Ludiomil (Maprotiline)

LUDIOMIL®

Novartis Pharmaceuticals

Maprotiline HCl

Antidepressant

Action And Clinical Pharmacology: Maprotiline has been shown to exhibit an antidepressant action.

Maprotiline strongly inhibits the uptake of norepinephrine in the brain and peripheral tissues, but has a notable lack of serotonergic uptake inhibition. It has markedly less pronounced alpha-adrenergic blocking activity than amitriptyline. Maprotiline has a strong antihistaminic activity and a weaker anticholinergic activity. Maprotiline also exerts a sedative effect on the anxiety component of depressive illness.

It is postulated that maprotiline exerts its antidepressant action by inhibition of presynaptic uptake of catecholamines, thereby increasing their concentration at the synaptic clefts in the brain. In single doses, the effect of maprotiline on the EEG included an increase in the alpha-wave density, a decrease of the alpha-wave frequency and an increase in the alpha-wave amplitude. However, as with other tricyclic antidepressants, maprotiline lowers the convulsive threshold.

In one as yet uncorroborated “sleep study”, it appears that maprotiline increased the REM phase of sleep in depressed patients, from its initially reduced base line, whereas imipramine reduced the REM phase of sleep.

Pharmacokinetics: Maprotiline is slowly, but completely, absorbed after oral administration. Serum protein binding is 88 to 90%. The half-life of unchanged maprotiline is relatively long, ranging from 27.4 to 57.6 hours. The mean systemic clearance is 514 mL/min.

After repeated doses of 150 mg maprotiline daily, steady state plasma concentrations between 100 and 400 ng/mL were reached in the second week. The same plasma levels are attained whether the daily dosage is given as a single dose of 150 mg, in 2 fractions of 75 mg or 3 fractions of 50 mg.

Maprotiline is metabolized by N-demethylation, deamination, aliphatic and aromatic hydroxylations and by formation of aromatic methoxy derivatives. Maprotiline is excreted primarily in the urine. Within 21 days after a single dose, 57% of the total dose is excreted in the urine, with about 30% in the bile. Only 2 to 4% of the dose is excreted unchanged in the urine. Ninety percent of the amount excreted in the urine consists of metabolites, 75% in the form of glucuronides.

Steady state plasma concentrations for a given dose are higher in elderly patients (aged >60 years) than in younger patients. The half-life and renal excretion of maprotiline are not significantly affected by impaired renal function (creatinine clearance: 24 to 37 mL/min), provided that hepatic function is still normal. Urinary excretion of metabolites is reduced, although this reduction is offset by increased fecal elimination of metabolites through biliary excretion.

Indications And Clinical Uses: The treatment of endogenous depressive illness, including the depressed phase of bipolar (manic-depressive) disorders, unipolar (psychotic) depression, and involutional melancholia. Maprotiline may also be useful in selected patients suffering severe depressive neurosis.

Contra-Indications: In patients who have known or suspected hypersensitivity to the drug or its excipients, or have known or suspected hypersensitivity to tricyclic antidepressants belonging to the dibenzazepine group.

Maprotiline should not be given in conjunction with, or within 14 days before or after treatment with a MAO inhibitor (see Precautions, Drug Interactions). The concomitant treatment with selective, reversible MAO-A inhibitors, such as moclobemide, is also contraindicated. Hypertensive crises, hyperactivity, hyperpyrexia, spasticity, severe convulsions or coma, and death have been reported in patients receiving such combinations.

Maprotiline is contraindicated during the acute recovery phase following a myocardial infarction and in the presence of acute congestive heart failure.

Maprotiline is contraindicated in patients with existing liver or kidney damage and should not be administered to patients with a history of blood dyscrasias.

Maprotiline is contraindicated in patients with glaucoma, as the condition may be aggravated due to the atropine-like effects of the drug.

Maprotiline should not be used in patients with known or suspected convulsive disorders since it is known to lower the seizure threshold (see Warnings).

