Hydrazine sulfate (HS)

Category

Herbs & Supplements

Synonyms

2,4-dinitro-phenylhydrazine, alpha-methyldopa-hydrazine, beta-phenylisopropylhydrazine, carbidopa, diamide, diamine, dimethylhydrazine, hydrazine, hydrazine monosulphate, hydrazine sulphate, hydrazinium sulphate, hydrazonium sulphate, idrazina solfato (Italian), Sehydrin®.

Background

Cachexia is defined as physical wasting with loss of weight and muscle mass caused by disease. Patients with advanced cancer, AIDS, and some other major chronic progressive diseases may appear cachectic. Anorexia (lack of appetite) and cachexia often occur together. Cachexia can occur in people who are eating enough, but who cannot absorb the nutrients. Cachexia is not the same as starvation. A healthy person's body can adjust to starvation by slowing down its use of nutrients, but in cachectic patients, the body does not make this adjustment.

Hydrazine is an industrial chemical marketed as having the potential to repress weight loss and cachexia associated with cancer and to improve general appetite status. However, in large randomized controlled trials, hydrazine has not been proven effective for improving appetite, reducing weight loss, or improving survival in adults with small cell lung cancer (when used as adjuvant therapy) or metastatic colorectal cancer (when used alone).

Hydrazine sulfate causes liver damage in rodents. It is associated with nausea and vomiting, fatigue, sensory and motor neuropathies, and a significantly reduced quality of life in cancer patients. It is currently being investigated as a potential treatment for endotoxin-mediated shock. Hydrazine sulfate has demonstrated significant mutagenic and carcinogenic potential in animal studies.

Hydrazine has not been well evaluated for safety or toxicity during pregnancy, lactation, or childhood.

Other applications of hydrazine include: corrosion inhibitor, herbicide and pesticide component, laboratory reagent, refining rare metals, soldering flux for light metals, silvering of mirrors, and rocket fuel.

Evidence

DISCLAIMER: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Cachexia (cancer related): The results of multiple clinical studies for the use of hydrazine sulfate in cancer-related cachexia are conflicting. The use of hydrazine sulfate cannot be fully recommended due to the lack well-designed studies and potential risks. More established therapies are recommended at this time.
Grade: C

Cancer treatment: The National Cancer Institute (NCI) sponsored studies of hydrazine sulfate that claimed efficacy in improving survival for some patients with advanced cancer. Trial results found that hydrazine sulfate did not prolong survival for cancer patients. The U.S. Food and Drug Administration (FDA) has received requests from individual physicians for approval to use hydrazine sulfate on a case-by-case "compassionate use" basis on the chance that patients with no other available effective therapy might benefit. The overall controversy in the use of hydrazine sulfate is ongoing, and relevance to clinical practice is unknown. The use of hydrazine sulfate needs to be evaluated further before any recommendations can be made. Side effects have been reported.
Grade: C

Tradition

WARNING: DISCLAIMER: The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.
Analytical tests for blood, anorexia, antidepressant, antioxidant, biocide for molds and fungi (onychomycosis), chemotherapy, impaired glucose tolerance, multi-drug resistance (tachyphylaxis), normalizing laboratory indices, nutritional support (improving caloric intake), pain, Parkinson's disease, sickle-cell anemia, tuberculosis, weight loss (prevention).

Dosing

Adults (over 18 years old)

Various clinical trials have used 60 milligrams of hydrazine sulfate taken by mouth one to three times daily for 30 days in patients with cancer and or cachexia. Injections have also been given by a healthcare provider.

Children (under 18 years old)

Insufficient available evidence.

Safety

DISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.

Allergies

Avoid if known allergy/hypersensitivity exists to hydrazine sulfate or any of its constituents.

Hydrazine sulfate is a sensitizer and can potentially cause allergic reactions. Rash has been reported.

Side Effects and Warnings

Hydrazine sulfate is a severe skin and mucus membrane irritant; effects when used internally include weakness and excitability. Side effects include nausea, vomiting, pruritus, headache, dizziness, drowsiness, insomnia, weakness, irregular breathing, confusion, low blood sugar, lethargy, violent behavior, restlessness, seizures, coma, and peripheral neuropathies (a disease or abnormality of the nervous system). Sweating has been reported in two patients in a small clinical trial.

