Potassium
Chloride -
Clinical
Pharmacology
The potassium
ion is the
principal
intracellular
cation of most
body tissues.
Potassium ions
participate in a
number of
essential
physiological
processes
including the
maintenance of
intracellular
tonicity; the
transmission of
nerve impulses;
the contraction
of cardiac,
skeletal, and
smooth muscle;
and the
maintenance of
normal renal
function.
The
intracellular
concentration of
potassium is
approximately
150 to 160 mEq
per liter. The
normal adult
plasma
concentration is
3.5 to 5 mEq per
liter. An active
ion transport
system maintains
this gradient
across the
plasma membrane.
Potassium is a
normal dietary
constituent and
under
steady-state
conditions the
amount of
potassium
absorbed from
the
gastrointestinal
tract is equal
to the amount
excreted in the
urine. The usual
dietary intake
of potassium is
50 to 100 mEq
per day.
Potassium
depletion will
occur whenever
the rate of
potassium loss
through renal
excretion and/or
loss from the
gastrointestinal
tract exceeds
the rate of
potassium
intake. Such
depletion
usually develops
as a consequence
of therapy with
diuretics,
primary or
secondary
hyperaldosteronism,
diabetic
ketoacidosis, or
inadequate
replacement of
potassium in
patients on
prolonged
parenteral
nutrition.
Depletion can
develop rapidly
with severe
diarrhea,
especially if
associated with
vomiting.
Potassium
depletion due to
these causes is
usually
accompanied by a
concomitant loss
of chloride and
is manifested by
hypokalemia and
metabolic
alkalosis.
Potassium
depletion may
produce
weakness,
fatigue,
disturbances or
cardiac rhythm
(primarily
ectopic beats),
prominent
U-waves in the
electrocardiogram,
and in advanced
cases, flaccid
paralysis and/or
impaired ability
to concentrate
urine.
If potassium
depletion
associated with
metabolic
alkalosis cannot
be managed by
correcting the
fundamental
cause of the
deficiency, eg,
where the
patient requires
long-term
diuretic
therapy,
supplemental
potassium in the
form of
high-potassium
food or
KCl may be
able to restore
normal potassium
levels.
In rare
circumstances
(eg, patients
with renal
tubular
acidosis)
potassium
depletion may be
associated with
metabolic
acidosis and
hyperchloremia.
In such patients
potassium
replacement
should be
accomplished
with potassium
salts other than
the chloride,
such as
potassium
bicarbonate,
potassium
citrate,
potassium
acetate, or
potassium
gluconate.
Indications and
Usage for
Potassium
Chloride
BECAUSE OF
REPORTS OF
INTESTINAL AND
GASTRIC
ULCERATION AND
BLEEDING WITH
CONTROLLED-RELEASE
Potassium
Chloride
PREPARATIONS,
THESE DRUGS
SHOULD BE
RESERVED FOR
THOSE PATIENTS
WHO CANNOT
TOLERATE OR
REFUSE TO TAKE
LIQUID OR
EFFERVESCENT
POTASSIUM
PREPARATIONS OR
FOR PATIENTS IN
WHOM THERE IS A
PROBLEM OF
COMPLIANCE WITH
THESE
PREPARATIONS.
-
For the
treatment of
patients
with
hypokalemia
with or
without
metabolic
alkalosis,
in digitalis
intoxication,
and in
patients
with
hypokalemic
familial
periodic
paralysis.
If
hypokalemia
is the
result of
diuretic
therapy,
consideration
should be
given to the
use of a
lower dose
of diuretic,
which may be
sufficient
without
leading to
hypokalemia.
-
For the
prevention
of
hypokalemia
in patients
who would be
at
particular
risk if
hypokalemia
were to
develop, eg,
digitalized
patients or
patients
with
significant
cardiac
arrhythmias.
The use of
KCl
salts in
patients
receiving
diuretics for
uncomplicated
essential
hypertension is
often
unnecessary when
such patients
have a normal
dietary pattern
and when low
doses of the
diuretic are
used. Serum
potassium should
be checked
periodically,
however, and if
hypokalemia
occurs, dietary
supplementation
with
potassium-containing
foods may be
adequate to
control milder
cases. In more
severe cases,
and if dose
adjustment of
the diuretic is
ineffective or
unwarranted,
supplementation
with potassium
salts may be
indicated.
Contraindications
Potassium
supplements are
contraindicated
in patients with
hyperkalemia
since a further
increase in
serum potassium
concentration in
such patients
can produce
cardiac arrest.
