Published: 7 March 2024


Drug-induced phospholipidosis

Published 7 March 2024
Prescriber Update 45(1): 18–19
March 2024

Key messages

  • Drug-induced phospholipidosis (DIPL) can affect any cell or organ in the body. Clinical signs and symptoms of DIPL are non-specific.
  • A principal histological feature of DIPL is the accumulation of phospholipids and the inducing medicine/metabolite in affected cells.
  • Stopping the suspect medicine usually reverses intracellular changes.

The hydroxychloroquine (Plaquenil) data sheet was recently updated to include warnings for drug-induced phospholipidosis. This article provides information about the disorder.

What is drug-induced phospholipidosis?

Drug-induced phospholipidosis (DIPL) is a lysosomal storage disorder.1,2 Lysosomes are cellular structures containing enzymes that break down proteins, nucleic acids, carbohydrates and lipids.3 A phospholipid membrane encloses the lysosome and maintains the acidic environment for the enzymes to function.3 In lysosomal storage disorders, undegraded material accumulates within the lysosomes of affected individuals.3

In DIPL, the inducing medicine causes lysosomal changes that lead to excessive but reversible accumulation of both phospholipids and the medicine in the lysosomes and the formation of lysosomal lamellar bodies.1,2 They are called lamellar bodies due to the concentric ring shape seen on electron microscopy.1 Given that nearly all cells contain lysosomes, and phospholipids are found in lysosome membranes, DIPL can affect any cell or organ in the body.1

DIPL onset may or may not be associated with clinical symptoms, including inflammatory reactions and histopathological changes, such as macrophagic infiltration or fibrosis.1,3 DIPL has been associated with organ toxicity, including of the heart, skeletal muscle, liver, lungs and kidneys.1


The exact mechanism of DIPL is not known, although there are two hypotheses. The first assumes that the suspect medicine binds directly to phospholipids, creating a drug-lipid complex. The complex then accumulates to form the lysosomal lamellar bodies. The second hypothesis suggests that medicines interact and inhibit phospholipase activity, resulting in an accumulation of phospholipids.1,4

Associated medicines

Over 50 medicines are associated with phospholipidosis. Examples of medicines with reports of clinically significant DIPL include:

  • amiodarone1
  • fluoxetine1
  • gentamicin1
  • hydroxychloroquine5
  • perhexiline1

Treat patients presenting with signs and symptoms of organ toxicity as per local clinical guidelines. If DIPL is suspected, discontinue the suspect medicine.


  1. Anderson N and Borlak J. 2006. Drug-induced phospholipidosis. FEBS Letters 580(23): 5533-40. DOI: 10.1016/j.febslet.2006.08.061 (accessed 16 January 2024).
  2. Breiden B and Sandhoff K. 2020. Emerging mechanisms of drug-induced phospholipidosis. Biological Chemistry 401(1): 31-46. DOI: 10.1515/hsz-2019-0270 (accessed 17 January 2024).
  3. Cooper GM. 2000. The Cell: A Molecular Approach (2nd edition). Sunderland (MA): Sinauer Associates. Available from: (accessed 5 February 2024).
  4. Larson A. 2023. Drug-induced liver injury. In: UpToDate 14 April 2023. URL: (accessed 17 January 2024).
  5. Pharmacy Retailing Limited. 2023. Plaquenil New Zealand Data Sheet 18 December 2023. URL: (accessed 17 January 2024).
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