Norpramin Information
Norpramin (Desipramine hcl) Suicidality And Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Norpramin (Desipramine hcl) or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Norpramin (Desipramine hcl) is not approved for use in pediatric patients. (See , , and .)
Norpramin (Desipramine hcl) Description
Norpramin (Desipramine hcl) (desipramine hydrochloride USP) is an antidepressant drug of the tricyclic type, and is chemically: 5-Dibenz[]azepine-5-propanamine,10,11-dihydro--methyl-, monohydrochloride.
Norpramin (Desipramine hcl) Inactive Ingredients
The following inactive ingredients are contained in all dosage strengths: acacia, calcium carbonate, corn starch, D&C Red No. 30 and D&C Yellow No. 10 (except 10 mg and 150 mg), FD&C Blue No. 1 (except 50 mg, 75 mg, and 100 mg), hydrogenated soy oil, iron oxide, light mineral oil, magnesium stearate, mannitol, polyethylene glycol 8000, pregelatinized corn starch, sodium benzoate (except 150 mg), sucrose, talc, titanium dioxide, and other ingredients.
Norpramin (Desipramine hcl) Clinical Pharmacology
Available evidence suggests that many depressions have a biochemical basis in the form of a relative deficiency of neurotransmitters such as norepinephrine and serotonin. Norepinephrine deficiency may be associated with relatively low urinary 3-methoxy-4-hydroxyphenyl glycol (MHPG) levels, while serotonin deficiencies may be associated with low spinal fluid levels of 5-hydroxyindoleacetic acid.
While the precise mechanism of action of the tricyclic antidepressants is unknown, a leading theory suggests that they restore normal levels of neurotransmitters by blocking the re-uptake of these substances from the synapse in the central nervous system. Evidence indicates that the secondary amine tricyclic antidepressants, including Norpramin (Desipramine hcl) , may have greater activity in blocking the re-uptake of norepinephrine. Tertiary amine tricyclic antidepressants, such as amitriptyline, may have greater effect on serotonin re-uptake.
Norpramin (Desipramine hcl) is not a monoamine oxidase (MAO) inhibitor and does not act primarily as a central nervous system stimulant. It has been found in some studies to have a more rapid onset of action than imipramine. Earliest therapeutic effects may occasionally be seen in 2 to 5 days, but full treatment benefit usually requires 2 to 3 weeks to obtain.
Tricyclic antidepressants, such as desipramine hydrochloride, are rapidly absorbed from the gastrointestinal tract. Tricyclic antidepressants or their metabolites are to some extent excreted through the gastric mucosa and reabsorbed from the gastrointestinal tract. Desipramine is metabolized in the liver, and approximately 70% is excreted in the urine.
The rate of metabolism of tricyclic antidepressants varies widely from individual to individual, chiefly on a genetically determined basis. Up to a 36-fold difference in plasma level may be noted among individuals taking the same oral dose of desipramine. The ratio of 2-hydroxydesipramine to desipramine may be increased in the elderly, most likely due to decreased renal elimination with aging.
Certain drugs, particularly the psychostimulants and the phenothiazines, increase plasma levels of concomitantly administered tricyclic antidepressants through competition for the same metabolic enzyme systems. Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressants. Conversely, decreases in plasma levels of the tricyclic antidepressants have been reported upon discontinuation of cimetidine, which may result in the loss of the therapeutic efficacy of the tricyclic antidepressant. Other substances, particularly barbiturates and alcohol, induce liver enzyme activity and thereby reduce tricyclic antidepressant plasma levels. Similar effects have been reported with tobacco smoke.
Research on the relationship of plasma level to therapeutic response with the tricyclic antidepressants has produced conflicting results. While some studies report no correlation, many studies cite therapeutic levels for most tricyclics in the range of 50 to 300 nanograms per milliliter. The therapeutic range is different for each tricyclic antidepressant. For desipramine, an optimal range of therapeutic plasma levels has not been established.
Norpramin (Desipramine hcl) Indications And Usage
Norpramin (Desipramine hcl) is indicated for the treatment of depression.
Norpramin (Desipramine hcl) Contraindications
Norpramin (Desipramine hcl) should not be given in conjunction with, or within 2 weeks of, treatment with MAO inhibitors or drugs with similar MAO inhibition activity, such as linezolid. Hyperpyretic crises, severe convulsions, and death have occurred in patients taking MAO inhibitors and tricyclic antidepressants. When Norpramin (Desipramine hcl) is substituted for an MAO inhibitor, at least 2 weeks should elapse between treatments. Norpramin (Desipramine hcl) should then be started cautiously and should be increased gradually.
Norpramin (Desipramine hcl) is contraindicated in the acute recovery period following myocardial infarction. It should not be used in those who have shown prior hypersensitivity to the drug. Cross-sensitivity between this and other dibenzazepines is a possibility.
Norpramin (Desipramine hcl) Warnings
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18–24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.
No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers.
Extreme caution should be used when this drug is given in the following situations:
This drug is capable of blocking the antihypertensive effect of guanethidine and similarly acting compounds.
The patient should be cautioned that this drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
In patients who may use alcohol excessively, it should be borne in mind that the potentiation may increase the danger inherent in any suicide attempt or overdosage.
Clinical studies of Norpramin (Desipramine hcl) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Lower doses are recommended for elderly patients. (See .)
The ratio of 2-hydroxydesipramine to desipramine may be increased in the elderly, most likely due to decreased renal elimination with aging.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Norpramin (Desipramine hcl) use in the elderly has been associated with a proneness to falling as well as confusional states. (See .)
Norpramin (Desipramine hcl) Precautions
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Norpramin (Desipramine hcl) and should counsel them in its appropriate use. A patient Medication Guide about "Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions" is available for Norpramin (Desipramine hcl) . The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Norpramin (Desipramine hcl) .
