Apomorphine is a subcutaneously administered dopamine receptor agonist used predominantly in the therapy of hypomobility of advanced Parkinson disease. The use of apomorphine has been limited, but it has not been associated with serum enzyme elevations during treatment nor has it been implicated in cases of acute liver injury.
Apomorphine (a" poe mor' feen) is a subcutaneously administered dopamine receptor agonist which has moderate affinity for the D2, D3, and D5 class of dopamine receptors in the central nervous system and little activity against the D1 class. It also has some alpha adrenergic activity. Apomorphine was shown to improve motor function in animal models of Parkinson disease and in clinical trials, was shown to decrease hypomobility in patients with advanced Parkinsonism. Apomorphine was approved for use in the United States in 2004, but had been used in Europe for more than a decade. Current indications are for acute and intermittent treatment of hypomobility of advanced Parkinson disease. It is also used for acute dystonic reactions. Apomorphine is available in a liquid solution of 10 mg/mL under the brand name Apokyn. It is given in 0.2 to 0.6 mL doses subcutaneously as needed up to 3 times daily. Apomorphine injections usually cause nausea and vomiting requiring antiemetics. It can cause hypotension, gastrointestinal upset, anxiety, confusion, dizziness, headache, hallucinations, vivid dreams and insomnia, symptoms typical of dopaminergic stimulation.
Apomorphine has not been reported to cause serum aminotransferase elevations or clinically apparent acute liver injury, but its use has been limited and is typically given in low doses for a limited period of time. Thus, if apomorphine causes liver injury it must be rare.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Mechanism of Injury
The metabolism of apomorphine has not been well defined; it appears to be minimally metabolized in the liver.
REPRESENTATIVE TRADE NAMES
Apomorphine – Apokyn®
Product labeling at DailyMed, National Library of Medicine, NIH
||CAS REGISTRY NUMBER
Top of page
updated: 20 July 2017
HJ. Antiparkinsonism drugs. In, Zimmerman HJ. Hepatotoxicity: the adverse
effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia:
Lippincott, 1999, pp. 715-7. (Expert
review of hepatotoxicity published in 1999; among anticholinergic agents, "only
trihexyphenidyl has been incriminated in hepatic injury"; other antiparkinsonism
drugs discussed include levodopa, lergotrile [no longer available], pergolide
D, Ripault MP. Hepatotoxicity of psychotropic drugs and drugs of abuse. In,
Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam:
Elsevier Inc, 2013, pp. 443-62. (Review
of hepatotoxicity of agents acting on the central nervous system).
DG, Roberson ED. Treatment of central nervous system degenerative disorders. In,
Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the
pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp.
of pharmacology and therapeutics).
F. Symposium on levodopa in Parkinson's disease. Clinical and pharmacological
aspects. Clinical laboratory abnormalities. Clin Pharmacol Ther 1971; 12:
analysis of laboratory abnormalities arising in 974 patients with Parkinson
disease treated with levodopa; AST elevations occurred in 9% of 5427
determinations, but were usually mild and transient returning to normal in 1-2
months without dose adjustment; AST levels rose to 1600 U/L in one patient who
later died of complications of diabetes).
Pinter MM, Helscher RJ, Mundsperger N, Binder H. Transient increase of pancreatic enzymes evoked by apomorphine in Parkinson's disease. J Neural Transm 1998; 105: 1237-44. PubMed Citation (Among 29 patients with Parkinson disease treated with apomorphine, transient asymptomatic elevations in amylase and lipase elevations occurred in 5; liver enzymes remained normal).
D, Waters CH. Comparative tolerability of the newer generation antiparkinsonian
agents. Drugs Aging 2000; 16: 55-65. PubMed
of mechanism of action, tolerability and safety of selegiline, pramipexole,
ropinirole, tolcapone and entacapone in Parkinson disease).
Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver
failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52:
Citation (Among 1198 patients
with acute liver failure enrolled in a US prospective study between 1998 and
2007, 133 were attributed to drug induced liver injury, but none were attributed
to agents used for Parkinson disease).
ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation,
and outcomes in patients with drug-induced liver injury in the general
population of Iceland. Gastroenterology 2013; 144: 1419-25,1425. PubMed
Citation (In a population
based study of drug induced liver injury from Iceland, 96 cases were identified
over a 2 year period, but none of the 96 were attributed to an agent used to
treat Parkinson disease).
for Parkinson's disease. Treat Guidel Med Lett 2013; 11 (135):
Citation (Concise review of
recommendations for therapy of Parkinson disease with description of mechanisms
of action, efficacy and adverse events).
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 Citation (Among 176 reports
of drug induced liver injury from Latin America published between 1996 and 2012,
none were attributed to an agent to treat Parkinson disease).
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. PubMed
Citation (Among 899 cases of
drug induced liver injury from the US enrolled in a prospective database between
2004 and 2012, none were attributed to an agent used to treat Parkinson
OTHER REFERENCE LINKS
Top of page