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
Nydrazid Side Effects, and Drug Interactions - Isoniazid
Nydrazid Side Effects, and Drug Interactions - Isoniazid
SIDE EFFECTS
The most frequent reactions are those affecting the nervous
system and the liver.
Nervous System REACTIONS
Peripheral neuropathy
is the most common toxic
effect. It is dose-related, occurs most often in the malnourished
and in those predisposed to neuritis (e.g., alcoholics and diabetics),
and is usually preceded by paresthesias of the feet
and hands. The incidence
is higher in "slow inactivators".
Other neurotoxic effects, which are uncommon with conventional
doses, are convulsions, toxic
encephalopathy,
optic neuritis
and atrophy, memory
impairment, and toxic
psychosis.
Hepatic REACTIONS: (See DESCRIPTION
,
boxed WARNING). Elevated serum
transaminase (SGOT
SGPT), bilirubinemia, bilirubinuria, jaundice,
and occasionally severe and sometimes fatal
hepatitis. The common prodromal
symptoms of hepatitis
are anorexia nausea,
vomiting, fatigue, malaise,
and weakness. Mild hepatic
dysfunction, evidenced by mild and transient
elevation of serum
transaminase levels
occurs in 10 to 20 percent
of patients taking isoniazid. This abnormality
usually appears in the first 1 to 3 months of treatment
but can occur at any time
during therapy. In most instances
enzyme levels return
to normal, and generally,
there is no necessity to
discontinue medication
during the period of
mild serum transaminase
elevation. In occasiona instances,
progressive liver
damage occurs, with accompanying symptoms. If the SGOT
value exceeds three to
five times the upper limit
of normal, discontinuation
of the isoniazid should be strongly considered. The frequency
of progressive liver
damage increases with age
It is rare in persons under 20, but occurs in up to 2.3 percent
of those over 50 years of age.
Gastrointestinal REACTIONS
Nausea, vomiting,
and epigastric distress.
Hematologic REACTIONS
Agranulocytosis; hemolytic, sideroblastic, or aplastic anemia,
thrombocytopenia; and eosinophilia.
Hypersensitivity REACTIONS
Fever, skin eruptions
(morbilliform, maculopapular,
purpuric, or exfoliative), lymphadenopathy, and vasculitis. Metabolic
And Endocrine Reaction: Pyridoxine deficiency, pellagra, hyperglycemia,
metabolic acidosis,
and gynecomastia.
Miscellanous REACTIONS
Rheumatic syndrome
and systemic lupus
erythematosus like syndrome.
DRUG INTERACTIONS
Food: Isoniazid should not be administered with food.
Studies have shown that the bioavailability
of isoniazid is reduced
significantly when administered with food.
Acetaminophen: A report
of severe acetaminophen
toxicity was reported in a patient
receiving Isoniazid. It is believed that the toxicity may have resulted
from a previously unrecognized interaction between isoniazid and
acetaminophen
and a molecular basis
for this interaction has been proposed. However, current
evidence suggests that
isoniazid does induce
P-450IIE1, a mixed-function oxidase
enzyme that appears to
generate the toxic metabolites,
in the liver. Furthermore it has been proposed that isoniazid resulted
In induction
of P-450IIE1 in the patients liver
which, in turn, resulted in a greater proportion of the ingested
acetaminophen being converted to the toxic
metabolites. Studies have demonstrated that pretreatment with isoniazid
potentiates a cetaminophen hepatoxicity in rats.
Carbamazepine: Isoniazid is known to slow
the metabolism of carbamazepine
and increase its serum
levels Carbamazepine levels should be determined prior to concurrent
administration
with isoniazid, signs and symptoms of carbamazepine
toxicity should be
monitored closely, and appropriate dosage
adjustment of the
anticonvulsant
should be made.
Ketoconazole: Potential interaction of Ketoconazole
and Isoniazid may exist. When Ketoconazole is given in combination
with isoniazid and rifampin
the AUC of ketoconazole
is decreased by as much as 88% after 5 months of concurrent Isoniazid
and Rifampin therapy.
Phenytoin: Isoniazid may increase serum
levels of phenytoin. To avoid phenytoin
intoxication, appropriate
adjustment of the
anticonvulsant should be made.
Therophylline: A recent study has shown that concomitan
administration of isoniazid
and theophylline
may cause elevated plasma
levels of theophylline, and in some instances a slight decrease
in the elimination of isoniazid. Since the therapeutic
range of theophylline
is narrow theophylline
serum levels should be
monitored closely, and appropriate dosage adjustments of theophylline
should be made.
Valproate: A recent case
study has shown a possible increase in the plasma
level of valproate when co administered with isoniazid. Plasma valproate
concentration
should be monitored when isoniazid
and valproate are co administered, and appropriate
dosage adjustments of
valproate should be made.
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