A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Fiorinal-Cod Side Effects, and Drug Interactions - Butalbital Compound With Codeine
Fiorinal-Cod Side Effects, and Drug Interactions - Butalbital Compound With Codeine
SIDE EFFECTS
Commonly Observed
The most commonly reported adverse events associated with the use
of Butalbital compound
with Codeine and not reported at an equivalent
incidence by placebo
treated patients were nausea
and/or abdominal pain,
drowsiness, and dizziness.
Associated with Treatment Discontinuation
Of the 382 patients treated with Butalbital compound
with Codeine in controlled clinical
trials, three (0.8%) discontinued treatment
with Butalbital compound with Codeine because of adverse events.
One patient each discontinued
treatment for the following reasons: gastrointestinal
upset; lightheadedness and heavy eyelids; and drowsiness
and generalized tingling.
Incidence in Controlled Clinical Trials
The following table summarizes
the incidence rates
of the adverse events reported by at least 1% of the Butalbital
compound with Codeine
treated patients in controlled clinical
trials comparing Butalbital compound
with Codeine to placebo,
and provides a comparison to the incidence
rates reported by the placebo-treated patients.
The prescriber should be aware that these figures cannot be used
to predict the incidence
of side effects in the
course of usual medical
practice where patient
characteristics and other factors differ from those that prevailed
in the clinical trials.
Similarly, the cited frequencies cannot be compared with figures
obtained from other clinical
investigations involving different treatments, uses, and investigators.
|
ADVERSE EVENTS REPORTED
BY AT LEAST 1% OF Butalbital compound
WITH CODEINE TREATED PATIENTS DURING PLACEBO CONTROLLED CLINICAL
TRIALS
|
|
BODY SYSTEM/ADVERSE EVENT
|
INCIDENCE R.T.
OF ADVERSE EVENTS
|
|
Butalbital cmp/COD
|
PLACEBO
|
|
(N=382)
|
(N=377)
|
| CENTRAL NERVOUS |
| Drowsiness |
2.4%
|
0.5%
|
| Dizziness/Lightheadedness |
2.6%
|
0.5%
|
| Intoxicated Feeling |
1.0%
|
0%
|
| GASTROINTESTINAL |
| Nausea/Abdominal Pain |
3.7%
|
0.8%
|
Other Adverse Events Reported During Controlled Clinical Trials
The listing that follows represents the proportion of the 382 patients
exposed to Butalbital compound
with Codeine while participating in the controlled clinical
trials who reported, on at least one occasion, an adverse event
of the type cited. All
reported adverse events, except those already presented in the previous
table, are included. It is important to emphasize that, although
the adverse events reported did occur while the patient was receiving
Butalbital compound
with Codeine, the adverse events were not necessarily caused by
Butalbital compound
with Codeine.
Adverse events are classified by body
system and frequency.
"Frequent" is defined as an adverse event which occurred
in at least 1/100 (1%) of the patients; all adverse events listed
in the previous table
are frequent. "Infrequent" is defined as an adverse event
that occurred in less than 1/100 patients but at least 1/1000 patients.
All adverse events tabulated below are classified as infrequent.
Central Nervous: headache,
shaky feeling, tingling, agitation,
fainting, fatigue, heavy eyelids, high energy, hot
spells, numbness, and sluggishness.
Autonomic Nervous: dry mouth
and hyperhidrosis.
Gastrointestinal: vomiting,
difficulty swallowing, and heartburn.
Cardiovascular: tachycardia.
Musculoskeletal: leg
pain and muscle
fatigue.
Genitourinary: diuresis.
Miscellaneous: pruritus,
fever, earache, nasal
congestion, and tinnitus.
Voluntary reports of adverse drug
events, temporally associated with Butalbital compound
with Codeine, that have been received since market introduction
and that were not reported in clinical
trials by the patients treated with Butalbital compound
with Codeine, are listed below. Many or most of these events may
have no causal relationship
with the drug and are listed
according to body system.
Central Nervous: Abuse, addiction,
anxiety, depression,
disorientation, hallucination, hyperactivity, insomnia,
libido decrease, nervousness,
neuropathy, psychosis, sedation,
sexual activity
increase, slurred speech, twitching, unconsciousness, vertigo.
Autonomic Nervous: epistaxis,
flushing, miosis, salivation.
