CHLORPROMAZINE
DESCRIPTION:
Megatil (chlorpromazine) is 10-(3-dimethylaminopropyl)-2-chlorphenothiazine, a
dimethylamine derivative of phenothiazine. It is present in oral and injectable
forms as the hydrochloride salt.
ACTIONS/CLINICAL PHARMACOLOGY:
The precise mechanism whereby the therapeutic effects of chlorpromazine are
produced is not known. The principal pharmacological actions are psychotropic.
It also exerts sedative and antiemetic activity. Chlorpromazine has actions at
all levels of the central nervous system- -primarily at subcortical levels--as
well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and
weaker peripheral anticholinergic activity; ganglionic blocking action is
relatively slight. It also possesses slight antihistaminic and antiserotonin
activity.
INDICATIONS AND USAGE:
For the management of manifestations of psychotic disorders.
To control nausea and vomiting.
For relief of restlessness and apprehension before surgery.
For acute intermittent porphyria.
As an adjunct in the treatment of tetanus.
To control the manifestations of the manic type of manic-depressive illness.
For relief of intractable hiccups.
For the treatment of severe behavioral problems in children (1 to 12 years of
age) marked by combativeness and/or explosive hyperexcitable behavior (out of
proportion to immediate provocations), and in the short-term treatment of
hyperactive children who show excessive motor activity with accompanying conduct
disorders consisting of some or all of the following symptoms: impulsivity,
difficulty sustaining attention, aggressivity, mood lability and poor
frustration tolerance.
CONTRAINDICATIONS:
Do not use in patients with known hypersensitivity to phenothiazines.
Do not use in comatose states or in the presence of large amounts of central
nervous system depressants (alcohol, barbiturates, narcotics, etc.).
WARNINGS:
THE EXTRAPYRAMIDAL SYMPTOMS WHICH CAN OCCUR SECONDARY TO MEGATIL
(CHLORPROMAZINE) MAY BE CONFUSED WITH THE CENTRAL NERVOUS SYSTEM SIGNS OF AN
UNDIAGNOSED PRIMARY DISEASE RESPONSIBLE FOR THE VOMITING, E.G., REYE'S SYNDROME
OR OTHER ENCEPHALOPATHY. THE USE OF MEGATIL AND OTHER POTENTIAL HEPATOTOXINS
SHOULD BE AVOIDED IN CHILDREN AND ADOLESCENTS WHOSE SIGNS AND SYMPTOMS SUGGEST
REYE'S SYNDROME.
TARDIVE DYSKINESIA: Tardive dyskinesia, a syndrome consisting of potentially
irreversible, involuntary, dyskinetic movements, may develop in patients treated
with neuroleptic (antipsychotic) drugs. Although the prevalence of the syndrome
appears to be highest among the elderly, especially elderly women, it is
impossible to rely upon prevalence estimates to predict, at the inception of
neuroleptic treatment, which patients are likely to develop the syndrome.
Whether neuroleptic drug products differ in their potential to cause tardive
dyskinesia is unknown.
Both the risk of developing the syndrome and the likelihood that it will become
irreversible are believed to increase as the duration of treatment and the total
cumulative dose of neuroleptic drugs administered to the patient increase.
However, the syndrome can develop, although much less commonly, after relatively
brief treatment periods at low doses.
There is no known treatment for established cases of tardive dyskinesia,
although the syndrome may remit, partially or completely, if neuroleptic
treatment is withdrawn. Neuroleptic treatment itself, however, may suppress (or
partially suppress) the signs and symptoms of the syndrome and thereby may
possibly mask the underlying disease process. The effect that symptomatic
suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, neuroleptics should be prescribed in a manner that
is most likely to minimize the occurrence of tardive dyskinesia. Chronic
neuroleptic treatment should generally be reserved for patients who suffer from
a chronic illness that, 1) is known to respond to neuroleptic drugs, and, 2) for
whom alternative, equally effective, but potentially less harmful treatments are
Not available or appropriate. In patients who do require chronic treatment, the
smallest dose and the shortest duration of treatment producing a satisfactory
clinical response should be sought. The need for continued treatment should be
reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics,
drug discontinuation should be considered. However, some patients may require
treatment despite the presence of the syndrome.
For further information about the description of tardive dyskinesia and its
clinical detection, please refer to the sections on PRECAUTIONS and ADVERSE
REACTIONS.
NEUROLEPTIC MALIGNANT SYNDROME (NMS): A potentially fatal symptom complex
sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported
in association with antipsychotic drugs. Clinical manifestations of NMS are
hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic
instability (irregular pulse or blood pressure, tachycardia, diaphoresis and
cardiac dysrhythmias).
