Amizide and hydrochlorothiazide may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
How to use Amizide-Hydrochlorothiazide
Take this medication by mouth with food, usually once or twice daily or as directed by your doctor.
If you take this drug too close to bedtime, you may need to wake up to urinate. Therefore, it is best to take this medication at least 4 hours before your bedtime. If you have any questions about how and when to take this medication, ask your doctor or pharmacist.
The dosage is based on your medical condition and response to treatment.
Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time(s) each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.
If you also take certain drugs to lower your cholesterol (bile acid-binding resins such as cholestyramine or colestipol), take this product at least 4 hours before or at least 4 to 6 hours after these medications.
Tell your doctor if your condition does not improve or if it worsens (such as your blood pressure readings remain high or increase).
Amizide HCl is usually well tolerated and, except for hyperkalemia (serum potassium levels greater than 5.5 mEq liter - see WARNINGS), significant adverse effects have been reported infrequently. Minor adverse reactions were reported relatively frequently (about 20%) but the relationship of many of the reports to Amizide HCl is uncertain and the overall frequency was similar in hydrochlorothiazide treated groups. Nausea/anorexia, abdominal pain, flatulence, and mild skin rash have been reported and probably are related to Amizide. Other adverse experiences that have been reported with Amizide are generally those known to be associated with diuresis, or with the underlying disease being treated.
The adverse reactions for Amizide HCl 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 (837 patients treated with Amizide HCl). 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 Amizide HCl and these adverse reactions, some of which have been reported only rarely.
Mechanism of Injury
The mechanism of Amizide hepatic injury is unknown, but is likely due to metabolic idiosyncrasy.
Before taking Amizide and hydrochlorothiazide,
- tell your doctor and pharmacist if you are allergic to Amizide, hydrochlorothiazide, sulfonamide containing medications, any other medications, or any of the ingredients in Amizide and hydrochlorothiazide tablets. Ask your pharmacist or check the patient information for a list of the ingredients.
- do not take Amizide and hydrochlorothiazide if you are taking spironolactone (Aldactone, in Aldactazide), other medications containing triamterene, or potassium supplements or potassium-containing medication supplements.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten), fosinopril, lisinopril (in Prinzide, in Zestoretic), moexipril (Univasc, in Uniretic), perindopril (Aceon), quinapril (Accupril, in Accuretic), ramipril (Altace), and trandolapril (Mavik, in Tarka); angiotensin II receptor antagonists (ARB) such as azilsartan (Edarbi, Edarbyclor), candesartan (Atacand, in Atacand HCT), eprosartan (Teveten, in Teveten HCT), irbesartan (Avapro, in Avalide), losartan (Cozaar, in Hyzaar), olmesartan (Benicar, in Azor, Benicar HCT), telmisartan (Micardis, in Micardis HCT), and valsartan (Diovan, in Diovan HCT, Exforge); barbiturates such as phenobarbital and secobarbital (Seconal); corticosteroids such as betamethasone (Celestone), budesonide (Entocort), cortisone (Cortone), dexamethasone (Decadron, others), fludrocortisone (Floriner), hydrocortisone (Cortef, Hydrocortone), methylprednisolone (Medrol), prednisolone (Prelone, others), prednisone (Rayos), and triamcinolone (Aristocort, Azmacort); corticotropin (ACTH H.P., Acthar Gel); cyclosporine (Gengraf, Neoral, Sandimmune); digoxin (Lanoxin); insulin and oral medications for diabetes; lithium (Lithobid); medications for high blood pressure; or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin, others), indomethacin (Indocin), and naproxen (Aleve, Naprosyn, others); or tacrolimus (Astagraf XL, Prograf). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- if you are taking cholestyramine or colestipol, take them 1 hour before or 4 hours after taking Amizide and hydrochlorothiazide.
- tell your doctor if you have kidney disease. Your doctor may tell you not to take Amizide and hydrochlorothiazide.
- tell your doctor if you have or have ever had diabetes, gout, or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking Amizide and hydrochlorothiazide, call your doctor immediately.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking Amizide and hydrochlorothiazide.
- you should know that Amizide and hydrochlorothiazide may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking Amizide and hydrochlorothiazide. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up. Alcohol can add to these side effects.
