|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(ma PROE ti leen)
Generic Available (U.S.)
Yes
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089129.pdf, must be dispensed with this medication.
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of major depressive disorder (MDD) or of anxiety associated with depression
Use: Unlabeled/Investigational
Chronic pain; panic attacks
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse effects were not seen in animal reproduction studies.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Breast milk concentrations of maprotiline are similar to maternal serum concentrations.
Contraindications
Hypersensitivity to maprotiline or any component of the formulation; seizure disorder; 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.
• Glaucoma: Use with caution in patients with narrow-angle glaucoma or increased intraocular pressure; condition may be exacerbated by cholinergic blockade.
• 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; use contraindicated in patients with a history of seizure disorder. The risk of seizures may be decreased by initiating therapy at a low dose and increasing it gradually to the minimally effective dose
• 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: Recommended to discontinue prior to elective surgery requiring general anesthesia. 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 (16%)
Gastrointestinal: Xerostomia (22%)
1% to 10%:
Central nervous system: Dizziness (8%), nervousness (6%), fatigue (4%), headache (4%), anxiety (3%), agitation (2%), insomnia (2%)
Gastrointestinal: Constipation (6%), nausea (2%)
Neuromuscular & skeletal: Weakness (4%), tremor (3%)
Ocular: Blurred vision (4%)
<1%, postmarketing, and/or case reports: Abdominal cramps, accommodation disturbances, agranulocytosis, akathisia, alopecia, arrhythmia, ataxia, bitter taste, black tongue, breast enlargement (female), confusion, delusions, diaphoresis (excessive), diarrhea, disorientation, dysarthria, dysphagia, edema, EEG alterations, eosinophilia, epigastric distress, EPS, feelings of unreality, fever, flushing, galactorrhea, gynecomastia (male), hallucinations, heart block, hyper-/hypoglycemia, hyper-/hypotension, hypomania, impotence, interstitial pneumonitis, itching, jaundice, libido decreased/increased, liver function tests altered, mania, memory impairment, MI, micturition delayed, motor hyperactivity, mydriasis, nasal congestion, nightmares, numbness, palpitation, paralytic ileus, peripheral neuropathy, petechiae, photosensitivity, psychosis exacerbation, purpura, rash, restlessness, salivation increased, seizure, Stevens-Johnson syndrome, stomatitis, stroke, sublingual adenitis, syncope, tachycardia, testicle edema, thrombocytopenia, tingling, tinnitus, toxic epidermal necrolysis, urinary frequency, urinary retention, vomiting, weight gain/loss
Metabolism/Transport Effects
Substrate of CYP2D6 (major)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
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
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. 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
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
MAO Inhibitors: Maprotiline may enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. 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
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
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
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. 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: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Storage
Store at 20°C to 25˚C (68°F to 77˚F). Protect from light.
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: 51 hours)
Time to peak, serum: Within 12 hours
Excretion: Urine (70%); feces (30%)
Dosage
Oral:
Adults:
Mild-to-moderate depression/anxiety: Initial: 75 mg/day for 2 weeks (lower doses may be considered in some patients); Maintenance: Increase by 25 mg as tolerated up to 150 mg/day; given in divided doses or in a single daily dose
Severe depression: Initial: 100-150 mg/day for 2 weeks; Maintenance: Increase by 25 mg as tolerated up to 225 mg/day; given in divided doses or in a single daily dose
Elderly: Depression/anxiety: Initial: 25 mg/day for 2 weeks; Maintenance: Increase by 25 mg as tolerated; usual 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; CBC in patients who develop fever or sore throat during therapy
Geriatric Considerations
Use with caution due to sedation and anticholinergic effects (eg, confusion, constipation, difficulty urinating, dry mouth).
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, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Maprotiline is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Maprotiline is considered as having a risk of causing torsade de pointes. Since 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, a medical consult is suggested.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as hydrochloride: 25 mg, 50 mg, 75 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Maprotiline HCl)
25 mg (60): $43.99
50 mg (60): $55.99
75 mg (60): $74.99
References
Alkalay D, Wagner WE Jr, Carlsen S, et al, "Bioavailability and Kinetics of Maprotiline," Clin Pharmacol Ther, 1980, 27(5):697-703.
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.
Maguire KP, Norman TR, Burrows GD, et al, "An Evaluation of Maprotiline Intravenous Kinetics and Comparison of Two Oral Doses," Eur J Clin Pharmacol, 1980, 18(3):249-54.
Wells BG and Gelenberg AJ, "Chemistry, Pharmacology, Pharmacokinetics, Adverse Effects, and Efficacy of the Antidepressant MaprotilineHydrochloride," Pharmacotherapy, 1981, 1(2):121-39.
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 May 2011
Content last modified May 2011
| 