Periarteritis nodosa and lupus has also been associated with hydrazine. Polyarteritis nodosa is a serious blood vessel disease in which small and medium-sized arteries become swollen and damaged when they are attacked by rogue immune cells. Lupus is a chronic inflammatory disease that can affect various parts of the body, especially the skin, joints, blood, and kidneys.

Hydrazine has been associated with low blood pressure, abnormal heart rhythms, septic shock, congestive heart failure, and facial swelling. A fatal case of liver and kidney failure has been reported.

Anorexia, heartburn, diarrhea, constipation, and hunger have been reported. Elevation of liver enzymes and "bad cholesterol" (LDH) have been reported.

In a clinical trial, there was a report of possible thrombophlebitis (vein inflammation), although it was unclear whether it was drug related. One report suggested hydrazine-induced platelet aggregation. Methemoglobinemia, a condition in which the iron in the hemoglobin molecule (the red blood pigment) is defective making it unable to carry oxygen effectively to the tissues, has been noted.

Hydrazine sulfate has been reported to cause paresthesia (upper and lower extremities), arthralgia or pain, depression, distorted sense of taste, palpebral tic, slurred speech, and hiccup; it may also affect fine motor functions. A paresthesia is a sensation of burning, prickling, tingling, or creeping on the skin that is often seen in multiple sclerosis (MS). Hydrazine sulfate either inhaled or used topically may cause irritation, burns, and permanent damage to the eye. Mydriasis (dilation of the pupil) and nystagmus (rapid involuntary oscillation/movement back and forth of the eyes) have been reported.

In a clinical trial, one patient had visual and auditory hallucinations.

A chest X-ray of a person who handled hydrazine for six months showed fluid in the lungs. An autopsy revealed severe trachea inflammation, bronchitis, and death due to pneumonia. Oral hydrazine sulfate may cause irregular breathing. Inhaled or topical use of hydrazine sulfate may cause bronchial mucus destruction, pulmonary edema, cancer, and death. Dyspnea (shortness of breath), rhinitis (inflammation of nasal mucosa), and cough have also been reported.

Pregnancy and Breastfeeding

Not recommended due to lack of sufficient data.

Interactions

Interactions with Drugs

One clinical study reported that a patient with lung cancer experienced flushing after alcohol ingestion while on hydrazine sulfate therapy.

Hydrazine is a monoamine oxidase inhibitor. Therefore, use of hydrazine with SSRIs, TCAs, tetracyclic, or other MAOI antidepressants should be avoided as it may result in hypertensive crisis (dangerously high blood pressure) and/or serotonin syndrome. A derivative of hydrazine has been used as an anti-depressant in the MAOI family for the treatment of minor depressive states, but failed to show any beneficial results.

Dr. Joseph Gold, the pioneer in hydrazine use in cancer patients, has conducted several studies on the effects of hydrazine sulfate; he suggested that patients using hydrazine sulfate refrain from using benzodiazepines and barbiturates.

Hydrazine sulfate used with bleomycin, a chemotherapy drug, may lead to an additive effect of both agents. Hydrazine sulfate used with cyclophosphamide, a chemotherapy drug, may lead to enhanced antitumor effects of cyclophosphamide.

Hydrazine sulfate may induce hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar). Use of hydrazine sulfate with diabetes medications/oral hypoglycemic agents may result in either additive or negative effects.

Hydrazine sulfate used along with isoniazid may lead to enhanced effects of hydrazine.

Hydrazine may increase the length of time that levodopa works.

Hydrazine sulfate used with methotrexate may lead to an additive effect of both agents.

Hydrazine sulfate used with mitomycin C may lead to enhanced antitumor effects of mitomycin C when these agents are administered six hours apart from each other. The study found that if hydrazine sulfate and mitomycin C are mixed in the same syringe, they inactivate each other.

Interactions with Herbs and Dietary Supplements

Interactions may occur with herbs and supplements with the following properties: amphetamine-like, anesthetic-like, anti-depressant-like, anxiolytic-like, barbiturate-like, beta-blocker-like, central adrenergic-like, demerol-like, hypoglycemic-like, insulin-like, sympathomimetic-like, or theophylline-like.

