OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Zinc – Generic, Galzin®

DRUG CLASS

Trace Elements and Metals; Chelating Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 25 July 2020

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999; zinc is not discussed).
• Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013.

  (Textbook on hepatotoxicity; agents for Wilson disease are not discussed).
• Byrns MC, Penning TM. Treatment of metal exposure. Environmental toxicology: carcinogens and heavy metals. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1311-5.

  (Textbook of pharmacology and therapeutics).
• Murphy JV. Intoxication following ingestion of elemental zinc. JAMA. 1970;212:2119–20. [PubMed: 5467786]

  (16 year old boy ingested 12 g of elemental zinc to help healing of a skin laceration and developed lethargy, light-headedness and ataxia which responded to hydration and dimercaprol [BAL] therapy; serum aminotransferase and bilirubin levels were normal).
• Brocks A, Reid H, Glazer G. Acute intravenous zinc poisoning. Br Med J. 1977;1(6073):1390–1. [PMC free article: PMC1606903] [PubMed: 405076]

  (72 year old woman on total parenteral nutrition was given an overdose of zinc sulfate [7.4 g] and she developed hypotension, diarrhea, vomiting, oliguria and jaundice with a cholestatic pattern that slowly resolved, but she died of pneumonia 47 days later).
• Stowe CM, Nelson R, Werdin R, Fangmann G, Fredrick P, Weaver G, Arendt TD. Zinc phosphide poisoning in dogs. J Am Vet Med Assoc. 1978;173:270. [PubMed: 689968]

  (Six cases of zinc toxicity in dogs due to zinc phosphide, a rodenticide, presenting with malodor, tremors, rigidity and seizures; no mention of liver injury).
• Potter JL. Acute zinc chloride ingestion in a young child. Ann Emerg Med. 1981;10:267–9. [PubMed: 6784612]

  (28 month old boy ingested 4 ounces of soldering flux [20% zinc chloride] and rapidly developed vomiting and lethargy followed by metabolic acidosis [zinc 1,644 μg/dL, AST 48 U/L, Alk P 197 U/L], recovering within 2 days with hydration and EDTA infusions).
• Chobanian SJ. Accidental ingestion of liquid zinc chloride: local and systemic effects. Ann Emerg Med. 1981;10:91–3. [PubMed: 6784611]

  (24 year old man accidentally ingested a zinc chloride solution with immediate vomiting and burning pain which resolved within 3 days with hydration and EDTA therapy; serum bilirubin and liver enzymes remaining normal).
• Hornfeldt CS, Koepke TE. A case of suspected zinc toxicity in a dog. Vet Hum Toxicol. 1984;26(3):214. [PubMed: 6610246]
• Allen JG, Masters HG, Peet RL, Mullins KR, Lewis RD, Skirrow SZ, Fry J. Zinc toxicity in ruminants. J Comp Pathol. 1983;93:363–77. [PubMed: 6886083]

  (In sheep and cattle, zinc toxicity can arise from use of galvanized troughs or zinc containing fertilizers or fungicides, presenting with diarrhea and vomiting, weakness and jaundice and death in severely affected animals, autopsies showing centrolobular [zone 3] hepatic necrosis).
• Ulmer DD. Trace elements. N Engl J Med. 1977;297:318–21. [PubMed: 876314]

  (Brief review of trace elements, their metabolic roles, deficiencies and toxicities).
• Hoogenraad TU, Van den Hamer CJ, Koevoet R, Korver EG. Oral zinc in Wilson's disease. Lancet. 1978;2(8102):1262. [PubMed: 82772]

  (16 year old with Wilson disease had cupruresis on penicillamine after failure during zinc therapy, although he had no clinical improvement until zinc was reintroduced).
• Brewer GJ, Hill GM, Prasad AS, Cossck ZT, Rabbani P. Oral zinc therapy for Wilson’s disease. Ann Intern Med. 1983;99:314–9. [PubMed: 6614680]

  (5 patients [25-34 years old, 3 men, 2 women] with stable Wilson disease after penicillamine therapy underwent careful copper balance studies while on zinc therapy alone, demonstrating a negative copper balance largely due to increased fecal loss).
• Hoogenraad TU, Van den Hamer CJ. 3 years of continuous oral zinc therapy in 4 patients with Wilson's disease. Acta Neurol Scand. 1983;67:356–64. [PubMed: 6613522]