Hyperkalemia may
complicate any
of the following
conditions:
chronic renal
failure,
systemic
acidosis, such
as diabetic
acidosis, acute
dehydration,
extensive tissue
breakdown as in
severe burns,
adrenal
insufficiency,
or the
administration
of a
potassium-sparing
diuretic (eg,
spironolactone,
triamterene,
amiloride).
Controlled-release
formulations of
Potassium
Chloride have
produced
esophageal
ulceration in
certain cardiac
patients with
esophageal
compression due
to enlarged left
atrium.
Potassium
supplementation,
when indicated
in such
patients, should
be given as a
liquid
preparation or
as an aqueous
suspension.
All solid oral
dosage forms of
Potassium
Chloride are
contraindicated
in any patient
in whom there is
structural,
pathological
(eg, diabetic
gastroparesis),
or pharmacologic
(use of
anticholinergic
agents or other
agents with
anticholinergic
properties at
sufficient doses
to exert
anticholinergic
effects) cause
for arrest or
delay in tablet
passage through
the
gastrointestinal
tract.
Warnings
Hyperkalemia
In patients with
impaired
mechanisms for
excreting
potassium, the
administration
of
KCl
salts can
produce
hyperkalemia and
cardiac arrest.
This occurs most
commonly in
patients given
potassium by the
intravenous
route but may
also occur in
patients given
potassium
orally.
Potentially
fatal
hyperkalemia can
develop rapidly
and be
asymptomatic.
The use of
KCl
salts in
patients with
chronic renal
disease, or any
other condition
which impairs
potassium
excretion,
requires
particularly
careful
monitoring of
the serum
potassium
concentration
and appropriate
dosage
adjustment.
Interaction with
Potassium-Sparing
Diuretics
Hypokalemia
should not be
treated by the
concomitant
administration
of
KCl
salts and a
potassium-sparing
diuretic (eg,
spironolactone,
triamterene, or
amiloride) since
the simultaneous
administration
of these agents
can produce
severe
hyperkalemia.
Interaction with
Angiotensin-Converting
Enzyme
Inhibitors
Angiotensin-converting
enzyme (ACE)
inhibitors (eg,
captopril,
enalapril) will
produce some
potassium
retention by
inhibiting
aldosterone
production.
Potassium
supplements
should be given
to patients
receiving ACE
inhibitors only
with close
monitoring.
Gastrointestinal
Lesions
Solid oral
dosage forms of
Potassium
Chloride can
produce
ulcerative
and/or stenotic
lesions of the
gastrointestinal
tract. Based on
spontaneous
adverse reaction
reports,
enteric-coated
preparations of
KCl are
associated with
an increased
frequency of
small bowel
lesions (40–50
per 100,000
patient years)
compared to
sustained
release wax
matrix
formulations
(less than one
per 100,000
patient years).
Because of the
lack of
extensive
marketing
experience with
microencapsulated
products, a
comparison
between such
products and wax
matrix or
enteric-coated
products is not
available.
Potassium
Chloride is a
tablet
formulated to
provide a
controlled rate
of release of
microencapsulated
KCl and
thus to minimize
the possibility
of a high local
concentration of
potassium near
the
gastrointestinal
wall.
Prospective
trials have been
conducted in
normal human
volunteers in
which the upper
gastrointestinal
tract was
evaluated by
endoscopic
inspection
before and after
1 week of solid
oral KCl
therapy. The
ability of this
model to predict
events occurring
in usual
clinical
practice is
unknown. Trials
which
approximated
usual clinical
practice did not
reveal any clear
differences
between the wax
matrix and
microencapsulated
dosage forms. In
contrast, there
was a higher
incidence of
gastric and
duodenal lesions
in subjects
receiving a high
dose of a wax
matrix
controlled-release
formulation
under conditions
which did not
resemble usual
or recommended
clinical
practice (ie, 96
mEq per day in
divided doses of
Potassium
Chloride
administered to
fasted patients,
in the presence
of an
anticholinergic
drug to delay
gastric
emptying). The
upper
gastrointestinal
lesions observed
by endoscopy
were
asymptomatic and
were not
accompanied by
evidence of
bleeding
(Hemoccult
testing). The
relevance of
these findings
to the usual
conditions (ie,
non-fasting, no
anticholinergic
agent, smaller
doses) under
which
controlled-release
Potassium
Chloride
products are
used is
uncertain;
epidemiologic
studies have not
identified an
elevated risk,
compared to
micro-encapsulated
products, for
upper
gastrointestinal
lesions in
patients
receiving wax
matrix
formulations.
