MAOI interactions

[johnep]

Lady 'phoned, been on Nardil (phenelzine) for years. Had a spot of tummy trouble and her son had bought her some kaolin and morphine. However, Nardil PIL said not with morphine. What did I think. I said would use loperamide but would research tonight. Stockley absent from thsi pharmacy.

So, please someone tell me re MAOIs and morphine interaction.
johnep

[pharmatron]

Lady 'phoned, been on Nardil (phenelzine) for years. Had a spot of tummy trouble and her son had bought her some kaolin and morphine. However, Nardil PIL said not with morphine. What did I think. I said would use loperamide but would research tonight. Stockley absent from thsi pharmacy.

So, please someone tell me re MAOIs and morphine interaction.
johnep

Cut and pasted directly from Stockley online. Hope it helps.

MAOIs + Opioids; Miscellaneous
Hypotension (profound in one case) has been seen in a few patients given morphine and an MAOI. One case of hypotension and stupor has occurred with papaveretum. Single cases of the safe use of methadone and hydromorphone have also been described.

Clinical evidence
(a) Hydromorphone
No problems were encountered when a patient taking tranylcypromine was given hydromorphone via a patient-controlled device for postoperative pain. 1 This patient also received sufentanil during surgery without problem.

(b) Methadone
A patient receiving methadone 30 mg daily was successfully and uneventfully treated for depression with tranylcypromine, initially 10 mg daily gradually increased to 30 mg daily. 2

(c) Morphine
A study in 15 patients who had been taking either phenelzine, isocarboxazid, iproniazid or Parstelin (tranylcypromine with trifluoperazine) for 3 to 8 weeks, had no changes in blood pressure, pulse rate or state of awareness when given test doses of up to 4 mg of intramuscular morphine. However, note that none of these patients showed an interaction with test doses of up to 40 mg of pethidine (meperidine). 3 One other study reported no adverse interaction in 3 patients taking isocarboxazid when they were given morphine premedication, 4 and a further study revealed no problems in 9 patients taking tranylcypromine who were given morphine for postoperative pain relief. 5 Another patient taking phenelzine was uneventfully treated with morphine postoperatively. 6 Two further patients taking MAOIs, who reacted adversely to pethidine (meperidine), 7,8 had not previously done so when given morphine. In an early report, intramuscular morphine was given without apparent problem to 5 patients who had developed severe headache while taking tranylcypromine. 9 Another author briefly noted that he knew of about 10 cases where morphine had been used in patients taking MAOIs with no adverse effects except a more prolonged morphine action. 10

However, a patient taking tranylcypromine 40 mg and trifluoperazine 20 mg daily and undergoing a preoperative test with morphine, developed pin point pupils, became unconscious and unresponsive to stimuli, and had a systolic blood pressure fall from 160 to 40 mmHg after receiving a total of 6 mg of morphine intravenously. Within 2 minutes of being given naloxone 4 mg intravenously, the patient was awake and rational with a systolic blood pressure fully restored. 11 A moderate fall in blood pressure (from 140/90 to 90/60 mmHg) was seen in another patient taking an MAOI and given morphine, 12 and a brief episode of hypotension treated with phenylephrine occurred in a patient taking phenelzine receiving continuous epidural morphine during surgery. 5

(d) Papaveretum
A 54-year-old woman taking phenelzine was given papaveretum 10 mg as premedication, and 50 minutes later she was found to be unrousable, sweating and hypotensive. 13

Mechanism, importance and management
Some limited evidence suggests that patients taking MAOIs who reacted adversely with pethidine did not do so when given morphine, 7,8 and quite a number of reports describe the safe uneventful use of morphine and MAOIs. The few hypotensive reactions cited here 5,11,12 are of a different character to the severe reaction seen with ‘pethidine’, and appear to be rare. However, many manufacturers of morphine have contraindicated its concurrent use with, or within 2 weeks of stopping an MAOI. 14-16 In contrast, the manufacturers of one morphine preparation note that as severe CNS excitation or depression (hypertension or hypotension) has been seen when pethidine was given with an MAOI, consideration should be given to using a reduced morphine dose in patients taking MAOIs. 17

Similarly, the manufacturers of several opioids contraindicate their use both with, and within 14 days, of the use of an MAOI. These include codeine, 18 diamorphine, 19 hydromorphone, 20 methadone, 21 and oxycodone. 22

However, information is conflicting, and the manufacturers of other opioids just advise caution if MAOIs are also given. These include codeine (increased effects of both drugs), 23 and dihydrocodeine. 24

Some authors recommend lower initial dosages of morphine or oxycodone, frequent monitoring, and gradual upward dose titration. 25 One author suggests that morphine, codeine, and oxycodone do not possess serotonin reuptake inhibitor activity and would therefore not be expected to cause serotonin syndrome when given with MAOIs. 26 In contrast, ‘pethidine’, ‘tramadol’, ‘dextropropoxyphene’, and methadone appear to be weak serotonin reuptake inhibitors, and these drugs, with the exception of methadone, have been implicated in reports of serotonin toxicity. 26

Clearly the advice is somewhat conflicting, with some taking a more cautious approach than others. If the decision is taken to give an opioid to a patient taking an MAOI, it would seem prudent to choose one that appears to lack serotonergic activity (e.g. codeine, morphine, oxycodone) wherever possible. Monitor concurrent use carefully for any signs of adverse effects.