  (4 patients [17 to 46 year old men] with Wilson disease previously treated with penicillamine were treated with oral zinc for at least 3 years and all showed clinical improvement and no adverse events, including no changes in liver tests during zinc therapy).
• Hill GM, Brewer GJ, Juni JE, Prasad AS, Dick RD. Treatment of Wilson's disease with zinc. II. Validation of oral 64copper with copper balance. Am J Med Sci. 1986;292:344–9. [PubMed: 3799705]

  (Assessment of copper update using a radioactive copper uptake study demonstrated that patients with Wilson disease on zinc have a low [<1%], while those on no therapy or on penicillamine or trientine had normal update levels [~6%]).
• Breitschwerdt EB, Armstrong PJ, Robinette CL, Dillman RC, Karl ML, Lowry EC. Three cases of acute zinc toxicosis in dogs. Vet Hum Toxicol. 1986;28:109–17. [PubMed: 3705436]

  (3 dogs with zinc toxicity, 2 from swallowing zinc nuts and one from licking zinc oxide ointment, presenting with vomiting, fever, pallor and jaundice with severe hemolytic anemia [bilirubin 1.7-14.9 mg/dL, ALT 143-159 U/L, Alk P 448-5400 U/L], 2 recovering and one dying of anemia and sepsis).
• Torrance AG, Fulton RB Jr. Zinc-induced hemolytic anemia in a dog. J Am Vet Med Assoc. 1987;191:443–4. [PubMed: 3654320]

  (1 year old Yorkie developed diarrhea, vomiting, fever and “depression” with severe anemia [hematocrit 15%] after ingesting a zinc nut from his cage [bilirubin 18.9 mg/dL, Alk P 1262 U/L], recovering after endoscopic removal of object).
• Hill GM, Brewer GJ, Prasad AS, Hydrick CR, Hartmann DE. Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens. Hepatology. 1987;7:522–8. [PubMed: 3570163]

  (Copper balance studies in 14 patients with previously treated Wilson disease showed a negative copper balance while on zinc [100-150 mg daily in 2-4 separate doses] compared to high positive copper balance in 3 patients on no therapy; no adverse events noted).
• Hoogenraad TU, Van Hattum J, Van den Hamer CJ. Management of Wilson’s disease with zinc sulphate: experience in a series of 27 patients. J Neurol Sci. 1987;77:137–46. [PubMed: 3819764]

  (Among 27 Dutch patients [ages 11 to 38 years] with Wilson disease treated with zinc sulfate for periods of 1 month to 27 years, 1 died of hepatic failure within the first month, the others all improved with normalization of free serum copper levels and no adverse events).
• Burkhart KK, Kulig KW, Rumack B. Whole-bowel irrigation as treatment for zinc sulfate overdose. Ann Emerg Med. 1990;19:1167–70. [PubMed: 1977339]

  (16 year old boy ingested 50 zinc sulfate tablets in a suicide attempt and was treated with emetics and whole bowel irrigation, with recovery in 2 days and no mention of liver injury or enzyme elevations).
• Broun ER, Greist A, Tricot G, Hoffman R. Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression. JAMA. 1990;264:1441–3. [PubMed: 2094240]

  (Two patients developed anemia due to zinc; a 31 year old schizophrenic man swallowed multiple coins and presented with nausea and abdominal pain with subsequent severe anemia resolving within 4 weeks; a 48 year old man on chronic zinc supplements developed fatigue and severe anemia, resolving within 2 weeks of stopping zinc intake; no mention of liver injury).
• Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, Dick RD, Wang Y. Treatment of Wilson's disease with zinc XII: dose regimen requirements. Am J Med Sci. 1993;305:199–202. [PubMed: 8475943]

  (Analysis of copper balance in 4 patients treated with 75 mg of zinc daily in 1, 2 or 3 divided doses indicated that once daily regimen did not reliably result in a negative copper balance, suggesting that zinc must be given in divided doses 2 or 3 times daily).
• McKinney PE, Brent J, Kulig K. Acute zinc chloride ingestion in a child: local and systemic effects. Ann Emerg Med. 1994;23:1383–7. [PubMed: 7515217]

  (16 month old boy ingested zinc chloride soldering solution and developed vomiting and lethargy with metabolic acidosis and liver test abnormalities [bilirubin normal, ALT 123 U/L, Alk P 527 U/L], resolving within 3 days, but with severe anemia lasting a week).
• Brewer GJ, Dick RD, Johnson VD, Brunberg JA, Kluin KJ, Fink JK. Treatment of Wilson's disease with zinc: XV long-term follow-up studies. J Lab Clin Med. 1998;132:264–78. [PubMed: 9794697]

