Approved Drug Label (PDF)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined
…
Nausea
and Vomiting
Advise
patients they may experience nausea and/or vomiting, which may be severe,
and that treatment with oral trimethobenzamide 300 mg 3 times per day for 3
days prior to starting APOKYN injections has been used to help minimize
these symptoms. Alternatively, starting APOKYN at a lower dose and titrating
based on individual tolerance and treatment effect may be attempted. Advise
patients that APOKYN taken with trimethobenzamide may increase the risks for
somnolence, dizziness, and falls, and to consult their healthcare
provider before discontinuing trimethobenzamide [see Warnings and Precautions (5.2)].
…
PATIENT
INFORMATION
Additions and/or revisions underlined
…
What
are the possible side effects of APOKYN?
…
nausea and vomiting. Nausea
and vomiting, which may be severe, can happen with APOKYN. Your healthcare
provider may prescribe a medicine to help decrease nausea and vomiting. Follow
your healthcare providers instructions on how to take and when to stop this
medicine.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.8 Hemolytic Anemia
Newly added subsection:
Hemolytic anemia requiring hospitalization has been reported with
apomorphine treatment in the postmarketing setting. Many of the reported cases included
positive direct antiglobulin test (Coombs test), suggesting a potential
immune-mediated hemolysis. Severe anemia, angina, and dyspnea have occurred
with hemolytic anemia. Some patients were treated with high dose
glucocorticoids or blood transfusions. Hemolytic anemia can appear at any time after
apomorphine treatment. If a patient develops anemia while taking APOKYN,
consider a workup for hemolytic anemia. If hemolytic anemia occurs, consider
discontinuing APOKYN treatment.
6
Adverse Reactions
Addition of the
following to the bulleted line listing:
·
Hemolytic Anemia [see
Warnings and Precautions (5.8)
6.2 Postmarketing Experience
Newly added
subsection:
The
following adverse reactions have been identified during postapproval use of apomorphine.
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.
Hematologic and Lymphatic
Systems: hemolytic
anemia [see Warnings and Precautions (5.8)]
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Newly
added information:
Hemolytic
Anemia
Inform
patients and caregivers that hemolytic anemia may occur and to contact their healthcare
provider if they develop any signs or symptoms [see Warnings and Precautions (5.8)].
PATIENT INFORMATION
Newly
added section; please refer to label
Approved Drug Label (PDF)
5
Warnings and Precautions
5.12 Hypersensitivity
(new
subsection added)
Hypersensitivity/allergic
reactions characterized by urticaria, rash, pruritus, and/or various
manifestations of angioedema may occur because of APOKYN or because of its
sulfite excipient. APOKYN contains sodium metabisulfite, a sulfite that may
cause allergic-type reactions, including anaphylactic symptoms and
life-threatening or less severe asthmatic episodes in certain susceptible
people. The overall prevalence of sulfite sensitivity in the general population
is unknown and probably low. Sulfite sensitivity is seen more frequently in
asthmatic than in nonasthmatic people.
5.4 Syncope /Hypotension / Orthostatic Hypotension
(additions
underlined)
…
In
a study of healthy subjects, the hypotensive effect of APOKYN on
systolic and diastolic blood pressure was exacerbated by the concomitant
use of alcohol or sublingual nitroglycerin (0.4 mg). Patients should
avoid alcohol when using APOKYN. Patients taking APOKYN should lie down
before and after taking sublingual nitroglycerin. Other vasodilators and
antihypertensives may also increase the hypotensive effects of APOKYN. Monitor blood
pressure for hypotension and orthostatic hypotension in patients taking APOKYN
with concomitant antihypertensive medications or vasodilators.
6
Adverse Reactions
(additions
underlined)
The
following serious adverse reactions are discussed in more detail in the
Warnings and Precautions section of labeling:
Serious Adverse Reactions After Intravenous
Administration
Nausea
and Vomiting
Falling Asleep During Activities of Daily Living and
Somnolence
Syncope/Hypotension/Orthostatic
Hypotension
Falls
Hallucinations/Psychotic-Like
Behavior
Dyskinesias
Impulse Control/Compulsive Behaviors
Coronary
Events
QTc Prolongation and Potential for Proarrhythymic
Effects
Withdrawal-Emergent Hyperpyrexia and Confusion
Hypersensitivity
Fibrotic Complications
Priapism
7
Drug Interactions
7.2 Antihypertensive Medications and Vasodilators
(additions
underlined)
…Some of the
events may be related to the increased incidence of hypotension in patients
receiving concomitant antihypertensive medications or vasodilators.
Concomitant
administration of 0.4 mg sublingual nitroglycerin with APOKYN in healthy
subjects causes greater decreases in
blood pressure compared to APOKYN alone. When nitroglycerin and APOKYN were
concomitantly administered to healthy subjects, the mean largest decrease (the
mean of each subject’s largest drop in blood pressure measured within the
6-hour period following administration
of APOKYN) in supine systolic and diastolic blood pressure (measured over 6
hours) was 9.7 mm Hg and 9.3 mm Hg, respectively. The mean largest decrease in standing systolic and diastolic
blood pressure was 14.3 mm Hg and 13.5 mm Hg, respectively. Some individuals
experienced very large decreases in standing systolic and diastolic blood
pressure, up to a maximum decrease of 65 mm Hg and 43 mm Hg, respectively. In
comparison, the mean largest decrease in supine systolic and diastolic blood
pressure when APOKYN was administered alone was 6.1 mm Hg and 7.3 mm Hg,
respectively, and in standing systolic and diastolic blood pressure was 6.7 mm
Hg and 8.4 mm Hg, respectively.
Patients
taking APOKYN should lie down before and after taking sublingual nitroglycerin.
