Product Elements:
Protriptyline hydrochloride protriptyline hydrochloride anhydrous lactose crospovidone anhydrous dibasic calcium phosphate magnesium stearate cellulose, microcrystalline polyethylene glycol 3350 polyvinyl alcohol talc titanium dioxide fd&c yellow no. 6 protriptyline hydrochloride protriptyline 4 protriptyline hydrochloride protriptyline hydrochloride anhydrous lactose crospovidone anhydrous dibasic calcium phosphate magnesium stearate cellulose, microcrystalline polyethylene glycol 3350 polyvinyl alcohol talc titanium dioxide fd&c yellow no. 6 d&c yellow no. 10 protriptyline hydrochloride protriptyline 7
Boxed Warning:
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 protriptyline hydrochloride 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. protriptyline hydrochloride is not approved for use in pediatric patients. (see warnings: clinical worsening and suicide risk , precautions: information for patients , and precautions: pediatric use )
Indications and Usage:
Indications and usage 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 its activating properties make it particularly suitable for withdrawn and anergic patients.
Warnings:
Warnings 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 ma
Read more...jor 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 . table 1 age range drug-placebo difference in number of cases of suicidality per 1000 patients treated increases compared to placebo <18 14 additional cases 18 to 24 5 additional cases decreases compared to placebo 25 to 64 1 fewer case >65 6 fewer cases 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 adverse reactions - withdrawal symptoms 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. such monitoring should include daily observation by families and caregivers. prescriptions for protriptyline hydrochloride tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. screening patients for bipolar disorder: a major depressive episode may be the initial presentation of bipolar disorder. it is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. whether any of the symptoms described above represent such a conversion is unknown. however, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. it should be noted that protriptyline hydrochloride is not approved for use in treating bipolar depression. 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: the pupillary dilation that occurs following use of many antidepressant drugs including protriptyline may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. usage in pregnancy: safe use in pregnancy and lactation has not been established; therefore, use in pregnant women, nursing mothers or women who may become pregnant requires that possible benefits be weighed against possible hazards to mother and child. in mice, rats, and rabbits, doses about ten times greater than the recommended human doses had no apparent adverse effects on reproduction.
Dosage and Administration:
Dosage and administration dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance. usual adult dosage fifteen to 40 mg a day divided into 3 or 4 doses. if necessary, dosage may be increased to 60 mg a day. dosages above this amount are not recommended. increases should be made in the morning dose. adolescent and elderly patients in general, lower dosages are recommended for these patients. five mg 3 times a day may be given initially, and increased gradually if necessary. in elderly patients, the cardiovascular system must be monitored closely if the daily dose exceeds 20 mg. when satisfactory improvement has been reached, dosage should be reduced to the smallest amount that will maintain relief of symptoms. minor adverse reactions require reduction in dosage. major adverse reactions or evidence of hypersensitivity require prompt discontinuation of the drug. the safety and effectiveness of protriptyline i
Read more...n pediatric patients have not been established.
Contraindications:
Contraindications 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.
Adverse Reactions:
Adverse reactions 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: myocardial infarction; stroke; heart block; arrhythmias; hypotension, particularly orthostatic hypotension; hypertension; tachycardia; palpitation. psychiatric: confusional states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation; hypomania; exacerbation of psychosis; insomnia, panic, and nightmares. neurological: seizures; incoordination; ataxia; tremors; peripheral neuropathy; numbness, tingli
Read more...ng, and paresthesias of extremities; extrapyramidal symptoms; drowsiness; dizziness; weakness and fatigue; headache; syndrome of inappropriate adh (antidiuretic hormone) secretion; tinnitus; alteration in eeg patterns. anticholinergic: paralytic ileus; hyperpyrexia; urinary retention, delayed micturition, dilatation of the urinary tract; constipation; blurred vision, disturbance of accommodation, increased intraocular pressure, mydriasis; dry mouth and rarely associated sublingual adenitis. allergic: drug fever; petechiae, skin rash, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); edema (general, or of face and tongue). hematologic: agranulocytosis; bone marrow depression; leukopenia; thrombocytopenia; purpura; eosinophilia. gastrointestinal: nausea and vomiting; anorexia; epigastric distress; diarrhea; peculiar taste; stomatitis; abdominal cramps; black tongue. endocrine: impotence, increased or decreased libido; gynecomastia in the male; breast enlargement and galactorrhea in the female; testicular swelling; elevation or depression of blood sugar levels. other: jaundice (simulating obstructive); altered liver function; parotid swelling; alopecia; flushing; weight gain or loss; urinary frequency, nocturia; perspiration. withdrawal symptoms: though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise. to report suspected adverse reactions , contact sigmapharm laboratories, llc, pharmacovigilance at 1-855-332-0731 or fda at 1-800-fda-1088 or www.fda.gov/medwatch .
