Maprotiline

Since maprotiline is metabolized by the CYP2D6 enzyme system, inhibitors of CYP2D6 may decrease the metabolism of maprotiline.

If the dosing schedule is more than once a day, the patient should take the missed dose as soon as possible unless it is less than 2 hours before the next dose (should not double the dose to make up for the missed one). If the dosing schedule is once at bedtime, don't take the dose in the morning because of sedation.

Patients should be kept under medical surveillance during treatment with maprotiline. Individualize dosing. Initiate therapy at the lowest possible dose and increase gradually, watching for adverse reactions. Therapeutic effects usually present after two to three weeks of maprotiline treatment. This lag time to effect is not normally shortened by dosage increases, but incidence of side effects may be increased. Daily dose should not exceed 200 mg to decrease seizure risk. Daily doses may be divided into twice or three-times daily dosing or given as a single evening dose. When discontinuing maprotiline, decrease dose gradually.

Solid oral dosage forms: 10 mg tablets, 25 mg tablets, 50 mg tablets, 75 mg tablets.

Maprotiline can be taken with or without food.

Isolated cases of hepatitis with or without jaundice.

Rare cases of diarrhea, elevated transaminases; isolated cases of: paralytic ileus, bitter taste, stomatitis, epigastric distress, black tongue, dysphagia, increased salivation.

Isolated cases of agranulocytosis, eosinophilia, leukopenia, purpura and thrombocytopenia.

Rare cases (>0.01-1%) of epileptic seizure; risk of seizures appears to be higher with maprotiline than with the tricyclic antidepressants; isolated cases of tinnitus, incoordination, ataxia, alterations in EEG patterns, extrapyramidal symptoms, myoclonus, speech disorders, weakness, parasthesias.

Isolated cases of gynecomastia (males), breast enlargement and galactorrhea (females), testicular swelling, elevation or depression of blood sugar levels, weight loss, syndrome of inappropriate antidiuretic hormone (SIADH), porphyrinogenicity (in susceptible patients).

Isolated cases of alopecia and edema (general or face and tongue), drug fever, systemic anaphylactic/anaphylactoid reactions which may present with hypotension.

Isolated cases of bronchospasm.

Isolated cases of mydriasis, glaucoma.

Isolated cases of: petechiae, itching, photosensitization. Patients treated with maprotiline should avoid excessive exposure to sunlight.

Isolated cases of aggressiveness.

Isolated cases (<0.01%) of hypertension, congestive heart failure, myocardial infarction, heart block, asystole, stroke, peripheral vasospastic reactions.

Isolated cases of nasal congestion.

Maprotiline is not recommended for use in children since safety and efficacy in children has not been established. There have been cases of sudden death in children treated with maprotiline.

All cases of accidental pediatric exposure or adult overdose should be monitored at a health care facility. Asymptomatic cases without ECG abnormalities should be monitored for a minimum of 6 hours. Plasma concentrations of maprotiline are of little use and should not guide management of the patient. In managing overdose, consider the possibility of multiple drug overdose, interactions among drugs and altered pharmacokinetics, including delayed absorption. Protect the patient's airway and support ventilation and perfusion. Closely monitor and maintain the patient's vital signs, ECG, blood gases, serum electrolytes, and acid-base balance. Minimize external stimulation to reduce the risk of seizures.

Consultation with a regional poison centre is advisable in all patients with TCA overdose. Activated charcoal (1 gram per kilogram) may reduce absorption of drug from the gastrointestinal tract, and should be considered in patients who present within 2 hours of ingestion. This can be given through a nasogastric tube if necessary. Although it should not be routinely performed, gastric lavage may be considered in the unusual case where a patient presents within 30 to 60 minutes of a massive TCA overdose, but only on the advice of a Poison Control Centre. If performed, gastric lavage should be followed by administration of activated charcoal. If the patient has a decreased level of consciousness, consideration should be given to placement of an endotracheal tube with cuff inflated before beginning the lavage procedure, to lessen the likelihood of aspiration of gastric contents.

Hypotension should be promptly corrected. If hypotension does not respond to a rapid isotonic fluid bolus and the patient has a widened QRS interval ( >0.1 seconds), sodium bicarbonate boluses should be administered at a dose of 1 to 2 mmol/kg (an average adult would typically receive 1 to 3 ampoules of 50 mmol/50 mL). If hypotension still hasn't responded, vasopressors should be employed, with a direct-acting agonist such as norepinephrine being the drug of choice.

Widened QRS intervals (>0.14 seconds) and ventricular arrhythmias should be treated with iv sodium bicarbonate. An iv bolus of 1 to 2 mmol/kg (one or two 50 mmol ampoules) should be administered and repeated if necessary to achieve a serum pH of 7.45 to 7.55. Maintain the pH between 7.45 and 7.55. Do not exceed pH 7.6. Monitor for hypokalemia and fluid overload. Hyperventilation may also be used to maintain alkalemia.