References
1. O’Hara JF, Maurer WG, Smith MP. Sufentanil-isoflurane-nitrous oxide anesthesia for a patient treated with monoamine oxidase inhibitor and tricyclic antidepressant. J Clin Anesth (1995) 7, 148–50.
2. Mendelson G. Narcotics and monoamine oxidase-inhibitors. Med J Aust (1979) 1, 400.
3. Evans-Prosser CDG. The use of pethidine and morphine in the presence of monoamine oxidase inhibitors. Br J Anaesth (1968) 40, 279–82.
4. Ebrahim ZY, O’Hara J, Borden L, Tetzlaff J. Monoamine oxidase inhibitors and elective surgery. Cleve Clin J Med (1993) 60, 129–130.
5. El-Ganzouri AR, Ivankovich AD, Braverman B, McCarthy R. Monoamine oxidase inhibitors: should they be discontinued preoperatively? Anesth Analg (1985) 64, 592–6.
6. Ure DS, Gillies MA, James KS. Safe use of remifentanil in a patient treated with the monoamine oxidase inhibitor phenelzine. Br J Anaesth (2000) 84, 414–16.
7. Shee JC. Dangerous potentiation of pethidine by iproniazid, and its treatment. BMJ (1960) 2, 507–9.
8. Palmer H. Potentiation of pethidine. BMJ (1960) 2, 944.
9. Brown DD, Waldron DH. An unusual reaction to tranylcypromine. Practitioner (1962) 189, 83–6.
10. Sargant W. Interactions with monoamine oxidase inhibitors. BMJ (1975) 4, 101.
11. Barry BJ. Adverse effects of MAO inhibitors with narcotics reversed with naloxone. Anaesth Intensive Care (1979) 7, 194.
12. Jenkins LC, Graves HB. Potential hazards of psychoactive drugs in association with anaesthesia. Can Anaesth Soc J (1965) 12, 121–8.
13. Spencer GT, Smith SE. Dangers of monoamine oxidase inhibitors. BMJ (1963) 1,750.
14. MST Continus Tablets (Morphine sulfate). Napp Pharmaceuticals Ltd. UK summary of product characteristics, June 2001.
15. Oramorph Oral Solution (Morphine sulfate). Boehringer Ingelheim. UK Summary of product characteristics, July 2006.
16. Morphgesic SR (Morphine sulfate). Amdipharm. UK Summary of product characteristics, January 2003
17. Morphine Sulfate Injection BP. Wockhardt UK Ltd. UK Summary of product characteristics, November 2004.
18. Solpadol (Codeine/Paracetamol). Sanofi-Aventis. UK Summary of product characteristics, June 2007.
19. Diamorphine hydrochloride BP for Injection. Novartis Vaccines. UK Summary of product characteristics, March 2004.
20. Palladone (Hydromorphone hydrochloride). Napp Pharmaceuticals Ltd. UK Summary of product characteristics, February 2007.
21. Methadone Oral Solution. Rosemont Pharmaceuticals Ltd. UK Summary of product characteristics, January 2005.
22. OxyNorm (Oxycodone hydrochloride). Napp Pharmaceuticals Ltd. UK Summary of product characteristics, March 2007.
23. Tylex (Codeine/Paracetamol). Schwarz Pharma Ltd. UK Summary of product characteristics, October 2006.
24. DHC Continus (Dihydrocodeine tartrate). Napp Pharmaceuticals Ltd. UK Summary of product characteristics, October 2006.
25. Gratz SS, Simpson GM. MAOI-Narcotic interactions. J Clin Psychiatry (1993) 54, 439.
26. Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth (2005) 95, 434–41.

[pharmatron]

Also, from Stockley's Interaction Alerts:

Phenelzine [systemic] + Morphine [systemic]
No adverse interaction normally occurs in patients taking MAOIs given morphine, but marked hypotension and unconsciousness occurred in one patient, which was reversed with naloxone.

Despite little evidence of an adverse effect, the manufacturers of several morphine preparations contraindicate the concurrent use of morphine during and for 2 weeks after an MAOI is given.

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Action: Avoid
Severity: Severe
Evidence: Theoretical
For further information, see Stockley's Drug Interactions.