Moclobemide

Initial management should focus first on establishing the airway and stabilizing the heart rate and blood pressure, and subsequently on management of rhabdomyolysis, hyperthermia, seizures and muscle rigidity. Gut decontamination can take place after the patient is stabilized.

Because severe hypertension is often short-lived, it is important to use agents with a shorter duration of action such as nitroprusside, nitroglycerin or phentolamine. These drugs should be titrated to response. Beta-blockers should not be used.

Hyperthermia should be aggressively managed using ice baths, cold water and fans. Benzodiazepines are useful for muscle rigidity, seizures and agitation. Dysrhythmias should be treated with lidocaine or procainamide. Once the patient is stable, a dose of activated charcoal 1 g/kg should be given. If the time of stabilization is within one hour post-ingestion, gastric lavage should be considered.

Consideration should be given to the possibility of mixed overdose and its potential medical implications.

Clinical effects of excessive MAO inhibition result from accumulation of amines such as serotonin and norepinephrine. Initial symptoms include hypertension, drowsiness, dizziness, confusion, tremors and headache, which may progress to agitation, muscle rigidity and seizures. Dysrhythmias, sweating, chills and hyperthermia can also occur. Late phase symptoms include hypotension, bradycardia, cardiovascular collapse, respiratory depression, pulmonary edema and coma. Potential complications are rhabdomyolysis, hemolysis, disseminated intravascular coagulation, acute renal failure (secondary to hypotension or rhabdomyolysis) and hypertensive crisis.

The risk of hypertensive crisis is increased in the presence of drugs such as amphetamines, cocaine, decongestants (e.g., pseudoephedrine, phenylephrine) or foods containing tyramine (e.g., aged cheese, smoked meats, red wine and beer). Other overdose symptoms may be exacerbated by co-ingestion of serotonergic drugs such as dextromethorphan, ergotamine, L-tryptophan, mirtazapine, pethidine (meperidine), sibutramine, SSRIs, SNRIs (duloxetine, venlafaxine), TCAs, triptans (except eletriptan, naratriptan).

Although reversible MAO inhibitors such as moclobemide are considered to be less toxic in overdose than their irreversible counterparts, at least one fatality attributed to a single ingestion of moclobemide has been reported.

Caution is advised in prescribing moclobemide to patients with thyrotoxicosis or pheochromocytoma, as conventional (irreversible, nonselective) MAO inhibitors may precipitate a hypertensive crisis in these patients.

Patients should be advised not to drive or perform other hazardous tasks while taking moclobemide until they are certain of how the drug affects them.

There is very little published information on the use of moclobemide during pregnancy. One case report described no harmful effects on the fetus following moclobemide 300 mg/day taken throughout pregnancy. As with any antidepressant, the possible risk of using moclobemide during pregnancy must be weighed against the potential effects of untreated depression on both mother and fetus.

Moclobemide is excreted in small amounts in breast milk. Levels in milk are highest 3 hours following a dose and undetectable after 12 hours. Clinical effects on the nursing infant are not known. If breast-feeding is continued during moclobemide therapy, it should be timed to minimize exposure of the infant to the drug.

Moclobemide should be discontinued at least 2 days prior to administration of anesthetic agents, particularly local or spinal anesthesia that includes epinephrine.

The possibility of suicide in depressed patients should always be taken into consideration. Therapy with moclobemide should be appropriately monitored and potentially suicidal patients should be prescribed limited quantities of moclobemide at a time.

Maximal plasma concentration is achieved within 1 to 2 hours after oral administration. Moclobemide is approximately 50% protein bound and is distributed extensively to tissues.

Moclobemide is well absorbed (> 95%) from the gastrointestinal tract. First-pass hepatic metabolism reduces the bioavailability of single doses to 45 to 70%, but with ongoing administration, first-pass metabolism becomes saturated and bioavailability stabilizes at around 80%.

Moclobemide binds to monoamine oxidase-A (MAO-A) in a competitive (reversible) manner, allowing for repletion of deactivated MAO within hours, as opposed to days for irreversible MAO inhibitors. Inhibition of MAO-A results in decreased metabolism of norepinephrine, serotonin and dopamine in neuronal cells and synapses.

Metabolites are excreted in the urine.

Moclobemide is extensively metabolized in the liver primarily by acetylation. Some metabolites may possess pharmacologic activity. The elimination half-life of moclobemide is approximately 1 to 2 hours.