Tablets 10mg: "geranium rose" coloured, biconvex, film coated tablets.
Parnate is indicated in depression. It is not recommended for use in mild depressive state resulting from temporary situational difficulties.
Begin with 20mg a day given as 10mg in the morning and in the afternoon. If there is no satisfactory response after two weeks, add one more tablet at midday. Continue this dosage for at least a week. A dosage of 3 tablets a day should only be exceeded with caution. When a satisfactory response is established, dosage may be reduced to a maintenance level. Some patients will be maintained on 20mg per day, some will need only 10mg daily. If no improvement occurs, continued administration is unlikely to be beneficial. When given together with a tranquilliser, the dosage of Parnate is not affected. When the drug is given concurrently with electroconvulsive therapy, the recommended dosage is 10mg twice a day during the series and 10mg a day afterwards as maintenance therapy.
Because the effect of many antidepressant medicines (including buspirone HCl) may persist for several days, do not commence tranylcypromine therapy within less than a week of discontinuing treatment with such drugs. Then use half the normal dosage for the first week. Similarly, allow a week to elapse between the discontinuance of tranylcypromine and the administration of any other medicines that is contraindicated with tranylcypromine. Tranylcypromine is contraindicated:
In patients with a previous history of hypersensitivity to tranylcypromine or excipients.
In patients with cerebrovascular or cardiovascular disease, a history of recurrent or frequent headaches, liver damage or blood dyscrasias. Tranylcypromine should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to an patient with cardiovascular disease or hypertension.
In patients with phaeochromocytoma. Tranylcypromine should not be used in the presence of phaeochromocytoma, or if it is suspected, as such tumors secrete pressor substances.
In combination with other MAO inhibitors, such as furazolidone, isocarboxazid, nialamid, pargyline, and phenelzine.
In combination with dibenzazepine derivatives, such as amitriptyline, desipramine, imipramine, nortriptyline, protriptyline and carbamazepine, as these combinations may induce hypertensive crises or severe convulsive seizures.
In combination with sympathomimetics, including amphetamines, ephedrine and over-the counter drugs such as cold, hay fever and weight-reducing preparations that contain vasoconstrictors. Also with methyldopa, dopamine, levodopa and tryptophan, as they may result in potentiation, precipitating hypertension, severe headache, and hyperpyrexia; cerebral haemorrhage may occur.
In combination with SSRIs. There have been reports of serious, sometimes fatal reactions when MAOIs are given before, with, or shortly after discontinuation with some SSRIs. It is recommended that MAOIs are not used in combination with SSRIs. If the two therapies are used in consecutively, a suitable washout period should be observed as follows:
MAOI followed by SSRI - 2 weeks Fluoxetine followed by MAOI - 5 weeks Other SSRI followed by MAOI - 2 weeks In combination with dextromethorphan. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behaviour. In combination with cheese or other foods with high tyramine content. Hypertensive crises have sometimes occurred during tranylcypromine therapy after ingestion of foods with a high tyramine content. In general, the patient should avoid protein foods in which aging or protein breakdown is used to increase flavour. In particular, patients should be instructed not to take foods such as cheese, sour cream, Chianti wine, sherry, beer (including non-alcoholic beer), caviar, pickled herrings, liver, canned figs, raisins, banana or avocados (particularly if overripe), chocolate, soy beans, the pods of broad beans, yeast extracts, or meals prepared with tenderizers. It is important, therefore, that patients be warned to avoid cheese, protein extracts and the other prohibited dietary items while taking tranylcypromine. Patients should be warned against self-medication with proprietary drugs such as cold, hay fever or weight-reducing drugs that contain pressor agents. They should also be advised not to consume excessive amounts of caffeine in any form.
Safety and efficacy have not been established in this population. Consequently, tranylcypromine should not be used in patients under 18 years of age (See Warnings).
