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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Ludiomil may be confused with Lamictal®, lamotrigine, Lomotil®
Pronunciation
(ma PROE ti leen)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of depression and anxiety associated with depression
Use: Unlabeled/Investigational
Bulimia; duodenal ulcers; enuresis; urinary symptoms of multiple sclerosis; pain; panic attacks; tension headache; cocaine withdrawal
Restrictions
An FDA-approved medication guide concerning the use of antidepressants in children, adolescents, and young adults must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. Dispense to parents or guardians of children and adolescents receiving this medication.
Pregnancy Risk Factor
B
Contraindications
Hypersensitivity to maprotiline or any component of the formulation; use of MAO inhibitors within 14 days; use in a patient during the acute recovery phase of MI
Warnings/Precautions
Boxed warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ?65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Maprotiline is not FDA approved for use in children.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Maprotiline is not FDA approved for the treatment of bipolar depression.
Concerns related to adverse effects:
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is moderate relative to other antidepressants.
• Orthostatic hypotension: May cause orthostatic hypotension (risk is moderate relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
• Sedation: May cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). The degree of sedation is high relative to other antidepressants.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities); the risk conduction abnormalities with this agent is moderate relative to other antidepressants.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
• Thyroid dysfunction: Use with caution in patients with hyperthyroidism or those receiving thyroid supplementation.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Elderly: Use with caution in the elderly.
Other warnings/precautions:
• Discontinuation of therapy: Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
Adverse Reactions
>10%:
Central nervous system: Drowsiness
Gastrointestinal: Xerostomia
1% to 10%:
Central nervous system: Anxiety, agitation, dizziness, fatigue, headache, insomnia, nervousness
Gastrointestinal: Constipation, nausea
Neuromuscular & skeletal: Tremor, weakness
Ocular: Blurred vision
<1%: Abdominal cramps, accommodation disturbances, akathisia, arrhythmia, ataxia, bitter taste, breast enlargement, confusion, decreased libido, delusions, diaphoresis (excessive), diarrhea, disorientation, dysarthria, dysphagia, edema of testicles, epigastric distress, EPS, exacerbation of psychosis, hallucinations, heart block, hyperglycemia, hyper-/hypotension, hypomania, impotence, mania, motor hyperactivity, mydriasis, nightmares, numbness, palpitation, petechiae, photosensitivity, rash, restlessness, seizure, syncope, tachycardia, tingling, tinnitus, urinary retention, vomiting, weight gain/loss
Metabolism/Transport Effects
Substrate of CYP2D6 (major)
Drug Interactions
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Sulfonylureas: Cyclic Antidepressants may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Mechanism of Action
Traditionally believed to increase the synaptic concentration of norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane. However, additional receptor effects have been found including desensitization of adenyl cyclase, down regulation of beta-adrenergic receptors, and down regulation of serotonin receptors.
Pharmacodynamics/Kinetics
Absorption: Slow
Protein binding: 88%
Metabolism: Hepatic to active and inactive compounds
Half-life elimination, serum: 27-58 hours (mean: 43 hours)
Time to peak, serum: Within 12 hours
Excretion: Urine (70%); feces (30%)
Dosage
Oral:
Adults: Depression/anxiety: 75 mg/day to start, increase by 25 mg every 2 weeks up to 150-225 mg/day; given in 3 divided doses or in a single daily dose
Elderly: Depression/anxiety: Initial: 25 mg at bedtime, increase by 25 mg every 3 days for inpatients and weekly for outpatients if tolerated; usual maintenance dose: 50-75 mg/day, higher doses may be necessary in nonresponders
Monitoring Parameters
Monitor blood pressure and pulse rate prior to and during initial therapy; evaluate mood and somatic complaints, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased); monitor appetite and weight; ECG in older adults
Geriatric Considerations
Use with caution due to sedation and anticholinergic effects (eg, confusion, constipation, difficulty urinating, dry mouth).
Additional Information
Odorless, bitter tasting; seizures are rarely seen 5-30 hours postdrug ingestion.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Although maprotiline is not a tricyclic antidepressant, it does block norepinephrine reuptake within CNS synapses as part of its mechanisms. It has been suggested that vasoconstrictor be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way, including maprotiline. Epinephrine and levonordefrin have been shown to have an increased pressor response in combination with TCAs. Maprotiline is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, levonordefrin [Neo-Cobefrin®]) be used with caution.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 25 mg, 50 mg, 75 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Maprotiline HCl)
25 mg (60): $29.99
50 mg (60): $39.99
75 mg (60): $47.99
References
Bergman RN and Watson WA, “Cardiac Toxicity Associated With Acute Maprotiline Self Poisoning,” Am J Emerg Med, 1983, 2(2):144-6.
Boakes AJ, Laurence DR, Teoh PC, et al, “Interactions Between Sympathomimetic Amines and Antidepressant Agents in Man,” Br Med J, 1973, 1(849):311-5.
Hrdina PD, Rovei V, Henry JF, et al, “Comparison of Single-Dose Pharmacokinetics of Imipramine and Maprotiline in the Elderly,” Psychopharmacology, 1980, 70(1):29-34.
Jastak JT and Yagiela JA, “Vasoconstrictors and Local Anesthesia: A Review and Rationale for Use,” J Am Dent Assoc, 1983, 107(4):623-30.
Larochelle P, Hamet P, and Enjalbert M, “Responses to Tyramine and Norepinephrine After Imipramine and Trazodone,” Clin Pharmacol Ther, 1979, 26(1):24-30.
Mitchell JR, “Guanethidine and Related Agents. III Antagonism by Drugs Which Inhibit the Norepinephrine Pump in Man,” J Clin Invest, 1970, 49(8):1596-604.
Pass SE and Simpson RW, “Discontinuation and Reinstitution of Medications During the Perioperative Period,” Am J Health Syst Pharm, 2004, 61(9):899-912.
Rundegren J, van Dijken J, Mörnstad H, et al, “Oral Conditions in Patients Receiving Long-Term Treatment With Cyclic Antidepressant Drugs,” Swed Dent J, 1985, 9(2):55-64.
Svedmyr N, “The Influence of a Tricyclic Antidepressive Agent (Protriptyline) on Some of the Circulatory Effects of Noradrenaline and Adrenalin in Man,” Life Sci, 1968, 7(1):77-84.
Wynn RL, “New Antidepressant Medications,” Gen Dent, 1997, 45(1):24-8.
Wyss PA, Serena S, and Meier PJ, “Dose-Dependency of Seizures in Maprotiline (Ludiomil®) Intoxications,” Vet Hum Toxicol, 1993, 35:341.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
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