Pseudoephedrine: very rare risk of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS)

There have been very rare reports of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) with pseudoephedrine.

From:
Medicines and Healthcare products Regulatory Agency
Published
20 February 2024
Therapeutic area:
Cardiovascular disease and lipidology, Dispensing GP practices, Ear, nose and throat, Haematology, Infectious disease, Neurology, Respiratory disease and allergy

Patients and caregivers should be advised to be alert to the symptoms for PRES and RCVS, to stop the medication immediately and to seek urgent medical attention if these occur. If someone presents with symptoms of PRES or RCVS, ask about their medication history.

Advice for healthcare professionals:

  • PRES and RCVS present with the following symptoms: sudden severe headache or thunderclap headache, sudden onset of nausea and vomiting, confusion, seizures and/or visual disturbances
  • PRES and RCVS are recognised very rare side effects with pseudoephedrine-containing medicines, which are used for the symptomatic treatment of nasal and sinus congestion with colds, flu and allergies
  • pseudoephedrine is for short term use only and should not be used for prolonged or extended use
  • use of the product is contraindicated in patients with severe hypertension or uncontrolled hypertension, or severe renal disease
  • report suspected adverse drug reactions associated with pseudoephedrine on a Yellow Card

Advice for healthcare professionals to provide to patients:

  • pseudoephedrine is used to relieve the symptoms of nasal and sinus congestion with colds, flu and allergies
  • pseudoephedrine-containing medicines are for short-term, symptomatic use only; people should follow the instructions for use in the Patient Information Leaflet
  • there has been a very small number of reports of PRES and RCVS with these medicines; PRES and RCVS are rare conditions that can involve inflammation and/or reduced blood supply to the brain
  • if you experience a severe headache that develops very quickly or you suddenly feel sick or are vomiting, confused or experiencing seizures or changes in vison, then stop taking the medicine immediately and seek urgent medical attention
  • do not take pseudoephedrine if you have very high blood pressure (hypertension) or hypertension not controlled by your medicines
  • do not take pseudoephedrine if you have severe acute (sudden) or chronic (long-term) kidney disease or kidney failure. Speak to your doctor or pharmacist if you are unsure
  • people who take a medicine may experience a non-serious side effect, and these are typically mild, but it is important to read the Patient Information Leaflet that comes with your medicine and to talk to a healthcare professional if you are experiencing problems

Review of PRES and RCVS with pseudoephedrine

Pseudoephedrine is a sympathomimetic and is approved as a single active substance or in fixed dose combinations with analgesics, antihistamines, and cough medicines. Pseudoephedrine is used for the symptomatic relief of nasal and sinus congestion associated with the common cold and flu in adults and adolescents. It is also used for the treatment of the symptoms of seasonal allergic rhinitis in patients, including use in children aged 2 to 12 years of age who have nasal congestion.

There have been very rare reports of PRES and RCVS with pseudoephedrine. A review of the available evidence, including the assessment of cumulative reporting of adverse drug reaction reports, was considered by the Pharmacovigilance Expert Advisory Group (PEAG) of the Commission on Human Medicines (CHM). The PEAG recommended updates to the Summary of Product Characteristics (SmPC) and the Patient Information Leaflet (PIL) to further describe the risk of PRES and RCVS and the potential risk factors for these conditions, and advised the MHRA to remind healthcare professionals and patients of these risks.

About PRES and RCVS

Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), is a rare condition in which parts of the brain are affected by swelling, usually as a result of an underlying cause such as severely elevated blood pressure, kidney failure, severe infections, certain medications, some autoimmune diseases and pre-eclampsia. The diagnosis is usually made by imaging of the brain, which may enable areas of swelling to be identified. PRES usually has an acute onset characterised by headaches and seizures; many people also experience visual changes, confusion and drowsiness, weakness of the arm and/or leg on one side of the body (hemiplegia), difficulty speaking, or more rarely other neurological symptoms.

Reversible cerebral vasoconstriction syndrome (RCVS), also known as Call-Fleming syndrome, is a rare condition characterised by thunderclap headaches which are sudden, intense headaches that can reoccur over a few days to weeks and are often associated with nausea and sensitivity to light. RCVS can also be associated with acute neurological symptoms such as seizure and stroke. Symptoms are thought to arise from transient constriction in the blood vessels of the brain. In some cases, RCVS may be associated with childbirth, vasoactive or illicit drug use, head trauma, autoimmune or blood disorders, or complications of pregnancy. RCVS is usually diagnosed by brain imaging with angiography, to identify constrictions in cerebral blood vessels.

For both conditions, patients typically fully recover within 3 months with early recognition and treatment.

UK reports of PRES and RCVS with pseudoephedrine

To date, the MHRA has received 4 Yellow Card reports of suspected PRES or RCVS with pseudoephedrine. This is in the context of widespread usage with over 4 million packets sold in the UK in 2022 alone.

Report suspected reactions on a Yellow Card

Please continue to report suspected adverse drug reactions to the Yellow Card scheme. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.

Article citation: Drug Safety Update volume 17, issue 7: February 2024: 2

Published 20 February 2024
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