Apomorphine (Systemic)


VA CLASSIFICATION
Primary: DX900

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Diagnostic aid (parkinsonism)—

Indications

Accepted

Parkinsonism (diagnosis)—Apomorphine is used in the differential diagnosis of idiopathic parkinsonism syndrome and as a diagnostic test for dopaminergic responsiveness in parkinsonian syndromes to determine whether a patient will respond or is still responsive to levodopa therapy. {05} {10} {11} {12} {14} {15}

Unaccepted
Apomorphine has been used as a centrally acting emetic in the treatment of acute oral drug overdose and accidental poisoning. {01} {03} {07} {09} However, this medication has been replaced by ipecac syrup, which is more convenient to use and does not produce central nervous system (CNS) or respiratory depression. {04} {08} {15} {16} {17}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    312.80

Mechanism of action/Effect:

Diagnostic aid (parkinsonism)—Apomorphine is a dopamine receptor agonist, whose clinical and pharmacological anti-parkinsonian effects resemble those of levodopa, but which is faster acting. Improvement of parkinsonian symptoms with apomorphine serves to predict responsiveness to levodopa. {10} {11} {12} {14} {15}


Other actions/effects:

Apomorphine induces vomiting by direct stimulation of the medullary chemoreceptor trigger zone (CTZ). Excitation of vestibular centers may also be involved since movement increases and recumbency decreases the emetic effect of apomorphine. {01} {02} {03} {09} {17}

Apomorphine also depresses medullary centers that control respiration and vasomotor tone and stimulates salivation. It increases plasma concentrations of human growth hormone and decreases serum prolactin concentrations by stimulating dopamine receptors. {03} {05}

Biotransformation:

Hepatic.

Onset of action:

Adults: 5 to 10 minutes. {01} {02} {17}

Children: 1 to 2 minutes.

Elimination:
    Renal. A very small percentage of a dose is excreted unchanged. {03}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to morphine or its derivatives may be sensitive to this medication also. {01}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans.

Studies have not been done in animals.

FDA Pregnancy Category C. {01}

Breast-feeding

It is not known whether apomorphine is distributed into breast milk. However, problems in humans have not been documented. {01}

Pediatrics

Apomorphine is not generally used in children.


Geriatrics


No information is available on the relationship of age to the effects of apomorphine in geriatric patients. However, it is known that geriatric patients exhibit increased sensitivity to morphine-like medications and may be more susceptible to the respiratory depressant effects of apomorphine, especially with large or repeated doses. {01} {05}

In addition, the increase in blood pressure that may result from the vomiting action may place geriatric patients at greater risk of hemorrhage and vascular accidents because of possible pathologic changes of their blood vessels; therefore, caution is recommended. {03} {15} {18}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Dronabinol    (prior administration of dronabinol may decrease the emetic response to apomorphine; also, concurrent use may potentiate the central nervous system depressant effects of either apomorphine or dronabinol)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Serum prolactin concentrations    (may be decreased)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist {01} {02} {03} {07} {09}:
» Any condition in which there is an increased risk of aspiration of vomitus, such as:
» Decreased patient alertness or
» Depressed gag reflex or
» Seizures or
» Unconsciousness    (risk of aspiration pneumonia)


» Narcosis due to opiates, barbiturates, or other CNS depressants or
» Shock    (increased risk of severe CNS, cardiovascular, and/or respiratory depression)


Sensitivity to apomorphine
Risk-benefit should be considered when the following medical problems exist {01} {02} {03} {05}
Cardiac decompensation or
Cerebrovascular disease    (vomiting may cause an increase in blood pressure that may lead to hemorrhage and vascular accidents {03} {15} {18})


Caution is also recommended in debilitated patients, since they may show an increased susceptibility to apomorphine.


Side/Adverse Effects

Note: Excessive doses of apomorphine may cause violent emesis, cardiac depression, and death.
Although the apomorphine test for parkinsonism is generally well tolerated, mild transient nausea and vomiting, moderate sedation, postural hypotension or vasovagal response, and yawning have been reported. These side effects usually resolve within thirty minutes. Apomorphine-induced side effects may be blocked by prior administration of domperidone, a peripheral dopamine antagonist. {05} {14} {15} {19}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
CNS depression (drowsiness; unusual tiredness or weakness)
    
increased salivation
    
increased sweating
    
nausea

Incidence less frequent or rare
    
CNS stimulation (false sense of well-being; fast heartbeat; fast or irregular breathing; restlessness; trembling)
    
orthostatic hypotension (dizziness or lightheadedness, especially when getting up from a lying or sitting position)—more frequent in patients with Parkinson's disease{14}{15}





Overdose
For specific information on the agents used in the management of apomorphine overdose, see:   • Atropine in Anticholinergics/Antispasmodics (Systemic) monograph; and/or
   • Naloxone (Systemic) monograph.