Gastrointestinal: anorexia,
appetite increased,
constipation, diarrhea,
esophagitis, gastroenteritis,
gastrointestinal
spasm, hiccup,
mouth burning, pyloric
ulcer.
Cardiovascular: chest
pain, hypotensive
reaction, palpitations,
syncope.
Skin: erythema,
erythema multiforme,
exfoliative dermatitis,
hives, rash, toxic epidermal
necrolysis.
Urinary: kidney
impairment, urinary
difficulty.
Miscellaneous: allergic
reaction, anaphylactic
shock, cholangiocarcinoma, drug interaction with erythromycin
(stomach upset), edema.
The following adverse drug
events may be borne in mind
as potential effects of the components of Butalbital compound
with Codeine. Potential effects of high dosage
are listed in the OVERDOSAGE section
of this insert.
Aspirin: occult
blood loss, hemolytic
anemia, iron
deficiency anemia,
gastric distress, heartburn, nausea,
peptic ulcer,
prolonged bleeding
time, acute airway obstruction,
renal toxicity
when taken in high doses for prolonged periods, impaired urate
excretion, hepatitis.
Caffeine: cardiac
stimulation, irritability, tremor,
dependence, nephrotoxicity
hyperglycemia.
Codeine: nausea,
vomiting, drowsiness,
lightheadedness, constipation, pruritus.
DRUG ABUSE AND DEPENDENCE
Butalbital compound
with Codeine is controlled by the Drug Enforcement Administration
and is classified under Schedule III.
Codeine
Codeine can produce drug
dependence of the
morphine type
and therefore, has the
potential for being
abused. Psychological dependence,
physical dependence, and tolerance
may develop upon repeated administration
and it should be prescribed and administered with the same degree
of caution appropriate to the use of other oral
narcotic medications.
Butalbital
Barbiturates May Be Habit
Forming: Tolerance, psychological
dependence, and physical
dependence may occur
especially following prolonged use of high doses of barbiturates.
The average daily dose
for the barbiturate addict is usually about 1,500 mg. As
tolerance to barbiturates
develops, the amount needed to maintain the same level of intoxication
increases; tolerance to a fatal
dosage, however, does
not increase more than two-fold. As this occurs, the margin
between an intoxication
dosage and fatal
dosage becomes smaller. The lethal
dose of a barbiturate is
far less if alcohol is also ingested. Major withdrawal
symptoms (convulsions and delirium) may occur within 16 hours and
last up to 5 days after abrupt cessation of these drugs. Intensity
of withdrawal symptoms
gradually declines over a period
of approximately 15 days. Treatment of barbiturate dependence consists
of cautious and gradual withdrawal
of the drug. Barbiturate-dependent patients can be withdrawn by
using a number of different
withdrawal regimens.
One method involves initiating
treatment at the patient's
regular dosage level
and gradually decreasing the daily dosage
as tolerated by the patient.
DRUG INTERACTIONS
The CNS effects of butalbital
may be enhanced by monoamine
oxidase (MAO) inhibitors.
In patients receiving concomitant
corticosteroids and chronic
use of aspirin, withdrawal
of corticosteroids may result in salicylism
because corticosteroids enhance renal
clearance of salicylates
and their withdrawal is followed by return to normal
rates of renal clearance.
Butalbital compound
with Codeine may enhance the effects of:
1. Oral anticoagulants, causing bleeding
by inhibiting prothrombin
formation in the liver
and displacing anticoagulants from plasma
protein binding sites.
2. Oral antidiabetic
agents and insulin,
causing hypoglycemia
by contributing an additive
effect, if dosage of
Butalbital compound
with Codeine exceeds maximum recommended daily dosage.
3. 6-mercaptopurine and methotrexate, causing bone
marrow toxicity
and blood dyscrasias by displacing these drugs from secondary
binding sites, and, in the case
of methotrexate, also reducing its excretion.
4. Non-steroidal anti-inflammatory
agents, increasing the risk
of peptic ulceration and bleeding
by contributing additive
effects.
5. Other narcotic
analgesics, alcohol,
general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics,
or other CNS depressants,
causing increased CNS depression.
Butalbital compound
with Codeine may diminish the effects of:
Uricosuric agents such
as probenecid and
sulfinpyrazone, reducing their effectiveness in the treatment
of gout. Aspirin competes with these agents for protein
binding sites.
(See Also PRECAUTIONS)
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