DRUGS & SUPPLEMENTS
INDICATIONS AND USAGE
Mylan-Amilazide tablets are indicated in those patients with hypertension or with congestive heart failure who develop hypokalemia when thiazides or other kaliuretic diuretics are used alone, or in whom maintenance of normal serum potassium levels is considered to be clinically important, e.g., digitalized patients, or patients with significant cardiac arrhythmias.
The use of potassium-conserving agents is often unnecessary in patients receiving diuretics for uncomplicated essential hypertension when such patients have a normal diet.
Mylan-Amilazide tablets may be used alone or as an adjunct to other antihypertensive drugs, such as methyldopa or beta blockers. Since Mylan-Amilazide enhances the action of these agents, dosage adjustments may be necessary to avoid an excessive fall in blood pressure and other unwanted side effects.
The fixed combination drug is not indicated for the initial therapy of edema or hypertension except in individuals in whom the development of hypokalemia cannot be risked.
Mylan-Amilazide tablets should not be used in the presence of elevated serum potassium levels.
Antikaliuretic Therapy or Potassium Supplementation
Mylan-Amilazide should not be given to patients receiving other potassium-conserving agents, such as spironolactone or triamterene. Potassium supplementation in the form of medication, potassium-containing salt substitutes or a potassium-rich diet should not be used with this product except in severe and/or refractory cases of hypokalemia. Such concomitant therapy can be associated with rapid increases in serum potassium levels. If potassium supplementation is used, careful monitoring of the serum potassium level is necessary.
Impaired Renal Function
Anuria, acute or chronic renal insufficiency, and evidence of diabetic nephropathy are contraindications to the use of Mylan-Amilazide. Patients with evidence of renal function impairment or diabetes mellitus should not receive the drug without careful, frequent and continuing monitoring of serum electrolytes, creatinine, and BUN levels. Potassium retention associated with the use of an antikaliuretic agent is accentuated in the presence of renal impairment and may result in the rapid development of hyperkalemia.
Mylan-Amilazide tablets is contraindicated in patients who are hypersensitive to this product, or to other sulfonamide-derived drugs.
Like other potassium-conserving diuretic combinations, amiloride and hydrochlorothiazide may cause hyperkalemia. In patients without renal impairment or diabetes mellitus, the risk of hyperkalemia with this combination product is about 1 to 2 percent. This risk is higher in patients with renal impairment or diabetes mellitus (even without recognized diabetic nephropathy). Since hyperkalemia, if uncorrected, is potentially fatal, it is essential to monitor serum potassium levels carefully in any patient receiving Mylan-Amilazide, particularly when it is first introduced, at the time of dosage adjustments, and during any illness that could affect renal function.
The risk of hyperkalemia may be increased when potassium-conserving agents, including Mylan-Amilazide, are administered concomitantly with an angiotensin-converting enzyme inhibitor, cylosporine or tacrolimus. Warning signs or symptoms of hyperkalemia include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, shock, and ECG abnormalities. Monitoring of the serum potassium level is essential because mild hyperkalemia is not usually associated with an abnormal ECG.
When abnormal, the ECG in hyperkalemia is characterized primarily by tall, peaked T waves or elevations from previous tracings. There may also be lowering of the R wave and increased depth of the S wave, widening and even disappearance of the P wave, progressive widening of the QRS complex, prolongation of the PR interval, and ST depression.
Treatment of Hyperkalemia
If hyperkalemia occurs in patients taking amiloride and hydrochlorothiazide, the drug should be discontinued immediately. If the serum potassium level exceeds 6.5 mEq per liter, active measures should be taken to reduce it. Such measures include the intravenous administration of sodium bicarbonate solution or oral or parenteral glucose with a rapid-acting insulin preparation. If needed, a cation exchange resin such as sodium polystyrene sulfonate may be given orally or by enema. Patients with persistent hyperkalemia may require dialysis.
In diabetic patients, hyperkalemia has been reported with the use of all potassium-conserving diuretics, including amiloride HCl, even in patients without evidence of diabetic nephropathy. Therefore, amiloride and hydrochlorothiazide should be avoided, if possible, in diabetic patients and, if it is used, serum electrolytes and renal function must be monitored frequently.
Amiloride and hydrochlorothiazide should be discontinued at least three days before glucose tolerance testing.
Metabolic or Respiratory Acidosis
Antikaliuretic therapy should be instituted only with caution in severely ill patients in whom respiratory or metabolic acidosis may occur, such as patients with cardiopulmonary disease or poorly controlled diabetes. If amiloride and hydrochlorothiazide is given to these patients, frequent monitoring of acid-base balance is necessary. Shifts in acid-base balance alter the ratio of extracellular/intracellular potassium, and the development of acidosis may be associated with rapid increases in serum potassium levels.
Electrolyte Imbalance and BUN Increases
Determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.
Patients should be observed for clinical signs of fluid or electrolytes imbalance: i.e., hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
Hyponatremia and hypochloremia may occur during the use of thiazides and other diuretics. Any chloride deficit during thiazide therapy is generally mild and may be lessened by the amiloride HCl component of this product. Hypochloremia usually does not require specific treatment except under extraordinary circumstances. Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the therapy of choice.
