UK Clinical Pharmacy Association


Issues for surgery

For Attention Deficit Hyperactivity Disorder (ADHD) or narcolepsy - risk of loss of symptom control if omitted.

Risk of withdrawal symptoms if omitted (see Further information).

Risk of serotonin syndrome if continued (see Interactions with common anaesthetic agents and Interactions with other common medicines used in the perioperative period).

Risk of perioperative hypertension if continued (see Further information).

Advice in the perioperative period

Elective surgery 

Omit dose(s) on day of surgery - see Further information.

Ensure anaesthetist is aware patient is taking regular amfetamines.

Check heart rate and blood pressure pre-operatively – see Further information.

Emergency surgery 

If patient has taken dose(s) on the day of surgery, inform anaesthetist – see Further information.

Post-operative advice

Restart post-operatively, when next dose due, once enteral intake resumes.

Monitor heart rate and blood pressure – see Further Information.

Patients who have received methylthioninium chloride (methylene blue)

Monitor for symptoms of CNS toxicity (see Interactions with common medicines used in the perioperative period and Further information).

Interactions with common anaesthetic agents

Inhalational anaesthetics

There is a risk of sudden blood pressure increase during surgery as both dexamfetamine and sevoflurane can cause hypertension. If surgery is planned, the manufacturer of dexamfetamine advises treatment should not be used on the day of surgery.

There is a recommendation that dexamfetamine use should be avoided for several days before surgery if sevoflurane use is necessary – see Further information.


Dexamfetamine acts as a noradrenaline reuptake inhibitor. Concomitant use of dexamfetamine with noradrenaline/norepinephrine and potentially other sympathomimetics may enhance the vasopressor effect of these medicines. Monitor blood pressure closely.


CNS excitation (serotonin syndrome)

Serotonin syndrome has rarely occurred in association with use of amfetamines, when given in conjunction with other serotonergic drugs.

Some opioids act as weak serotonin reuptake inhibitors (SRIs) and can precipitate serotonin syndrome in conjunction with other serotonergic medication such as dexamfetamine. Symptoms of serotonin syndrome may occur if dexamfetamine is given concomitantly with:

  • fentanyl
  • methadone
  • pentazocine
  • pethidine
  • tapentadol
  • tramadol

Patients should be monitored closely, and the possibility of serotonin toxicity considered if patients experience altered mental state, autonomic dysfunction, or neuromuscular adverse effects with concomitant treatment.

Potentiation of analgesic effect

Dexamfetamine may potentiate the analgesic effects of some opioids. This increased analgesic effect may be beneficial perioperatively, although bear in mind lower than expected doses of opioids may be necessary.

Interactions with other common medicines used in the perioperative period

CNS excitation (serotonin syndrome)


See Interactions with common anaesthetic agents above.

Methylthioninium chloride (methylene blue)

Serotonergic symptoms may be possible in patients given methylthioninium chloride and dexamfetamine concurrently (see Further information).

Other medicines

There is an increased risk of developing serotonin syndrome when dexamfetamine or lisdexamfetamine is used concurrently with the following:

  • granisetron
  • ondansetron
  • linezolid

Monitor patient for symptoms of serotonin syndrome such as fever, tremors, diarrhoea, and agitation. Concurrent treatment should be stopped if serotonin syndrome occurs.



The effects of amphetamines are opposed by some phenothiazines, and this reaction may occur with prochlorperazine if it is a class effect. If concurrent use is undertaken monitor for efficacy.


See also CNS excitation (serotonin syndrome) above.

Ondansetron may attenuate some of the subjective feelings produced by amfetamines although this is not thought to be of clinical relevance.


Haloperidol inhibits the central stimulant effect of amphetamines; hence amfetamines might be less effective in those taking haloperidol. 

Acute dystonia has been noted with concurrent administration of haloperidol and dexamfetamine.

Further information

Sevoflurane and amfetamines

The manufacturer of sevoflurane recommends that amfetamine use should be avoided several days before anaesthesia involving sevoflurane due to the risk of pre-operative hypertensive crisis. If there is a clinical need for a patient to receive sevoflurane in preference to alternative anaesthesia, there needs to be clinical consideration of the risks associated with discontinuation of amfetamine therapy. Appropriate planning for elective surgery should occur in conjunction with the patient, the specialist and anaesthetist. There are no clear recommendations on the number of days amfetamines should be stopped prior to sevoflurane use and the decision of when to stop should form part of the planning discussions. Patients undergoing emergency surgery must not be given sevoflurane anaesthesia.


Cessation of, or reduction in, dexamfetamine use that has been heavy and prolonged can result in withdrawal symptoms; these include dysphoric mood, fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, psychomotor retardation, or agitation, anhedonia, and drug craving. Abrupt withdrawal should be avoided.


Stimulant medicines cause a modest increase in average blood pressure (about 2 – 4 mmHg) and average heart rate (about 3 – 6 bpm), and individuals may have larger increases. Caution is therefore required in patients administered any medication that is also likely to increase heart rate or blood pressure during the perioperative period.

Methylthioninium chloride (methylene blue)

Off label use of intravenous methylthioninium chloride a visualising agent, i.e., for parathyroid and thyroid surgery should be carefully evaluated in view of the potential for CNS toxicity. If intravenous methylthioninium chloride cannot be avoided, the lowest possible dose should be used and the patient observed closely for CNS effects for up to 4 hours after administration.


Joint Formulary Committee. British National Formulary [online] London: Pharmaceutical Press. [Accessed on 14th April 2023].

Summary of Product Characteristics – Amfexa® (dexamfetamine) 10mg Tablets. Medice UK LTD. Accessed via 14/04/2023 [date of revision of the text February 2022]

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. [Accessed on 22nd March 2023]

Summary of Product Characteristics – Sevoflurane 100% Inhalation Vapour, liquid. Piramal Critical Care Ltd. Accessed via 14/07/2023 [date of revision of the text November 2021]

MHRA Drug Safety Update. Methylthioninium chloride (methylene blue): update on central nervous system (CNS) toxicity. Volume 2, Issue 9, April 2009. Accessed via 16/06/2023