Apokyn (Apomorphine Hydrochloride) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Clinical Trial Experience

Adverse Events Incidence in Controlled Clinical Studies:

APOKYN^® has been administered to 550 Parkinson’s disease patients who were taking some form of L-Dopa along with other Parkinson’s disease medications. Eighty-six percent of patients were taking a concomitant dopamine agonist. All patients had some degree of spontaneously occurring hypomobility (“off episodes”) at baseline. Adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using MEDDRA dictionary terminology.

The most common adverse events seen in controlled trials were yawning, dyskinesias, nausea and/or vomiting, somnolence, dizziness, rhinorrhea, hallucinations, edema, chest pain, increased sweating, flushing, and pallor.

The most extensive experience with apomorphine in randomized, controlled trials comes from a multicenter randomized placebo-controlled parallel group trial conducted in apomorphine-naïve PD patients treated for up to 4 weeks (Table 1). Individual apomorphine doses in this trial ranged from 2-10 mg, optimized to achieve control of symptoms comparable to each patient’s response to his or her usual dose of L-dopa. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. However, the cited figures do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse-event incidence rate in the population studied.

Table 1 Summary of Adverse Events Occurring in Two or More Patients
Adverse Event	APOMORPHINE		PLACEBO
	n = 20		n = 9
	N	%	N	%
Any Adverse Reaction	17	85	8	89
Yawning	8	40	0	0
Dyskinesias	7	35	1	11
Drowsiness or Somnolence	7	35	0	0
Nausea and/or Vomiting	6	30	1	11
Dizziness or Postural Hypotension	4	20	0	0
Rhinorrhea	4	20	0	0
Chest Pain/Pressure/Angina	3	15	1	11
Hallucination or Confusion	2	10	0	0
Edema/Swelling of Extremities	2	10	0	0

Other Adverse Events Observed During All Phase 2/3 Clinical Trials:

APOKYN has been administered to 550 patients; 89% had at least one adverse event (AE). The most common AEs in addition to those in Table 1 (occurring in at least 5% of the patients and at least plausibly related to treatment) in descending order were injection site complaint, fall, arthralgia, insomnia, headache, depression, urinary tract infection, anxiety, congestive heart failure, limb pain, back pain, Parkinson’s disease aggravated, pneumonia, confusion, sweating increased, dyspnea, fatigue, ecchymosis, constipation, diarrhea, weakness, and dehydration.

Post Marketing Experience

In addition to the adverse events reported during clinical trials, the following adverse reactions have been identified during post-approval use of APOKYN^® in Parkinson’s disease patients. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following psychiatric disorders were reported: impulse control symptoms, pathological gambling, and increased libido (including hypersexuality).

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO APOKYN

Possible Apokyn side effects / adverse reactions in 69 year old male

Reported by a physician from United States on 2007-01-17

Patient: 69 year old male weighing 102.5 kg (225.5 pounds)

Reactions: Back Pain, Arthralgia, Drug Ineffective, Nerve Compression, Blood Pressure Decreased, Arthritis, Pharmaceutical Product Complaint, Spinal Column Stenosis

Adverse event resulted in: hospitalization

Suspect drug(s):
Apokyn
    Dosage: 0.4 ml sc
    Indication: Parkinson's Disease
    Start date: 2006-06-06
    End date: 2006-10-25

Apokyn
    Dosage: 0.4 ml variable sc
    Indication: Parkinson's Disease
    Start date: 2006-11-01
    End date: 2006-11-01

Apokyn
    Dosage: var variable sc
    Indication: Parkinson's Disease

Other drugs received by patient: Tasmar; Sinemet; Amantadine HCL; Celebrex; Nexium; Lipitor; Aspirin; Mirapex; Rasagiline; Tylenol; Folic Acid; Flomax; Methotrexate

Possible Apokyn side effects / adverse reactions in 75 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2007-01-23

Patient: 75 year old female weighing 83.9 kg (184.6 pounds)

Reactions: Movement Disorder, Spinal Cord Compression, Dysstasia, Diabetic Neuropathy, Sensory Disturbance

Adverse event resulted in: hospitalization

Suspect drug(s):
Apokyn
    Dosage: see image
    Indication: Parkinson's Disease
    Start date: 2006-09-27
    End date: 2006-01-01

Apokyn
    Dosage: see image
    Indication: Parkinson's Disease
    Start date: 2006-01-01

Other drugs received by patient: Macrodantin; Sinemet; Mirapex; Neurontin; Pravachol; Glipizide; Atenolol; Metformin HCL; Isorbide; Diovan; Bethanechol; Tigan

Possible Apokyn side effects / adverse reactions in 70 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2007-01-23

Patient: 70 year old male weighing 86.2 kg (189.6 pounds)

Reactions: Blood Pressure Increased, Flushing, Dyspnoea, Chest Pain, Headache, Feeling Abnormal

Suspect drug(s):
Apokyn
    Dosage: 0.2 ml once sc
    Indication: Parkinson's Disease
    Start date: 2007-01-03
    End date: 2007-01-03

Apokyn
    Dosage: df sc
    Indication: Parkinson's Disease
    Start date: 2007-01-01

Other drugs received by patient: Carbidopa and Levodopa; Clonazepam; Neurontin; Aciphex; Mirapex; Comtan; Demerol; Valium; Talwin; Benadryl