Trimeprazine Tartrate
A white or slightly cream-coloured odourless or almost
odourless crystalline powder. It darkens in colour on exposure
to light. Trimeprazine tartrate 25 mg is approximately equiv-
lent to 20 mg of trimeprazine.
BP solubilities are ; soluble 1 in 2 of water, 1 in 20 of alco-
hol, 1 in 5 of chloroform, and 1 in 1800 either. A 2% solu- tion
in water has a pH of 5.0 to 6.5. Store in airtight
Containers. Protect from light.
Adverse Effects and Precautions are as for the sedating antihistamines in general, like promethazine whose details are given below :
PRECAUTIONS:
Promethazine may significantly affect the actions of other drugs. It may
increase, prolong, or intensify the sedative action of central-nervous- system
depressants, such as alcohol, sedative hypnotics (including barbiturates),
general anesthetics, narcotics, narcotic analgesics, tranquilizers, etc. When
given concomitantly with promethazine hydrochloride, the dose of barbiturates
should be reduced by at least one- half, and the dose of narcotics should be
reduced by one-quarter to one-half. Dosage must be individualized. Excessive
amounts of promethazine relative to a narcotic may lead to restlessness and
motor hyperactivity in the patient with pain; these symptoms usually disappear
with adequate control of the pain. Promethazine should be used cautiously in
persons with cardiovascular disease or impairment of liver function.
Although reversal of the vasopressor effect of epinephrine has not been reported
with promethazine, the possibility should be considered in case of promethazine
overdose.
ADVERSE REACTIONS:
CNS EFFECTS
Drowsiness is the most prominent CNS effect of this drug. Extrapyramidal
reactions may occur with high doses; this is almost always responsive to a
reduction in dosage. Other reported reactions include dizziness, lassitude,
tinnitus, incoordination, fatigue, blurred vision, euphoria, diplopia,
nervousness, insomnia, tremors, convulsive seizures, oculogyric crises,
excitation, catatonic-like states, and hysteria.
CARDIOVASCULAR EFFECTS
Tachycardia, bradycardia, faintness, dizziness, and increases and decreases in
blood pressure have been reported following the use of promethazine
hydrochloride injection. Venous thrombosis at the injection site has been
reported. INTRA-ARTERIAL INJECTION MAY RESULT IN GANGRENE OF THE AFFECTED
EXTREMITY ("see WARNINGS").
GASTROINTESTINAL
Nausea and vomiting have been reported, usually in association with surgical
procedures and combination drug therapy.
ALLERGIC REACTIONS
These include urticaria, dermatitis, asthma, and photosensitivity. Angioneurotic
edema has been reported.
OTHER REPORTED REACTIONS
Leukopenia and agranulocytosis, usually when Phenergan has been used in
association with other known toxic agents, have been reported. Thrombocytopenic
purpura and jaundice of the obstructive type have been associated with the use
of promethazine. The jaundice is usually reversible on discontinuation of the
drug. Subcutaneous injection has resulted in tissue necrosis. Nasal stuffiness
may occur. Dry mouth has been reported.
LABORATORY TESTS
The following laboratory tests may be affected in patients who are receiving
therapy with promethazine hydrochloride:
Pregnancy Tests--Diagnostic pregnancy tests based on immunological reactions
between HCG and anti- HCG may result in false-negative or false- positive
interpretations.
Glucose Tolerance Test--An increase in glucose tolerance has been reported in
patients receiving promethazine hydrochloride.
PARADOXICAL REACTIONS (OVERDOSAGE)
Hyperexcitability and abnormal movements, which have been reported in children
following a single administration of promethazine, may be manifestations of
relative overdosage, in which case, consideration should be given to the
discontinuation of the promethazine and to the use of other drugs. Respiratory
depression, nightmares, delirium, and agitated behavior have also been reported
in some of these patients.
Children : There have been reports of adverse effects in chil-
dren given trimeprazine tartrate by mouth. Fatal malignant
hyperthermia and severe cardiovascular depression have oc-
curred after its use for premedication, and severe respiratory
and CNS depression after use as a postoperative sedative.
Doses in these 3 reports ranged from 2.4 to 4.4 mg per kg
body-weight. A possible association between phenothiazine
sedatives and sudden infant death syndrome has also been
suggested, but has not been confirmed (see Promethazine Hy-
drochloride). The UK manufacturers no longer indi-
cate trimeprazine tartrate for short-term sedation in children
and recommend that it should not be used in infants less than
2 years of age. The maximum recommended dose for pre-
medication for children aged 2 to 7 years is 2 mg per kg bodv-
weicht by mouth. There has recently been a warning that the
use of trimeprazine for sedation in diagnostic and thera-
peutic procedures in children is associated with prolonged
drowsiness and that standards of monitoring, starvation, and
post procedural care should be similar to those with general
anaesthesia.
Interactions as for the sedating antihistamines in general like promethazine whose details are given below :
DRUG INTERACTIONS:
NARCOTICS AND BARBITURATES
The CNS-depressant effects of narcotics and barbiturates are additive with
promethazine hydrochloride.
MONOAMINE OXIDASE INHIBITORS (MAOI)
Drug interactions, including an increased incidence of extrapyramidal effects,
have been reported when some MAOI and phenothiazines are used concomitantly.
Although such a reaction has not been reported with promethazine, the
possibility should be considered.
Uses and Administration
Trimeprazine, a phenothiazine derivative, a sedat-
ing antihistamine with antiemetic activity and pro-
nounced sedative effects. It also has some
antimuscarinic actions. It is used mainly for its
marked effect in the relief of pruritus and in
the UK, for pre-operative medication in children.
Trimeprazine may also be used in compound prepa-
rations for the symptomatic treatment of coughs.
Trimeprazine tartrate is administered by mouth:
doses in the UK are given as the amount of trimepra-
zine tartrate: those in the USA are expressed in
terms of the equivalent amount of trimeprazine.
Even allowing for this, lower doses are used in the
USA. The dose of trimeprazine tartrate used in the
UK for the relief of pruritus in adults is 10 mg two
or three times daily: up to 100 mg daily has been
given in refractory cases. Elderly patients are given
10 mg once or twice daily and children over 2 years
of age 2.5 to 5 mg three or four times daily. In the
USA the dose is the equivalent of trimeprazine
2.5 mg four times daily, or 5 mg twice daily as a
modified-release preparation. Children in the USA
between 2 and 3 years of age have been given
1.25 mg at night or three times daily; for older chil-
dren this dose has been increased to 2.5 mg.
The usual recommended dose for premedication in
children over 2 years is 2 mg per kg body-weight
given by mouth about one to two hours before the
operation.
Anaesthesia. Trimeprazine tartrate may be used for anaes-
thetic premedication in children when the oral
route of administration is preferred to the more usual
parenteral route of other phenothiazine antihistamines. Ad-
verse effects have. however, been reported in children (see
Administration in Children under Adverse Effects and Pre-
cautions above). The U.K. manufacturers recommend that tri-
meprazine tartrate should not be used in infants less than 2
years of age.
Insomnia. Antihistamines such as trimeprazine tartrate have
been used as alternatives to benzodiazepines for the treatment
of insomnia, particularly for children. However, they
are only indicated for short-term use. and antimuscarinic
side-effects may prove troublesome.
Regimens involving a short course of trimeprazine tartrate in
high dosage were tried in order to alter the sleep pattern of
children with sleeping difficulties. Adverse effects have.
however, been reported in children. The
UK manufacturers no longer indicate trimeprazine tartrate for
short-term sedation in children and recommend that it should
not be used in infants less than 2 years of age.