amgevita Uses, Dosage, Side Effects, Precautions & Warnings

what is amgevita medication used for and indication

Generic drug of the Therapeutic class: Immunology Medicines

Active ingredients: Adalimumab

what is amgevita medication used for and indication?

Rheumatoid arthritis

AMGEVITA in combination with methotrexate is indicated for:

the treatment of moderately to severely active rheumatoid arthritis in adults when the response to DMARDs, including methotrexate, is inadequate.
the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
AMGEVITA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
AMGEVITA slows the progression of structural damage to the joints measured by radiography and improves functional capacity when administered in combination with methotrexate.

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis

AMGEVITA in combination with methotrexate is indicated for the treatment of progressive polyarticular juvenile idiopathic arthritis in patients from 2 years of age in case of insufficient response to one or more DMARDs. AMGEVITA can be administered as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is unsuitable (for efficacy as monotherapy, see section Pharmacodynamic properties). Adalimumab has not been studied in patients less than 2 years of age.

Enthesitis-related arthritis

AMGEVITA is indicated for the treatment of active arthritis associated with enthesitis in patients from 6 years of age with insufficient response or intolerance to conventional therapy (see section 5.1).

Axial spondyloarthritis

Ankylosing spondylitis (AS)

AMGEVITA is indicated for the treatment of severe and active ankylosing spondylitis in adults who have had an inadequate response to conventional therapy.

Axial spondyloarthritis without radiographic evidence of AS

AMGEVITA is indicated for the treatment of severe axial spondyloarthritis without radiographic evidence of AS, but with objective evidence of inflammation on MRI and / or elevated CRP in adults who have had an inadequate response or intolerance to anti -nonsteroidal inflammatory drugs.

Psoriatic arthritis

AMGEVITA is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying therapy has been inadequate. AMGEVITA slows the progression of peripheral joint structural damage as measured by radiography, in patients with symmetrical polyarticular forms of the disease (see section 5.1) and improves functional capacity.

Psoriasis

AMGEVITA is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who require systemic therapy.

Plaque psoriasis in children and adolescents

AMGEVITA is indicated for the treatment of severe chronic plaque psoriasis in children from 4 years of age and adolescents with insufficient response to topical treatment and light therapy or when these treatments are inappropriate.

Hidradenitis suppurativa (HS)

AMGEVITA is indicated for the treatment of active, moderate to severe hidradenitis suppurativa (Verneuil’s disease) in adults and adolescents from 12 years of age in case of insufficient response to conventional systemic therapy for HS (see section Properties). Pharmacodynamics and Pharmacokinetic Properties).

Crohn’s disease

AMGEVITA is indicated for the treatment of moderate to severe active Crohn’s disease in adult patients who have not responded despite appropriate and well-managed treatment with a corticosteroid and / or immunosuppressant; or in which these treatments are contraindicated or poorly tolerated.

Crohn’s disease in children and adolescents

AMGEVITA is indicated for the treatment of moderate to severe active Crohn’s disease in children and adolescents from 6 years of age who have not responded to conventional therapy including first-line nutritional therapy and a corticosteroid and / or an immunomodulator, or in which these treatments are poorly tolerated or contraindicated.

Ulcerative colitis

AMGEVITA is indicated for the treatment of active, moderate to severe ulcerative colitis in adult patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or in whom these treatments are contraindicated or poorly tolerated.

Uveitis

AMGEVITA is indicated for the treatment of non-infectious, intermediate, posterior uveitis and panuveitis in adult patients who have had an insufficient response to corticosteroid therapy, in patients requiring corticosteroid sparing, or in whom corticosteroid therapy is inappropriate.

Uveitis in children and adolescents

AMGEVITA is indicated for the treatment of chronic non-infectious anterior uveitis in children and adolescents from 2 years of age with insufficient response or intolerance to conventional treatment or for whom conventional treatment is inappropriate.

amgevita Dosage

The
treatment AMGEVITA should be initiated and supervised by a physician
qualified specialist in the diagnosis and treatment of
pathologies in which AMGEVITA indicated. It is recommended that
ophthalmologists consult an appropriate specialist before
initiating treatment with AMGEVITA (see section 4.4). A special surveillance card will be given to patients treated with AMGEVITA.