Extended Release
Tablets should
be discontinued
immediately and
the possibility
of ulceration,
obstruction, or
perforation
should be
considered if
severe vomiting,
abdominal pain,
distention, or
gastrointestinal
bleeding occurs.
Metabolic
Acidosis
Hypokalemia in
patients with
metabolic
acidosis should
be treated with
an alkalinizing
potassium salt
such as
potassium
bicarbonate,
potassium
citrate,
potassium
acetate, or
potassium
gluconate.
Precautions
General
The diagnosis of
potassium
depletion is
ordinarily made
by demonstrating
hypokalemia in a
patient with a
clinical history
suggesting some
cause for
potassium
depletion. In
interpreting the
serum potassium
level, the
physician should
bear in mind
that acute
alkalosis per se
can produce
hypokalemia in
the absence of a
deficit in total
body potassium
while acute
acidosis per se
can increase the
serum potassium
concentration
into the normal
range even in
the presence of
a reduced total
body potassium.
The treatment of
potassium
depletion,
particularly in
the presence of
cardiac disease,
renal disease,
or acidosis
requires careful
attention to
acid-base
balance and
appropriate
monitoring of
serum
electrolytes,
the
electrocardiogram,
and the clinical
status of the
patient.
Information for
Patients
Physicians
should consider
reminding the
patient of the
following:
To take each
dose with meals
and with a full
glass of water
or other liquid.
To take each
dose without
crushing,
chewing, or
sucking the
tablets. If
those patients
are having
difficulty
swallowing whole
tablets, they
may try one of
the following
alternate
methods of
administration:
-
Break the
tablet in
half, and
take each
half
separately
with a glass
of water.
-
Prepare an
aqueous
(water)
suspension
as follows:
-
Place
the
whole
tablet(s)
in
approximately
1/2
glass of
water (4
fluid
ounces).
-
Allow
approximately
2
minutes
for the
tablet(s)
to
disintegrate.
-
Stir for
about
half a
minute
after
the
tablet(s)
has
disintegrated.
-
Swirl
the
suspension
and
consume
the
entire
contents
of the
glass
immediately
by
drinking
or by
the use
of a
straw.
-
Add
another
1 fluid
ounce of
water,
swirl,
and
consume
immediately.
-
Then,
add an
additional
1 fluid
ounce of
water,
swirl,
and
consume
immediately.
Aqueous
suspension of
Potassium
Chloride that is
not taken
immediately
should be
discarded. The
use of other
liquids for
suspending
KCl Tablets
is not
recommended.
To take this
medicine
following the
frequency and
amount
prescribed by
the physician.
This is
especially
important if the
patient is also
taking diuretics
and/or digitalis
preparations.
To check with
the physician at
once if tarry
stools or other
evidence of
gastrointestinal
bleeding is
noticed.
Laboratory Tests
When blood is
drawn for
analysis of
plasma potassium
it is important
to recognize
that artifactual
elevations can
occur after
improper
venipuncture
technique or as
a result of in
vitro hemolysis
of the sample.
Drug
Interactions
Potassium-sparing
diuretics,
angiotensin-converting
enzyme
inhibitors (see
WARNINGS).
Carcinogenesis,
Mutagenesis,
Impairment of
Fertility
Carcinogenicity,
mutagenicity,
and fertility
studies in
animals have not
been performed.
Potassium is a
normal dietary
constituent.
Pregnancy
Category C
Animal
reproduction
studies have not
been conducted
with Potassium
Chloride. It is
unlikely that
potassium
supplementation
that does not
lead to
hyperkalemia
would have an
adverse effect
on the fetus or
would affect
reproductive
capacity.
Nursing Mothers
The normal
potassium ion
content of human
milk is about 13
mEq per liter.
Since oral
potassium
becomes part of
the body
potassium pool,
so long as body
potassium is not
excessive, the
contribution of
KCl
supplementation
should have
little or no
effect on the
level in human
milk.
Pediatric Use
Safety and
effectiveness in
pediatric
patients have
not been
established.
Geriatric Use
Clinical studies
of this salt 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.
Adverse
Reactions
One of the most
severe adverse
effects is
hyperkalemia
(see
CONTRAINDICATIONS,
WARNINGS, and
OVERDOSAGE).