7.3 Alcohol
(new
subsection added)
Concomitant
administration of high dose (0.6 g/kg) or low dose (0.3 g/kg) ethanol with
APOKYN in healthy subjects causes greater decreases in blood pressure compared
to APOKYN alone.
When
high dose ethanol and APOKYN were concomitantly administered to healthy
subjects, the mean largest decrease (the mean of each subject’s largest drop in
blood pressure measured within the 6-hour period following administration of
APOKYN) for supine systolic and diastolic blood pressure was 9.1 mm Hg and 10.5
mm Hg, respectively. The mean largest
standing systolic and diastolic blood pressure decrease was 11.3 mm Hg and 12.6
mm Hg, respectively. In some individuals, the decrease was as high as 61 mm Hg
and 51 mm Hg, respectively, for standing systolic and diastolic blood pressure.
When
low dose ethanol and APOKYN were concomitantly administered, the mean largest
decrease in supine systolic and diastolic blood pressure was 10.2 mm Hg and 9.9
mm Hg, respectively. The mean largest decrease in standing systolic and
diastolic blood pressure was 8.4 mm Hg and 7.1 mm Hg, respectively.
In
comparison, the mean largest decrease in supine systolic and diastolic blood
pressure when APOKYN was administered alone was 6.1 mm Hg and 7.3 mm Hg,
respectively, and in standing systolic and diastolic blood pressure was 6.7 mm
Hg 8.4 mm Hg, respectively.
Patients
should avoid drinking alcohol after using APOKYN.
8
Use in Specific Populations
8.7 Hepatic Impairment
(addition
underlined)
Caution
should be exercised when administrating APOKYN to patients with mild and
moderate hepatic impairment because of the increased Cmax and AUC in these
patients. Closely monitor patients with mild and moderate hepatic impairment.
Studies of subjects with severe hepatic impairment have not been conducted.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(additions
underlined)
…
Hypotension
/ Orthostatic Hypotension
…Inform patients
that alcohol and nitroglycerin (and
possibly other vasodilators and antihypertensive medications) may potentiate
the hypotensive effect of APOKYN. Instruct
patients ideally to lie down before taking sublingual nitroglycerin and to
remain supine and avoid standing for at least 45 minutes after nitroglycerin.
Instruct patients taking APOKYN to avoid alcohol while using APOKYN and of the
increased hypotensive effects of APOKYN taken with nitroglycerin or by taking
APOKYN after alcohol ingestion.
…
PATIENT INFORMATION
(updates
made, please refer to label for more information)
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Nausea and Vomiting
(Additions and/or revisions are underlined)
The effect of
trimethobenzamide on reducing nausea and vomiting during treatment with APOKYN
was evaluated in a 12-week, placebo-controlled study in 194 patients. The study
suggests that trimethobenzamide reduces the incidence of nausea and vomiting
during the first 4 weeks of APOKYN treatment (incidence of nausea and vomiting
43% on trimethobenzamide vs. 59% on placebo). However, over the 12-week period,
compared with placebo, patients treated with trimethobenzamide had a greater
incidence of somnolence (19% for trimethobenzamide vs. 12% for placebo),
dizziness (14% for trimethobenzamide vs. 8% for placebo), and falls (8% for
trimethobenzamide vs. 1% for placebo). Therefore, the benefit of treatment with
trimethobenzamide must be balanced with the risk for those adverse events, and
treatment with trimethobenzamide should only be continued as long as necessary
to control nausea and vomiting, and generally no longer than two months.
8
Use in Specific Populations
8.1 Pregnancy
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion;
additions and/or revisions are
underlined)
Risk Summary
There are no
adequate data on the developmental risk associated with use of APOKYN in
pregnant women. In animal reproduction studies, apomorphine had adverse developmental
effects in rats (increased neonatal deaths) and rabbits (increased incidence of
malformation) when administered during pregnancy at clinically relevant doses.
These doses were also associated with maternal toxicity. In the U.S.
general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%,
respectively. The background risk of major birth defects and miscarriage for
the indicated population is unknown.
Data
Animal Data
adverse
developmental effects were observed when apomorphine (0.3, 1, or 3
mg/kg/day) was administered by subcutaneous injection to pregnant rats
throughout organogenesis; the highest dose tested is 1.5 times the maximum
recommended human dose (MRHD) of 20 mg/day on a mg/m squared basis.
Administration of apomorphine (0.3, 1, or 3 mg/kg/day) by subcutaneous
injection to pregnant rabbits throughout organogenesis resulted in an increased
incidence of malformations of the heart and/or great vessels at the mid and
high doses; maternal toxicity was observed at the highest dose tested. The no-
effect dose for adverse developmental effects is less than the MRHD on a mg/m
squared basis.
Apomorphine (0.3, 1,
or 3 mg/kg/day), administered by subcutaneous injection to females
throughout gestation and lactation, resulted in increased offspring mortality
at the highest dose tested, which was associated with maternal toxicity…
8.2 Lactation
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion;
additions and/or revisions are
underlined)
Risk Summary
There are no
data on the presence of apomorphine in human milk, the effects of apomorphine
on the breastfed infant, or the effects of apomorphine on milk production. The
developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for APOKYN and any potential adverse effects on
the breastfed infant from APOKYN or from the underlying maternal condition.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions are underlined)
Administration
with the APOKYN Pen
Instruct patients
and caregivers to read the “APOKYN Pen Instructions for Use” and Patient
Information…
Nausea and
Vomiting
…Advise patients
that APOKYN taken with trimethobenzamide may increase the risks for somnolence,
dizziness, and falls. Inform
patients that their healthcare provider will tell them when
trimethobenzamide can be discontinued.
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