ISONIAZID 100MG TABLETS

Active substance: ISONIAZID

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Isoniazid 100 mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains
100 mg of the active ingredient, Isoniazid.
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Tablets
White, circular, biconvex, uncoated tablets having plain surface on both the sides.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Isoniazid 100 mg Tablets are indicated for the treatment of all forms of pulmonary
and extra-pulmonary tuberculosis.
Consideration should be given to official guidance on the appropriate use of
antibacterial agents.

4.2

Posology and method of administration
Official guidance should always be consulted when selecting the dose
regimens to be used for adults and children (according to age and body
weight), the duration of therapy and the total content of the combination
treatment regimen.
Isoniazid 100 mg tablets should be taken preferably on an empty stomach, i.e.
at least 30 minutes before a meal or 2 hours after a meal. Tablets must be
swallowed whole and not chewed.
Adults:

The dose of isoniazid for the treatment of tuberculosis is commonly 4 to 5 mg
per kilogram bodyweight daily given by mouth in single or divided doses up
to a maximum of 300 mg daily. Up to 10 mg per kilogram body-weight daily
may be given particularly during the first 1 to 2 weeks of treatment of
tuberculous meningitis. A dose of 15 mg per kilogram has been given two or
three times weekly in intermittent treatment regimens.
Elderly:
No dosage reduction is necessary in the elderly, but caution should be
exercised due to the possible decrease in renal and hepatic function.
Children:
The usual daily dose for children is from 5 up to 20 mg per kilogram bodyweight daily in single or divided doses up to a maximum of 300mg/daily.
4.3

Contraindications
Patients who are known to be hypersensitive to isoniazid or any of the
excipients. (see section 4.5).
Previous experience of severe adverse reaction to Isoniazid including drug
induced liver disease. (See section 4.4).

4.4

Special warnings and precautions for use
All patients should have baseline liver function tests performed and repeated at
regular intervals during treatment. If serum AST rises to more than three times
normal, or there is any increase in bilirubin, treatment should be withdrawn. Special
precautions are required in patients with impaired liver function. Any deterioration in
liver function in these patients is an indication for stopping treatment.
Isoniazid should not be given to patients who have experience severe adverse
reactions including drug-induced liver disease. Care should be taken in giving
isoniazid to patients suffering from convulsive disorders, diabetes mellitus, chronic
alcoholism, or impaired liver or kidney function or to patients taking other potentially
hepatoxic agents. If symptoms of hepatitis such as malaise, fatigue, anorexia, and
nausea develop isoniazid should be discontinued immediately.
Isoniazid should be used with caution in patients with a history of psychosis.
Advanced age, female gender, slow acetylators, malnutrition, HIV infection,
preexisting liver disease, and extra-pulmonary tuberculosis were identified as risk
factors for isoniazid-induced hepatotoxicity.
Patients who are at risk of neuropathy or pyridoxine deficiency, including those who
are diabetic, alcoholic, malnourished, uraemic, pregnant, or infected with HIV, should
be given pyridoxine.

4.5

Interaction with other medicinal products and other forms of interaction
When isoniazid is given to patients who inactivate it slowly or to patients receiving
paraminosalicyclic acid concurrently, tissue concentrations may be enhanced and
adverse effects are more likely to appear. There may be an increased risk of liver
damage in patients receiving rifampicin and isoniazid but liver enzymes are raised
only transiently.
Concurrent use of other hepatotoxic medications with isoniazid may increase the
potential for hepatotoxicity.
Isoniazid can inhibit the hepatic metabolism of a number of drugs, in some cases
leading to increased toxicity. These include the antiepileptics carbamazepine,
primidone, and phenytoin, the benzodiazepines diazepam and triazolam,
chlorzoxazone, and disulfiram. Concomitant benzodiazepine (diazepam, triazolam)
and isoniazid therapy has been reported to result in an increased risk of
benzodiazepine toxicity (sedation, respiratory depression).
Isoniazid has been reported to cause substantial elevations of serum concentrations of
carbamazepine and symptoms of carbamazepine toxicity at isoniazid doses of 200 mg
daily or more. The concurrent used is not recommended unless the effects can be
closely monitored and suitable downward dosage adjustments made (a reduction
between one-half or one-third was reported effective).
Phenytoin dosage adjustment maybe necessary during and after isoniazid therapy
especially in slow acetylators of isoniazid.
Isoniazid may increase renal excretion of pyridoxine; requirements for pyridoxine
may be increased in patients receiving isoniazid concurrently. Concurrent use of
isoniazid may reduce the metabolism of theophylline, increasing theophylline plasma
concentrations. Propranolol has been reported to cause a significant reduction in the
clearance of concurrently administered isoniazid. Concurrent use of cycloserine with
isoniazid results in increased incidence of central nervous system effects such as
dizziness or drowsiness, dosage adjustment may be necessary and patients should be
monitored closely for signs or central nervous system toxicity especially if
performing tasks requiring alertness.
Isoniazid may reduce the therapeutic effects of levodopa.
Concomitant administration of isoniazid with itraconazole may result in significant
decreases in itraconazole serum concentrations and therapeutic failure. Coadministration is not recommended. Isoniazid may decrease ketoconazole serum
levels. Concurrent use should be well monitored and dosage increases made if
necessary.
Because the clearance of isoniazid was found doubled when zalcitabine was given in
HIV positive patients, concurrent use of isoniazid and zalcitabine should be
monitored to ensure isoniazid effectiveness.
There may be an increased risk of distal sensory neuropathy when isoniazid is used in
patients taking stavudine (d4T).
Concurrent use of isoniazid with other neurotoxic medication may produce additive
neurotoxicity.