Manufacturers’ Warnings In Clinical States: Seizures: Tricyclic agents are known to lower the convulsive threshold and maprotiline should, therefore, be used with extreme caution in patients with a history of convulsive disorders and other predisposing factors, e.g., brain damage of varying etiology, concomitant use of neuroleptics, alcoholism and withdrawal from alcohol, and concomitant use with other drugs that lower the seizure threshold. It appears that the occurrence of seizures is dose dependent. Therefore, the recommended total daily doses should not be exceeded (see Dosage).

Seizures have been reported in patients without a history of seizures who were treated with maprotiline at therapeutic dose levels. However, in some of these patients other confounding factors such as concomitant medications known to lower seizure threshold were also present. The risk of seizures may be increased when maprotiline is taken concomitantly with phenothiazines, when the dosage of benzodiazepines is rapidly tapered in patients receiving maprotiline, or when the recommended dosage of maprotiline is rapidly exceeded. While a cause-and-effect relationship has not been established, the risk of seizures may be reduced by: initiating therapy at a low dose; maintaining the initial dosage for 2 weeks before raising it gradually in small increments (see Dosage) due to the long half-life of maprotiline (average 51 hours); keeping the maintenance dosage at a minimally effective level (dosages below 200 mg/day); cautious alteration in, or avoidance of, concomitant prescribing of drugs that lower the seizure threshold (i.e., phenothiazines) or rapid tapering of benzodiazepines.

Concurrent administration of electroconvulsive therapy and maprotiline may be hazardous and such treatment should be limited to patients for whom it is essential. Physicians should discuss with patients the risk of taking maprotiline while engaging in activities in which a sudden loss of consciousness could result in serious injury to the patient or others, e.g., the operation of complex machinery, driving, swimming, or climbing.

Cardiovascular: Tricyclic antidepressants, particularly in high doses, have been reported to produce sinus tachycardia, changes in conduction time and arrhythmias. A few instances of unexpected death have been reported in patients with cardiovascular disorders. Myocardial infarction and stroke have also been reported with drugs of this class. Therefore, maprotiline should be administered with extreme caution to patients with a history of cardiovascular disorders, especially those with cardiovascular insufficiency, conduction disorders (e.g., atrioventricular block grades I to III) or other arrhythmias, those with circulatory lability and elderly patients. Maprotiline also has a hypotensive action which may be detrimental in these circumstances. In such cases, treatment should be initiated at low doses with progressive increases only if required and tolerated, and the patients should be under close surveillance at all dosage levels. Monitoring of cardiac function and the ECG is indicated in such patients as well as in the elderly.

Use in Concomitant Illness: Caution should be observed when prescribing maprotiline for hyperthyroid patients or for patients receiving thyroid medication. Transient cardiac arrhythmias have occurred in rare instances in patients who have been receiving other tricyclic compounds concomitantly with thyroid medication.

Because of its anticholinergic properties, maprotiline should be used with caution in patients with increased intraocular pressure, narrow angle glaucoma or urinary retention, particularly in the presence of prostatic hypertrophy.

Tricyclic antidepressants may give rise to paralytic ileus, particularly in the elderly and in hospitalized patients. Therefore, appropriate measures should be taken if constipation occurs.

Caution is called for when employing maprotiline in patients with tumors of the adrenal medulla (e.g., pheochromocytoma, neuroblastoma), in whom the drug may provoke a hypertensive crisis.

Children: Maprotiline is not recommended for use in children since safety and efficacy in the pediatric age group have not been established (cases of sudden death in children treated with maprotiline have been reported).

Maprotiline should be kept in a safe place, well out of reach of children.

Pregnancy: The safety of use in pregnant women has not been established. Therefore, maprotiline should not be administered to women of childbearing potential, or during pregnancy, unless, in the opinion of the physician, the expected benefit to the patient outweighs the potential risk to the fetus. Withdrawal symptoms including tremors, dyspnea, lethargy, colic, irritability, hypotonia/hypertonia, convulsions and respiratory depression have been reported in neonates whose mothers received tricyclic antidepressants during the third trimester of pregnancy. To avoid such symptoms, maprotiline should, if possible, be gradually withdrawn at least 7 weeks before the calculated date of confinement.