The diagnostic evaluation of patients with this syndrome is complicated. In
arriving at a diagnosis, it is important to identify cases where the clinical
presentation includes both serious medical illness (e.g., pneumonia, systemic
infection, etc.) and untreated or inadequately treated extrapyramidal signs and
symptoms (EPS). Other important considerations in the differential diagnosis
include central anticholinergic toxicity, heat stroke, drug fever and primary
central nervous system (CNS) pathology.
The management of NMS should include 1) immediate discontinuation of
antipsychotic drugs and other drugs not essential to concurrent therapy, 2)
intensive symptomatic treatment and medical monitoring, and 3) treatment of any
concomitant serious medical problems for which specific treatments are
available. There is no general agreement about specific pharmacological
treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the
potential reintroduction of drug therapy should be carefully considered. The
patient should be carefully monitored, since recurrences of NMS have been
reported.
An encephalopathic syndrome (characterized by weakness, lethargy, fever,
tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated
serum enzymes, BUN and FBS) has occurred in a few patients treated with lithium
plus a neuroleptic. In some instances, the syndrome was followed by irreversible
brain damage. Because of a possible causal relationship between these events and
the concomitant administration of lithium and neuroleptics, patients receiving
such combined therapy should be monitored closely for early evidence of
neurologic toxicity and treatment discontinued promptly if such signs appear.
This encephalopathic syndrome may be similar to or the same as neuroleptic
malignant syndrome (NMS).
Megatil (chlorpromazine) ampuls and multi-dose vials contain sodium bisulfite
and sodium sulfite, sulfites that may cause allergic-type reactions including
anaphylactic symptoms and life-threatening or less severe asthmatic episodes in
certain susceptible people. The overall prevalence of sulfite sensitivity in the
general population is unknown and probably low. Sulfite sensitivity is seen more
frequently in asthmatic than in nonasthmatic people.
Patients with bone marrow depression or who have previously demonstrated a
hypersensitivity reaction (e.g., blood dyscrasias, jaundice) with a
phenothiazine should not receive any phenothiazine, including Megatil, unless
in the judgment of the physician the potential benefits of treatment outweigh
the possible hazard.
Megatil may impair mental and/or physical abilities, especially during the
first few days of therapy. Therefore, caution patients about activities
requiring alertness (e.g., operating vehicles or machinery).
The use of alcohol with this drug should be avoided due to possible additive
effects and hypotension.
Megatil may counteract the antihypertensive effect of guanethidine and related
compounds.
USAGE IN PREGNANCY: Safety for the use of Megatil (chlorpromazine) during
pregnancy has not been established. Therefore, it is not recommended that the
drug be given to pregnant patients except when, in the judgment of the
physician, it is essential. The potential benefits should clearly outweigh
possible hazards. There are reported instances of prolonged jaundice,
extrapyramidal signs, hyperreflexia or hyporeflexia in newborn infants whose
mothers received phenothiazines.
Reproductive studies in rodents have demonstrated potential for embryotoxicity,
increased neonatal mortality and nursing transfer of the drug. Tests in the
offspring of the drug-treated rodents demonstrate decreased performance. The
possibility of permanent neurological damage cannot be excluded.
NURSING MOTHERS: There is evidence that chlorpromazine is excreted in the breast
milk of nursing mothers. Because of the potential for serious adverse reactions
in nursing infants from chlorpromazine, 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.
PRECAUTIONS:
GENERAL
Given the likelihood that some patients exposed chronically to neuroleptics will
develop tardive dyskinesia, it is advised that all patients in whom chronic use
is contemplated be given, if possible, full information about this risk. The
decision to inform patients and/or their guardians must obviously take into
account the clinical circumstances and the competency of the patient to
understand the information provided.
Megatil (chlorpromazine) should be administered cautiously to persons with
cardiovascular, liver or renal disease. There is evidence that patients with a
history of hepatic encephalopathy due to cirrhosis have increased sensitivity to
the C.N.S. effects of Megatil (i.e., impaired cerebration and abnormal slowing
of the EEG).
Because of its C.N.S. depressant effect, Megatil should be used with caution
in patients with chronic respiratory disorders such as severe asthma, emphysema
and acute respiratory infections, particularly in children (1 to 12 years of
age).
Because Megatil can suppress the cough reflex, aspiration of vomitus is
possible.
