Phenelzine drug interactions

Graber MA, Hoehns TB, Perry PJ. SertraUne-phenelzine drug interaction a serotonin n-drome reaction. Ann Pharmacother ( 994) 28, 732-5. 

Phenelzine, an MAOI, is effective, but is reserved for treatment-resistant patients because of dietary restrictions, potential drug interactions, and adverse effects. 

Although most physicians avoid the combination of an MAOl with most other antidepressants, a number of reports indicate that MAOIs combined with a TCA can be effective and safe in treatment-resistant patients. This combination should be used only by a physician skilled in their use and familiar with their potential adverse effects and drug interactions. Generally, tertiary amine TCAs have been used in combination with MAOIs. Once the dose of the TCA is established, the MAOl should be slowly added. Never attempt the reverse order without a 2-week delay. It may also be prudent to lower the TCA dose slightly before starting the MAOl. An example might be the addition of phenelzine to amitriptyline, starting with an initial dose of 15 mg and subsequent dose increments weekly as needed. The total dose of an MAOl, used in combination with TCA, is usually lower than when used alone (e.g., 30 to 60 mg per day). When the combination is discontinued, the MAOl should be stopped first. 

These two classes of drugs are subject to life-threatening interactions (e.g., mania, convulsions, hypertension, heart arrythmias) with monoamine oxidase (MAO) inhibitors, such as isocarboxazide, phenelzine, selegiline, and tranylcypromine, because they inhibit the metabolism of serotonin and sympathomimetic amines (19,120). This interaction is one of the earliest toxic drug-drug interactions to be recognized however, these interactions are not often observed because the MAO inhibitors are now used sparingly. 

Doses above f 0 mg/day may increase the risk of hypertensive crisis, tyramine interactions, and drug interactions similar to those of phenelzine and franylcypromine... 

MAO inhibitors (MAOIs) These drugs (eg, phenelzine, tranylcypromine, isocarboxazid) are stmcturally related to amphetamines and are orally active. They inhibit both MAO-A (which metabolizes norepinephrine, serotonin, and tyramine) and MAO-B (which metabolizes dopamine). Tranylcypromine is the fastest in onset of effect but has a shorter duration of action (about a week) than do other MAO inhibitors (with durations of 2-3 weeks). In spite of these prolonged actions, the MAO inhibitors are given daily. These drugs are inhibitors of hepatic drug-metabolizing enzymes and cause many drug interactions. 

The drug interaction between the inhibitors of monoamine oxidase used for depression and the drugs which selectively block serotonin reuptake (SSRIs) is called the serotonin syndrome. In the case of phenelzine and fluoxetine, the interaction has resulted in a fatal outcome. Key interventions include control of hyperthermia and seizures. The answer is (E). 

Monoamine Oxidase Inhibitors (MAOIs). Early studies also evaluated the effectiveness of the MAOl phenelzine. Phenelzine, relative to TCAs, provided greater benefit for PTSD however, its usefulness is limited by its potential for drug and food interactions. A recent open label study suggests that the reversible MAOI moclobemide might be helpful for PTSD. It is not available in the United States. 

Ginseng interacts with phenelzine, a drug used to treat depression, stimulating the central nervous system. 

Phenelzine Blockade of MAO-A and MAO-B (phenelzine, nonselective) MAO-B irreversible selective MAO-B inhibition (low dose selegiline) Transdermal absorption of selegiline achieves levels that inhibit MAO-A Major depression unresponsive to other drugs Very slow elimination Toxicity Hypotension, insomnia Interactions Hypertensive crisis with tyramine, other indirect sympathomimetics serotonin syndrome with serotonergic agents, meperidine... 

Monoamine oxidase inhibitors (eg, tranylcypromine, phenelzine) are older antidepressants that are occasionally used for resistant depression. They can cause severe hypertensive reactions when interacting foods or drugs are taken (see Chapters 9 and 30), and they can interact with the selective serotonin reuptake inhibitors (SSRIs). 

Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, interact with drugs including clarithromycin, warfarin, phenelzine, benzotropine, chlorpromazine, diazepam, and cyproheptadine. Cigarette smokers metabolize SSRIs faster. 

Interactions The vitamin pyridoxine (B6) increases the peripheral breakdown of levodopa and diminishes its effectiveness (Figure 8.6). Concomitant administration of levodopa and monoamine oxidase (MAO) inhibitors, such as phenelzine (see p. 124), can produce a hypertensive crisis caused by enhanced catecholamine production therefore, caution is required when they are used simultaneously. In many psychotic patients, levodopa exacerbates symptoms, possibly through the buildup of central amines. In patients with glaucoma, the drug can cause an increase in intraocular pressure. Cardiac patients should be carefully monitored because of the possible development of cardiac arrhythmias. Antipsychotic drugs are contraindicated in parkinsonian patients, since these block dopamine receptors and produce a parkinsonian syndrome themselves. 

Clinically important, potentially hazardous interactions with dihydroergotamine, ergot-containing drugs, isocarboxazid, MAO inhibitors, methysergide, naratriptan, phenelzine, propanolol, sibutramine, St John s wort, sumatriptan, tranylcypromine, zolmitriptan... 

MAO INHIBITORS (isocarboxazid, phenelzine, tranylcypromine) Hypotension restlessness insomnia daytime sleepiness mania urinary retention tremors sexual disturbances paresthesias dry mouth nausea constipation anorexia weight gain edema rash hepatitis tinnitus muscle spasm lupus-like reaction leukopenia hyperthermia hypertension interactions with other drugs or foods may be severe MAPROTILINE... 

Cases of death have been reported from MDMA interactions with the irreversible MAOl phenelzine and the reversible MAOl moclobemide. Linezolid, a new antibacterial with mild MAOl properties, may also interact dangerously with MDMA. The plasma concentration of MDMA increases 9-15% when the drug is taken with alcohol. More importantly, this combination leads to a longer-lasting feeling of euphoria and the false impression that one s performance of a task has improved when it has actually been impaired. 

There is no clear evidence that either of these adverse reactions was due to an interaction between phenelzine and cloral hydrate, and there do not seem to be any other reports to suggest that an interaction between these drugs is likely. 

A woman who had been taking phenelzine 15 mg three times daily for about 3 weeks eomplained of weakness, ataxia, vertigo, tinnitus, musele pains and paraesthesias within 7 days of starting to take sulfafurazole 1 g four times daily. These adverse effeets eontinued until the 10-day sulfonamide eourse was eompleted, and did not oeeur again in the following 8 weeks. The reasons are not understood, but as these adverse effeets are a combination of the adverse effects of both drugs, it seems possible that a mutual interaction (perhaps saturation of the acelylating mechanisms in the liver) was responsible. This appears to be an isolated report, but bear it in mind in the event of an unexpected response to treatment. 

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