Lactation: Maprotiline passes into breast milk. After repeated administration of 150 mg/day for 5 days, concentrations of maprotiline in breast milk exceeded that in blood by a factor of 1.3 to 1.5. Therefore, maprotiline should be gradually withdrawn or the infant weaned if the patient is breast-feeding.

Precautions: Suicide: The possibility of a suicide attempt is inherent in depression. These patients should be carefully supervised during treatment with maprotiline and hospitalization or concomitant electroconvulsive therapy may be required. One study in which maprotiline was given as prophylactic treatment for unipolar depression suggested an increase in suicidal behavior in the treated group. To minimize the risk of an intentional overdose by a depressed patient, prescriptions for maprotiline should be written for the smallest possible quantity of the drug consistent with good patient management.

Psychosis, Mania-Hypomania and Other Neuropsychiatric Phenomena: In patients treated with tricyclic antidepressants, activation of latent schizophrenia or aggravation of existing psychotic manifestations in schizophrenic patients may occur. Patients with manic-depressive tendencies may experience hypomanic or manic shifts. Hyperactive or agitated patients may become over-stimulated. A reduction in dose or discontinuation of maprotiline should be considered under these circumstances.

In predisposed and elderly patients, tricyclic antidepressants may, particularly at night, provoke pharmacogenic (delirious) psychoses that disappear within a few days of withdrawing the drug.

Occupational Hazards: Since maprotiline may produce sedation, particularly during the initial phase of therapy, patients should be cautioned about the danger of engaging in activities requiring mental alertness, judgment and physical coordination.

Cardiovascular: Before initiating treatment, it is advisable to check the patient’s blood pressure, because individuals with hypotension or a labile circulation may react to the drug with a fall in blood pressure. Regular measurements of blood pressure should be performed in suceptible patients. Postural hypotension may be controlled by reducing the dosage or administering circulatory stimulants.

ECG abnormalities have been observed in patients treated with maprotiline. The most common ECG changes were premature ventricular contractions (PVCs), ST-T wave changes, and abnormalities in intraventricular conduction. These changes were rarely associated with significant clinical symptoms. Nevertheless, caution is necessary when treating patients with heart disease, as well as elderly subjects. In these patients cardiac function should be monitored and ECG examinations performed during long-term therapy. Gradual dose titration is also recommended.

Hepatic Changes: Isolated cases of obstructive jaundice have been reported. Caution is indicated in treating patients with known liver disease and periodic monitoring of hepatic function is recommended in such patients.

Hematological Changes: Isolated cases of bone marrow depression with agranulocytosis have been reported. Leukocyte and differential blood cell counts are recommended in patients receiving treatment with maprotiline over prolonged periods, and should be performed for patients who develop fever, an influenzal infection or sore throat. In the event of an allergic skin reaction, maprotiline should be withdrawn.

Withdrawal Symptoms: A variety of withdrawal symptoms have been reported in association with abrupt discontinuation of maprotiline, including dizziness, nausea, vomiting, headache, malaise, sleep disturbance, hyperthermia and irritability. In addition, such patients may experience a worsening of psychiatric status. While the withdrawal effects of maprotiline have not been systematically evaluated in controlled trials, they are well known with closely related tricyclic antidepressants. It is recommended that the dosage be tapered gradually and the patient monitored carefully during discontination. Sudden withdrawal of maprotiline may result in serious hypotension.

Metabolic Effects: Tricyclic antidepressants have been associated with porphyrinogenicity in susceptible patients.

Renal Function: It is advisable to monitor renal function during long-term therapy with tricyclic antidepressants.

Dental Effects: Lengthy treatment with tricyclic antidepressants can lead to an increased incidence of dental caries.

Lacrimation: Decreased lacrimation and accumulation of mucoid secretions, due to the anticholinergic properties of tricyclic antidepressants, may cause damage to the corneal epithelium in patients with contact lenses.

Drug Interactions: Patients should be warned that, while taking maprotiline, their responses to alcoholic beverages, other CNS depressants (e.g., barbiturates, benzodiazepines or general anesthetics) or anticholinergic agents (e.g., atropine, antihistamines, biperiden, levodopa) may be exaggerated.