Megatil (chlorpromazine) prolongs and intensifies the action of CNS
depressants such as anesthetics, barbiturates and narcotics. When Megatil is
administered concomitantly, about 1/4 to 1/2 the usual dosage of such agents is
required. When Megatil is not being administered to reduce requirements of CNS
depressants, it is best to stop such depressants before starting Megatil
treatment. These agents may subsequently be reinstated at low doses and
increased as needed.
Note: Megatil does Not intensify the anticonvulsant action of barbiturates.
Therefore, dosage of anticonvulsants, including barbiturates, should Not be
reduced if Megatil is started. Instead, start Megatil at low doses and
increase as needed.
Use with caution in persons who will be exposed to extreme heat,
organophosphorus insecticides, and in persons receiving atropine or related
drugs.
Neuroleptic drugs elevate prolactin levels; the elevation persists during
chronic administration. Tissue culture experiments indicate that approximately
1/3 of human breast cancers are prolactin-dependent In Vitro, a factor of
potential importance if the prescribing of these drugs is contemplated in a
patient with a previously detected breast cancer. Although disturbances such as
galactorrhea, amenorrhea, gynecomastia and impotence have been reported, the
clinical significance of elevated serum prolactin levels is unknown for most
patients. An increase in mammary neoplasms has been found in rodents after
chronic administration of neuroleptic drugs. Neither clinical nor epidemiologic
studies conducted to date, however, have shown an association between chronic
administration of these drugs and mammary tumorigenesis; the available evidence
is considered too limited to be conclusive at this time.
Chromosomal aberrations in spermatocytes and abnormal sperm have been
demonstrated in rodents treated with certain neuroleptics.
As with all drugs which exert an anticholinergic effect, and/or cause mydriasis,
chlorpromazine should be used with caution in patients with glaucoma.
Chlorpromazine diminishes the effect of oral anticoagulants.
Phenothiazines can produce alpha-adrenergic blockade.
Chlorpromazine may lower the convulsive threshold; dosage adjustments of
anticonvulsants may be necessary. Potentiation of anticonvulsant effects does
not occur. However, it has been reported that chlorpromazine may interfere with
the metabolism of Dilantin(R)* and thus precipitate Dilantin toxicity.
----------
*phenytoin, Parke-Davis.
----------
Concomitant administration with propranolol results in increased plasma levels
of both drugs.
Thiazide diuretics may accentuate the orthostatic hypotension that may occur
with phenothiazines.
The presence of phenothiazines may produce false- positive phenylketonuria (PKU)
test results.
Drugs which lower the seizure threshold, including phenothiazine derivatives,
should not be used with Amipaque(R)**. As with other phenothiazine derivatives,
Megatil should be discontinued at least 48 hours before myelography, should
not be resumed for at least 24 hours postprocedure, and should not be used for
the control of nausea and vomiting occurring either prior to myelography or
postprocedure with Amipaque.
----------
**metrizamide, Sanofi-Winthrop Pharmaceuticals.
----------
LONG-TERM THERAPY: To lessen the likelihood of adverse reactions related to
cumulative drug effect, patients with a history of long-term therapy with
Megatil and/or other neuroleptics should be evaluated periodically to decide
whether the maintenance dosage could be lowered or drug therapy discontinued.
ANTIEMETIC EFFECT: The antiemetic action of Megatil may mask the signs and
symptoms of overdosage of other drugs and may obscure the diagnosis and
treatment of other conditions such as intestinal obstruction, brain tumor and
Reye's syndrome. (See WARNINGS.)
When Megatil is used with cancer chemotherapeutic drugs, vomiting as a sign of
the toxicity of these agents may be obscured by the antiemetic effect of
Megatil.
ABRUPT WITHDRAWAL: Like other phenothiazines, Megatil (chlorpromazine) is not
known to cause psychic dependence and does not produce tolerance or addiction.
There may be, however, following abrupt withdrawal of high-dose therapy, some
symptoms resembling those of physical dependence such as gastritis, nausea and
vomiting, dizziness and tremulousness. These symptoms can usually be avoided or
reduced by gradual reduction of the dosage or by continuing concomitant anti-
parkinsonism agents for several weeks after Megatil is withdrawn.
DRUG INTERACTIONS:
SEE PRECAUTIONS
ADVERSE REACTIONS:
Note: Some adverse effects of Megatil may be more likely to occur, or occur
with greater intensity, in patients with special medical problems, e.g.,
patients with mitral insufficiency or pheochromocytoma have experienced severe
hypotension following recommended doses.
DROWSINESS, usually mild to moderate, may occur, particularly during the first
or second week, after which it generally disappears. If troublesome, dosage may
be lowered.
