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
Tegretol Side Effects, and Drug Interactions - Carbamazepine
Tegretol Side Effects, and Drug Interactions - Carbamazepine
SIDE EFFECTS
If adverse reactions are of such
severity that the drug
must be discontinued, the physician
must be aware that abrupt discontinuation of any anticonvulsant
drug in a responsive epileptic
patient may lead
to seizures or even status epilepticus with its life-threatening
hazards.
The most severe adverse reactions have been observed in the hemopoietic
system (see DESCRIPTION: BOXED
WARNING) , the skin
and the cardiovascular
system.
The most frequently observed adverse reactions, particularly during
the initial phases of
therapy, are dizziness,
drowsiness, unsteadiness,
nausea, and vomiting. To minimize the possibility of such
reactions, therapy should be initiated at the low dosage
recommended.
The following additional adverse reactions have been reported:
Hemopoietic System: Aplastic anemia,
agranulocytosis,
pancytopenia, bone marrow
depression, thrombocytopenia,
leukopenia, leukocytosis,
eosinophilia, acute intermittent
porphyria.
Skin: Pruritic and erythematous rashes, urticaria,
toxic epidermal necrolysis
(Lyell's Syndrome) (see WARNINGS),
Stevens-Johnson syndrome
(see WARNINGS), photosensitivity
reactions, alterations in skin
pigmentation,
exfoliative dermatitis, erythema
multiforme and nodosum, purpura,
aggravation of disseminated lupus erythematosus, alopecia,
and diaphoresis. In certain
cases, discontinuation of therapy
may be necessary. Isolated cases of hirsutism
have been reported, but a causal relationship is not clear.
Cardiovascular System: Congestive heart
failure, edema, aggravation
of hypertension,
hypotension, syncope
and collapse, aggravation of coronary artery disease,
arrhythmias and AV block, primary
thrombophlebitis,
recurrence of thrombophlebitis,
and adenopathy
or lymphadenopathy. Some of these cardiovascular complications
have resulted in fatalities. Myocardial infarction
has been associated with other tricyclic compounds.
Liver: Abnormalities in liver
function tests, cholestatic
and hepatocellular jaundice,
hepatitis.
Respiratory System: Pulmonary hypersensitivity
characterized by fever,
dyspnea, pneumonitis
or pneumonia.
Genitourinary System: Urinary frequency, acute
urinary retention,
oliguria with elevated blood
pressure, azotemia,
renal failure, and impotence.
Albuminuria, elevated BUN
and microscopic deposits in the urine
have also been reported. Testicular atrophy
occurred in rats receiving carbamazepine orally from 4 to 52 weeks
at dosage levels of
50 to 400 mg/kg/day. Additionally, rats receiving carbamazepine
in the diet for two years
at dosage levels of
25, 75, and 250 mg/kg/day had a dose
related incidence
of testicular atrophy and aspermatogenesis. In
dogs, it produced a brownish discoloration, presumably a metabolite,
in the urinary bladder
at dosage levels of
50 mg/kg and higher. Relevance of these findings to humans is
unknown.
Nervous System: Dizziness, drowsiness,
disturbances of coordination, confusion, headache,
fatigue, blurred vision,
visual hallucinations,
transient diplopia, oculomotor
disturbances, nystagmus,
speech disturbances,
abnormal involuntary movements, peripheral
neuritis and paresthesias,
depression with agitation,
talkativeness, tinnitus,
and hyperacusis. There have been reports of associated paralysis
and other symptoms of cerebral arterial insufficiency, but the
exact relationship of these reactions to the drug has not been
established.
Digestive System: Nausea, vomiting,
gastric distress
and abdominal pain, diarrhea,
constipation,
anorexia, and dryness
of the mouth and pharynx,
including glossitis
and stomatitis.
Eyes: Scattered punctate
cortical lens
opacities, as well as conjunctivitis, have been reported. Although
a direct causal relationship has not been established, many phenothiazines
and related drugs have been shown to cause
eye changes.
Musculoskeletal System: Aching joints and muscles, and
leg cramps.
Metabolism: Fever and chills. Inappropriate antidiuretic
hormone (ADH) secretion
syndrome has been
reported. Cases of frank
water intoxication,
with decreased serum
sodium (hyponatremia)
and confusion, have
been reported in association
with carbamazepine
use (see PRECAUTIONS, Laboratory
Tests).
Other: Isolated cases of lupus
erythematosus-like syndrome
have been reported. There have been occasional reports of elevated
levels of cholesterol, HDL
cholesterol and
triglycerides
in patients taking anticonvulsants.
A case of aseptic meningitis,
accompanied by myoclonus
and peripheral eosinophilia, has been reported in a patient
taking carbamazepine
in combination with other medications. The patient
was successfully dechallenged, and the meningitis
reappeared upon rechallenge with carbamazepine.
Drug Abuse and Dependence
No evidence of abuse
potential has been
associated with carbamazepine, nor is there evidence
of psychological
or physical dependence
in humans.
DRUG INTERACTIONS
The simultaneous administration
of phenobarbital, phenytoin, or primidone, or a combination of two,
produces a marked lowering of serum
levels, of carbamazepine. The effect
of valproic acid on carbamazepine
blood levels is not clearly
established, although an increase in the ratio
of active 10, 11-epoxide metabolite
to parent compound
is a consistent finding.
The half-lives of phenytoin, warfarin, doxycycline, and theophylline
were significantly shortened when administered concurrently with
carbamazepine. Haloperidol and valproic acid
serum levels may be reduced
when these drugs are administered with carbamazepine. The doses
of these drugs may therefore have to be increased when carbamazepine
is added to the therapeutic
regimen.
Concomitant administration
of carbamazepine
with erythromycin, cimetidine, propoxyphene, isoniazid, fluoxetine
or calcium channel
blockers has been reported to result in elevated plasma
levels of carbamazepine
resulting in toxicity
in some cases. Also concomitant
administration
of carbamazepine and lithium
may increase the risk of
neurotoxic side effects.
Alterations of thyroid
function have been
reported in combination therapy with other anticonvulsant
medications.
Breakthrough bleeding
has been reported among patients receiving concomitant oral contraceptives
and their reliability
may be adversely affected.
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