When tricyclic antidepressants are given in combination with anticholinergics or neuroleptics with an anticholinergic action, hyperexcitation states or delirium may occur, as well as attacks of glaucoma.

Tricyclic antidepressants should not be employed in combination with antiarrhythmic agents of the quinidine type (see Warnings, Cardiovascular).

Since maprotiline may diminish or abolish the antihypertensive effects of guanethidine, bethanidine, clonidine, reserpine or alpha-methyldopa, patients requiring concomitant treatment for hypertension should be given antihypertensives of a different type (e.g., diuretics, vasodilators, beta-blockers).

Maprotiline may potentiate the cardiovascular effects of norepinephrine or epinephrine, amphetamine, as well as nasal drops and local anesthetics containing sympathomimetics (e.g., isoprenaline, ephedrine, phenylephrine).

Fluoxetine, fluvoxamine and other selective serotonin reuptake inhibitors (SSRIs) may increase the activity and plasma concentrations of tricyclic antidepressants with corresponding adverse effects.

Caution should be exercised if maprotiline is administered together with cimetidine or methylphenidate since these drugs have been shown to inhibit the metabolism of several tricyclic antidepressants. Clinically significant increases in plasma levels of maprotiline may occur, necessitating a dosage reduction.

Substances which activate the hepatic mono-oxygenase enzyme system (e.g., barbiturates, carbamazepine, phenytoin, nicotine and oral contraceptives) may lower plasma concentrations of tricyclic antidepressants and so reduce their antidepressive effects. In addition, maprotiline may increase plasma levels of phenytoin and carbamazepine, therefore, it may be necessary to adjust the dosage of these drugs.

Maprotiline should not be administered for a period of at least 14 days after the discontinuation of treatment with MAO inhibitors due to the potential for severe interactions (see Contraindications). The same caution should also be observed when administering a MAO inhibitor after previous treatment with maprotiline.

Maprotiline should be discontinued prior to elective surgery for as long as clinically feasible, since little is known about the interaction with general anesthetics.

Concomitant treatment with neuroleptic agents (e.g., phenothiazines and butyrophenones) may result in increased plasma concentrations of maprotiline, a lowered convulsion threshold and seizures. Combination with thioridazine may produce severe cardiac arrhythmias. No such effects are known to occur in combination with diazepam, but it might be necessary to lower the dosage of maprotiline if administered concomitantly with alprazolam or disulfiram.

Tricyclic antidepressants may potentiate the anticoagulant effect of coumarin drugs by inhibiting hepatic metabolism of these drugs. Careful monitoring of plasma prothrombin is therefore advised.

Comedication with oral sulfonylureas or insulin may potentiate their hypoglycemic effect. Diabetic patients should monitor their blood glucose levels when treatment with maprotiline has been initiated or discontinued.

If administered concomitantly with estrogens, the dose of maprotiline should be reduced since steroid hormones inhibit the metabolism of maprotiline.

Adverse Reactions: Adverse reactions with maprotiline have been mild and transient, usually disappearing with continued treatment or following a reduction in the dosage. Adverse reactions do not always correlate with plasma levels or dose. It is often difficult to differentiate certain adverse reactions from symptoms of depression such as fatigue, sleep disturbances, agitation, anxiety, constipation and dry mouth.

The most common adverse reactions reported with maprotiline are due to its anticholinergic, largely autonomic, effects which include: dry mouth, day sedation, vertigo, blurred vision, constipation, headache and nervousness.

If severe neurological or psychiatric reactions occur, maprotiline should be withdrawn.

Elderly patients are particularly susceptible to anticholinergic, psychiatric, neurological and cardiovascular effects.

The following adverse reactions have been reported either with maprotiline or other similar tricyclic antidepressant drugs: (Frequency estimates: Frequent >10%; Occasional >1 to 10%; Rare >0.01 to 1%).
Neurological: Frequent: tremors. Occasional: dizziness, headache, paresthesia (numbness, tingling sensation, symptoms suggestive of peripheral neuropathy), delirium. Rare: epileptic seizures. Isolated cases: tinnitus, incoordination, ataxia, alterations in EEG patterns, extrapyramidal symptoms, myoclonus, speech disorders, weakness.