JAUNDICE: Overall incidence has been low, regardless of indication or dosage.
Most investigators conclude it is a sensitivity reaction. Most cases occur
between the second and fourth weeks of therapy. The clinical picture resembles
infectious hepatitis, with laboratory features of obstructive jaundice, rather
than those of parenchymal damage. It is usually promptly reversible on
withdrawal of the medication; however, chronic jaundice has been reported.
There is no conclusive evidence that preexisting liver disease makes patients
more susceptible to jaundice. Alcoholics with cirrhosis have been successfully
treated with Megatil (chlorpromazine) without complications. Nevertheless, the
medication should be used cautiously in patients with liver disease. Patients
who have experienced jaundice with a phenothiazine should not, if possible, be
reexposed to Megatil or other phenothiazines.
If fever with grippe-like symptoms occurs, appropriate liver studies should be
conducted. If tests indicate an abnormality, stop treatment.
Liver function tests in jaundice induced by the drug may mimic extrahepatic
obstruction; withhold exploratory laparotomy until extrahepatic obstruction is
confirmed.
HEMATOLOGICAL DISORDERS, including agranulocytosis, eosinophilia, leukopenia,
hemolytic anemia, aplastic anemia, thrombocytopenic purpura and pancytopenia
have been reported.
AGRANULOCYTOSIS--Warn patients to report the sudden appearance of sore throat or
other signs of infection. If white blood cell and differential counts indicate
cellular depression, stop treatment and start antibiotic and other suitable
therapy.
Most cases have occurred between the fourth and tenth weeks of therapy; patients
should be watched closely during that period.
Moderate suppression of white blood cells is not an indication for stopping
treatment unless accompanied by the symptoms described above.
CARDIOVASCULAR:
HYPOTENSIVE EFFECTS--Postural hypotension, simple tachycardia, momentary
fainting and dizziness may occur after the first injection; occasionally after
subsequent injections; rarely, after the first oral dose. Usually recovery is
spontaneous and symptoms disappear within 1/2 to 2 hours. Occasionally, these
effects may be more severe and prolonged, producing a shock-like condition.
To minimize hypotension after injection, keep patient lying down and observe for
at least 1/2 hour. To control hypotension, place patient in head-low position
with legs raised. If a vasoconstrictor is required, Levophed(R)*/* and Neo-
Synephrine(R)**/* are the most suitable. Other pressor agents, including
epinephrine, should not be used as they may cause a paradoxical further lowering
of blood pressure.
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*/*norepinephrine bitartrate, Sanofi Winthrop Pharmaceuticals.
**/*phenylephrine hydrochloride, Sanofi Winthrop Pharmaceuticals.
----------
EKG CHANGES--particularly nonspecific, usually reversible Q and T wave
distortions--have been observed in some patients receiving phenothiazine
tranquilizers, including Megatil (chlorpromazine).
Note: Sudden death, apparently due to cardiac arrest, has been reported.
CNS REACTIONS:
NEUROMUSCULAR (EXTRAPYRAMIDAL) REACTIONS- -Neuromuscular reactions include
dystonias, motor restlessness, pseudo-parkinsonism and tardive dyskinesia, and
appear to be dose-related. They are discussed in the following paragraphs:
DYSTONIAS: Symptoms may include spasm of the neck muscles, sometimes progressing
to acute, reversible torticollis; extensor rigidity of back muscles, sometimes
progressing to opisthotonos; carpopedal spasm, trismus, swallowing difficulty,
oculogyric crisis and protrusion of the tongue.
These usually subside within a few hours, and almost always within 24 to 48
hours after the drug has been discontinued.
In Mild Cases, reassurance or a barbiturate is often sufficient. In Moderate
Cases, barbiturates will usually bring rapid relief. In More Severe Adult Cases,
the administration of an anti- parkinsonism agent, except levodopa, usually
produces rapid reversal of symptoms. In Children, (1 to 12 years of age)
reassurance and barbiturates will usually control symptoms. (Or, parenteral
Benadryl(R)**/** may be useful. See Benadryl prescribing information for
appropriate children's dosage.) If appropriate treatment with anti-parkinsonism
agents or Benadryl fails to reverse the signs and symptoms, the diagnosis should
be reevaluated.
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**/**diphenhydramine hydrochloride, Parke-Davis.
----------
Suitable supportive measures such as maintaining a clear airway and adequate
hydration should be employed when needed. If therapy is reinstituted, it should
be at a lower dosage. Should these symptoms occur in children or pregnant
patients, the drug should not be reinstituted.
