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

First Degree Atrioventricular Block (First Degree Heart Block) (see First Degree Atrioventricular Block)
Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I)
Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II)
Third Degree Atrioventricular Block (Third Degree Heart Block, Complete Heart Block) (see Third Degree Atrioventricular Block)

Hypotension (see Hypotension)

Clinical: may occur

Sinus Bradycardia (see Bradycardia)

Clinical: may occur

Ventricular Tachycardia/Fibrillation (see Ventricular Tachycardia)

Clinical: may occur

Gastroenterologic Manifestations

Abdominal Pain (see Abdominal Pain): usually colicky
Anorexia (see Anorexia)
Diarrhea (see Diarrhea)
Nausea/Vomiting (see Nausea and Vomiting)

Neurologic Mental Status

Ataxia (see Ataxia)
Altered Mental Status/Drowsiness (see Coma)
Dizziness
Mydriasis (see Mydriasis)
Seizures (see Seizures)
Tremor (see Tremor)

Renal Manifestations

Hyperkalemia (see Hyperkalemia)

Other Manifestations

Circumoral Erythema

Fetal Manifestations with Maternal Ingestion

Bradycardia (see Bradycardia)
Seizures (see Seizures)

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)

Digibind (see Digibind, [[Digibind]]): may be effective [MEDLINE] [MEDLINE]

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)