Behavioral: Occasional: drowsiness, fatigue, insomnia, confusional states with hallucinations (particularly in geriatric patients and patients suffering from Parkinson’s disease), anxiety, agitation, restlessness, nightmares, hypomania, mania, decrease in memory, feeling of unreality. Rare: activation of latent psychosis. Isolated cases: aggressiveness.

Anticholinergic: Frequent: dry mouth and rarely associated sublingual adenitis, blurred vision, disturbances of visual accommodation, constipation, perspiration, hot flushes. Occasional: delayed micturition, dilation of the urinary tract. Isolated cases: mydriasis, glaucoma, paralytic ileus.

Cardiovascular: Frequent: hypotension, particularly orthostatic hypotension with associated vertigo, sinus tachycardia, ECG changes (including flattening or inversion of T wave, depressed S-T segments) in patients of normal cardiac status. Occasional: arrhythmia, disturbances in cardiac conduction (e.g., widening of QRS complex, PQ changes, bundle-branch block), palpitation, syncope. Isolated cases: hypertension, congestive heart failure, myocardial infarction, heart block, asystole, stroke, peripheral vasospastic reactions.

Hematologic: Isolated cases: agranulocytosis, eosinophilia, leukopenia, purpura and thrombocytopenia may occur as an idiosyncratic response.

Gastrointestinal: Occasional: nausea, vomiting, anorexia, abdominal cramps. Rare: diarrhea, elevated transaminases. Isolated cases: bitter taste, stomatitis, epigastric distress, black tongue, dysphagia, increased salivation, hepatitis with or without jaundice.

Respiratory: Isolated cases: bronchospasm.

Endocrine: Frequent: weight gain. Occasional: increased or decreased libido, impotence. Isolated cases: gynecomastia in the male, breast enlargement and galactorrhea in the female, testicular swelling, elevation or depression of blood sugar levels, weight loss, inappropriate antidiuretic hormone (SIADH) secretion syndrome.

Allergic or Toxic: Occasional: skin rash, urticaria. Isolated cases: petechiae, itching, photosensitization (avoid excessive exposure to sunlight), edema (general or of face and tongue), drug fever, obstructive jaundice, nasal congestion, alopecia, allergic alveolitis (pneumonia) with or without eosinophilia, systemic anaphylactic/anaphylactoid reactions including hypotension.

Withdrawal Symptoms: Abrupt cessation of treatment with tricyclic antidepressants after prolonged administration may occasionally produce nausea, vomiting, abdominal pain, diarrhea, insomnia, nervousness, anxiety, headache and malaise. These symptoms are not indicative of addiction.

Symptoms And Treatment Of Overdose: Since children may be more sensitive than adults to acute overdosage with tricyclic antidepressants, and since fatalities in children have been reported, effort should be made to avoid potential overdose, particularly in this age group.Symptoms: These may vary in severity depending upon factors such as the amount of drug absorbed, the interval between drug ingestion and the start of treatment and the age of the patient. Accidental ingestion in children should be regarded as serious and potentially fatal.

Symptoms generally appear within 4 hours of ingestion and reach maximum severity after 24 hours. Owing to delayed absorption (increased anticholinergic effect due to overdose), long half-life and enterohepatic recycling of the drug, the patient may be at risk for up to 4 to 6 days.

Symptoms may include drowsiness, stupor, ataxia, vomiting, cyanosis, restlessness, agitation, delirium, severe perspiration, hyperactive reflexes, muscle rigidity, athetoid and choreiform movements and/or convulsions. Hyperpyrexia, mydriasis, bowel and bladder paralysis, oliguria or anuria and respiratory depression may occur.