Pediatric Use:
Pediatric use safety and effectiveness in the pediatric population have not been established (see box warnings and warnings â clinical worsening and suicide risk ). anyone considering the use of protriptyline hydrochloride in a child or adolescent must balance the potential risks with the clinical need.
Geriatric Use:
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 warnings , dosage and administration , and adverse reactions .)
Overdosage:
Overdosage 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. manifestations critical manifestations of overdosage 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. 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 adverse reactions . management general obtain an ecg and immediately initiate cardiac monitoring. protect the patientâs airway, establish an intravenous line and initiate gastric decontamination. a minimum of six hours of observation with cardiac monitoring and observation for signs of cns or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. if signs of toxicity occur at any time during this period, extended monitoring is required. there are case reports of patients succumbing to fatal dysrhythmias late after overdose. these patients had clinical evidence of significant poisoning prior to death and most received inadequate gastrointestinal decontamination. monitoring of plasma drug levels should not guide management of the patient. gastrointestinal decontamination all patients suspected of a tricyclic antidepressant overdose should receive gastro-intestinal decontamination. this should include large volume gastric lavage followed by activated charcoal. if consciousness is impaired, the airway should be secured prior to lavage. emesis is contraindicated. cardiovascular a maximal limb-lead qrs duration of â¥0.10 seconds may be the best indication of the severity of the overdose. intravenous sodium bicarbonate should be used to maintain the serum ph in the range of 7.45 to 7.55. if the ph response is inadequate, hyperventilation may also be used. concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent ph monitoring. a ph > 7.60 or a pco2 of <20mm hg is undesirable. dysrhythmias unresponsive to sodium bicarbonate/ hyperventilation may respond to lidocaine, bretylium or phenytoin. type 1a and 1c antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide). in rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. however, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic antidepressant poisoning. cns in patients with cns depression, early intubation is advised because of the potential for abrupt deterioration. seizures should be controlled with benzodiazepines or, if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin). physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in close consultation with a poison control center. psychiatric follow-up since overdosage is often deliberate, patients may attempt suicide by other means during the recover phase. psychiatric referral may be appropriate. pediatric management the principles of management of child and adult overdosages are similar. it is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.
Description:
Description protriptyline hcl is n-methyl-5h dibenzo [a,d]-cycloheptene-5-propanamine hydrochloride. its molecular formula is c 19 h 21 nâ¢hcl and its structural formula is: protriptyline hcl, 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 anhydrous lactose, crospovidone, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, fd&c yellow#6, and the 10 mg tablets contain d & c yellow#10. protriptyline structure
Clinical Pharmacology:
Clinical 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.
How Supplied:
How supplied protriptyline hydrochloride tablets: 5 mg - orange, round, film-coated tablets in bottles of 100 (ndc 42794-004-02). debossed âΣâ on one side and â4â on the other. 10 mg - yellow, round, film-coated tablets in bottles of 100 (ndc 42794-007-02). debossed âΣâ on one side and â7â on the other. dispense in a tight container as defined in the usp. store at 20°-25°c (68°-77°f) [see usp controlled room temperature]. metabolism metabolic studies indicate that protriptyline is well absorbed from the gastrointestinal tract and is rapidly sequestered in tissues. relatively low plasma levels are found after administration, and only a small amount of unchanged drug is excreted in the urine of dogs and rabbits. preliminary studies indicate that demethylation of the secondary amine moiety occurs to a significant extent, and that metabolic transformation probably takes place in the liver. it penetrates the brain rapidly in mice and
Read more... rats, and moreover that which is present in the brain is almost all unchanged drug. studies on the disposition of radioactive protriptyline in human test subjects showed significant plasma levels within 2 hours, peaking at 8 to 12 hours, then declining gradually. urinary excretion studies in the same subjects showed significant amounts of radioactivity in 2 hours. the rate of excretion was slow. cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. the fecal route of excretion did not seem to be important. sigmapharm laboratories, llc bensalem, pa 19020 os007a-00 rev.0219
Package Label Principal Display Panel:
Protriptyline 5 mg label
Protriptyline 10 mg label