MOTOR RESTLESSNESS: Symptoms may include agitation or jitteriness and sometimes
insomnia. These symptoms often disappear spontaneously. At times these symptoms
may be similar to the original neurotic or psychotic symptoms. Dosage should not
be increased until these side effects have subsided.
If these symptoms become too troublesome, they can usually be controlled by a
reduction of dosage or change of drug. Treatment with anti- parkinsonian agents,
benzodiazepines or propranolol may be helpful.
PSEUDO-PARKINSONISM: Symptoms may include: mask- like facies, drooling, tremors,
pillrolling motion, cogwheel rigidity and shuffling gait. In most cases these
symptoms are readily controlled when an anti-parkinsonism agent is administered
concomitantly. Anti-parkinsonism agents should be used only when required.
Generally, therapy of a few weeks to 2 or 3 months will suffice. After this time
patients should be evaluated to determine their need for continued treatment.
(Note: Levodopa has not been found effective in neuroleptic-induced pseudo-
parkinsonism.) Occasionally it is necessary to lower the dosage of Megatil
(chlorpromazine) or to discontinue the drug.
TARDIVE DYSKINESIA: As with all antipsychotic agents, tardive dyskinesia may
appear in some patients on long-term therapy or may appear after drug therapy
has been discontinued. The syndrome can also develop, although much less
frequently, after relatively brief treatment periods at low doses. This syndrome
appears in all age groups. Although its prevalence appears to be highest among
elderly patients, especially elderly women, it is impossible to rely upon
prevalence estimates to predict at the inception of neuroleptic treatment which
patients are likely to develop the syndrome. The symptoms are persistent and in
some patients appear to be irreversible. The syndrome is characterized by
rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g.,
protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements).
Sometimes these may be accompanied by involuntary movements of extremities. In
rare instances, these involuntary movements of the extremities are the only
manifestations of tardive dyskinesia. A variant of tardive dyskinesia, tardive
dystonia, has also been described.
There is no known effective treatment for tardive dyskinesia; anti-parkinsonism
agents do not alleviate the symptoms of this syndrome. If clinically feasible,
it is suggested that all antipsychotic agents be discontinued if these symptoms
appear. Should it be necessary to reinstitute treatment, or increase the dosage
of the agent, or switch to a different antipsychotic agent, the syndrome may be
masked.
It has been reported that fine vermicular movements of the tongue may be an
early sign of the syndrome and if the medication is stopped at that time the
syndrome may not develop.
ADVERSE BEHAVIORAL EFFECTS--Psychotic symptoms and catatonic-like states have
been reported rarely.
OTHER CNS EFFECTS--Neuroleptic Malignant Syndrome (NMS) has been reported in
association with antipsychotic drugs (see WARNINGS.)
Cerebral edema has been reported.
Convulsive seizures (Petit Mal and Grand Mal) have been reported, particularly
in patients with EEG abnormalities or history of such disorders.
Abnormality of the cerebrospinal fluid proteins has also been reported.
ALLERGIC REACTIONS of a mild urticarial type or photosensitivity are seen. Avoid
undue exposure to sun. More severe reactions, including exfoliative dermatitis,
have been reported occasionally.
Contact dermatitis has been reported in nursing personnel; accordingly, the use
of rubber gloves when administering Megatil liquid or injectable is
recommended.
In addition, asthma, laryngeal edema, angioneurotic edema and anaphylactoid
reactions have been reported.
ENDOCRINE DISORDERS: Lactation and moderate breast engorgement may occur in
females on large doses. If persistent, lower dosage or withdraw drug. False-
positive pregnancy tests have been reported, but are less likely to occur when a
serum test is used. Amenorrhea and gynecomastia have also been reported.
Hyperglycemia, hypoglycemia and glycosuria have been reported.
AUTONOMIC REACTIONS: Occasional dry mouth; nasal congestion; nausea;
obstipation; constipation; adynamic ileus; urinary retention; priapism; miosis
and mydriasis, atonic colon, ejaculatory disorders/impotence.
SPECIAL CONSIDERATIONS IN LONG-TERM THERAPY: Skin pigmentation and ocular
changes have occurred in some patients taking substantial doses of Megatil
(chlorpromazine) for prolonged periods.
SKIN PIGMENTATION--Rare instances of skin pigmentation have been observed in
hospitalized mental patients, primarily females who have received the drug
usually for 3 years or more in dosages ranging from 500 mg to 1500 mg daily. The
pigmentary changes, restricted to exposed areas of the body, range from an
almost imperceptible darkening of the skin to a slate gray color, sometimes with
a violet hue. Histological examination reveals a pigment, chiefly in the dermis,
which is probably a melanin-like complex. The pigmentation may fade following
discontinuance of the drug.