Hypokalemia may develop during thiazide therapy, especially with brisk diuresis, when severe cirrhosis is present, during concomitant use of corticosteroids or ACTH, or after prolonged therapy. However, this usually is prevented by the Mylan-Amilazide component of this combination drug product.
Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. Mylan-Amilazide, a component of this combination product, has been shown to decrease the enhanced urinary excretion of magnesium which occurs when a thiazide or loop diuretic is used alone.
Increases in BUN levels have been reported with Mylan-Amilazide and with hydrochlorothiazide. These increases usually have accompanied vigorous fluid elimination, especially when diuretic therapy was used in seriously ill patients, such as those who had hepatic cirrhosis with ascites and metabolic alkalosis, or those with resistant edema. Therefore, when amiloride and hydrochlorothiazide is given to such patients, careful monitoring of serum electrolyte and BUN levels is important. In patients with pre-existing severe liver disease, hepatic encephalopathy, manifested by tremors, confusion, and coma, and increased jaundice, have been reported in association with diuretic therapy including amiloride HCl and hydrochlorothiazide.
In patients with renal disease, diuretics may precipitate azotemia. Cumulative effects of the components of Mylan-Amilazide may develop in patients with impaired renal function. If renal impairment becomes evident, amiloride and hydrochlorothiazide should be discontinued.
In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when amiloride and hydrochlorothiazide plus non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained. Since indomethacin and potassium-sparing diuretics, including this product, may each be associated with increased serum potassium levels, the potential effects on potassium kinetics and renal function should be considered when these agents are administered concurrently.
When amiloride HCl is administered concomitantly with an angiotensin-converting enzyme inhibitor, cyclosporine or tacrolimus, the risk of hyperkalemia may be increased. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium.
When given concurrently the following drugs may interact with thiazide diuretics.
Alcohol, Barbiturates, or Narcotics
Potentiation of orthostatic hypotension may occur.
Dosage adjustment of the antidiabetic drug may be required.
Other Antihypertensive Drugs
Additive effect or potentiation.
Cholestyramine and Colestipol Resins
Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of cholestyramine and colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.
Intensified electrolyte depletion, particularly hypokalemia.
Possible decreased response to pressor amines but not sufficient to preclude their use.
Skeletal Muscle Relaxants, Nondepolarizing
Possible increased responsiveness to the muscle relaxant.
Generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with this combination product.
Metabolic and Endocrine Effects
In diabetic patients, insulin requirements may be increased, decreased, or unchanged due to the hydrochlorothiazide component. Diabetes mellitus that has been latent may become manifest during administration of thiazide diuretics.
Because calcium excretion is decreased by thiazides, amiloride and hydrochlorothiazide should be discontinued before carrying out tests for parathyroid function. Pathologic changes in the parathyroid glands, with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy; however, the common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen.
Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazide therapy.
In patients receiving thiazides, sensitivity reactions may occur with or without a history of allergy or bronchial asthma. The possibility of exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
Carcinogenesis, Mutagenicity, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the effects upon fertility, mutagenicity or carcinogenic potential of Mylan-Amilazide.
There was no evidence of a tumorigenic effect when Mylan-Amilazide was administered for 92 weeks to mice at doses up to 10 mg/kg/day. Mylan-Amilazide has also been administered for 104 weeks to male and female rats at doses up to 6 and 8 mg/kg/day (15 and 20 times the maximum daily dose for humans, respectively) and showed no evidence of carcinogenicity.
Mylan-Amilazide was devoid of mutagenic activity in various strains of Salmonella typhimurium with or without a mammalian liver microsomal activation system (Ames test).
Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.
Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese Hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 mcg/mL, and in the Aspergillus nidulans non-disjunction assay at an unspecified concentration.
Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to conception and throughout gestation.
Pregnancy Category B
Teratogenicity studies have been performed with combinations of Mylan-Amilazide in rabbits and mice at doses up to 25 times the expected maximum daily dose for humans and have revealed no evidence of harm to the fetus. No evidence of impaired fertility in rats was apparent at dosage levels up to 25 times the expected maximum human daily dose. A perinatal and postnatal study in rats showed a reduction in maternal body weight gain during and after gestation at a daily dose of 25 times the expected maximum daily dose for humans. The body weights of alive pups at birth and at weaning were also reduced at this dose level. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, and because of the data listed below with the individual components, this drug should be used during pregnancy only if clearly needed.
Teratogenicity studies with Mylan-Amilazide in rabbits and mice given 20 and 25 times the maximum human dose, respectively, revealed no evidence of harm to the fetus, although studies showed that the drug crossed the placenta in modest amounts. Reproduction studies in rats at 20 times the expected maximum daily dose for humans showed no evidence of impaired fertility. At approximately 5 or more times the expected maximum daily dose for humans, some toxicity was seen in adult rats and rabbits and a decrease in rat pup growth and survival occurred.
Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg hydrochlorothiazide/kg, respectively, provided no evidence of harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women.
Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.
Studies in rats have shown that amiloride is excreted in milk in concentrations higher than those found in blood, but it is not known whether amiloride HCl is excreted in human milk. However, thiazides appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Mylan-Amilazide tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger 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 decreased hepatic, renal or cardiac function, and the comitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Mylan-Amilazide is usually well tolerated and significant clinical adverse effects have been reported infrequently. The risk of hyperkalemia with Mylan-Amilazide is about 1 to 2 percent in patients without renal impairment or diabetes mellitus. Minor adverse reactions to Mylan-Amilazide have been reported relatively frequently (about 20%) but the relationship of many of the reports to amiloride HCl is uncertain and the overall frequency was similar to hydrochlorothiazide treated groups. Nausea/anorexia, abdominal pain, flatulence, and mild skin rash have been reported and probably are related to amiloride. Other adverse experiences that have been reported with amiloride and hydrochlorothiazide are generally those known to be associated with diuresis, thiazide therapy, or with the underlying disease being treated. Clinical trials have not demonstrated that combining amiloride and hydrochlorothiazide increases the risk of adverse reactions over those seen with the individual components.
The adverse reactions for amiloride and hydrochlorothiazide listed in the following table have been arranged into two groups: (1) incidence greater than one percent; and (2) incidence one percent or less. The incidence for group (1) was determined from clinical studies conducted in the United States (607 patients treated with amiloride and hydrochlorothiazide). The adverse effects listed in group (2) include reports from the same clinical studies and voluntary reports since marketing. The probability of a causal relationship exists between amiloride and hydrochlorothiazide and these adverse reactions, some of which have been reported only rarely.
Other adverse reactions that have been reported with the individual components and within each category are listed in order of decreasing severity:
Body as a Whole: Painful extremities, neck/shoulder ache, fatigability.
Digestive: Activation of probable pre-existing peptic ulcer, abnormal liver function, jaundice, dyspepsia, heartburn.
Hematologic: Aplastic anemia, neutropenia.
Integumentary: Alopecia, itching, dry mouth.
Nervous System/Psychiatric: Encephalopathy, tremors, decreased libido.
Respiratory: Shortness of breath, cough.
Special Senses: Increased intraocular pressure, tinnitus.
Urogenital: Bladder spasms, polyuria, urinary frequency.
Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation.
Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia.
Hypersensitivity: Anaphylactic reactions, necrotizing angiitis (vasculitis, cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, purpura.
Metabolic: Electrolyte imbalance, hyperglycemia, glycosuria, hyperuricemia.
Nervous System/Psychiatric: Restlessness.
Special Senses: Transient blurred vision, xanthopsia.
Urogenital: Interstitial nephritis.
No data are available in regard to overdosage in humans. The oral LD50 of the combination drug is 189 and 422 mg/kg for female mice and female rats, respectively.
It is not known whether the drug is dialyzable.
No specific information is available on the treatment of overdosage with amiloride and hydrochlorothiazide and no specific antidote is available. Treatment is symptomatic and supportive. Therapy with amiloride and hydrochlorothiazide should be discontinued and the patient observed closely. Suggested measures include the induction of emesis and/or gastric lavage.
No data are available in regard to overdosage in humans.
The oral LD50 of Mylan-Amilazide is 56 mg/kg in mice and 36 to 85 mg/kg in rats, depending on the strain.
The most common signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance. If hyperkalemia occurs, active measures should be taken to reduce the serum potassium levels.
The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
DOSAGE AND ADMINISTRATION
Mylan-Amilazide tablets should be administered with food.
The usual starting dosage is 1 tablet a day. The dosage may be increased to 2 tablets a day, if necessary. More than 2 tablets of Mylan-Amilazide daily usually are not needed and there is no controlled experience with such doses.
Hydrochlorothiazide can be given at doses of 12.5 to 50 mg per day when used alone. Patients usually do not require doses of hydrochlorothiazide in excess of 50 mg daily when combined with other antihypertensive agents. The daily dose is usually given as a single dose but may be given in divided doses. Once an initial diuresis has been achieved, dosage adjustment may be necessary. Maintenance therapy may be on an intermittent basis.
Mylan-Amilazide Tablets USP are available as:
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Store at 20º to 25ºC (68º to 77ºF).
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
TEVA PHARMACEUTICALS USA, INC.
North Wales, PA 19454
Rev. A 3/2016
5 mg/50 mg
Mylan-Amilazide 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.
Mylan-Amilazide 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.
Mylan-Amilazide 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.
Mylan-Amilazide 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.
Mylan-Amilazide 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.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Mylan-Amilazide?
Depending on the reaction of the Mylan-Amilazide after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Mylan-Amilazide 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 Mylan-Amilazide 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.
ReviewsDrugs.com conducted a study on Mylan-Amilazide, 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 Mylan-Amilazide 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.
The information was verified by Dr. Arunabha Ray, MD Pharmacology