Hypotension and initial hypertension may occur. However, the usual finding is increasing hypotension which may eventually lead to shock. Serious cardiovascular disturbances are frequently present, including tachycardia, cardiac arrhythmias (flutter, atriofibrillation, premature ventricular beats and ventricular tachycardia) as well as impaired myocardial conduction, atrioventricular and intraventricular block, ECG abnormalities (such as widened QRS complexes and marked S-T shifts), signs of congestive heart failure and cardiac arrest. Coma may ensue.

One case of acute intoxication with 5 g of maprotiline in a 58 year old woman has been reported, in which full recovery occurred. Other cases of recorded clinical recovery have been reported in the dose range of 1.6 to 2 g of maprotiline. A 22 year old woman, however, died from cardiac arrest 5 days after ingestion of 3 g of the drug. Fatal outcomes have also been reported in combined intoxication with tricyclic antidepressants, sedatives or hypnotics in the maprotiline dose range of 2 to 10 g.

Treatment: Patients in whom overdosage is suspected should be admitted to hospital without delay. No specific antidote is available and treatment is essentially symptomatic and supportive.

Gastric lavage or aspiration should be performed promptly and is recommended up to 12 hours or even more after the overdose, since the anticholinergic effect of the drug may delay gastric emptying. Administration of activated charcoal may help reduce absorption of the drug. As maprotiline is largely protein bound, forced diuresis, peritoneal dialysis and hemodialysis are unlikely to be of value.

Treatment should be designed to insure maintenance of the vital functions. An open airway should be maintained in comatose patients and assisted ventilation instituted, if necessary, but respiratory stimulants should not be used. Hyperpyrexia should be controlled by external measures, such as ice packs and cooling sponge baths. Acidosis may be treated by cautious administration of sodium bicarbonate. Adequate renal function should be maintained.

ECG monitoring in an intensive care unit is recommended in all patients, particularly in the presence of ECG abnormalities, and should be maintained for several days after the cardiac rhythm has returned to normal. Unexpected deaths attributed to cardiac arrhythmias have been reported several days following an apparent recovery from tricyclic antidepressant overdose. Correction of hypoxia and acidosis, if present, may be beneficial. Correction of metabolic acidosis and low potassium concentrations by means of bicarbonate i.v. and potassium substitution may also be effective for treatment of arrhythmias. If bradyarrhythmia or AV block occur, consider temporary insertion of a cardiac pacemaker. Because of its effect on cardiac conduction, digitalis should be used only with caution. If rapid digitalization is required for the treatment of congestive heart failure, special care should be exercised in using the drug.

External stimulation should be minimized to reduce the tendency to convulsions. If convulsions occur, anticonvulsants (preferably i.v. diazepam) should be administered. Barbiturates may intensify respiratory depression, particularly in children, and aggravate hypotension and coma. Paraldehyde may be used in some children to counteract muscular hypertonus and convulsions with less likelihood of causing respiratory depression. If the patient fails to respond rapidly to anticonvulsants, artificial ventilation should be instituted. Prompt control of convulsions is essential since they aggravate hypoxia and acidosis and may thereby precipitate cardiac arrhythmias and arrest.

Shock should be treated with supportive measures such as i.v. fluids, plasma expanders, and oxygen. The use of corticosteroids in shock is controversial and may be contraindicated in tricyclic antidepressant overdose. Hypotension usually responds to elevation of the foot of the bed. Pressor agents, (but not epinephrine) should be given cautiously, if indicated. In the event of reduced myocardial function, consider recourse to treatment with dopamine or dobutamine by i.v. drip.

Since it has been reported that physostigmine may cause severe bradycardia, asystole and seizures, its use is not recommended in cases of overdosage with maprotiline.

Deaths by deliberate or accidental overdosage have occurred with this class of drugs. Since the propensity for suicide is high in depressed patients, a suicide attempt by other means may occur during the recovery phase. The possibility of simultaneous ingestion of other drugs should also be considered.

Dosage And Administration: Patients should be kept under medical surveillance during treatment with maprotiline.

The dosage of maprotiline should be individualized according to the requirements of each patient. Treatment should be initiated at the lowest recommended dose and increased gradually, noting carefully the clinical response and any evidence of intolerance. It should be kept in mind that a lag in therapeutic response usually occurs at the onset of therapy, lasting from several days to a few weeks. Increasing the dosage does not normally shorten this latent period and may increase the incidence of side effects.

