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Amiloride Hydrochloride

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names, main trade names
   1.6 Main manufacturers, main importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Other characteristics
      3.4.1 Shelf-life of the substance
      3.4.2 Storage conditions
4. USES
   4.1 Indications
      4.1.1 Indications
      4.1.2 Description
   4.2 Therapeutic dosage
      4.2.1 Adults
      4.2.2 Children
   4.3 Contraindications
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
   7.1 Mode of action
      7.1.1 Toxicodynamics
      7.1.2 Pharmacodynamics
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Animal Data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological analyses and their interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple qualitative tests(s)
         8.2.1.2 Advanced qualitative confirmation test(s)
         8.2.1.3 Simple quantitative method(s)
         8.2.1.4 Advanced quantitative method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple qualitative test(s)
         8.2.2.2 Advanced qualitative confirmation test(s)
         8.2.2.3 Simple quantitative method(s)
         8.2.2.4 Advanced quantitative method(s)
         8.2.2.5 Other dedicated method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretations
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effect
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central Nervous System (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks: pregnancy, breast-feeding, enzyme deficiencies
   9.5 Other
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic/specific treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE ADDRESSES
    AMILORIDE HYDROCHLORIDE

    International Programme on Chemical Safety
    Poisons Information Monograph 026
    Pharmaceutical

    1.  NAME

        1.1  Substance

             Amiloride Hydrochloride

        1.2  Group

             ATC code: C03DB01 Cardiovascular system, diuretics,
             other potassium-sparing agents

        1.3  Synonyms

             Guanamprazine; Amipramidin; Amipramizide

        1.4  Identification numbers

             1.4.1  CAS number

                    2609-46-3

             1.4.2  Other numbers

                    None

        1.5  Main brand names, main trade names

             Midamor, MSD. Moduretic (amiloride and hydrochlothiazide),
             MSD

        1.6  Main manufacturers, main importers

             MSD-Merck Sharp & Dohme

    2.  SUMMARY

        2.1  Main risks and target organs

             The major potential toxic effect is hyperkalemia which
             can cause life-threatening cardiac arrhythmias.

        2.2  Summary of clinical effects

             The signs and symptoms of hyperkalemia include cardiac
             dysrrhythmias and arrest. Fatigue, weakness, gastrointestinal
             distress, and paresthesia.

        2.3  Diagnosis

             Based primarily on history of ingestion, serum potassium
             levels, and signs and symptoms of hyperkalemia.

        2.4  First aid measures and management principles

             Evaluate airway, breathing and circulation. Consider
             gastrointestinal decontamination with activated charcoal or
             ipecac syrup. Obtain serum potassium level, electrocardiogram,
             and signs and symptoms of hyperkalemia.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Amiloride is a pyrazine carbonyl-quanidine
             derivative.

        3.2  Chemical structure

             Structural name: 3,5-Diamino-N-(aminoiminomethyl)-6-     
                              chlorpyrazine carboxamide
             Molecular formula: C6H8ClN7O
             Molecular weight of amiloride: 229.65
             Molecular weight of chlorhydrate salt: 302.12

        3.3  Physical properties

             3.3.1  Colour

                    Yellow to greenish yellow

             3.3.2  State/Form

                    Solid-crystal

             3.3.3  Description

                    Odourless
                    Solubility in water: 0.52 g/100 mL; in alcohol
                    1.96
                    g/100 mL at 25C; practically insoluble in ether
                    pKa 8.7; at room temperature solid;
                    melting point 240.5 to 241.5C
                    pH (0.5% solution in water) 3.8 to 5.2

        3.4  Other characteristics

             3.4.1  Shelf-life of the substance

                    36 months. No known toxic products are produced.

             3.4.2  Storage conditions

                    Store in well-closed containers ideally between
                    15 to 30C. Avoid freezing or a temperature greater
                    than 40C.  Protect from light.