Hydrazine sulfate may alter blood sugar levels (induce hypoglycemia or hyperglycemia). Use with other herbs or supplements that alter blood sugar may result in either additive or negative effects when taken with hydrazine.

Based on animal studies, hydrazine is a monoamine oxidase inhibitor and therefore use of hydrazine with SSRIs, TCAs, tetracyclic, or other MAOI acting herbs or supplements should be avoided as it may result in hypertensive crisis and/or serotonin syndrome. An example is St. John's wort. A derivative of hydrazine has been used as an anti-depressant in the MAOI family for treatment of minor depressive states but failed to show any beneficial results.

Hydrazine sulfate is typically suggested as a cancer treatment, and thus hydrazine sulfate may interact with herbs or supplements also used for cancer. Caution is advised.

Attribution

This information is based on a systematic review of scientific literature, and was peer-reviewed and edited by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Mary McGarry, RPh (University of Kansas); Ethan Basch, MD (Memorial Sloan-Kettering Cancer Center); Dawn Costa, BA, BS (Natural Standard Research Collaboration); Nicole Giese, MS (Natural Standard Research Collaboration); Irina Gladkikh, RN, JD (Natural Standard Research Collaboration); Dana A. Hackman, BS (Northeastern University); Evelyn Hermes-DeSantis, PharmD, BCPS (Rutgers University); Nikos Linardakis, MD (Natural Standard Research Collaboration); Lisa Scully, PharmD (Massachusetts College of Pharmacy); Erica Seamon, PharmD (Nova Southeastern University); Kristopher Swinney, PharmD (Massachusetts College of Pharmacy); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Mamta Vora, PharmD (Northeastern University); Wendy Weissner, BA (Natural Standard Research Collaboration); Shannon Welch, PharmD (Northeastern University); Denise Wong, PharmD (Northeastern University).

Bibliography

DISCLAIMER: Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

Chlebowski RT, Heber D, Richardson B, et al. Influence of hydrazine sulfate (HS) on carbohydrate metabolism in cancer cachexia: a randomized, placebo controlled trial [abstract]. Proc Am Soc Clin Oncol 1982;1:59.

Chlebowski RT, Bulcavage L, Grosvenor M, et al. Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience. Cancer 1987;59(3):406-410.

Durant PJ, Harris RA. Hydrazine and lupus. N Engl J Med 1980;303(10):584-585.

Freese E, Sklarow S, Freese EB. DNA damage caused by antidepressant hydrazines and related drugs. Mutat Res 1968;5(3):343-348.

Gershanovich ML, Danova LA, Kondratyev VB, et al. Clinical data on the antitumor activity of hydrazine sulfate. Cancer Treat Rep 1976;60(7):933-935.

Kulkarni SG, Nawaz M. Acute hepatic encephalopathy following hydrazine - hydrate poisoning. J Assoc Physicians India 1982;30(3):171-172.

Lerner HJ, Regelson W. Clinical trial of hydrazine sulfate in solid tumors. Cancer Treat Rep 1976;60(7):959-960.

Morris J, Densem JW, Wald NJ, et al. Occupational exposure to hydrazine and subsequent risk of cancer. Occup Environ Med 1995;52(1):43-45.

Ochoa M, Jr., Wittes RE, Krakoff IH. Trial of hydrazine sulfate (NSC-150014) in patients with cancer. Cancer Chemother Rep 1975;59(6):1151-1154.

Reidenberg MM, Durant PJ, Harris RA, et al. Lupus erythematosus-like disease due to hydrazine. Am J Med 1983;75(2):365-370.

Rosenkranz HS, Carr HS. Hydrazine antidepressants and isoniazid: potential carcinogens. Lancet 1971;1(7713):1354-1355.

Sotaniemi E, Hirvonen J, Isomaki H, et al. Hydrazine toxicity in the human. Report of a fatal case. Ann Clin Res 1971;3(1):30-33.

Wald NJ. Hydrazine: epidemiological evidence. IARC Sci Publ 1985;(65):75-81.

Wald N, Boreham J, Doll R, et al. Occupational exposure to hydrazine and subsequent risk of cancer. Br J Ind Med 1984;41(1):31-34.

Wiernikowski A, Langer D. [Acute poisoning with orally ingested hydrazine hydrate]. Polski Tygodnik Lekarski 1975;30(29):1231-1232.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.