Ventricular arrhythmias refractory to sodium bicarbonate may respond to lidocaine. Quinidine, procainamide and other type IA or IC antiarrhythmics should not be used because they may exacerbate arrhythmias and conduction slowing due to the overdosage. Overdrive pacing should be considered in patients whose arrhythmias are not responsive to drug therapy.

Seizures should be aggressively treated with iv benzodiazepines such as lorazepam or diazepam. If this is unsuccessful, barbiturates and other measures should be employed as for status epilepticus. However, phenytoin is no longer recommended for the treatment of TCA-induced seizures.

Diuresis, hemoperfusion and dialysis are not helpful in TCA overdose.

Flumazenil is contraindicated in any patient with an altered level of consciousness who has or may have taken a TCA or any drug that can cause seizures or arrhythmias, as it may precipitate seizures or even cardiac arrest. This is true even in cases of mixed overdose where the patient is known to have coingested benzodiazepines.

Because maprotiline shares the pharmacologic properties of tricyclic antidepressants (TCAs), the information in this section pertains to TCAs in general. Note: the incidence of seizures and cardiac arrhythmias and the duration of coma are greater with maprotiline toxicity compared to TCAs.

TCAs are extremely toxic in overdose. Consultation with a Poison Control Centre is recommended. See the CPS Directory section for contact numbers.

Cardiac arrhythmias and CNS involvement pose the greatest threat and may occur suddenly even when initial symptoms appear to be mild. The toxic dose is variable but, in general, acute ingestion of 10 to 20 mg/kg may result in serious toxicity and may be lethal. TCA overdose has one of the highest mortality rates of any type of ingestion. Toxicity most commonly begins within two hours of ingestion. The onset of symptoms is frequently precipitous, with patients progressing from a wakeful, interactive state to having severe CNS and cardiac involvement within a matter of minutes.

Peripheral anticholinergic symptoms may include urinary retention, dry mucous membranes, mydriasis, constipation, and occasionally adynamic ileus. Patients may also be hyperpyrexic. CNS signs and symptoms can be highly variable and may range from somnolence to agitation, irritability, confusion, delirium, and hallucinations. In severe cases, patients may display extreme drowsiness, areflexia, respiratory depression, and coma. Patients may occasionally become hypothermic. Seizures are common and may precipitate cardiac toxicity.

Cardiac irregularities are frequent. Sinus tachycardia is common. Its presence is not a reliable predictor of serious toxicity, and its absence does not ensure a benign clinical course. An effect on cardiac conduction similar to that of quinidine may be seen with slowing of conduction, widening of the QRS complex, rightward shift in the axis of the terminal 40 milliseconds of the QRS complex, prolongation of the PR and QT intervals, right bundle branch and AV block, ventricular tachyarrhythmias (including torsades de pointes and fibrillation), and death. Prolongation of the QRS duration to more than 0.1 seconds is generally associated with more severe toxicity. Bradycardia may be seen in severely poisoned patients. Hypotension is common and may be severe, resulting from vasodilation, central and peripheral alpha-adrenergic blockade, and myocardial depression. Metabolic and/or respiratory acidosis may occur secondary to seizures, poor tissue perfusion, respiratory depression or poor gas exchange. In an otherwise healthy young person, prolonged resuscitation may be required.

Because they cause dry mouth, prolonged use of tricyclic antidepressants has been associated with an increased incidence of dental caries. The anticholinergic effects of maprotiline may cause constipation and, rarely, gastrointestinal obstruction.

Safe use of maprotiline in pregnant women has not been established. As a result, maprotiline should not be administered during pregnancy unless the expected benefit to the patient outweighs the potential risk to the fetus. To date there are no published reports of congenital defects, however data from limited surveillance suggest a possible association between oral cleft and first trimester exposure. Neonates whose mothers received tricyclic antidepressants during the third trimester of pregnancy have presented with the following withdrawal symptoms tremors, dyspnea, lethargy, colic, irritability, hypotonia/hypertonia, convulsions, and respiratory depression. If possible, gradually withdraw maprotiline at least 7 weeks before the calculated delivery date.

Abrupt withdrawal of maprotiline may be associated with serious hypotension, dizziness, nausea, vomiting, headache, malaise, sleep disturbance, hyperthermia, irritability, and worsening of the psychiatric condition. Monitor the patient carefully while tapering gradually.

Patients with contact lenses may suffer damage to the corneal epithelium as a result of the decreased lacrimation caused by the anticholinergic properties of tricyclic antidepressants. The anticholinergic effects of maprotiline may be harmful in patients with narrow-angle glaucoma.

Maprotiline is not recommended for use in children. There have been cases of sudden death in children treated with maprotiline.

Agitated patients may become over stimulated when using maprotiline. Reduce dose or discontinue the drug. There have been reports of patients receiving TCAs experiencing activation of latent schizophrenia or aggravation of existing psychotic manifestations in schizophrenia. Individuals with evidence of a bipolar disorder may be at risk of experiencing hypomania or mania.

