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Protriptyline hydrochloride
Overview
What is Protriptyline hydrochloride?
Protriptyline HCl is N-methyl-5H dibenzo [a,d]-cycloheptene-5-propanamine hydrochloride. Its molecular formula is CHN●HCl
Protriptyline HCl, a dibenzocycloheptene derivative, has a molecular weight of 299.84. It is a white to yellowish powder that is freely soluble in water and soluble in dilute HCl. Protriptyline HCl is supplied as 5 mg or 10 mg film-coated tablets. Inactive ingredients are microcrystalline cellulose, pregelatinized starch, lactose monohydrate, dibasic calcium phosphate, sodium starch glycolate, magnesium stearate, hypromellose, triacetin, polysorbate, titanium dioxide and FD&C yellow 6 aluminum lake. The 10 mg tablet also contains polyethylene glycol and polysorbate 80.
What does Protriptyline hydrochloride look like?
What are the available doses of Protriptyline hydrochloride?
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What should I talk to my health care provider before I take Protriptyline hydrochloride?
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How should I use Protriptyline hydrochloride?
Protriptyline hydrochloride tablets are indicated for the treatment of symptoms of mental depression in patients who are under close medical supervision. Its activating properties make it particularly suitable for withdrawn and anergic patients.
Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.
What interacts with Protriptyline hydrochloride?
Protriptyline hydrochloride tablets are contraindicated in patients who have shown prior hypersensitivity to it.
It should not be given concomitantly with a monoamine oxidase inhibiting compound. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. When it is desired to substitute protriptyline for a monoamine oxidase inhibitor, a minimum of 14 days should be allowed to elapse after the latter is discontinued. Protriptyline should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.
Protriptyline is contraindicated in patients taking cisapride because of the possibility of adverse cardiac interactions including prolongation of the QT interval, cardiac arrhythmias and conduction system disturbances.
This drug should not be used during the acute recovery phase following myocardial infarction.
What are the warnings of Protriptyline hydrochloride?
Mixing or the prior or intercurrent use of any other local anesthetic with MARCAINE cannot be recommended because of insufficient data on the clinical use of such mixtures.
Clinical Worsening and Suicide Risk
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 (aged 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 analysis of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders including 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.
If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see for a description of the risks of discontinuation of protriptyline hydrochloride tablets).
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.
Screening Patients for Bipolar Disorder:
Protriptyline may block the antihypertensive effect of guanethidine or similarly acting compounds.
Protriptyline should be used with caution in patients with a history of seizures, and, because of its autonomic activity, in patients with a tendency to urinary retention, or increased intraocular tension.
Tachycardia and postural hypotension may occur more frequently with protriptyline than with other antidepressant drugs. Protriptyline should be used with caution in elderly patients and patients with cardiovascular disorders; such patients should be observed closely because of the tendency of the drug to produce tachycardia, hypotension, arrhythmias, and prolongation of the conduction time. Myocardial infarction and stroke have occurred with drugs of this class.
On rare occasions, hyperthyroid patients or those receiving thyroid medication may develop arrhythmias when this drug is given.
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.
Angle-Closure Glaucoma:
Usage in Pregnancy:
In mice, rats, and rabbits, doses about ten times greater than the recommended human doses had no apparent adverse effects on reproduction.
What are the precautions of Protriptyline hydrochloride?
General
When protriptyline HCl is used to treat the depressive component of schizophrenia, psychotic symptoms may be aggravated. Likewise, in manic-depressive psychosis, depressed patients may experience a shift toward the manic phase if they are treated with an antidepressant drug. Paranoid delusions, with or without associated hostility, may be exaggerated. In any of these circumstances, it may be advisable to reduce the dose of protriptyline or to use a major tranquilizing drug concurrently.
Symptoms, such as anxiety or agitation, may be aggravated in overactive or agitated patients.
The possibility of suicide in depressed patients remains during treatment and until significant remission occurs. This type of patient should not have access to large quantities of the drug.
Concurrent administration of protriptyline and electroshock therapy may increase the hazards of therapy. Such treatment should be limited to patients for whom it is essential.
Discontinue the drug several days before elective surgery, if possible.
Both elevation and lowering of blood sugar levels have been reported.
Information for Patients
Prescribers or other health professionals should inform patients, their families and their caregivers about the benefits and risks associated with treatment with protriptyline hydrochloride and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for protriptyline hydrochloride. 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 protriptyline hydrochloride.
Patients should be advised that taking protriptyline hydrochloride tablets can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.
Clinical Worsening and Suicide Risk
Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.
While on therapy with protriptyline, patients should be advised as to the possible impairment of mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.