Like other potassium-conserving agents, Amizide may cause hyperkalemia (serum potassium levels greater than 5.5 mEq per liter) which, if uncorrected, is potentially fatal. Hyperkalemia occurs commonly (about 10%) when Amizide is used without a kaliuretic diuretic. This incidence is greater in patients with renal impairment, diabetes mellitus (with or without recognized renal insufficiency), and in the elderly. When Amizide is used concomitantly with a thiazide diuretic in patients without these complications, the risk of hyperkalemia is reduced to about 1-2%. It is thus essential to monitor serum potassium levels carefully in any patient receiving Amizide, particularly when it is first introduced, at the time of diuretic dosage adjustments, and during any illness that could affect renal function.
The risk of hyperkalemia may be increased when potassium-conserving agents, including Amilor >PRECAUTIONS , Drug Interactions. ) 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 Amizide HCl, 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 Amizide HCl, even in patients without evidence of diabetic nephropathy. Therefore, Amizide HCl should be avoided, if possible, in diabetic patients and, if it is used, serum electrolytes and renal function must be monitored frequently.
Amizide HCl should be discontinued at least 3 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 Amizide HCl 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.
See Also Warning section.
Before taking Amizide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Before using this medication, tell your doctor or pharmacist your medical history, especially of: untreated salt/mineral imbalance (such as high potassium, low sodium level), kidney disease, liver disease, diabetes, loss of too much body water (dehydration).
Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).
This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).
Significant loss of body water from too much sweating, vomiting, or diarrhea can also lower your blood pressure and worsen dizziness. Drink plenty of fluids to prevent these effects and dehydration. If you are on restricted fluid intake, consult your doctor for further instructions. Contact your doctor if you are unable to drink fluids or if you have persistent diarrhea/vomiting.
This drug may increase the potassium levels in your blood. Limit foods high in potassium such as bananas and orange juice. Consult your doctor or pharmacist before using any products containing potassium (such as potassium supplements, salt substitutes).
During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.
It is unknown if this drug passes into breast milk. Discuss the risks and benefits with your doctor before breast-feeding.
Electrolyte Imbalance and BUN Increases: Hyponatremia and hypochloremia may occur when MIDAMOR (Amizide) is used with other diuretics and increases in BUN levels have been reported. 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 MIDAMOR (Amizide) is given with other diuretics to such patients, careful monitoring of serum electrolytes 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 diuretics, including Amizide HCl.
Carcinogenicity, Mutagenicity, Impairment of Fertility
There was no evidence of a tumorigenic effect when Amizide HCl was administered for 92 weeks to mice at doses up to 10 mg/kg/day (25 times the maximum daily human dose). Amizide HCl 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.
Amizide HCl was devoid of mutagenic activity in various strains of Salmonella typhimurium with or without a mammalian liver microsomal activation system (Ames test).
Pregnancy Category B: Teratogenicity studies with Amizide HCl 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.
There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Studies in rats have shown that Amizide is excreted in milk in concentrations higher than those found in blood, but it is not known whether MIDAMOR (Amizide) is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from MIDAMOR (Amizide) , 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 (Midamor (Amizide) /Moduretic) 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 of concomitant 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. (See CONTRAINDICATIONS, Impaired Renal Function.)
Amizide HCl, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is the salt of a moderately strong base (pKa 8.7). It is designated chemically as 3,5-diamino-6-chloro-N-(diaminomethylene) pyrazinecarboxamide monohydrochloride, dihydrate and has a molecular weight of 302.12. Its empirical formula is C 6 H 8 ClN 7 O † HCl † 2H 2 O and its structural formula is:
MIDAMOR (Amizide HCl) is available for oral use as tablets containing 5 mg of anhydrous Amizide HCl. Each tablet contains the following inactive ingredients: calcium phosphate, D&C Yellow 10, iron oxide, lactose, magnesium stearate and starch.
When Amizide HCl is administered concomitantly with an angiotensin-converting enzyme inhibitor, 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. (See WARNINGS.)
Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Read circulars for lithium preparations before use of such concomitant therapy.
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 MIDAMOR (Amizide) and 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 MIDAMOR (Amizide) , 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.
Pregnancy Category B . Teratogenicity studies with Amizide HCl 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.
There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Amizide HCl should not be used in the presence of elevated serum potassium levels (greater than 5.5 mEq per liter).
Antikaliuretic Therapy or Potassium Supplementation
Amizide HCl 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 Amizide HCl 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 Amizide HCl. Patients with evidence of renal functional impairment (blood urea nitrogen levels over 30 mg per 100 mL or serum creatinine levels over 1.5 mg per 100 mL) 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.