Patients of any age with Major Depressive Disorder may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Young adults aged 18-24 years are at increased risk as improvement may not occur during the initial treatment period (usually one to two months). Patients should be closely monitored for clinical worsening of suicidality, especially at the beginning of therapy or when the dose is changed (dose increase or dose decrease), until such improvement occurs. There has been a long-standing concern that some antidepressants may have a role in the emergence of suicidality in some patients. The possible risk of increased suicidality in patients applies to all classes of antidepressant medicines, as available data are not adequate to exclude this risk for any antidepressant. Therefore, consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms. Generally, when stopping an antidepressant, doses should be tapered rather than stopped abruptly. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and paediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric. 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, consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients for whom such symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric and non-psychiatric disorders. Note: The Medicines Act 1981 allows a doctor to prescribe a medicine for any indication regardless of whether it is approved or not for that indication. There are limitations to this authority embedded in the Code of Health and Disability Services Consumers' Rights 1996. Unapproved use of medicines must comply with this Code, which states that the patient has the right to treatment of an appropriate ethical and professional standard, and the doctor has the responsibility to ensure that treatment, whether approved or unapproved, meets this standard. The patient also has the right to be fully informed. If the use of a medicine is unapproved, the patient should be so advised and the doctor should be frank about the level of evidence for the medicine's efficacy as well as any safety concerns. The doctor must fully discuss the risk/benefit issues with the patient/parent, and in appropriate circumstances this may lead to the use of an antidepressant with informed consent. (For more information on unapproved use of medicines see Medsafe article: www.medsafe.govt.nz/Profs/RIss/unapp.htm)
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 any antidepressant alone may increase the likelihood of a mixed/manic episode in patients at risk for bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder. It should be noted that tranylcypromine is not approved for use in treating bipolar depression.
When giving tranylcypromine with the following drugs: guanethidine, as its action may be antagonised; reserpine, as hyperactivity may occur; other hypotensive agents; because of the possibility of additive hypotensive effects; barbiturates, as their action may be prolonged or potentiated; anti-parkinsonism agents, as the combination may result in potentiation, with profuse sweating, tremulousness, and rise in body temperature; and clomipramine hydrochloride, as this drug, in combination with an MAO inhibitor, has been reported to result in hyperpyrexia, diffuse intravascular coagulation, and status epilepticus.
In elderly patients, because of the possibility of existing cerebral sclerosis with damaged blood vessels.
In patients with diabetes. Some MAO inhibitors have contributed to hypoglycaemic episodes in diabetic patients receiving insulin or oral hypoglycaemic agents. Tranylcypromine should therefore be used with caution in diabetics under treatment with these drugs.
In epileptic patients. Because the influence of tranylcypromine on the convulsive threshold is variable in animal experiments, suitable precautions should be taken if epileptic patients are treated with tranylcypromine.
In surgery. Although excretion of tranylcypromine is rapid, it is advisable wherever possible to discontinue tranylcypromine therapy at least 7 days before surgery, because of possible interference with the action of certain anaesthetics and analgesics.
In patients with impaired renal function, since there is a possibility of cumulative effects in such patients.
In hyperthyroid patients, because of their increased sensitivity to pressor amines.
MAO inhibitors may have the capacity to suppress anginal pain that would otherwise serve as a warning of myocardial ischaemia.
See Special Warnings and Special Precautions for Use.
Adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available. Therefore, tranylcypromine should be used in pregnant or lactating women only if clearly needed and if the potential benefits justify the potential risk. Epidemiological studies have suggested an increased risk of congenital abnormalities associated with use of antidepressants in pregnancy. Neonates exposed to antidepressants late in the third trimester have shown drug withdrawal symptoms such as dyspnoea, lethargy, colic irritability, hypotension or hypertension and tremor or spasms. Epidemiological data suggests that the use of antidepressants in pregnancy may be associated with an increase in pre-term delivery.
May affect ability to drive or operate machinery.