Drug Interactions
When protriptyline is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required.
Hyperpyrexia has been reported when tricyclic antidepressants are administered with anticholinergic agents or with neuroleptic drugs, particularly during hot weather.
Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side-effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well-controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants.
Tricyclic antidepressants may enhance the seizure risk in patients taking ULTRAM (tramadol hydrochloride).
Protriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants.
Drugs Metabolized by Cytochrome P450 2D6
The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquine hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasian are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA).
In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics, propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRls), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRl involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRls and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).
Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6.
Pediatric Use
Safety and effectiveness in the pediatric population have not been established (see and ). Anyone considering the use of protriptyline hydrochloride in a child or adolescent must balance the potential risks with the clinical need.
Geriatric Use
Clinical studies of protriptyline 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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. (see , , and .)
What are the side effects of Protriptyline hydrochloride?
To report contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Within each category the following adverse reactions are listed in order of decreasing severity. Included in the listing are a few adverse reactions which have not been reported with this specific drug. However, the pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when protriptyline is administered. Protriptyline is more likely to aggravate agitation and anxiety and produce cardiovascular reactions such as tachycardia and hypotension.
Cardiovascular:
Psychiatric:
Neurological:
Anticholinergic:
Allergic:
Hematologic:
Gastrointestinal:
Endocrine:
Other:
Withdrawal Symptoms:
What should I look out for while using Protriptyline hydrochloride?
Protriptyline hydrochloride tablets are contraindicated in patients who have shown prior hypersensitivity to it.
It should not be given concomitantly with a monoamine oxidase inhibiting compound. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. When it is desired to substitute protriptyline for a monoamine oxidase inhibitor, a minimum of 14 days should be allowed to elapse after the latter is discontinued. Protriptyline should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.
Protriptyline is contraindicated in patients taking cisapride because of the possibility of adverse cardiac interactions including prolongation of the QT interval, cardiac arrhythmias and conduction system disturbances.
This drug should not be used during the acute recovery phase following myocardial infarction.
Clinical Worsening and Suicide Risk
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 (aged 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 analysis of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders including 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.
If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see for a description of the risks of discontinuation of protriptyline hydrochloride tablets).
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.
Screening Patients for Bipolar Disorder:
Protriptyline may block the antihypertensive effect of guanethidine or similarly acting compounds.
Protriptyline should be used with caution in patients with a history of seizures, and, because of its autonomic activity, in patients with a tendency to urinary retention, or increased intraocular tension.
Tachycardia and postural hypotension may occur more frequently with protriptyline than with other antidepressant drugs. Protriptyline should be used with caution in elderly patients and patients with cardiovascular disorders; such patients should be observed closely because of the tendency of the drug to produce tachycardia, hypotension, arrhythmias, and prolongation of the conduction time. Myocardial infarction and stroke have occurred with drugs of this class.
On rare occasions, hyperthyroid patients or those receiving thyroid medication may develop arrhythmias when this drug is given.
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.
Angle-Closure Glaucoma:
Usage in Pregnancy:
In mice, rats, and rabbits, doses about ten times greater than the recommended human doses had no apparent adverse effects on reproduction.
What might happen if I take too much Protriptyline hydrochloride?
Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As management of overdose 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.
How should I store and handle Protriptyline hydrochloride?
Storage:[See USP controlled room temperature]Protect from moisture.Storage:[See USP controlled room temperature]Protect from moisture.Storage:[See USP controlled room temperature]Protect from moisture.Protriptyline Hydrochloride Tablets USP, 5 mg are dark orange, round, biconvex, film coated tablets, de-bossed “96” on one side, and plain on the other side, available in bottles of 100’s.Protriptyline Hydrochloride Tablets USP, 10 mg are light orange, round, biconvex, film coated tablets, de-bossed “97” on one side, and plain on the other side, available in bottles of 100’s.Dispense in a tight container as defined in the USP.Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].Protriptyline Hydrochloride Tablets USP, 5 mg are dark orange, round, biconvex, film coated tablets, de-bossed “96” on one side, and plain on the other side, available in bottles of 100’s.Protriptyline Hydrochloride Tablets USP, 10 mg are light orange, round, biconvex, film coated tablets, de-bossed “97” on one side, and plain on the other side, available in bottles of 100’s.Dispense in a tight container as defined in the USP.Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].Protriptyline Hydrochloride Tablets USP, 5 mg are dark orange, round, biconvex, film coated tablets, de-bossed “96” on one side, and plain on the other side, available in bottles of 100’s.Protriptyline Hydrochloride Tablets USP, 10 mg are light orange, round, biconvex, film coated tablets, de-bossed “97” on one side, and plain on the other side, available in bottles of 100’s.Dispense in a tight container as defined in the USP.Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].Protriptyline Hydrochloride Tablets USP, 5 mg are dark orange, round, biconvex, film coated tablets, de-bossed “96” on one side, and plain on the other side, available in bottles of 100’s.Protriptyline Hydrochloride Tablets USP, 10 mg are light orange, round, biconvex, film coated tablets, de-bossed “97” on one side, and plain on the other side, available in bottles of 100’s.Dispense in a tight container as defined in the USP.Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
Protriptyline hydrochloride is an antidepressant agent. The mechanism of its antidepressant action in man is not known. It is not a monoamine oxidase inhibitor, and it does not act primarily by stimulation of the central nervous system.