Older individuals generally show a more marked response to maprotiline than younger patients as they are particularly susceptible to anticholinergic, psychiatric, neurological and cardiovascular effects. All older individuals receiving antidepressants should be considered at increased risk of falls and appropriate preventive measures should be taken.

Appropriate measures should be taken to avoid or treat constipation since tricyclic antidepressants have caused paralytic ileus particularly in elderly or hospitalized patients. Older individuals are also at higher risk of urinary retention when taking maprotiline. Especially at night, elderly patients may experience delirious psychosis with the use of tricyclic antidepressants. This symptom disappears within a few days of discontinuing the tricyclic.

Because isolated cases of obstructive jaundice have been reported, use caution in treating patients with known liver disease. Periodic liver function testing is recommended in these patients.

The anticholinergic effects of maprotiline cause urinary retention, especially in men with benign prostatic hypertrophy.

Although rare, cases of bone marrow depression with agranulocytosis have been reported. Differential blood cell counts and leukocyte counts are recommended in patients receiving long-term treatment with maprotiline. These blood tests should also be performed in patients receiving maprotiline who present with fever, an influenzal infection or sore throat. Maprotiline should be discontinued in patients with significant neutropenia.

Carefully weigh risk to the infant versus benefit to the mother. Maprotiline passes into breast milk with milk concentrations of 0.2 μg/mL (unchanged maprotiline) after multiple doses. A milk:plasma ratio of approximately 1.5 has been reported after 150 mg per day for three days. It is not known whether the active metabolite is also present in breast milk. Effects of exposure to these small amounts of maprotiline during chronic ingestion is unknown.

Maprotiline appears to share the toxic potential of tricyclic antidepressants. Concurrent administration of maprotiline and electroconvulsive therapy should only be used by those experienced with this combination.

The potential for attempted suicide must always be considered in depressed patients. It is considered prudent to provide a limited supply of maprotiline to patients thought to be at high risk of suicide.

Maprotiline use in patients with tumors of the adrenal medulla (e.g., pheochromocytoma, neuroblastoma) may provoke a hypertensive crisis.

Seizures have been reported in patients without a history of seizures who were treated with maprotiline at therapeutic doses (see boxed warning above).

Because potential for interaction with general anesthetic is not known, maprotiline use should be tapered prior to elective surgery.

Monitor cardiac function and perform ECG examinations during long-term therapy in patients with pre-existing cardiovascular disease. Regularly measure both lying and standing blood pressure in patients susceptible to hypotension.

Differential blood cell counts and leukocyte counts are recommended in patients receiving long-term treatment with maprotiline. These blood tests should also be performed in patients receiving maprotiline who present with fever, a flu-like infection or sore throat.

Periodic liver function testing is recommended in patients with known liver disease.

Cases of the syndrome of inappropriate antidiuretic hormone (SIADH) have been reported in patients receiving tricyclic antidepressants.

Especially when starting therapy, maprotiline may produce sedation. Caution patients who may be engaging in activities requiring mental alertness, judgment and physical coordination.

Withdraw maprotiline if the patient presents with an allergic skin reaction.

Tricyclic antidepressants and maprotiline may prolong conduction time and produce sinus tachycardia and arrhythmias. The most common ECG changes that occurred in patients using maprotiline were premature ventricular contractions (PVCs), ST-T wave changes, and abnormalities in intraventricular conduction. These changes were rarely associated with significant clinical symptoms.

Myocardial infarct, strokes and cardiac arrest have been reported with tricyclic antidepressants. In patients with cardiovascular disease, especially conduction disorders (e.g., atrioventricular block), other arrhythmias or congestive heart failure, monitor cardiac function and perform ECG examinations during long-term therapy. Gradual dose titration is recommended. Measure patients's lying and standing blood pressure before starting treatment and regularly during treatment as hypotension may occur. Postural hypotension may be controlled by reducing the dosage or administering maprotiline as a single bedtime dose.

Transient cardiac arrhythmias have occurred in rare instances in patients receiving thyroid medications with tricyclic antidepressants.

Maprotiline metabolism may be altered in hepatic function impairment.

Half-life of maprotiline is extended in older individuals (average 66 h).

Plasma protein binding is 88 to 90%. Antidepressant effects usually occur within 2 to 3 weeks in most patients who respond and may occur within 3 to 7 days.

Maprotiline is slowly but completely absorbed after oral administration. Peak plasma concentrations occur within approximately 8 to 24 hours.

Maprotiline is excreted primarily in the urine (mostly as glucuronide metabolites) with about 30% excreted in feces. 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.

If hepatic function is normal, the half-life and renal excretion of maprotiline are not significantly affected by impaired renal function (creatinine clearance: 24 to 37 mL/min). Urinary excretion of metabolites is reduced. This reduction is normally offset by increased fecal elimination through biliary excretion.

Maprotiline is metabolized in the liver by hydroxylation and oxidation to form active and inactive metabolites. Maprotiline is metabolized by the CYP2D6 isoenzyme.

Your Shopping Cart

You currently have no items in your cart.