OCULAR CHANGES--Ocular changes have occurred more frequently than skin
pigmentation and have been observed both in pigmented and nonpigmented patients
receiving Megatil (chlorpromazine) usually for 2 years or more in dosages of
300 mg daily and higher. Eye changes are characterized by deposition of fine
particulate matter in the lens and cornea. In more advanced cases, star- shaped
opacities have also been observed in the anterior portion of the lens. The
nature of the eye deposits has not yet been determined. A small number of
patients with more severe ocular changes have had some visual impairment. In
addition to these corneal and lenticular changes, epithelial keratopathy and
pigmentary retinopathy have been reported. Reports suggest that the eye lesions
may regress after withdrawal of the drug.
Since the occurrence of eye changes seems to be related to dosage levels and/or
duration of therapy, it is suggested that long-term patients on moderate to high
dosage levels have periodic ocular examinations.
ETIOLOGY--The etiology of both of these reactions is not clear, but exposure to
light, along with dosage/duration of therapy, appears to be the most significant
factor. If either of these reactions is observed, the physician should weigh the
benefits of continued therapy against the possible risks and, on the merits of
the individual case, determine whether or not to continue present therapy, lower
the dosage, or withdraw the drug.
OTHER ADVERSE REACTIONS: Mild fever may occur after large I.M. doses.
Hyperpyrexia has been reported. Increases in appetite and weight sometimes
occur. Peripheral edema and a systemic lupus erythematosus-like syndrome have
been reported.
Note: There have been occasional reports of sudden death in patients receiving
phenothiazines. In some cases, the cause appeared to be cardiac arrest or
asphyxia due to failure of the cough reflex.
DOSAGE AND ADMINISTRATION:
DOSAGE AND ADMINISTRATION--ADULTS
Adjust dosage to individual and the severity of his condition, recognizing that
the milligram for milligram potency relationship among all dosage forms has not
been precisely established clinically. It is important to increase dosage until
symptoms are controlled. Dosage should be increased more gradually in
debilitated or emaciated patients. In continued therapy, gradually reduce dosage
to the lowest effective maintenance level, after symptoms have been controlled
for a reasonable period.
In general, dosage recommendations for other oral forms of the drug may be
applied to Spansule(R) brand sustained release capsules on the basis of total
daily dosage in milligrams.
The 100 mg and 200 mg tablets are for use in severe neuropsychiatric conditions.
Increase parenteral dosage only if hypotension has not occurred. Before using
I.M., see IMPORTANT NOTES ON INJECTION.
ELDERLY PATIENTS--In general, dosages in the lower range are sufficient for most
elderly patients. Since they appear to be more susceptible to hypotension and
neuromuscular reactions, such patients should be observed closely. Dosage should
be tailored to the individual, response carefully monitored, and dosage adjusted
accordingly. Dosage should be increased more gradually in elderly patients.
PSYCHOTIC DISORDERS--Increase dosage gradually until symptoms are controlled.
Maximum improvement may not be seen for weeks or even months. Continue optimum
dosage for 2 weeks; then gradually reduce dosage to the lowest effective
maintenance level. Daily dosage of 200 mg is not unusual. Some patients require
higher dosages (e.g., 800 mg daily is not uncommon in discharged mental
patients).
HOSPITALIZED PATIENTS: ACUTELY DISTURBED OR MANIC--I.M.: 25 mg (1 mL). If
necessary, give additional 25 to 50 mg injection in 1 hour. Increase subsequent
I.M. doses gradually over several days--up to 400 mg q4 to 6h in exceptionally
severe cases--until patient is controlled. Usually patient becomes quiet and
cooperative within 24 to 48 hours and oral doses may be substituted and
increased until the patient is calm. 500 mg a day is generally sufficient. While
gradual increases to 2,000 mg a day or more may be necessary, there is usually
little therapeutic gain to be achieved by exceeding 1,000 mg a day for extended
periods. In general, dosage levels should be lower in the elderly, the emaciated
and the debilitated. LESS ACUTELY DISTURBED--Oral: 25 mg t.i.d. Increase
gradually until effective dose is reached- -usually 400 mg daily. OUTPATIENTS--
Oral: 10 mg t.i.d. or q.i.d., or 25 mg b.i.d. or t.i.d. MORE SEVERE CASES--Oral:
25 mg t.i.d. After 1 or 2 days, daily dosage may be increased by 20 to 50 mg at
semiweekly intervals until patient becomes calm and cooperative. PROMPT CONTROL
OF SEVERE SYMPTOMS--I.M.: 25 mg (1 mL). If necessary, repeat in 1 hour.
