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Active ingredient: Tranylcypromine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Anti-anxiety Agents
  • Antidepressants

Dosage Forms

  • Tablets (10 mg, for oral administration)

Brands / Synonyms

Dl-Tranylcypromine; Parnate; Transamine

Indications

For the treatment of major depressive episode without melancholia.

Pharmacology

Tranylcypromine belongs to a class of antidepressants called monoamine oxidase inhibitors (MAOIs). Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor with a rapid onset of activity. It increases the concentration of epinephrine, norepinephrine, and serotonin in storage sites throughout the nervous system and, in theory, this increased concentration of monoamines in the brain stem is the basis for its antidepressant activity.

Mechanism of Action

Tranylcypromine irreversibly inhibits monoamine oxidase (MAO). Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms.

Absorption

Not Available

Toxicity

In overdosage, some patients exhibit insomnia, restlessness and anxiety, progressing in severe cases to agitation, mental confusion and incoherence. Hypotension, dizziness, weakness and drowsiness may occur, progressing in severe cases to extreme dizziness and shock. A few patients have displayed hypertension with severe headache and other symptoms. Rare instances have been reported in which hypertension was accompanied by twitching or myoclonic fibrillation of skeletal muscles with hyperpyrexia, sometimes progressing to generalized rigidity and coma.

Biotrnasformation / Drug Metabolism

Hepatic.

Contraindications

Parnate (tranylcypromine sulfate) should not be administered in combination with any of the following: MAO inhibitors or dibenzazepine derivatives; sympathomimetics (including amphetamines); some central nervous system depressants (including narcotics and alcohol); anti-hypertensive, diuretic, antihistaminic, sedative or anesthetic drugs; bupropion HCl; buspirone HCl; dextromethorphan; cheese or other foods with a high tyramine content; or excessive quantities of caffeine.

Parnate (tranylcypromine sulfate) should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease, hypertension or history of headache.

(For complete discussion of contraindications and warnings, see below.)


Parnate (tranylcypromine sulfate) is contraindicated:
  1. In patients with cerebrovascular defects or cardiovascular disorders
    PARNATE should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease or hypertension.
  2. In the presence of pheochromocytoma
    PARNATE should not be used in the presence of pheochromocytoma since such tumors secrete pressor substances.
  3. In combination with MAO inhibitors or with dibenzazepine-related entities
    Parnate (tranylcypromine sulfate) should not be administered together or in rapid succession with other MAO inhibitors or with dibenzazepine-related entities. Hypertensive crises or severe convulsive seizures may occur in patients receiving such combinations.

    In patients being transferred to PARNATE from another MAO inhibitor or from a dibenzazepine-related entity, allow a medication-free interval of at least a week, then initiate PARNATE using half the normal starting dosage for at least the first week of therapy. Similarly, at least a week should elapse between the discontinuance of PARNATE and the administration of another MAO inhibitor or a dibenzazepine-related entity, or the readministration of PARNATE .

    The following list includes some other MAO inhibitors, dibenzazepine-related entities and tricyclic antidepressants, and the companies which market them.

  4. Other MAO Inhibitors
    Generic Name Source
    Furazolidone
    Isocarboxazid Marplan® (Oxford Pharm Services)
    Pargyline HCl  
    Pargyline HCl and methyclothiazide  
    Phenelzine sulfate Nardil® (Parke-Davis)
    Procarbazine HCl Matulane® (Sigma Tau)
       
    Dibenzazepine-Related and Other Tricyclics
    Generic Name Source
    Amitriptyline HCl Elavil® (Zeneca)
    Perphenazine and amitriptyline HCl Etrafon® (Schering)
    Triavil® (Lotus Biochemical)
    Clomipramine hydrochloride Anafranil® (Geneva)
    Desipramine HCl Norpramin® (Aventis)
    Imipramine HCl JanimineTM (Geneva)
    Tofranil® (Novartis)
    (Geneva)
    Nortriptyline HCl Pamelor® (Mallinckrodt)
    Protriptyline HCl Vivactil® (Merck & Co., Inc.)
    Doxepin HCl Sinequan® (Pfizer)
    Carbamazepine Tegretol® (Novartis)
    Cyclobenzaprine HCl Flexeril® (Merck & Co., Inc.)
    Amoxapine (Geneva)
    Maprotiline HCl (Mylan)
    Trimipramine maleate Surmontil® (Wyeth-Ayerst Pharmaceuticals)