There have also
been reports of
upper and lower
gastrointestinal
conditions
including
obstruction,
bleeding,
ulceration, and
perforation (see
CONTRAINDICATIONS
and WARNINGS).
The most common
adverse
reactions to
oral potassium
salts are
nausea,
vomiting,
flatulence,
abdominal
pain/discomfort,
and diarrhea.
These symptoms
are due to
irritation of
the
gastrointestinal
tract and are
best managed by
diluting the
preparation
further, taking
the dose with
meals or
reducing the
amount taken at
one time.
Overdosage
The
administration
of oral
potassium salts
to persons with
normal excretory
mechanisms for
potassium rarely
causes serious
hyperkalemia.
However, if
excretory
mechanisms are
impaired or if
potassium is
administered too
rapidly
intravenously,
potentially
fatal
hyperkalemia can
result (see
CONTRAINDICATIONS
and WARNINGS).
It is important
to recognize
that
hyperkalemia is
usually
asymptomatic and
may be
manifested only
by an increased
serum potassium
concentration
(6.5–8.0 mEq/L)
and
characteristic
electrocardiographic
changes (peaking
of T-waves, loss
of P-waves,
depression of
S-T segment, and
prolongation of
the
QT-interval).
Late
manifestations
include muscle
paralysis and
cardiovascular
collapse from
cardiac arrest
(9–12 mEq/L).
Treatment
measures for
hyperkalemia
include the
following:
-
Patients
should be
closely
monitored
for
arrythmias
and
electrolyte
changes.
-
Elimination
of foods and
medications
containing
potassium
and of any
agents with
potassium-sparing
properties
such as
potassium-sparing
diuretics,
ARBS, ACE
inhibitors,
NSAIDS,
certain
nutritional
supplements
and many
others.
-
Intravenous
calcium
gluconate if
the patient
is at no
risk or low
risk of
developing
digitalis
toxicity.
-
Intravenous
administration
of 300 to
500 mL/hr of
10% dextrose
solution
containing
10–20 units
of
crystalline
insulin per
1,000 mL.
-
Correction
of acidosis,
if present,
with
intravenous
sodium
bicarbonate.
-
Use of
exchange
resins,
hemodialysis,
or
peritoneal
dialysis.
In treating
hyperkalemia, it
should be
recalled that in
patients who
have been
stabilized on
digitalis, too
rapid a lowering
of the serum
potassium
concentration
can produce
digitalis
toxicity.
The extended
release feature
means that
absorption and
toxic effects
may be delayed
for hours.
Consider
standard
measures to
remove any
unabsorbed drug.
Potassium
Chloride Dosage
and
Administration
The usual
dietary intake
of potassium by
the average
adult is 50 to
100 mEq per day.
Potassium
depletion
sufficient to
cause
hypokalemia
usually requires
the loss of 200
or more mEq of
potassium from
the total body
store.
Dosage must be
adjusted to the
individual needs
of each patient.
The dose for the
prevention of
hypokalemia is
typically in the
range of 20 mEq
per day. Doses
of 40–100 mEq
per day or more
are used for the
treatment of
potassium
depletion.
Dosage should be
divided if more
than 20 mEq per
day is given
such that no
more than 20 mEq
is given in a
single dose.
Potassium
Chloride Tablets
should be taken
with meals and
with a glass of
water or other
liquid. This
product should
not be taken on
an empty stomach
because of its
potential for
gastric
irritation (see
WARNINGS).
Patients having
difficulty
swallowing whole
tablets may try
one of the
following
alternate
methods of
administration:
-
Break the
tablet in
half, and
take each
half
separately
with a glass
of water.
-
Prepare an
aqueous
(water)
suspension
as follows:
-
Place
the
whole
tablet(s)
in
approximately
1/2
glass of
water (4
fluid
ounces).
-
Allow
approximately
2
minutes
for the
tablet(s)
to
disintegrate.
-
Stir for
about
half a
minute
after
the
tablet(s)
has
disintegrated.
-
Swirl
the
suspension
and
consume
the
entire
contents
of the
glass
immediately
by
drinking
or by
the use
of a
straw.
-
Add
another
1 fluid
ounce of
water,
swirl,
and
consume
immediately.
-
Then,
add an
additional
1 fluid
ounce of
water,
swirl,
and
consume
immediately.
For
an
exhaustive
write up on
the subject
please go to
University
of Potassium
Chloride.