    4.  USES

        4.1  Indications

             4.1.1  Indications

             4.1.2  Description

                    Hypokalemia induced by kaliuretic diuretic
                    (potassium-wasting diuretic) unresponsive to potassium
                    supplements, or in patient who cannot tolerate
                    potassium supplements.
                    Edema associated with congestive heart failure,
                    hepatic cirrhosis, or hyperaldosteronism. Amiloride
                    generally should not be used alone, without other more
                    potent diuretics.
                    Hypertension. Though amiloride has mild hypotensive
                    activity, the medication is generally used
                    concurrently with a thiazide or a loop diuretic to
                    prevent or treat diuretic-induced hypokalemia.
                    Hyperaldosteronism. Amiloride has been effectively
                    used to treat both primary and secondary
                    hyperaldosteronism, such as with hepatic cirrhosis
                    although spironolactone is generally considered more
                    effective.

        4.2  Therapeutic dosage

             4.2.1  Adults

                    Antihypertensive: 5 to 10 mg daily, up to 20 mg per
                                      day.
                    Diuretic: 5 to 20 mg daily

             4.2.2  Children

                    None identified

        4.3  Contraindications

             Hyperkalemia. Amiloride should be used with extreme
             caution in patients with impaired renal function, diabetes
             mellitus, or in the elderly.

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Most common.

        5.2  Inhalation

             Not available.

        5.3  Dermal

             Not available.

        5.4  Eye

             Not available.

        5.5  Parenteral

             Not available.

        5.6  Other

             No data

    6.  KINETICS

        6.1  Absorption by route of exposure

             Mean 50% when taken without food (range 15 to 90%); mean
             30% when taken with food. Information on other routes is not
             available.

        6.2  Distribution by route of exposure

             The apparent volume of distribution is 350 to 380 L
             (estimate 5L/kg). This suggests the drug has a large
             extravascular distribution. Protein binding is minimal.

        6.3  Biological half-life by route of exposure

             Based on limited data, the elimination half-life is
             reportedly 6 to 9 hours. In patients with reduced renal
             function (creatinine clearance ranging between 5 to 46
             mL/minute), the half-life is prolonged from 21 to 144
             hours.

        6.4  Metabolism

             Amiloride does not appear to be significantly
             metabolized.

        6.5  Elimination by route of exposure

             Of an oral dose, up to 50% is eliminated unchanged in
             urine, and up to 40% is eliminated unchanged in the stool by
             72 hours.

    7.  PHARMACOLOGY AND TOXICOLOGY

        7.1  Mode of action

             7.1.1  Toxicodynamics

                    Although amiloride is usually given with a
                    saliuretic, hyperkalemia may occur when the drug is
                    given with potassium supplementation or an ACE-
                    inhibitor or the patient has renal insufficiency,
                    diabetes or is elderly. An increase in serum potassium
                    causes depolarization of cardiac and skeletal muscle
                    cells. Such depolarization is particularly harmful to
                    cardiac cells, leading to abnormal impulse conduction.
                    Specifically hyperkalemia effects electrical
                    myocardial conductance causing arrhythmias,
                    bradycardia and hypotension. When used alone,
                    amiloride is also uricosuric. It also increases
                    urinary excretion of aldosterone, and plasma renin
                    concentrations.

             7.1.2  Pharmacodynamics

                    Amiloride inhibits directly Na/K exchange in
                    the distal tubule of the nephron.
                    Amiloride decreases sodium reabsorption in the distal
                    tubule by inhibiting cellular sodium transport
                    mechanism such as the conductive sodium influx pathway
                    and possibly the sodium-hydrogen exchange system.
                    Amiloride's effect on sodium transport results in a
                    lower transtubular electrical potential difference
                    which inhibits passive distal tubular potassium
                    secretion.

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             Toxic acute and chronic dosages have
                             not been established.

                    7.2.1.2  Children

                             Toxic acute and chronic dosages have
                             not been established.

             7.2.2  Animal Data

                    Oral LD50 of amiloride in mice is 56 mg/kg;
                    in rats, 36 to 86 mg/kg; and in dogs, 40 mg/kg
    
                    Relevant animal data
    
                    Amiloride has been observed to cross the placenta in
                    modest amounts in rabbits and mice.

             7.2.3  Relevant in vitro data

                    None available.

        7.3  Carcinogenicity

             No human data is available.

