Tripgard

Light yellow to dark yellow, round shaped, biconvex, plain on both sides.
Each film-coated tablet contains: Amitriptyline (as hydrochloride), USP 25 mg.

Pharmacology: Mechanism of Action: Amitriptyline hydrochloride is an antidepressant with sedative effects. Its mechanism of action in man is not known. It is not a monoamine oxidase inhibitor, and it does not act primarily by stimulation of the central nervous system.
Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
Pharmacokinetics: Amitriptyline is readily absorbed from the gastrointestinal tract, peak plasma concentrations occurring within about 6 hours after oral doses.
Amitriptyline undergoes extensive first-pass metabolism and is demethylated in the liver by the cytochrome P450 isoenzymes CYP3A4, CYP2C9, and CYP2D6 to its primary active metabolite, nortriptyline. Other paths of metabolism of amitriptyline include hydroxylation (possibly to active metabolites) by CYP2D6 and N-oxidation; nortriptyline follows similar paths. Amitriptyline is excreted in the urine, mainly in the form of its metabolites, either free or in conjugated form.
Amitriptyline and nortriptyline are widely distributed throughout the body and are extensively bound to plasma and tissue protein. Amitriptyline has been estimated to have an elimination half-life ranging from about 9 to 25 hours, which may be considerably extended in overdosage. Plasma concentrations of amitriptyline and nortriptyline vary very widely between individuals and no simple correlation with therapeutic response has been established.

For the treatment of depression.
Endogenous depression is more likely to be alleviated than are other depressive states.

Amitriptyline, a dibenzocycloheptadiene, is usually given by mouth as the hydrochloride and doses are expressed in terms of this salt. Amitriptyline hydrochloride is also given by intramuscular or slow intravenous injection; doses may be expressed in terms of the base or the hydrochloride. Amitriptyline hydrochloride 75 mg is equivalent to about 66.3 mg of the base. Amitriptyline has also been given by mouth as the embonate and as the oxide (amitriptylinoxide).
Administration: 10 to 20 mg for children aged 6 to 10 years.
25 to 50 mg for children over 11 years of age.
The dose should be given 30 minutes before bedtime and treatment, including a period of gradual withdrawal, should not continue for longer than 3 months. A full physical examination is recommended before a further course. Or as prescribed by the physician.

Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Sign and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose, therefore, hospital monitoring is required as soon as possible.

Amitriptyline hydrochloride is contraindicated in patients who have shown prior hypersensitivity to it.
It should not be given concomitantly with monoamine oxidase inhibitors. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. When it is desired to replace a monoamine oxidase inhibitor with amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. Amitriptyline hydrochloride should then be initiated cautiously with a gradual increase in dosage until optimum response is achieved.

Antidepressant increases the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders and those considering use of these agents must balance risk with the clinical need.

The antimuscarinic effects of tricyclic antidepressants warrant care in patients with urinary retention, prostatic hyperplasia, or chronic constipation; caution has also been advised in untreated angle-closure glaucoma and in phaeochromocytoma.
The epileptogenic potential of tricyclic antidepressants requires care in patients with a history of epilepsy. In addition, because of their potential cardiotoxicity, tricyclics should be used with caution in patients with cardiovascular disease and avoided in those with heart block, cardiac arrhythmias, or in the immediate recovery period after myocardial infarction. Caution has also been recommended in patients with hyperthyroidism as tricyclics may increase the risk of developing cardiac arrhythmias.
Suicidal thoughts and behaviour may also develop during early treatment with antidepressants for other disorders; the same precautions observed when treating patients with depression should therefore be followed when treating patients with other disorders.
If tricyclic antidepressants are used for the depressive component of bipolar disorder, mania may be precipitated; similarly, psychotic symptoms may be aggravated if tricyclics are used for a depressive component of schizophrenia.

Pregnancy Category C: Teratogenic effects were not observed in mice, rats, or rabbits when amitriptyline was given orally at doses of 20 to 40 mg/kg/day (up to 13 times the maximum recommended human dose¹). Studies in literature have shown amitriptyline to be administration at doses of 28 to 100 mg/kg/day (9 to 33 times the maximum malformations. Another study in the rat reported that an oral dose of 25 mg/kg/day (8 times the maximum recommended human dose) produced delays in ossification of fetal vertebral bodies without other signs of embryotoxicity. In rabbits, an oral dose of 60 mg/kg/day (20 times the maximum recommended human dose) was reported to cause incomplete ossification of cranial bones.
Amitriptyline has been shown to cross the placenta. Although a causal relationship has not been established, there have been a few reports of adverse events, including CNS effects, limb deformities, or developmental delay, in infants whose mothers had taken amitriptyline during pregnancy.
There are no adequate and well-controlled studies in pregnant women. Amitriptyline hydrochloride should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
(¹ Based on a maximum recommended amitriptyline dose of 150 mg/day or 3 mg/kg/day for a 50 kg patient.)
Lactation: Amitriptyline is excreted into breast milk. In one report in which a patient received amitriptyline 100 mg/day while nursing her infant, levels of 83 to 141 ng/mL were detected in the mother's serum. Levels of 135 to 151 ng/mL were found in the breast milk, but no trace of the drug could be detected in the infant's serum.
Because of the potential for serious adverse reactions in nursing infants from amitriptyline, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account the importance of the drug to the mother.

Many adverse effects of amitriptyline and similar tricyclic antidepressants are caused by their antimuscarinic actions. Antimuscarinic effects are relatively common and occur before an antidepressant effect is obtained. They include dry mouth, constipation occasionally leading to paralytic ileus, urinary retention, blurred vision and disturbances in accommodation, increased intra-ocular pressure, and hyperthermia. Tolerance is often achieved if treatment is continued and adverse effects may be less troublesome if treatment is begun with small doses and then increased gradually, although this may delay the clinical response.
Drowsiness may also be common, although a few tricyclic antidepressants possess little or no sedative potential and may produce nervousness and insomnia. Other neurological adverse effects include headache, peripheral neuropathy, tremor, ataxia, epileptiform seizures, tinnitus, and occasional extrapyramidal symptoms including speech difficulties (dysarthria). Confusion, hallucinations, or delirium may occur, particularly in the elderly, and mania or hypomania, and behavioural disturbances (particularly in children) have been reported.

Different antidepressants have been used together under expert supervision in refractory cases of depression. For this reason an appropriate drug-free interval should elapse between stopping some types of antidepressant and starting another. Tricyclic antidepressants should not generally be given to patients receiving MAOIs or for at least 2 weeks (3 weeks if starting clomipramine or imipramine) after their withdrawal. No treatment-free period is necessary after stopping a reversible inhibitor of monoamine oxidase type A (RIMA) and starting a tricyclic. At least 1 to 2 weeks (3 weeks in the case of clomipramine or imipramine) should elapse between withdrawing a tricyclic antidepressant and starting any drug liable to provoke a serious reaction (e.g. phenelzine).

Store at temperatures not exceeding 30°C.

Antidepressants

N06AA09 - amitriptyline ; Belongs to the class of non-selective monoamine reuptake inhibitors. Used in the management of depression.

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