Parnate (Tranylcypromine Sulfate) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

OVERDOSAGE

Symptoms

The characteristic symptoms that may be caused by overdosage are usually those described above.

However, an intensification of these symptoms and sometimes severe additional manifestations may be seen, depending on the degree of overdosage and on individual susceptibility. 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.

Treatment

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 crises is described under WARNINGS in the HYPERTENSIVE CRISES section.

External cooling is recommended if hyperpyrexia occurs. Barbiturates have been reported to help relieve myoclonic reactions, but frequency of administration should be controlled carefully because PARNATE may prolong barbiturate activity. When hypotension requires treatment, the standard measures for managing circulatory shock should be initiated. If pressor agents are used, the rate of infusion should be regulated by careful observation of the patient because an exaggerated pressor response sometimes occurs in the presence of MAO inhibition. Remember that the toxic effect of PARNATE may be delayed or prolonged following the last dose of the drug. Therefore, the patient should be closely observed for at least a week. It is not known if tranylcypromine is dialyzable.

SUMMARY OF CONTRAINDICATIONS

PARNATE 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); antihypertensive, diuretic, antihistaminic, sedative, or anesthetic drugs; bupropion HCl; buspirone HCI; dextromethorphan; cheese or other foods with a high tyramine content; or excessive quantities of caffeine.

PARNATE 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.)

CONTRAINDICATIONS

PARNATE 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 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.

   Other MAO Inhibitors

   Generic Name	Source
   Furazolidone
   Isocarboxazid	Marplan® (Oxford Pharm Services)
   Pargyline HCl
   Pargyline HCl and methyclothiazide
   Phenelzine sulfate	Nardil® (Pfizer)
   Procarbazine HCl	Matulane® (Sigma Tau)

   Dibenzazepine-Related and Other Tricyclics

   Generic Name	Source
   Amitriptyline HCl	(Sandoz)
   Perphenazine and amitriptyline HCl	(Sandoz)
   Clomipramine hydrochloride	Anafranil® (Mallinckrodt)
   Desipramine HCl	(Sandoz)
   Imipramine HCl	(Sandoz) Tofranil® (Mallinckrodt)
   Nortriptyline HCl	(Mylan) Pamelor® (Mallinckrodt)
   Protriptyline HCl	Vivactil® (Odyssey Pharmaceuticals, Inc.)
   Doxepin HCl	Sinequan® (Pfizer)
   Carbamazepine	Tegretol® (Novartis)
   Cyclobenzaprine HCl	(Mylan) Flexeril® (McNeil)
   Amoxapine	(Watson)
   Maprotiline HCl	(Mylan)
   Trimipramine maleate	Surmontil® (Odyssey Pharmaceuticals, Inc.)

4. In combination with bupropion

   The concurrent administration of an MAO inhibitor and bupropion hydrochloride (Wellbutrin^®, Wellbutrin SR^®, Wellbutrin XL^®, Zyban^®, GlaxoSmithKline) is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion hydrochloride.

5. In combination with dexfenfluramine hydrochloride

   Because dexfenfluramine hydrochloride is a serotonin releaser and reuptake inhibitor, it should not be used concomitantly with PARNATE.

6. 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^®, Eli Lilly and Company) in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued fluoxetine and are then started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, fluoxetine and other SSRIs should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an 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 an MAOI.

   At least 2 weeks should be allowed after stopping sertraline (Zoloft^®, Pfizer) or paroxetine (Paxil^®, GlaxoSmithKline) before starting an MAOI.

7. In combination with buspirone

   PARNATE should not be used in combination with buspirone HCl, 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.

8. In combination with sympathomimetics

   PARNATE 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 therapy with PARNATE, 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. The combination of MAOIs and tryptophan has been reported to cause behavioral and neurologic syndromes including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyperreflexia, shivering, ocular oscillations, and Babinski's signs.

9. 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.

10. In combination with dextromethorphan

    The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior.

11. In combination with cheese or other foods with a high tyramine content

    Hypertensive crises have sometimes occurred during therapy with PARNATE 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.

12. 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 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.