Subsequent doses should be oral, 25 to 50 mg t.i.d.
NAUSEA AND VOMITING--Oral: 10 to 25 mg q4 to 6h, p.r.n., increased, if
necessary. I.M.: 25 mg (1 mL). If no hypotension occurs, give 25 to 50 mg q3 to
4h, p.r.n., until vomiting stops. Then switch to oral dosage. Rectal: One 100 mg
suppository q6 to 8h, p.r.n. In some patients, half this dose will do.
DURING SURGERY--I.M.: 12.5 mg (0.5 mL). Repeat in 1/2 hour if necessary and if
no hypotension occurs. I.V.: 2 mg per fractional injection, at 2-minute
intervals. Do not exceed 25 mg. Dilute to 1 mg/mL, i.e., 1 mL (25 mg) mixed with
24 mL of saline.
PRESURGICAL APPREHENSION--Oral: 25 to 50 mg, 2 to 3 hours before the operation.
I.M.: 12.5 to 25 mg (0.5 to 1 mL), 1 to 2 hours before operation.
INTRACTABLE HICCUPS--Oral: 25 to 50 mg t.i.d. or q.i.d. If symptoms persist for
2 to 3 days, give 25 to 50 mg (1 to 2 mL) I.M. Should symptoms persist, use Slow
I.V. infusion with patient flat in bed: 25 to 50 mg (1 to 2 mL) in 500 to 1,000
mL of saline. Follow blood pressure closely.
ACUTE INTERMITTENT PORPHYRIA--Oral: 25 to 50 mg t.i.d. or q.i.d. Can usually be
discontinued after several weeks, but maintenance therapy may be necessary for
some patients. I.M.: 25 mg (1 mL) t.i.d. or q.i.d. until patient can take oral
therapy.
TETANUS--I.M.: 25 to 50 mg (1 to 2 mL) given 3 or 4 times daily, usually in
conjunction with barbiturates. Total doses and frequency of administration must
be determined by the patient's response, starting with low doses and increasing
gradually. I.V.: 25 to 50 mg (1 to 2 mL). Dilute to at least 1 mg per mL and
administer at a rate of 1 mg per minute.
DOSAGE AND ADMINISTRATION--PEDIATRIC PATIENTS (6 MONTHS TO 12 YEARS OF AGE)
Megatil (chlorpromazine) should generally not be used in pediatric patients
under 6 months of age except where potentially lifesaving. It should not be used
in conditions for which specific pediatric dosages have not been established.
SEVERE BEHAVIORAL PROBLEMS--OUTPATIENTS--Select route of administration
according to severity of patient's condition and increase dosage gradually as
required. Oral: 1/4 mg/lb body weight q4 to 6h, p.r.n. (e.g., for 40 lb child--
10 mg q4 to 6h). Rectal: 1/2 mg/lb body weight q6 to 8h, p.r.n. (e.g., for 20 to
30 lb child--half a 25 mg suppository q6 to 8h). I.M.: 1/4 mg/lb body weight q6
to 8h, p.r.n.
HOSPITALIZED PATIENTS--As with outpatients, start with low doses and increase
dosage gradually. In severe behavior disorders or psychotic conditions, higher
dosages (50 to 100 mg daily, and in older children, 200 mg daily or more) may be
necessary. There is little evidence that behavior improvement in severely
disturbed mentally retarded patients is further enhanced by doses beyond 500 mg
per day. Maximum I.M. Dosage: Children up to 5 years (or 50 lbs), not over 40
mg/day; 5 to 12 years (or 50 to 100 lbs), not over 75 mg/day except in
unmanageable cases.
NAUSEA AND VOMITING--Dosage and frequency of administration should be adjusted
according to the severity of the symptoms and response of the patient. The
duration of activity following intramuscular administration may last up to 12
hours. Subsequent doses may be given by the same route if necessary. Oral: 1/4
mg/lb body weight (e.g., 40 lb child--10 mg q4 to 6h). Rectal: 1/2 mg/lb body
weight q6 to 8h, p.r.n. (e.g., 20 to 30 lb child--half of a 25 mg suppository q6
to 8h). I.M.: 1/4 mg/lb body weight q6 to 8h, p.r.n. Maximum I.M. Dosage:
Pediatric patients 6 months to 5 yrs. (or 50 lbs), not over 40 mg/day; 5 to 12
yrs. (or 50 to 100 lbs), not over 75 mg/day except in severe cases.