  (Description of patterns of change in urinary, hepatic and serum copper and zinc levels and liver tests in 141 patients with Wilson disease treated with zinc; adverse reactions were "minimal", the most common being initial abdominal discomfort).
• Anderson LA, Hakojarvi SL, Boudreaux SK. Zinc acetate treatment in Wilson's disease. Ann Pharmacother. 1998;32:78–87. [PubMed: 9475826]

  (Systematic review of the literature on safety and efficacy of oral zinc therapy of Wilson disease concluded that zinc acetate was effective in maintenance of copper balance in patients with Wilson disease and has negligible toxicity).
• Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson's disease. Lancet. 2007;369(9559):397–408. [PubMed: 17276780]

  (Review of the clinical features, pathogenesis, genetics, diagnosis and treatment including role of zinc).
• Gurnee CM, Drobatz KJ. Zinc intoxication in dogs: 19 cases (1991-2003). J Am Vet Med Assoc. 2007;230:1174–9. [PubMed: 17501656]

  (Retrospective review of 19 cases of zinc toxicosis in dogs seen over an 8 year period at one veterinary hospital; dogs presented with vomiting and lethargy with pallor and jaundice, bilirubin elevations in 80% [0.5-23 mg/dL], ALT in 7% [3-92 U/L], Alk P in 92% [107-1422 U/L] and 2 deaths [10%], source of zinc being coins, tacks and bolts).
• Roberts EA, Schilsky ML. AASLD. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47:2089–111. [PubMed: 18506894]

  (Thorough review of the cause, natural history, diagnosis and treatment of Wilson disease, with specific recommendations for use of penicillamine, trientine and zinc).
• Linn FH, Howen RH, van Hattum J, van der Kleij S, van Erpecum KJ. Long-term exclusive zinc monotherapy in symptomatic Wilson disease: experience in 17 patients. Hepatology. 2009;50:1442–52. [PubMed: 19731238]

  (Among 17 Dutch patients [ages 13 to 26] with symptomatic Wilson disease treated with zinc only for 2-30 years, most had a clinical response to treatment, but 2 patients with a neurologic presentation developed liver injury after 6 and 7 years of therapy, and 2 patients with cirrhosis initially developed liver decompensation after 15 and 24 years of therapy; the efficacy of copper elimination appeared less in those with hepatic than neurologic presentations).
• Walshe JM. The conquest of Wilson's disease. Brain. 2009;132(Pt 8):2289–95. [PubMed: 19596747]

  (History of the initial description of Wilson disease, its link to copper accumulation, and therapies several of which were developed by the author).
• Weiss KH, Stremmel W. Evolving perspectives in Wilson disease diagnosis: treatment and monitoring. Curr Gastroenterol Rep. 2012;14:1–7. [PubMed: 22083169]

  (Review of the diagnosis and management of Wilson disease, including the role of genetic testing and the choice of medical therapies).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol. 2014;13:231–9. [PubMed: 24552865]

  (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, none of which was attributed to penicillamine or other agents used to treat Wilson disease).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, one case was attributed to penicillamine but none were attributed to zinc).
• Pfeiffenberger J, Beinhardt S, Gotthardt DN, Haag N, Freissmuth C, Reuner U, Gauss A, et al. Pregnancy in Wilson's disease: management and outcome. Hepatology. 2018;67:1261–9. [PubMed: 28859232]

  (Among 282 pregnancies in 136 patients with Wilson disease analyzed in a retrospective, multicenter study, spontaneous abortion was less common among patients being treated with penicillamine [17%] or zinc [10%] than untreated patients [41%], which was proportionally greater than with trientine [28%] and similar to that in patients who discontinued therapy during pregnancy [36%]; worsening of liver disease arose in some patients on treatment but was self-limiting and resolved after delivery; birth defects were found in 7 of 209 [3%] newborns overall and in 4 of 98 women taking penicillamine).
• Roberts EA. Update on the diagnosis and management of Wilson disease. Curr Gastroenterol Rep. 2018;20:56. [PubMed: 30397835]

  (Review of recent advances in the understanding of the pathogenesis, clinical features, diagnosis, and treatment of Wilson disease).
• Appenzeller-Herzog C, Mathes T, Heeres MLS, Weiss KH, Houwen RHJ, Ewald H. Comparative effectiveness of common therapies for Wilson disease: A systematic review and meta-analysis of controlled studies. Liver Int. 2019;39:2136–52. [PubMed: 31206982]

  (Systematic review of literature on therapies of Wilson disease found no differences in outcomes with penicillamine vs zinc, but higher rates of adverse events and discontinuations with penicillamine; no mention of hepatotoxicity or ALT elevations).