Protriptyline has been found in some studies to have a more rapid onset of action than imipramine or amitriptyline. The initial clinical effect may occur within one week. Sedative and tranquilizing properties are lacking. The rate of excretion is slow.
Non-Clinical Toxicology
Protriptyline hydrochloride tablets are contraindicated in patients who have shown prior hypersensitivity to it.It should not be given concomitantly with a monoamine oxidase inhibiting compound. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. When it is desired to substitute protriptyline for a monoamine oxidase inhibitor, a minimum of 14 days should be allowed to elapse after the latter is discontinued. Protriptyline should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.
Protriptyline is contraindicated in patients taking cisapride because of the possibility of adverse cardiac interactions including prolongation of the QT interval, cardiac arrhythmias and conduction system disturbances.
This drug should not be used during the acute recovery phase following myocardial infarction.
Clinical Worsening and Suicide Risk
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 (aged 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 analysis of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders including 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.
If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see for a description of the risks of discontinuation of protriptyline hydrochloride tablets).
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.
Screening Patients for Bipolar Disorder:
Protriptyline may block the antihypertensive effect of guanethidine or similarly acting compounds.
Protriptyline should be used with caution in patients with a history of seizures, and, because of its autonomic activity, in patients with a tendency to urinary retention, or increased intraocular tension.
Tachycardia and postural hypotension may occur more frequently with protriptyline than with other antidepressant drugs. Protriptyline should be used with caution in elderly patients and patients with cardiovascular disorders; such patients should be observed closely because of the tendency of the drug to produce tachycardia, hypotension, arrhythmias, and prolongation of the conduction time. Myocardial infarction and stroke have occurred with drugs of this class.
On rare occasions, hyperthyroid patients or those receiving thyroid medication may develop arrhythmias when this drug is given.
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.
Angle-Closure Glaucoma:
Usage in Pregnancy:
In mice, rats, and rabbits, doses about ten times greater than the recommended human doses had no apparent adverse effects on reproduction.
When protriptyline is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required.
Hyperpyrexia has been reported when tricyclic antidepressants are administered with anticholinergic agents or with neuroleptic drugs, particularly during hot weather.
Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side-effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well-controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants.
Tricyclic antidepressants may enhance the seizure risk in patients taking ULTRAM (tramadol hydrochloride).
Protriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants.
When protriptyline HCl is used to treat the depressive component of schizophrenia, psychotic symptoms may be aggravated. Likewise, in manic-depressive psychosis, depressed patients may experience a shift toward the manic phase if they are treated with an antidepressant drug. Paranoid delusions, with or without associated hostility, may be exaggerated. In any of these circumstances, it may be advisable to reduce the dose of protriptyline or to use a major tranquilizing drug concurrently.
Symptoms, such as anxiety or agitation, may be aggravated in overactive or agitated patients.
The possibility of suicide in depressed patients remains during treatment and until significant remission occurs. This type of patient should not have access to large quantities of the drug.
Concurrent administration of protriptyline and electroshock therapy may increase the hazards of therapy. Such treatment should be limited to patients for whom it is essential.
Discontinue the drug several days before elective surgery, if possible.
Both elevation and lowering of blood sugar levels have been reported.
To report contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Within each category the following adverse reactions are listed in order of decreasing severity. Included in the listing are a few adverse reactions which have not been reported with this specific drug. However, the pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when protriptyline is administered. Protriptyline is more likely to aggravate agitation and anxiety and produce cardiovascular reactions such as tachycardia and hypotension.
Cardiovascular:
Psychiatric:
Neurological:
Anticholinergic:
Allergic:
Hematologic:
Gastrointestinal:
Endocrine:
Other:
Withdrawal Symptoms:
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
Review
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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
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Interactions
Interactions
A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).