Amiloride Hydrochloride (Page 2 of 3)
GENERAL PRECAUTIONS
Electrolyte Imbalance and BUN Increases
Hyponatremia and hypochloremia may occur when amiloride 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 amiloride 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 amiloride HCl.
Drug Interactions
When amiloride HCl is administered concomitantly with an angiotensin-converting enzyme inhibitor, an angiotensin II receptor antagonist, 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. (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 amiloride HCl 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 amiloride HCl, 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.
Carcinogenesis and Mutagenesis and Impairment of Fertility
There was no evidence of a tumorigenic effect when amiloride HCl was administered for 92 weeks to mice at doses up to 10 mg/kg/day (25 times the maximum daily human dose). Amiloride 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.
Amiloride HCl was devoid of mutagenic activity in various strains of Salmonella typhimurium with or without a mammalian liver microsomal activation system (Ames test).
Pregnancy
Pregnancy Category B. Teratogenicity studies with amiloride 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.
Nursing Mothers
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 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 amiloride HCl, 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.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Clinical studies of amiloride HCI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond 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.)
ADVERSE REACTIONS
Amiloride 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 amiloride 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 amiloride. Other adverse experiences that have been reported with amiloride are generally those known to be associated with diuresis, or with the underlying disease being treated.
The adverse reactions for amiloride 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 amiloride 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 amiloride HCl and these adverse reactions, some of which have been reported only rarely.
*Reactions occurring in 3% to 8% of patients treated with amiloride HCl. | |
(Those reactions occurring in less than 3% of the patients are unmarked.) | |
**See WARNINGS. | |
Incidence > 1% | Incidence ≤ 1% |
Body as a Whole | |
Headache* | Back pain |
Weakness | Chest pain |
Fatigability | Neck/shoulder ache |
| Pain, extremities |
Cardiovascular | |
None | Angina pectoris |
| Orthostatic hypotension |
Arrhythmia | |
| Palpitation |
Digestive | |
Nausea/anorexia* | Jaundice |
Diarrhea* | GI bleeding |
Vomiting* | Abdominal fullness |
Abdominal pain | GI disturbance |
Gas pain | Thirst |
Appetite changes | Heartburn |
Constipation | Flatulence |
Dyspepsia | |
Metabolic Elevated serum potassium levels (>5.5 mEq per liter)** | None |
Skin | |
None | Skin rash |
Itching | |
Dryness of mouth | |
Pruritus | |
Alopecia | |
Musculoskeletal | |
Muscle cramps | Joint pain |
Leg ache | |
Nervous | |
Dizziness | Paresthesia |
Encephalopathy | Tremors |
Vertigo | |
Psychiatric | |
None | Nervousness |
Mental confusion | |
Insomnia | |
Decreased libido | |
Depression | |
Somnolence | |
Respiratory | |
Cough | Shortness of Breath |
Dyspnea | |
Special Senses | |
None | Visual disturbances |
Nasal congestion | |
Tinnitus | |
Increased intraocular pressure | |
Urogenital | |
Impotence | Polyuria |
Dysuria | |
Urinary frequency | |
Bladder spasms | |
Gynecomastia |
Causal Relationship Unknown
Other reactions have been reported but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to serve as alerting information to physicians.
Activation of probable pre-existing peptic ulcer
Aplastic anemia
Neutropenia
Abnormal liver function
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