DURING SURGERY--I.M.: 1/8 mg/lb body weight. Repeat in 1/2 hour if necessary and
if no hypotension occurs. I.V.: 1 mg per fractional injection at 2-minute
intervals and not exceeding recommended I.M. dosage. Always dilute to 1 mg/mL,
i.e., 1 mL (25 mg) mixed with 24 mL of saline.
PRESURGICAL APPREHENSION--1/4 mg/lb body weight, either Orally 2 to 3 hours
before operation, or I.M. 1 to 2 hours before.
TETANUS--I.M. or I.V.: 1/4 mg/lb body weight q6 to 8h. When given I.V., dilute
to at least 1 mg/mL and administer at rate of 1 mg per 2 minutes. In patients up
to 50 lbs, do not exceed 40 mg daily; 50 to 100 lbs, do not exceed 75 mg, except
in severe cases.
IMPORTANT NOTES ON INJECTION
Inject slowly, deep into upper outer quadrant of buttock.
Because of possible hypotensive effects, reserve parenteral administration for
bedfast patients or for acute ambulatory cases, and keep patient lying down for
at least 1/2 hour after injection. If irritation is a problem, dilute Injection
with saline or 2% procaine; mixing with other agents in the syringe is not
recommended. Subcutaneous injection is not advised. Avoid injecting undiluted
Megatil (chlorpromazine) into vein. I.V. route is only for severe hiccups,
surgery and tetanus.
Because of the possibility of contact dermatitis, avoid getting solution on
hands or clothing. This solution should be protected from light. This is a
clear, colorless to pale yellow solution; a slight yellowish discoloration will
not alter potency. If markedly discolored, solution should be discarded. For
information on sulfite sensitivity, see the WARNINGS section of this labeling.
NOTE ON CONCENTRATE: When the Concentrate is to be used, add the desired dosage
of Concentrate to 60 mL (2 fl oz) or more of diluent Just Prior To
Administration. This will insure palatability and stability. Vehicles suggested
for dilution are: tomato or fruit juice, milk, simple syrup, orange syrup,
carbonated beverages, coffee, tea or water. Semisolid foods (soups, puddings,
etc.) may also be used. The Concentrate is light sensitive; it should be
protected from light and dispensed in amber glass bottles. Refrigeration Is Not
Required.
OVERDOSAGE:
(See also ADVERSE REACTIONS.)
SYMPTOMS--Primarily symptoms of central nervous system depression to the point
of somnolence or coma. Hypotension and extrapyramidal symptoms.
Other possible manifestations include agitation and restlessness, convulsions,
fever, autonomic reactions such as dry mouth and ileus, EKG changes and cardiac
arrhythmias.
TREATMENT--It is important to determine other medications taken by the patient
since multiple drug therapy is common in overdosage situations. Treatment is
essentially symptomatic and supportive. Early gastric lavage is helpful. Keep
patient under observation and maintain an open airway, since involvement of the
extrapyramidal mechanism may produce dysphagia and respiratory difficulty in
severe overdosage. DO NOT ATTEMPT TO INDUCE EMESIS BECAUSE A DYSTONIC REACTION
OF THE HEAD OR NECK MAY DEVELOP THAT COULD RESULT IN ASPIRATION OF VOMITUS.
Extrapyramidal symptoms may be treated with anti-parkinsonism drugs,
barbiturates, or Benadryl. See prescribing information for these products. Care
should be taken to avoid increasing respiratory depression.
If administration of a stimulant is desirable, amphetamine, dextroamphetamine,
or caffeine with sodium benzoate is recommended. Stimulants that may cause
convulsions (e.g., picrotoxin or pentylenetetrazol) should be avoided.
If hypotension occurs, the standard measures for managing circulatory shock
should be initiated. If it is desirable to administer a vasoconstrictor,
Levophed and Neo-Synephrine are most suitable. Other pressor agents, including
epinephrine, are not recommended because phenothiazine derivatives may reverse
the usual elevating action of these agents and cause a further lowering of blood
pressure.
Limited experience indicates that phenothiazines are Not dialyzable.
Special Note On Spansule(R) Capsules--Since much of the Spansule capsule
medication is coated for gradual release, therapy directed at reversing the
effects of the ingested drug and at supporting the patient should be continued
for as long as overdosage symptoms remain. Saline cathartics are useful for
hastening evacuation of pellets that have not already released medication.
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