Isoniazid may cause niacin deficiency by inhibiting niacin incorporation into
nicotinamide adenine dinucleotide.
There may be a potential interaction between isoniazid and foods containing
histamine or tyramine.

4.6

Fertility, pregnancy and lactation
Animal studies show there is a teratogenic risk to the embryo. There is limited
experience in humans but without evidence of a clinically relevant risk (trimester 1)
Isoniazid passes into breast milk. As the effects on the infant are unknown, your
doctor may advise you discontinue breast feeding whilst being treated with Isoniazid.

4.7

Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been
performed.

4.8

Undesirable effects
Hypersensitivity reactions: Fever, anaphylactic reactions.
Nervous system: Vertigo; polyneuritis, presenting as paraesthesia, muscle weakness,
loss of tendon reflexes, hyperreflexia. Other neurotoxic effects are convulsions, toxic
encephalopathy, optic neuritis and atrophy, diplopia, strabismus, sensory
disturbances, headache, dizziness, tremors, memory impairment, depression and
psychosis (maniform, catatonic or paranoid) as well as irritability, anxiety, lack of
concentration. The incidence is higher in "slow acetylators”.
The possibility that the frequency of seizures may be increased in patients with
epilepsy should be borne in mind.
Cutaneous: Rash, acne, Stevens-Johnson syndrome, exfoliative dermatitis and
pemphigus, pellagra, photosensitivity, erythema multiforme, vasculitis
Hematologic: Eosinophilia, granulocytopaenia, agranulocytosis, thrombocytopenia,
anaemia, aplastic anaemia and haemolytic anaemia, panmyelopathy, clotting
disorders
Gastrointestinal: Pancreatitis, constipation, dry mouth, nausea, vomiting, diarrhoea,
and epigastric distress.
Hepatic: increased transaminases, hepatitis including severe and sometimes fatal
hepatitis
Investigations: anti-nuclear antibodies
Metabolism and Nutrition Disorders: hyperglycaemia, hypoglycaemia
Renal and bladder: urinary retention

Endocrine system: Usually reversible hyperactivity of the adrenal cortex (Cushing's
syndrome) and pituitary disorders in women with menstrual disorders and
gonadotropic / gynaecomastia
Cardiovascular system: Heart rhythm disturbances, blood pressure dysregulation with
vertigo
Respiratory system: asthma
Miscellaneous: systemic lupus erythematosus-like syndrome, fatigue, purpura
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Symptoms of overdose with isoniazid are slurred speech, metabolic acidosis,
hyperglycaemia, hallucinations, respiratory and central nervous system depression,
vertigo, convulsions and coma.
Treatment of overdosage may include gastric lavage following intubation and the
control of convulsions by anti-convulsants given intravenously as well as the
intravenous injection of large doses of pyridoxine. Metabolic acidosis is corrected
with sodium bicarbonate. Forced diuresis may be tried and haemodialysis or
peritoneal dialysis has been used.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Antimycobacterial
ATC code: J04AC01
Isoniazid has no significant antibacterial action against any micro-organisms except
the Mycobacteria; It is believed to act by inhibition of mycolic acid synthesis and
disruption of cell wall in susceptible organisms. It is primarily active against actively
dividing mycobacteria and considered bacteriostatic against semidormant organisms.
Isoniazid is used mainly in the treatment of pulmonary tuberculosis but it appears to
be effective also in the treatment of extrapulmonary lesions, including meningitis and
genito-urinary disease.

5.2

Pharmacokinetic properties
Absorption

Readily and completely absorbed after oral administration.
Distribution
Readily diffuses into all tissues and fluids including the cerebrospinal fluid. Isoniazid
is retained in the skin and in infected tissue; it crosses the placenta and is secreted in
the milk of lactating mothers.
Protein binding
Isoniazid does not appear to be bound in the blood.
Half-life
Plasma elimination half-life, in rapid acetylators about 1.2 hours and in slow
acetylators about 3.5 hours.
Metabolic reactions
Acetylation, hydrolysis and glycine conjugation, hydrazone formation, and nmethylation; acetylation is polymorphic and two groups of acetylators have been
identified, rapid and slow acetylators. The rate of hydrolysis is more rapid in the rapid
acetylators than in the slow ones. The metabolites formed include acetyl isoniazid,
isonicotinic acid, isonicotinuric acid, isonicotinoylhydrazones of pyruvic and glutaric
acids, and n-methylisoniazid.
Excretion
Over 90% of a dose is excreted in the urine in 24 hours, most being excreted in the
first 12 hours, 4-32% is unchanged, but no more than 10% of a dose is excreted in the
faeces.

5.3

Preclinical safety data
Not applicable since isoniazid tablets have been used in clinical practice for many
years and its effects in man are well known.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Calcium Hydrogen Phosphate
Maize Starch (dried)
Purified Talc
Colloidal Anhydrous Silica
Magnesium stearate

6.2

Incompatibilities
Not applicable

6.3

Shelf life

36 months

6.4

Special precautions for storage
Store below 25°C.

6.5

Nature and contents of container
White opaque PVC/PVdC/Aluminium blisters available in pack sizes of 7, 10,
14, 20, 28, 30, 56, 60, 84, 90, 100 and 112 tablets.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements

7

MARKETING AUTHORISATION HOLDER
Morningside Healthcare Ltd
115 Narborough Road
Leicester
LE3 0PA
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 20117/0233

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
17/07/2014

10

DATE OF REVISION OF THE TEXT
17/07/2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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