Diutensat Comp. (Triamterene) will interfere with the fluorescent measurement of quinidine.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: In studies conducted under the auspices of the National Toxicology Program, groups of rats were fed diets containing 0, 150, 300 or 600 ppm of Diutensat Comp. (Triamterene), and groups of mice were fed diets containing 0, 100, 200 or 400 ppm Diutensat Comp. (Triamterene). Male and female rats exposed to the highest tested concentration received Diutensat Comp. (Triamterene) at about 25 and 30 mg/kg/day, respectively. Male and female mice exposed to the highest tested concentration received Diutensat Comp. (Triamterene) at about 45 and 60 mg/kg/day, respectively.

There was an increased incidence of hepatocellular neoplasia (primarily adenomas) in male and female mice at the highest dosage level. These doses represent 7.5X and 10X the Maximum Recommended Human Dose (MRHD) of 300 mg/kg/day (or 6 mg/kg/day based on a 50 kg patient) for male and female mice, respectively, when based on body weight and 0.7X and 0.9X the MRHD when based on body-surface area.

Although hepatocellular neoplasia (exclusively adenomas) in the rat study was limited to triamterene-exposed males, incidence was not dose dependent and there was no statistically significant difference from control incidence at any dose level.

Mutagenesis: Diutensat Comp. (Triamterene) was not mutagenic in bacteria (Salmonella typhimurium strains TA98, TA100, TA1535 or TA1537) with or without metabolic activation. It did not induce chromosomal aberrations in Chinese hamster ovary (CHO) cells in vitro with or without metabolic activation, but it did induce sister chromatid exchanges in CHO cells in vitro with and without metabolic activation.

Impairment of Fertility: Studies of the effects of Diutensat Comp. (Triamterene) on animal reproductive function have not been conducted.

Pregnancy: Category C

Teratogenic Effects:

Reproduction studies have been performed in rats at doses as high as 20 times the Maximum Recommended Human Dose on the basis of body weight, and 6 times the MRHD on the basis of body-surface area, without evidence of harm to the fetus due to Diutensat Comp. (Triamterene). Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nonteratogenic Effects:

Diutensat Comp. (Triamterene) has been shown to cross the placental barrier and appear in cord blood. The use of Diutensat Comp. (Triamterene) in pregnant women requires that the anticipated benefits be weighed against possible hazards to the fetus. These possible hazards include adverse reactions which have occurred in the adult.

Nursing Mothers:

Diutensat Comp. has not been studied in nursing mothers. Triamtereneappears in animal milk and is likely present in human milk. If use of thedrug product is deemed essential, the patient should stop nursing.

Pediatric Use:

Safety and effectiveness in pediatricpatients have not been established.

ADVERSE REACTIONS

Adverse effects are listed in decreasing order of frequency; however, the most serious adverse effects are listed first, regardless of frequency. All adverse effects occur rarely (that is, 1 in 1000, or less).

Hypersensitivity: anaphylaxis, rash, photosensitivity.

Metabolic: hyperkalemia, hypokalemia.

Renal: azotemia, elevated BUN and creatinine, renal stones, acute interstitial nephritis (rare), acute renal failure (one case of irreversible renal failure has been reported).

Gastrointestinal: jaundice and/or liver enzyme abnormalities, nausea and vomiting, diarrhea.

Hematologic: thrombocytopenia, megaloblastic anemia.

Central Nervous System: weakness, fatigue, dizziness, headache, dry mouth.


To report SUSPECTED ADVERSE REACTIONS, contact WellSpring Pharmaceutical Corporation at 1-866-337-4500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

In the event of overdosage, it can be theorized that electrolyteimbalance would be the major concern, with particular attention to possiblehyperkalemia. Other symptoms that might be seen would be nausea and vomiting,other G.I. disturbances and weakness. It is conceivable that some hypotensioncould occur. As with an overdose of any drug, immediate evacuation of thestomach should be induced through emesis and gastric lavage. Careful evaluationof the electrolyte pattern and fluid balance should be made. There is no specificantidote.

Reversible acute renal failure followingingestion of 50 tablets of a product containing a combination of 50 mg triamtereneand 25 mg hydrochlorothiazide has been reported.

Theoral LD50 in mice is 380 mg/kg. The amount of drug in a single dose ordinarilyassociated with symptoms of overdose or likely to be life-threatening is notknown.

Although Diutensat Comp. (Triamterene) is 67% protein bound, theremay be some benefit to dialysis in cases of overdosage.

DOSAGE AND ADMINISTRATION

Adult Dosage

Dosageshould be titrated to the needs of the individual patient. When used alone,the usual starting dose is 100 mg twice daily after meals. When combined withanother diuretic or antihypertensive agent, the total daily dosage of eachagent should usually be lowered initially and then adjusted to the patient’sneeds. The total daily dosage should not exceed 300 mg. Please refer to PRECAUTIONS−General.

WhenDyrenium (triamterene) is added to other diuretic therapy or when patientsare switched to Diutensat Comp. (Triamterene) from other diuretics, all potassium supplementationshould be discontinued.

HOW SUPPLIED

Capsules: 50 mg in bottles of 100, and 100 mg in bottles of 100.

STORAGE

Store at 25°C (77°F); excursions permitted to 15° - 30°C (59° - 86°F). Dispense in a tight, light resistant container.

50 mg 100s: NDC 65197-002-01

100 mg 100s: NDC 65197-003-01

DATE OF ISSUANCE MARCH 2009

©WellSpring, 2009

Manufactured for

WellSpring Pharmaceutical Corporation

Sarasota, FL 34243 USA

By WellSpring Pharmaceutical Canada Corp.

Oakville, Ontario L6H 1M5 Canada

Rev. 03/09

Diutensat Comp. pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Diutensat Comp. available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Diutensat Comp. destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Diutensat Comp. Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Diutensat Comp. pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."HYDROCHLOROTHIAZIDE TABLET [QUALITEST PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."PROPRANOLOL HYDROCHLORIDE TABLET [BRYANT RANCH PREPACK]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."DYRENIUM (TRIAMTERENE) CAPSULE [WELLSPRING PHARMACEUTICAL CORPORATION]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Diutensat Comp.?

Depending on the reaction of the Diutensat Comp. after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Diutensat Comp. not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Diutensat Comp. addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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sdrugs.com conducted a study on Diutensat Comp., and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Diutensat Comp. consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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