Initial Dosage: Adults: The recommended initial dosage is 75 mg daily 2 or 3 divided doses. Because of the long half-life of maprotiline, this dosage should usually be maintained for 2 weeks. It may then be increased gradually in increments of 25 mg as necessary and tolerated, preferably by adding to the late afternoon or bedtime dose. The maximum recommended dose in outpatients is 150 mg daily, although doses up to 200 mg may be required in some patients. In the treatment of severely depressed hospitalized patients, a higher initial dose of 100 mg daily in 2 or 3 divided doses may be indicated. The usual optimal dose in these patients is 150 mg daily, but some patients may require up to 225 mg in divided doses. When these higher doses are used, it is essential to exclude a history of convulsive disorders.

Elderly and Debilitated Patients: In general, lower dosages are recommended for these patients, and doses should only be increased in gradual increments. This approach is particularly important in elderly patients, since these individuals generally show a more marked response to maprotiline than patients in younger age groups. The initial recommended dose is 10 mg 3 times daily, with very gradual increments, depending on tolerance and response, up to 75 mg daily in divided doses. A maintenance dose of 50 to 75 mg daily is usually satisfactory. Blood pressure and cardiac rhythm should be checked frequently, particularly in patients who have unstable cardiovascular function.

Maintenance Dosage: Dosage during maintenance therapy should be kept at the lowest effective level. Medication should be continued for the expected duration of the depressive episode in order to minimize the possibility of relapse following clinical improvement.

When a maintenance dosage has been established as described above, maprotiline may be administered in a single daily dose at bedtime, provided such a dosage regimen is well tolerated. However, if the total daily dose exceeds 150 mg, it should be administered in divided doses.

Availability And Storage: 10 mg: Each cream-colored, round, film-coated, biconvex tablet, engraved CIBA on one side and CO on the other, contains: maprotiline HCl 10 mg. Nonmedicinal ingredients: cellulose compounds, colloidal silicon dioxide, cornstarch, iron oxides, lactose, magnesium stearate, polysorbates, stearic acid, talc, titanium dioxide and tribasic calcium phosphate. Energy: 1.1 kJ (0.26 kcal). Bottles of 100.

25 mg: Each orange-brown, round, beveled-edged, film-coated, biconvex tablet, engraved CIBA on one side and DP on the other, contains: maprotiline HCl 25 mg. Nonmedicinal ingredients: cellulose compounds, colloidal silicon dioxide, cornstarch, iron oxides, lactose, magnesium stearate, polysorbates, stearic acid, talc, titanium dioxide and tribasic calcium phosphate. Energy: 0.91 kJ (0.21 kcal). Bottles of 100.

50 mg: Each brownish-yellow, round, beveled-edged, film-coated, biconvex tablet, engraved CIBA on one side and ER on the other, contains: maprotiline HCl 50 mg. Nonmedicinal ingredients: cellulose compounds, colloidal silicon dioxide, cornstarch, iron oxides, lactose, magnesium stearate, polysorbates, stearic acid, talc, titanium dioxide and tribasic calcium phosphate. Energy: 0.92 kJ (0.22 kcal). Bottles of 100.

75 mg: Each reddish-brown, round, film-coated, biconvex tablet, engraved CIBA on one side and FS with bisect on the other, contains: maprotiline HCl 75 mg. Nonmedicinal ingredients: cellulose compounds, colloidal silicon dioxide, cornstarch, iron oxides, lactose, magnesium stearate, polysorbates, stearic acid, talc, titanium dioxide and tribasic calcium phosphate. Energy: 1.3 kJ (0.32 kcal). Bottles of 100.

Alcohol-, bisulfite-, gluten-, parabens-, sodium- and tartrazine-free. Protect from heat (store between 2 and 30°C). Keep out of reach of children. (Shown in Product Recognition Section)

LUDIOMIL® Novartis Pharmaceuticals Maprotiline HCl Antidepressant

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