Safety and effectiveness in the pediatric population have not been established (see and ). Therefore, Norpramin (Desipramine hcl) (desipramine hydrochloride) is not recommended for use in children.
Anyone considering the use of Norpramin (Desipramine hcl) in a child or adolescent must balance the potential risks with the clinical need (see also ).
It is important that this drug be dispensed in the least possible quantities to depressed outpatients, since suicide has been accomplished with this class of drug (see). Ordinary prudence requires that children not have access to this drug or to potent drugs of any kind; if possible, this drug should be dispensed in containers with child-resistant safety closures. Storage of this drug in the home must be supervised responsibly.
If serious adverse effects occur, dosage should be reduced or treatment should be altered.
Norpramin (Desipramine hcl) therapy in patients with manic-depressive illness may induce a hypomanic state after the depressive phase terminates.
The drug may cause exacerbation of psychosis in schizophrenic patients.
Both elevation and lowering of blood sugar levels have been reported.
Leukocyte and differential counts should be performed in any patient who develops fever and sore throat during therapy; the drug should be discontinued if there is evidence of pathologic neutrophil depression.
Clinical experience in the concurrent administration of ECT and antidepressant drugs is limited. Thus, if such treatment is essential, the possibility of increased risk relative to benefits should be considered.
This drug should be discontinued as soon as possible prior to elective surgery because of possible cardiovascular effects. Hypertensive episodes have been observed during surgery in patients taking desipramine hydrochloride.
Norpramin (Desipramine hcl) Adverse Reactions
Included in the following listing are a few adverse reactions that have not been reported with this specific drug. However, the pharmacologic similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when Norpramin (Desipramine hcl) is given.
Cardiovascular:
There has been a report of an "acute collapse" and "sudden death" in an 8-year-old (18 kg) male, treated for 2 years for hyperactivity.
There have been additional reports of sudden death in children. (See )
Psychiatric:
Neurologic:
Symptoms attributed to Neuroleptic Malignant Syndrome have been reported during desipramine use with and without concomitant neuroleptic therapy.
Anticholinergic:
Allergic:
Hematologic:
Gastrointestinal:
Endocrine:
Other:
Withdrawal Symptoms:
Norpramin (Desipramine hcl) Overdosage
Deaths may occur from overdosage with this class of drugs. Overdose of desipramine has resulted in a higher death rate compared to overdoses of other tricyclic antidepressants. 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. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible. There is no specific antidote for desipramine overdosage.
Critical manifestations of overdose include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Early changes in the QRS complex include a widening of the terminal 40 msec with a rightward axis in the frontal plane, recognized by the presence of a terminal S wave in Lead 1 and AVL and an R wave in AVR.
Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the symptoms listed under .
Norpramin (Desipramine hcl) Dosage And Administration
Not recommended for use in children (see ).
Lower dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients compared to hospitalized patients, who are closely supervised. Dosage should be initiated at a low level and increased according to clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a period of time and should be at the lowest dose that will maintain remission.
Norpramin (Desipramine hcl) How Supplied
10 mg blue coated tablets imprinted 68-7 NDC 0068-0007-01: bottles of 100
25 mg yellow coated tablets imprinted Norpramin (Desipramine hcl) 25 NDC 0068-0011-01: bottles of 100
50 mg green coated tablets imprinted Norpramin (Desipramine hcl) 50 NDC 0068-0015-01: bottles of 100
75 mg orange coated tablets imprinted Norpramin (Desipramine hcl) 75 NDC 0068-0019-01: bottles of 100
100 mg peach coated tablets imprinted Norpramin (Desipramine hcl) 100 NDC 0068-0020-01: bottles of 100
150 mg white coated tablets imprinted Norpramin (Desipramine hcl) 150 NDC 0068-0021-50: bottles of 50
Norpramin (Desipramine hcl) tablets should be stored at room temperature, preferably below 86°F (30°C). Protect from excessive heat. Dispense in tight container.
Norpramin (Desipramine hcl)
Norpramin (Desipramine hcl) Medication Guidenorpramin® (desipramine Hydrochloride Tablets Usp)antidepressant Medicines, Depression And Other Serious Mental Illnesses, And Suicidal Thoughts Or Actions
Read the Medication Guide that comes with your, or your family member's, antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to sanofi-aventis U.S. at 1-800-633-1610.
Norpramin (Desipramine hcl)
Norpramin (Desipramine hcl) Principal Display Panel - Mg Tablet
NDC 0068-0007-01
ATTN: DISPENSE WITH MEDICATION GUIDEFROM TEAR-OFF PAD
Norpramin (Desipramine hcl) Principal Display Panel - Mg Tablet
NDC 0068-0011-01
ATTN: DISPENSE WITH MEDICATION GUIDEFROM TEAR-OFF PAD
Norpramin (Desipramine hcl) Principal Display Panel - Mg Tablet
NDC 0068-0015-01
ATTN: DISPENSE WITH MEDICATION GUIDEFROM TEAR-OFF PAD
Norpramin (Desipramine hcl) Principal Display Panel - Mg Tablet
NDC 0068-0019-01
ATTN: DISPENSE WITH MEDICATION GUIDEFROM TEAR-OFF PAD
Norpramin (Desipramine hcl) Principal Display Panel - Mg Tablet
NDC 0068-0020-01
ATTN: DISPENSE WITH MEDICATION GUIDEFROM TEAR-OFF PAD
Norpramin (Desipramine hcl) Principal Display Panel - Mg Tablet
NDC 0068-0021-50
ATTN: DISPENSE WITH MEDICATION GUIDEFROM TEAR-OFF PAD
