About Herbs, Botanicals & Other Products

Scientific Name
Nerium oleander
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Common Name

Rose laurel, adelfa, rosenlorbeer, karavira

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Brand Name

Anvirzel™

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Clinical Summary

Nerium oleander is an ornamental shrub native to northern Africa, the eastern Mediterranean basin and Southeast Asia. It is used in traditional medicine to treat hemorrhoids, ulcers, leprosy, and as an abortifacient.
Data from animal studies showed cardioprotective properties of oleander flower extract (14). Oleandrin, a cardiac glycoside derived from the leaves causes apoptosis in various cancer cell lines (1) (2) (3) and increases the sensitivity of PC-3 human prostate cells to radiotherapy (4). A hot water extract of this plant known as Anvirzel™, is being used to treat cancer, HIV/AIDS, and congestive heart failure. It consists of a mixture of polysaccharides and a polyphenolic cardiac glycoside known as oleandrin and is currently under investigation for its antitumor effects. Results from a phase I study indicate that oleandrin can be administered at doses up to 1.2ml/m2/day intramuscularly with no dose-limiting toxicities (5).

Anvirzel™ is not an approved drug in the United States. Until more data regarding efficacy and toxicity are available, this product should not be used outside of clinical trials.

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Purported Uses
  • Cancer treatment
  • Congestive heart failure
  • Hepatitis
  • HIV and AIDS
  • Psoriasis
  • Rheumatoid arthritis
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Constituents
  • Cardiac glycosides: Oleandrin, odoroside, neritaloside, aglycone oleandrigenin
  • Polysaccharides
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Mechanism of Action

Oleandrin is claimed to have analgesic properties (11).
Results from in vitro studies indicate that oleandrin suppresses the activity of NF-kB in various cell lines (U937, CaOV3, human epithelial cells, and T cells) (1) and induces apoptosis in PC3 cells (6). Putative mechanisms of action include improved cellular export of fibroblast growth factor-2 (FGF-2) (3), induction of apoptosis through Fas gene expression in tumor cells, (7), formation of superoxide radicals that cause tumor cell injury via mitochondrial disruption (8), inhibition of interleukin-8 that mediates tumorigenesis (9), and induction of tumor cell autophagy (10).

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Pharmacokinetics

Oleandrin, the principal glycoside in Nerium oleander, is well absorbed following oral administration. Biologic half-life is not determined, but pharmacodynamic activity lasts for approximately 2.5 days. After intravenous administration of oleandrin in mice, the active metabolite is found to concentrate in the liver. About half of circulating oleandrin is bound to plasma proteins. Both biliary and renal elimination have been shown. (8)

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Warnings

Unprocessed leaves from the Nerium oleander plant are highly toxic.

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Contraindications

Patients with hypercalcemia, hypokalemia, bradycardia, ventricular tachycardia, or heart failure should not use this product. (12)

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Adverse Reactions
  • Common (Raw botanical): Consumption of one Nerium oleander leaf may be fatal. Onset of toxicity occurs several hours following consumption and includes vomiting, abdominal pain, cyanosis, hypotension, hypothermia, vertigo, respiratory paralysis, and death. Symptoms of toxicity can occur at a serum oleandrin level between 1.0 and 2.0 ng/ml. (12)
  • Reported (Anvirzel™)
    Nausea, vomiting, diarrhea, pruritus, pain at injection site, tumor pain, mastalgia, leukocytosis, tachycardia, and arrhythmias.
    Consumption of oleander leaves resulted in the death of an adult diabetic male. The oleandrin levels in the blood were roughly 10 ng/ml (13).
  • Case Report
    Daily intramuscular injections of Nerium oleander extract for two months are suspected as probable cause of death of a 43-year-old patient with Metastatic Synovial Sarcoma of the Knee. Her symptoms included nausea, vomiting, severe stomach pain, and bloating followed by a gradual reduction of liver enzymes and cardiopulmonary arrest (15).
     
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Herb-Drug Interactions

Digoxin: Theoretically, the cardiac glycosides in Nerium oleander may have an additive effect with digoxin, causing toxicity.

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Literature Summary and Critique

Studies are underway to determine the antitumor effects of Oleandrin.  