        7.4  Teratogenicity

             In humans, only one case report of exposure to amiloride
             during pregnancy was located.  The infant was exposed to
             captopril and propranolol as well as amiloride.  The child
             had a major limb anomaly.  In rats, traces of radiolabeled
             amiloride has been shown to cross the placenta.  Rabbits and
             mice given 20 and 25 times the maximum daily human dose,
             respectively, during pregnancy showed no teratogenic effects. 
             Rats and rabbits given comparable doses (up to 8 mg/kg/day),
             however, have shown both reduced maternal and fetal growth
             rate. (Briggs et al., 1986).

        7.5  Mutagenicity

             No human data are available. Various strains of
             Salmonella typhimurium exposed to amiloride did not develop
             mutagenesis.

        7.6  Interactions

             Hyperkalemia is more likely to occur if amiloride is
             used concurrently with other potassium sparing agents
             (spironolactone, triamterene), angiotensin-converting enzyme
             inhibitors (captopril, enalapril), or potassium-containing
             medications including potassium supplements.
             Hypotension can occur if amiloride (a mild anti-
             hypertensive) is used with other antihypertensive agents.
             Nonsteroidal anti-inflammatory agents may decrease the
             diuretic, natriuretic, and hypotensive effect of amiloride by
             inhibition of prostaglandin synthetase.
             The renal clearance of lithium is reduced by amiloride
             which increases the risk of lithium toxicity.
    

             Concomitant use of digoxin and amiloride can alter the
             clinical response to digoxin, hence patients should be
             carefully monitored if the use of both drugs is
             necessary.
             The alterations of response can occur by several mechanisms.
             First, amiloride increases renal clearance but decreases
             extrarenal clearance of digoxin. This usually results in
             elevated digoxin levels. Second, amiloride inhibits positive
             inotropic effects of digoxin, probably by increasing serum
             potassium.

        7.7  Main adverse effects

             Hyperkalemia.

    8.  TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                             Amiloride concentrations in serum,
                             blood or urine are not well established and
                             not clinically relevant.

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological analyses and their interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple qualitative tests(s)

                    8.2.1.2  Advanced qualitative confirmation test(s)

                    8.2.1.3  Simple quantitative method(s)

                    8.2.1.4  Advanced quantitative method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple qualitative test(s)

                    8.2.2.2  Advanced qualitative confirmation test(s)

                    8.2.2.3  Simple quantitative method(s)

                    8.2.2.4  Advanced quantitative method(s)

                    8.2.2.5  Other dedicated method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                             Close monitoring of serum
                             electrolyte and urea are essential.

                    8.3.1.2  Urine

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

                    In severe cases, determine arterial pH to check
                    for metabolic acidosis.

             8.3.3  Haematological analyses

             8.3.4  Interpretation of biomedical investigations

                    Patients with hyperkalemia (serum potassium
                    greater than 5.5 mEq/L) should be continuously
                    monitored by electrocardiogram and treated
                    appropriately.

        8.4  Other biomedical (diagnostic) investigations and their
             interpretations

        8.5  Overall interpretation of all toxicological analyses and
             toxicological investigations

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Expected route since only commercially
                    available forms are oral tablets. Hyperkalemia due to
                    acute ingestion is the principal potential life-
                    threatening effect of amiloride. Elevated serum
                    potassium levels occur as a result of amiloride
                    potassium-sparing effects on the distal nephron
                    tubule. Hyperkalemia occurs most commonly in patients
                    who also take potassium supplements, or potassium
                    containing medicines, ACE-inhibitors, in patients with
                    renal failure, diabetes mellitus or elderly.

             9.1.2  Inhalation

                    No data available

             9.1.3  Skin exposure

                    No data available

             9.1.4  Eye contact

                    No data available

             9.1.5  Parenteral exposure

                    No data available

             9.1.6  Other

                    Not applicable.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    Most commonly expected route. Hyperkalemia due
                    to chronic ingestion is the principal potential life-
                    threatening effect of amiloride. Elevated serum
                    potassium levels occur as a result of amiloride
                    potassium-sparing effects on the distal nephron
                    tubule. Hyperkalemia occurs most commonly in patients
                    who also take potassium supplements, or potassium
                    containing medicines, ACE-inhibitors, in patients with
                    renal failure, diabetes mellitus or elderly.

