Nerium Oleander (Other Scientific Names: Oleandri Polium, Thevetia Peruviana/Common Names: Dogbane, Laurier Rose, Rosebay/Pharmaceutical Names: Anvirzel, Xenavex, SAOB-0401)

Epidemiology

  • Both human and livestock deaths have been reported due to toxic ingestion of plant or plant extracts
  • Two deaths have been linked to the pharmacologic use of Anvirzel

Characteristics of Nerium Oleander Plant

  • Evergreen Shrub/Small Tree with Fragrant White/Red/Pink/Purple Flowers
    • Long, slender leathery leaves: grow in pairs opposite each other or in whorls of three
    • Thevetia Peruviana = yellow oleander
  • Geography: grows in mild climates or indoors
    • Native plant in the Mediterranean region
    • Distributed widely throughout the US south and southwest
    • Distributed widely in Australia and southern Africa
  • Extraction
    • While active ingredients are usually extracted from the leaves, all parts of the plant are toxic
    • There is some evidence that red flowered varieties are more toxic [LINK]

Regulation

  • Oleander leaf is on Germany’s regulatory Commission E list of unapproved herbs

Human Exposure

  • Ingestion of Raw/Cooked Plant or Extracts: toxic
    • Leaf/Leaf Extracts
    • Honey Made from Nectar
    • Tea [MEDLINE]
  • Rectal Administration of Plant or Extracts: toxic [MEDLINE]
  • Inhalation of Smoke from Burning Plant: toxic
  • Topical Application: no reports of toxicity

Uses of Nerium Oleander Plant

Historical Uses of Nerium Oleander

  • Use by Arab Physicians (During 8th Century): used as potential anti-cancer treatment
  • Use in Mesopotamia (During 15th Century): used for potential healing properties
  • Use in Babylonia: used in mixture with licorice for the treatment of hangover
  • Use in Greece: Pliny the Elder wrote about the appearance and properties of the Nerium Oleander plant
  • Use as Cardiac Medication (During the 1930’s)
  • Investigation by the Turkish Physician, Huseyin Z. Ozel, MD (During the 1960’s)
    • He recognized the folk tradition of using Nerium oleander to treat leukemia
    • He developed and patented a Nerium oleander extract in the US and Europe as Anvirzel
  • Use as Insecticide
  • Use as Rodenticide
  • Use as Remedy for Indigestion/Fever/Ringworm/Malaria/Leprosy/Venereal Disease
  • Use as Abortifacient

Promoted Clinical Uses of Nerium Oleander

  • Asthma
  • Cancer
  • Corns
  • Epilepsy
  • Heart Disease
  • Menstrual Pain
  • Muscle Cramps
  • Paralysis
  • Skin Disease

Clinical Trials of Anvirzel

  • Lack of US Food and Drug Administration (FDA) Approval: despite some supportive basic science data, Anvirzel has not demonstrated any benefit in trials and therefore, has not been approved by the FDA for any clinical indication
  • FDA Warning to Anvirzel Manufacturer in March, 2000: FDA warned Anvirzel’s manufacturer to stop promoting the product due to presence of misleading information on their website (which was derived from preliminary and inconclusive data)

Pharmacology

  • Oleandrin (best studied component): cardiac glycoside -> inhibition of the Na-K ATPase pump
    • Increases intracellular sodium concentration -> lowers the membrane potential threshold, increasing cardiac excitability
    • Increased serum potassium concentration
    • Chronotropic effect is primarily central: mediated by an increase in vagal tone which decreases the rate of sinoatrial node depolarization
  • Other Cardiac Glycosides: there are at least 10 other glycosides whose chemical structure has been identified

Clinical Manifestations of Intoxication (Ingestion/Rectal Administration/Inhalation)

General Comments

  • Intoxication has been reported with plant ingestion, but not with topical application

Cardiovascular Manifestations

Atrioventricular Heart Blocks

Hypotension (see Hypotension)

  • Clinical: may occur

Sinus Bradycardia (see Bradycardia)

  • Clinical: may occur

Ventricular Tachycardia/Fibrillation (see Ventricular Tachycardia)

  • Clinical: may occur

Gastroenterologic Manifestations

Neurologic Mental Status

Renal Manifestations

Other Manifestations

  • Circumoral Erythema

Fetal Manifestations with Maternal Ingestion


Clinical Manifestations (Topical Application)

General Comments

  • No reports of toxicity

Dermatoligic Manifestations

  • Skin Irritation: may occur
  • Allergic Reaction: may occur

Treatment of Intoxication (Ingestion/Rectal Administration/Inhalation)


References

  • Oleander tea: herbal draught of death. Ann Emerg Med. 1985 Apr;14(4):350-3 [MEDLINE]
  • Possible yellow oleander toxicity in a neonate. Indian Pediatr. 1986;23:393
  • Oleandrin distribution in a fatality from rectal and oral Nerium oleander extract administration. J Anal Toxicol. 1987 Sep-Oct;11(5):219-21 [MEDLINE]
  • Oleander poisoning: treatment with digoxin-specific Fab antibody fragments. Ann Emerg Med. 1988 Jul;17(7):732-5 [MEDLINE]
  • Digoxin-specific Fab fragments in the treatment of oleander toxicity in a canine model. Ann Emerg Med. 1991;20:1073-1077 [MEDLINE]
  • Oleander toxicity: examination of human and animal toxic exposures. Toxicology. 1996;109:1-13 [MEDLINE]
  • Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; 1998
  • Cytotoxic effect of nerium oleander extract (Anvirzel) on bladder cancer cells. In: Program and abstracts of the American Society of Clinical Oncology (ASCO) annual meeting; May 15-19, 1999; Atlanta, Georgia. Abstract 1328
  • Knight, A. P. (1999). “Guide to Poisonous Plants: Oleander”. Colorado State University [LINK] (Accessed 6/5/14)
  • Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells. Cancer Res. 2000;60:3807-3812
  • Oleander poisoning. Arch Dis Child. 2001;84:9
  • PDR for Herbal Medicines. 3rd ed. Montvale, NJ: Thomson PDR; 2004
  • Professional’s Handbook of Complementary & Alternative Medicines. Philadelphia, PA: Lippincott Williams & Wilkins; 2004
  • INCHEM (2005). Nerium oleander L. (PIM 366). International Programme on Chemical Safety: INCHEM [LINK] (Accessed 6/5/14)
  • US National Institutes of Health. Clinical trial announcement: a phase I/II multicenter, off-label, dose escalation study of Xenavex in patients with advanced (stage IIIB or IV) non-small cell lung cancer; for whom previous therapy has failed. Clinical Trials Web site. Accessed at www.clinicaltrials.gov on October 18, 2005. Content no longer available
  • Phase 1 trial of Anvirzel in patients with refractory solid tumors. Inves New Drugs. 2006;24:423-427
  • Cytotoxic effects of leaf, stem and root extracts of Nerium oleander on leukemia cell lines and role of the p-glycoprotein in this effect. J Exp Ther Oncol. 2006;6:31-38
  • Oleander (nerium oleander, thevetia peruviana). Aetna InteliHealth Web site. Accessed at www.intelihealth.com/IH/ihtIH/WSIHW000/8513/31402/351437.html on June 6, 2008
  • A fatal case of oleandrin poisoning. Forensic Sci Int. 2008 Aug 6;179(2-3):e31-6. doi: 10.1016/j.forsciint.2008.05.002. Epub 2008 Jul 7 [MEDLINE]
  • American Cancer Society (http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/herbsvitaminsandminerals/oleander-leaf) (Accessed 6/3/14)