Amizide HCl is contraindicated in patients who are hypersensitive to this product.
What Is Amilor >
Amizide is a potassium-sparing diuretic (water pill) that prevents your body from absorbing too much salt and keeps your potassium levels from getting too low.
Amizide is used to treat or prevent hypokalemia (low potassium levels in the blood) in people with high blood pressure or congestive heart failure.
Amizide is usually given together with other medicines.
Amizide may also be used for purposes not listed in this medication guide.
You should not use Amizide if you have kidney problems, if you are unable to urinate, or if you have high levels of potassium in your blood. Do not use potassium supplements or other diuretics while you are taking Amizide.
Amizide can raise the levels of potassium in your blood. You will need frequent blood tests while taking this medicine.
Call your doctor right away if you have unusual tiredness, numbness or tingling, slow heartbeats, muscle weakness or limp feeling.
You should not use Amizide if you are allergic to it, or if:
- you have kidney disease or are unable to urinate;
- you have problems with your kidneys caused by diabetes;
- you have high potassium levels (hyperkalemia);
- you take a potassium supplement; or
- you take another potassium-sparing diuretic such Moduretic, spironolactone, or triamterene.
To make sure Amizide is safe for you, tell your doctor if you have:
- heart disease;
- breathing problems;
- cirrhosis or other liver disease;
- if you are on a low-salt diet; or
- if you are severely ill or debilitated.
Amizide is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.
It is not known whether Amizide passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.
Why is this medication prescribed?
Amizide is usually used in combination with other diuretics ('water pills') to treat high blood pressure and heart failure in patients who have low amounts of potassium in their bodies or for whom low potassium levels in the body could be dangerous. Amizide is in a class of medications called diuretics. It works by causing the kidneys to get rid of unneeded water and salt from the body into the urine, but reduces the loss of potassium.
High blood pressure is a common condition, and when not treated it can cause damage to the brain, heart, blood vessels, kidneys, and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.
Amizide (a mil' oh ride) is a pyrazinoylguanidine derivative that acts on the sodium channels of renal epithelial cells causing an increase in sodium excretion with little or no effect on potassium excretion, thus accounting for its potassium-sparing characteristics. Amizide is similar in action to triamterene, but differs in chemical structure. Amizide was approved for use in the United States in 1986, but is not widely used. Amizide is available in 5 mg tablets in generic forms and under the brand name of Midamor. The typical dose of Amizide is 5 to 20 mg in one or two doses daily. Amizide causes only a modest diuresis and it is often used in combination with a thiazide diuretic (such as hydrochlorothiazide: Moduretic), which takes advantage of it potassium-sparing characteristics to offset the potassium-wasting characteristics of the thiazides. The major side effects of Amizide include hyperkalemia, headache, dizziness, gastrointestinal upset and rash.
How should this medicine be used?
The combination of Amizide and hydrochlorothiazide comes as a tablet to take by mouth. It usually is taken once a day in the morning with food. To help you remember to take Amizide and hydrochlorothiazide, take it around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take Amizide and hydrochlorothiazide exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
This medication controls high blood pressure and heart failure but does not cure these conditions. Continue to take Amizide and hydrochlorothiazide even if you feel well. Do not stop taking Amizide and hydrochlorothiazide without talking to your doctor.
Electrolyte Imbalance and BUN Increases
Hyponatremia and hypochloremia may occur when Amizide HCl is used with other diuretics and increases in BUN levels have been reported. 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 Amizide HCl is given with other diuretics to such patients, careful monitoring of serum electrolytes 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 diuretics, including Amizide HCl.
Mechanism of Action
Exerts its potassium sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. This mechanism accounts in large part for the potassium sparing action of Amizide.
Inhibits Na/K-ATPase, decreases Ca++, Mg++ and hydrogen excretion
Amizide is a potassium-sparing diuretic used in the therapy of edema often in combination with thiazide diuretics. Amizide has been linked to rare cases of clinically apparent drug induced liver disease.
What other drugs will affect Amizide?
Tell your doctor about all your current medicines and any you start or stop using, especially:
- medicine to prevent organ transplant rejection --cyclosporine, tacrolimus;
- an ACE inhibitor (angiotensin converting enzyme) --benazepril, captopril, enalapril, fosinipril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril;
- heart or blood pressure medication --azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan; or
- NSAIDs (nonsteroidal anti-inflammatory drugs) --aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.
This list is not complete. Other drugs may interact with Amizide, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.