             9.2.2  Inhalation

                    No data

             9.2.3  Skin exposure

                    No data

             9.2.4  Eye contact

                    No data

             9.2.5  Parenteral exposure

                    No data

             9.2.6  Other

                    No data

        9.3  Course, prognosis, cause of death

             Prognosis based on amiloride dose or amiloride blood
             levels has not been established.  Determination of the
             severity of intoxication is based on serum potassium levels.
             Death secondary to hyperkalemia is due to cardiac
             arrest.

        9.4  Systematic description of clinical effect

             9.4.1  Cardiovascular

                    Signs and symptoms described secondary to
                    hyperkalemia. There are no direct effects from
                    amiloride. Electrocardiographic abnormalities include
                    tall, peaked T waves, low voltage R waves, increased
                    depth of the S wave, widening or absence of the P

                    wave, progressive widening of the QRS complex,
                    prolongation of the PR interval, or depression of the
                    ST segment.

             9.4.2  Respiratory

                    No direct complications.

             9.4.3  Neurological

                    9.4.3.1  Central Nervous System (CNS)

                             Headache reportedly occurs in 3 to
                             8% of patients receiving amiloride.
                             Other adverse symptoms occurring in 1 to 3%
                             of patients include fatigue, dizziness,
                             tinnitus, vertigo and encephalopathy.

                    9.4.3.2  Peripheral nervous system

                             Paresthesias.

                    9.4.3.3  Autonomic nervous system

                             No effects.

                    9.4.3.4  Skeletal and smooth muscle

                             Weakness and flaccid paralysis occur
                             secondary to hyperkalemia. Muscle cramps
                             occur in about 1 to 3% of patients receiving
                             amiloride.

             9.4.4  Gastrointestinal

                    Symptoms include nausea, vomiting, anorexia,
                    flatulence, dyspepsia, diarrhoea, or constipation,
                    abdominal pain, and gastrointestinal bleeding.

             9.4.5  Hepatic

                    Jaundice has been reported in less than 1% of
                    patients receiving amiloride.  Transient mild
                    abnormalities of liver function tests has reportedly
                    occurred with amiloride use.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Transient elevations in BUN or serum
                             creatinine have been reported.  No
                             significant renal dysfunction has been
                             reported.

                    9.4.6.2  Other

                             Polyuria, dysuria, increased urinary
                             frequency or bladder spasms have occurred in
                             1 to 3%. Mild proteinuria and transient
                             glycosuria rarely occur.

             9.4.7  Endocrine and reproductive systems

                    Impotence, gynecomastia.

             9.4.8  Dermatological

                    Erythematous rash, pruritus, and alopecia has
                    occurred in less than 1% of patients; rash has been
                    reported in 3 to 8% of patients taking
                    amiloride.

             9.4.9  Eye, ear, nose throat: local effects

                    Dryness of mouth, taste alteration and
                    increased thirst occur in less than 1% of patients.
                    Tinnitus, vertigo, and nasal congestion occur
                    rarely.

             9.4.10 Haematological

                    Eosinophilia, leukopenia, neutropenia, and
                    aplastic anemia have rarely been reported with
                    amiloride use. A causal relationship has not been
                    established.

             9.4.11 Immunological

                    No data.

             9.4.12 Metabolic

                    9.4.12.1 Acid base disturbances

                             Metabolic acidosis has been
                             reported in several patients receiving
                             amiloride. Severity and frequency of
                             occurence does not seem to be related to
                             dose.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Hyperkalemia. In general, amiloride
                             does not cause clinically significant
                             hyponatremia or hypochloremia. Diuresis can
                             result in a decreased intravascular volume.

                    9.4.12.3 Others

                             No data.

             9.4.13 Allergic reactions

                    No data.

             9.4.14 Other clinical effects

                    No data.

             9.4.15 Special risks: pregnancy, breast-feeding, enzyme
                    deficiencies

                    Reported experience with its use during
                    pregnancy in humans is limited, and there is no
                    evidence of teratogenic effects in animals. Fetal
                    growth rates were diminished in high-dose animal
                    studies. Amiloride is distributed into the milk of
                    lactating animals; it is not known if this occurs in
                    humans.

        9.5  Other

             No data.