  5. In combination with bupropion
    The concurrent administration of a MAO inhibitor and bupropion hydrochloride (Wellbutrin®, Wellbutrin SR®, Zyban®, GlaxoSmithKline) is contraindicated. At least 14 days should elapse between discontinuation of a MAO inhibitor and initiation of treatment with bupropion hydrochloride.
  6. In combination with dexfenfluramine hydrochloride
    Because Redux (dexfenfluramine hydrochloride, Wyeth) is a serotonin releaser and reuptake inhibitor, it should not be used concomitantly with Parnate (tranylcypromine sulfate).
  7. In combination with selective serotonin reuptake inhibitors (SSRIs)
    As a general rule, PARNATE should not be administered in combination with any SSRI. There have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) in patients receiving fluoxetine (Prozac®, Lilly) in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued fluoxetine and are then started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, fluoxetine and other SSRIs should not be used in combination with a MAOI, or within 14 days of discontinuing therapy with a MAOI. Since fluoxetine and its major metabolite have very long elimination half-lives, at least 5 weeks should be allowed after stopping fluoxetine before starting a MAOI.
    At least 2 weeks should be allowed after stopping sertraline (Zoloft®, Roerig) or paroxetine (Paxil®, SmithKline Beecham Pharmaceuticals) before starting a MAOI.
  8. In combination with buspirone
    Parnate (tranylcypromine sulfate) should not be used in combination with buspirone HCl (BuSpar®, Bristol-Myers Squibb), since several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone HCl. At least 10 days should elapse between the discontinuation of PARNATE and the institution of buspirone HCl.
  9. In combination with sympathomimetics
    Parnate (tranylcypromine sulfate) should not be administered in combination with sympathomimetics, including amphetamines, and over-the-counter drugs such as cold, hay fever or weight-reducing preparations that contain vasoconstrictors.
    During PARNATE therapy, it appears that certain patients are particularly vulnerable to the effects of sympathomimetics when the activity of certain enzymes is inhibited. Use of sympathomimetics and compounds such as guanethidine, methyldopa, reserpine, dopamine, levodopa and tryptophan with PARNATE may precipitate hypertension, headache and related symptoms. In addition, use with tryptophan may precipitate disorientation, memory impairment and other neurologic and behavioral signs.
  10. In combination with meperidine
    Do not use meperidine concomitantly with MAO inhibitors or within 2 or 3 weeks following MAOI therapy. Serious reactions have been precipitated with concomitant use, including coma, severe hypertension or hypotension, severe respiratory depression, convulsions, malignant hyperpyrexia, excitation, peripheral vascular collapse and death. It is thought that these reactions may be mediated by accumulation of 5-HT (serotonin) consequent to MAO inhibition.
  11. In combination with dextromethorphan
    The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior.
  12. In combination with cheese or other foods with a high tyramine content
    Hypertensive crises have sometimes occurred during PARNATE 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 flavor. In particular, patients should be instructed not to take foods such as cheese (particularly strong or aged varieties), sour cream, Chianti wine, sherry, beer (including nonalcoholic beer), liqueurs, pickled herring, anchovies, caviar, liver, canned figs, dried fruits (raisins, prunes, etc.) bananas, raspberries, avocados, overripe fruit, chocolate, soy sauce, sauerkraut, the pods of broad beans (fava beans), yeast extracts, yogurt, meat extracts or meat prepared with tenderizers.
  13. In patients undergoing elective surgery
    Patients taking PARNATE should not undergo elective surgery requiring general anesthesia. Also, they should not be given cocaine or local anesthesia containing sympathomimetic vasoconstrictors. The possible combined hypotensive effects of PARNATE and spinal anesthesia should be kept in mind. Parnate should be discontinued at least 10 days prior to elective surgery.

ADDITIONAL CONTRAINDICATIONS

In general, the physician should bear in mind the possibility of a lowered margin of safety when Parnate (tranylcypromine sulfate) is administered in combination with potent drugs.

  1. PARNATE should not be used in combination with some central nervous system depressants such as narcotics and alcohol, or with hypotensive agents. A marked potentiating effect on these classes of drugs has been reported.
  2. Anti-parkinsonism drugs should be used with caution in patients receiving PARNATE since severe reactions have been reported.
  3. PARNATE should not be used in patients with a history of liver disease or in those with abnormal liver function tests.
  4. Excessive use of caffeine in any form should be avoided in patients receiving Parnate.

Drug Interactions

No Information Provided.

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