For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (See Poison Control Center Listing ).

Clinical effects of overdose {01} {03} {09} {17}
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Bradycardia (slow heartbeat)

CNS depression, severe (ranging from severe drowsiness to profound coma)

respiratory depression (shortness of breath; troubled breathing)

vomiting, continuing

Note: CNS depression may also occur at therapeutic doses. {01}


Treatment of overdose


Specific treatment:
Naloxone, to antagonize emetic effects and CNS and respiratory depression. {01} {02} {03} {17}

Atropine, to treat bradycardia. {03}



Supportive care—:
Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



Parenteral Dosage Forms

APOMORPHINE HYDROCHLORIDE INJECTION

Usual adult dose
Diagnostic aid (parkinsonism)
Subcutaneous, 1, 2, 4, and 5 mg of a solution containing 10 mg per mL, until a positive response is recorded (up to 10 mg), with thirty minutes between doses. {12} {19} {20}


Note: The oral administration of domperidone, 20 mg three times a day for two to three days prior to the administration of apomorphine and 20 mg three times during the day of apomorphine administration beginning thirty to sixty minutes prior to the apomorphine dose, is recommended to reduce the incidence of side effects. {12} {19} {20} {21}


Usual adult prescribing limits
Up to 10 mg per twenty-four hours.

Usual geriatric dose
See Usual adult dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). {13}

Stability:
Solution should not be used if it turns green {13} or brown or contains a precipitate.

Incompatibilities:
Physically incompatible with alkalis, iodides, tannins, iron salts, and oxidizing agents. {03}



Revised: 10/16/2000



References
  1. Apomorphine package insert (Lilly—US), Rev 4/13/88, Rec 1/89.
  1. Gilman AG, Goodman LS, Rall TW, Murad F, editors. Goodman and Gilman's the pharmocological basis of therapeutics. 7th ed. New York: Macmillan, 1985: 482, 508, 1600.
  1. McEvoy GK, editor. AHFS Drug information 89. Bethesda, MD: American Society of Hospital Pharmacists, 1989: 1596.
  1. AMA Drug evaluations. 6th ed. Chicago: American Medical Association, September 1986: 1634.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 29th ed. London: The Pharmaceutical Press, 1989: 1010.
  1. The United States pharmacopeia. The national formulary. USP 22nd revision (January 1, 1990). NF 17th ed (January 1, 1990). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1990: 107-8.
  1. Aronow R, editor. Handbook of common poisonings in children. 2nd ed. Evanston, IL: American Academy of Pediatrics, 1983: 3-4.
  1. Willis GA, Freeman DA, editors. The British Columbia drug and poison information centre. Poison management manual. Ottawa: Canadian Pharmaceutical Association, 1984.
  1. Wheeler-Usher DH, Wanke LA, Bayer MJ. Gastric emptying—Risk versus benefit in the treatment of acute poisoning. Med Toxicol 1986; 1: 142-53.
  1. Stibe CMH, Kempster PA, Lees AJ, Stern GM. Subcutaneous apomorphine in parkinsonian on-off oscillation. Lancet 1988; 8582: 403-6.
  1. Barker R, Duncan J, Lees AJ. Subcutaneous apomorphine as a diagnostic test for dopaminergic responsiveness in parkinsonian syndrome. Lancet 1989; 1: 675.
  1. Oertel WH, Gasser T, Ippisch R, Trenkwalder C. Apomorphine test for dopaminergic responsiveness. Lancet 1989; 1: 1262-3.
  1. Personal communication, Deprenyl Research Ltd., 3/2/94.
  1. Hughes AJ, Lees AJ, Stern GM. Apomorphine test to predict dopaminergic responsiveness in parkinsonian syndromes. Lancet 1990; 336: 32-4.
  1. Panel comment, 01/16/91.
  1. Clinical Toxicology/Substance Abuse Advisory Panel Meeting, 05/18/91.
  1. Ellenhorn MJ, Barceloux DG, editors. Medical toxicology. Diagnosis and treatment of human poisoning. New York: Elsevier, 1988: 56-7, 84.
  1. Klein-Schwartz W, Gorman RL, Oderda GM. Ipecac use in the elderly: the unanswered question. Ann Emerg Med 1984; 13: 1152-4.
  1. Panel comment, 1/94.
  1. Panel comment, 2/94.
  1. Panel comment, 2/94.
  1. Rodgers GC, Matyunas NJ. Gastrointestinal decontamination for acute poisoning. Pediatr Clin North Am 1986; 33: 261-85.
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