    10. MANAGEMENT

        10.1 General principles

             Prompt evaluation for signs and symptoms of
             hyperkalemia including monitoring of vital signs and the
             electrocardiogram. Analysis of serum potassium, sodium,
             chloride and bicarbonate should be performed. If evidence of

             clinical signs and symptoms of hyperkalemia are observed
             and/or hyperkalemia is identified, prompt medical treatment
             should be undertaken.

        10.2 Life supportive procedures and symptomatic/specific treatment 

             Evaluate and provide support for airway, breathing, and
             circulation.
             Treatment varies based on severity of hyperkalemia.
             Mild Hyperkalemia: normal ECG or with peaked T waves,
             normal vital signs, and no other symptoms; stop amiloride and
             any sources of potassium.
             Moderate Hyperkalemia: only T wave peaking on ECG, normal
             vital signs, and no symptoms; treatment described above for
             mild hyperkalemia plus: intravenous glucose and insulin;
             consider intravenous sodium bicarbonate; cation exchange
             resin.
             Severe Hyperkalemia: absent P waves, widened QRS or
             ventricular arrhythmias, bradycardia, hypotension, or other
             symptoms associated with hyperkalemia; treatment as outlined
             with above plus: intravenous calcium gluconate and consider
             hemodialysis, especially with renal failure.

        10.3 Decontamination

             Gastrointestinal decontamination is indicated for
             recent substantial oral ingestions. If patient is awake and
             alert, ipecac (adult 30 mL; child 1 to 12 yrs 15 mL) may be
             given.  Alternately charcoal may be given alone (1 mg/kg body
             weight). Charcoal may be mixed with water or sorbitol 70%, 1
             to 2 mL/kg body weight.

        10.4 Enhanced elimination

             Hemodialysis: It has not been established whether
             amiloride is dialyzable, but dialysis may be necessary to
             remove potassium if signs and symptoms of severe hyperkalemia
             persist despite aggressive and maximal supportive treatment,
             especially if the patient has decreased renal function.

        10.5 Antidote treatment

             10.5.1 Adults

                    No antidote available

             10.5.2 Children

                    No antidote available

        10.6 Management discussion

             Prompt evaluation and treatment of hyperkalemia is
             essential. Aggressiveness of therapy should be based on the
             severity of the signs and symptoms of hyperkalemia.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             No data available

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             No data available

        12.2 Other

             No data available

    13. REFERENCES

        Briggs GC, Freeman RK, Yaffe SJ (1986) Amiloride. Drugs in
        pregnancy and lactation.  Baltimore, MD, Williams and Wilkins.
    
        Brumwald E (1987) Fluids and Electrolytes. Harrison's Principles
        of Internal Medicine, Eleventh Edition. New York, McGraw-Hill
        Books.
    
        Budavari S (1989) Amiloride. The Merck Index. Rahway NJ, Merc and
        Co.

        Ellenhorn MJ, Barceloux DG (1988) Potassium-Sparing Diuretics.
        Medical Toxicology: Diagnosis and treatment of human poisoning.
        New York, Elsevier.
    
        McEvoy GK (1989) Potassium-Sparing Diuretics. The American
        Hospital Formulary Service.  Bethesda, MD, American Society of the
        Hospital Pharmacists.
    
        Reynolds JEF (1989) Amiloride. Martindale: the extra
        pharmacopoeia. London, Pharmaceutical Press.
    
        West JB (1985) Potassium balance and the regulations of potassium
        excretion. Best and Taylors physiological basis of medical
        practice, eleventh edition. Baltimore, Williams and Wilkins.

    14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE
        ADDRESSES

        Author: Dr M.A. McGuigan
                Poisons Control Centre
                Hospital for Sick Children
                555, University Avenue
                Toronto, Ontario M5G 1X8
                Canada
    
                Tel: 416 598 5823
                Fax: 416 598 7489
    
        Reviewer: J Szajewski, August 1997
    
        Peer review: INTOX-10 Meeting, Rio,Brazil, 4 September, 1997
        (M Kowalczyk, L Lubomirov, R McKneown, P Rosen, J Szajewski, W
        Watson)
    
        Finalization/Edition: Drs MO Rambourg Schepens & M Ruse
        October, 1997
    


    See Also:
       Toxicological Abbreviations