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References
  1. Manna SK, Sah NK, Newman RA, et al. Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase. Cancer Res. Jul 15 2000;60(14):3838-3847.
  2. Pathak S, Multani AS, Narayan S, et al. Anvirzel, an extract of Nerium oleander, induces cell death in human but not murine cancer cells. Anticancer Drugs. Jul 2000;11(6):455-463.
  3. Smith JA, Madden T, Vijjeswarapu M, et al. Inhibition of export of fibroblast growth factor-2 (FGF-2) from the prostate cancer cell lines PC3 and DU145 by Anvirzel and its cardiac glycoside component, oleandrin. Biochem Pharmacol. Aug 15 2001;62(4):469-472.
  4. Nasu S, Milas L, Kawabe S, et al. Enhancement of radiotherapy by oleandrin is a caspase-3 dependent process. Cancer Lett. Nov 28 2002;185(2):145-151.
  5. Mekhail T, Kaur H, Ganapathi R, et al. Phase 1 trial of Anvirzel in patients with refractory solid tumors. Invest New Drugs. Sep 2006;24(5):423-427.
  6. McConkey DJ, Lin Y, Nutt LK, et al. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells. Cancer Res. Jul 15 2000;60(14):3807-3812.
  7. Sreenivasan Y, Raghavendra PB, Manna SK. Oleandrin-mediated expression of Fas potentiates apoptosis in tumor cells. J Clin Immunol. Jul 2006;26(4):308-322.
  8. Newman RA, Yang P, Hittelman WN, et al. Oleandrin-mediated oxidative stress in human melanoma cells. J Exp Ther Oncol. 2006;5(3):167-181.
  9. Manna SK, Sreenivasan Y, Sarkar A. Cardiac glycoside inhibits IL-8-induced biological responses by downregulating IL-8 receptors through altering membrane fluidity. J Cell Physiol. Apr 2006;207(1):195-207.
  10. Newman RA, Kondo Y, Yokoyama T, et al. Autophagic cell death of human pancreatic tumor cells mediated by oleandrin, a lipid-soluble cardiac glycoside. Integr Cancer Ther. Dec 2007;6(4):354-364.
  11. Ozel HZ, Ozel HZOzel HZs. Extracts of Nerium species, methods of preparation, and use therefore. US patent 5,135,745, 1992.
  12. Schulz V, Rudolf H, Tyler VE. Rational Phytotherapy: A Physician's Guide to Herbal Medicine. 4th ed. New York: Springer; 2001.
  13.  Wasfi IA, Zorob O, Al katheeri NA, Al Awadhi AM. A fatal case of oleandrin poisoning. Forensic Sci Int. 2008 Aug 6;179(2-3):e31-6.
  14. Gayathri V, Ananthi S, Chandronitha C, et al. Cardioprotective effect of nerium oleander flower against isoproterenol-induced myocardial oxidative stress in experimental rats. J Cardiovasc Pharmacol Ther. 2011 Mar;16(1):96-104.
  15. Altan E, Bitik B, Kalpakci Y, Dogan E, Altundag K. Probable hepatotoxicity related to Nerium oleander extract in a patient with metastatic synovial sarcoma of the knee. J Altern Complement Med. 2009 Feb;15(2):113.
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How It Works

Bottom Line: Oleandrin can inhibit the growth of some cancer cells, but it has not been shown to be an effective cancer treatment.

Oleandrin is an extract from the plant, Nerium oleander, which contains substances that are similar to the active chemical found in the heart medication, digoxin. In the laboratory, Anvirzel™, a brand of oleandrin, is able to suppress growth and cause cell death in certain cancer cell lines. It also has been seen to increase the sensitivity of prostate cancer cell lines to radiation therapy. However, it is unclear whether these effects occur in the human body. Oleandrin has also been used to treat heart disease, HIV, hepatitis, and rheumatoid arthritis.

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Purported Uses
  • To treat cancer
    Laboratory studies show some anticancer activity in cancer cell lines, but clinical trials have not evaluated the anticancer activities of oleandrin in humans.

    There is no scientific evidence to support the following claims:
  • To treat congestive heart failure
  • To treat hepatitis C
  • To treat HIV and AIDS
  • To treat psoriasis
  • To treat rheumatoid arthritis
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Research Evidence

Studies are underway to determine the antitumor effects of Oleandrin.  

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Patient Warnings
  • The raw plant from which AnvirzelTM is extracted, Nerium oleander, is highly toxic. Consumption of only one Nerium oleander leaf may be fatal. The onset of toxicity occurs several hours after consumption and includes vomiting, abdominal pain, cyanosis (bluish discoloration of the skin), low blood pressure, hypothermia (low body temperature), dizziness, respiratory paralysis, and death.
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Do Not Take If
  • You are taking digoxin (because Anvirzel™ contains the cardiac glycosides, the same active chemical in digoxin, the two medications may have an additive effect, causing toxicity).
  • You have hypercalcemia (high blood levels of calcium), hypokalemia (low blood levels of potassium), bradycardia (abnormally slow heart rate), ventricular tachycardia (abnormally fast ventricular heart rate), or NYHA stage III or IV heart failure. (Anvirzel™ contains the cardiac glycosides, the same active chemical in digoxin, and is therefore contraindicated in people with these conditions).
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Side Effects
  • Nausea and vomiting
  • Diarrhea
  • Itching
  • Pain at injection site
  • Tumor pain
  • Mastalgia (breast pain)
  • Leukocytosis (abnormally high white blood cell count)
  • Tachycardia (abnormally fast heart rate)
  • Cardiac arrhythmias
  • Case Report
  • Consumption of oleander leaves resulted in the death of an adult diabetic male. The oleandrin levels in the blood were roughly 10 ng/ml.
  • Case Report
    Daily intramuscular injections of Nerium oleander extract for two months are suspected as probable cause of death of a 43-year-old patient with Metastatic Synovial Sarcoma of the Knee. Her symptoms included nausea, vomiting, severe stomach pain, and bloating followed by a gradual reduction of liver enzymes and cardiopulmonary arrest.
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Special Point

Anvirzel™ is considered an “investigational new drug” in the United States and is not available for use except under approved clinical trials. Until more test results showing this product is effective and safe are published, it should not be used outside of clinical trials.

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Dosage (Inside MSKCC Only)
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Aliases
Anvirzel™
Nerium Oleander
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Last updated: December 14, 2011
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