The most frequently seen side effect is insomnia, which can usually be overcome by giving the last dose of the day not later than 3 pm, by reducing the dose, or by prescribing a mild hypnotic. Occasional cases of dizziness, palpitation, weakness, dry mouth and drowsiness have been reported. Palpitations or unusually frequent headaches, unaccompanied by paroxysmal hypertension, may possibly be dose-related in some patients. Such symptoms may respond to reduction of dosage. If improvement is not rapid, the medicine should be discontinued. Hypotension, which may be postural, has been observed during tranylcypromine therapy. Syncope has been rarely seen. Dosage should not be increased in the presence of hypotension. This side effect is usually temporary, but if it persists, the medicine should be discontinued. The blood pressure will then return rapidly to pre-treatment level. Overstimulation, which may include increased anxiety and agitation, and manic symptoms, may sometimes occur with normal dosage but is more commonly associated with overdosage. Reduction of the dose is indicated. In certain instances it may be helpful to administer a sedative phenothiazine tranquilizer, such as chlorpromazine, concomitantly.
The most important adverse reaction associated with tranylcypromine is the occurrence of hypertensive crises which have sometimes been fatal.
These crises are characterized by some or all of the following symptoms: Occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, nausea or vomiting, sweating with early pallor followed later by flushing. Either tachycardia or bradycardia may be present; and associated mydriasis may also occur. This headache, together with pain and stiffness in the cervical muscles, may mimic subarachnoid haemorrhage, but can equally be associated with actual intracranial bleeding, as in other conditions where a sudden rise in blood pressure occurs. Cases of such bleeding have been reported, some of which have been fatal. Therapy should be discontinued immediately upon the occurrence of palpitation or frequent headache during tranylcypromine therapy. Patients should be instructed to report promptly the occurrence of headache or other symptoms.
Recommended treatment in hypertensive reactions:
If a hypertensive reaction occurs, tranylcypromine should be discontinued and therapy to lower blood pressure should be instituted immediately, if indicated. Headache tends to abate as blood pressure falls. On the basis of present evidence, phentolamine is recommended (the dosage reported for phentolamine is 5mg I.V. ). Reserpine should not be used. Care should be taken to administer this drug slowly in order to avoid producing an excessive hypotensive effect. Fever should be managed by means of external cooling. Other symptomatic and supportive measures may be desirable in particular cases. Acute symptoms generally subside within 24 hours. Haematological disorders including anaemia, leukopenia, agranulocytosis, and thrombocytopenia have been reported. Oedema, rashes, micturation difficulty.
The characteristic symptoms that may be caused by overdosage are usually those described under adverse reactions. Tachycardia, sweating and hyperpyrexia with restlessness and excitement are usually produced. Depression, stupor or coma may, however, be present or develop. Blood pressure may be raised, but hypotension may supervene.
Gastric lavage is helpful if performed early. Treatment should normally consist of general supportive measures, close observation of vital signs and steps to counteract specific symptoms as they occur since MAO inhibition may persist. The management of hypertensive reactions is described above. External cooling is recommended if hyperpyrexia occurs. Barbiturates have been reported to help myoclonic reactions, but frequency of administration should be controlled carefully because tranylcypromine may prolong barbiturate activity. When hypotension requires treatment, the standard measures for managing circulatory shock should be initiated. If pressor agents are required, noradrenaline is the most suitable; however, its action may be potentiated, and the rate of infusion should be regulated by careful observation of the patient. Mephentermine or metaraminol may be required if marked refractory hypotension occurs (left ventricular failure should be excluded). A successful recovery following haemodialysis after a self-administered overdosage of 350 mg of tranylcypromine has been reported.
Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor with a rapid onset of activity. It increases the concentration of adrenaline, noradrenaline, and serotonin in storage sites throughout the nervous system, and in theory, this increased concentration of monoamines in the brainstem is the basis for its antidepressant activity. When tranylcypromine is withdrawn, monoamine oxidase activity is recovered in 3 to 5 days, although the drug is excreted in 24 hours.
Tranylcypromine is rapidly absorbed from the gastrointestinal tract following oral administration and distributed widely throughout the body. Peak plasma concentrations occur within 1 hour of dosing. The drug is excreted in the urine, mainly in the form of metabolites.
No further information of clinical relevance.
None known.
18 months.
Store below 25degC.
Prescription Medicine
Blister packs of 50 tablets.
Boucher & Muir (New Zealand) Ltd t/a Mercury Pharma (New Zealand) 39 Anzac Road Browns Bay 0753 Auckland
10 July 2012