After
proper training in the injection technique, patients can
self-inject AMGEVITA, if their doctor considers it possible, under the
guise of appropriate medical supervision.

While taking
AMGEVITA, other concomitant therapies (such
as corticosteroids and / or immunomodulators) should be optimized.

Dosage

Rheumatoid arthritis

In
adult patients with rheumatoid arthritis, the
recommended dose of AMGEVITA is a single dose of 40 mg adalimumab
administered every two weeks, subcutaneously. Administration of methotrexate should be continued during treatment with AMGEVITA.
The
glucocorticoids, salicylates, nonsteroidal anti-inflammatory
drugs or analgesics may be continued during
treatment with AMGEVITA. As regards the combination with other
anti-rheumatic drugs other than methotrexate (see
sections Warnings and precautions for use and Pharmacodynamic properties).
As
monotherapy, some patients with decreased
response to AMGEVITA 40 mg every other week may
benefit from an increase in dosage to adalimumab 40 mg
every week or 80 mg every other week. .
The
available data for adalimumab suggest that
clinical response is usually achieved within 12 weeks of treatment. The
Continued therapy should be reconsidered in patients who have
not responded within this time.

Interruption of treatment

It
may be necessary to stop treatment, eg before
surgery or in patients with severe infection.
The
re-introduction of AMGEVITA after a period of 70 days or more should
lead to clinical response of the same magnitude and a profile
similar to that observed tolerance before treatment interruption.

Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS, and psoriatic arthritis

The
recommended dosage of AMGEVITA for patients with
ankylosing spondylitis, axial spondyloarthritis without
radiographic evidence of AS and for patients with
psoriatic arthritis is 40 mg adalimumab as a single dose every two
weeks, by injection.

subcutaneous.

The
available data suggest that the clinical response is
usually achieved within 12 weeks of treatment. Continuation of
treatment should be reconsidered in a patient who has not responded
within these time limits.

Psoriasis

The
recommended dose of AMGEVITA to start treatment in
adults is 80 mg subcutaneously. The dosage will continue
one week later with 40 mg subcutaneously every other week.
The
continuing treatment beyond 16 weeks should be carefully
reconsidered in a patient not responding within this time.
Beyond
16 weeks, in case of insufficient response to AMGEVITA 40 mg every
other week, patients may benefit from an increase
in dosage to 40 mg every week or 80 mg every other
week. The benefits and risks of continuous treatment of 40 mg
weekly or 80 mg every two weeks should be
carefully reconsidered in a patient with
insufficient response after increasing the dose (see section 5.1).
If sufficient response is obtained with 40 mg every week or
80 mg every two weeks, the dosage may then be reduced
to 40 mg every 2 weeks.

Hidradenitis suppurativa

The
recommended dosage regimen of AMGEVITA in adult
patients with hidradenitis suppurativa (HS) is an initial dose of 160
mg on Day 1 (given as 4 injections of 40 mg in one
day or 2 injections of 40 mg mg per day for two
consecutive days ), followed by a dose of 80 mg two weeks after on Day 15
(given as 2 injections of 40 mg over one day). Two
weeks later (Day 29), continue with a dose of 40 mg every
week or 80 mg every two weeks (given as
two 40 mg injections per day). If necessary, antibiotics
can be continued during treatment with AMGEVITA. During
during treatment with AMGEVITA, it is recommended that the patient cleanse
his lesions daily with a topical antiseptic.
The
continuing treatment beyond 12 weeks should be carefully
reconsidered in patients showing no improvement during
this period.
If
treatment is interrupted, AMGEVITA 40 mg every week or 80
mg every other week may be reintroduced (see section 5.1).
The benefit and risk of continued long-term treatment should be assessed regularly.

Crohn’s disease

In
adult patients with moderate to
severe active Crohn’s disease , the recommended induction regimen of AMGEVITA is
80 mg at week 0, followed by 40 mg at week 2. If it is
necessary to obtain faster response to treatment, schedule
160 mg at week 0 (given as 4 injections of 40 mg
per day or 2 injections of 40 mg per day for two
consecutive days ), 80 mg at week 2 (given in the form of two
injections of 40 mg per day), can be used knowing that the risk
of adverse events is then higher during this
induction phase .
Following
induction therapy, the recommended dose is 40
mg administered every two weeks by subcutaneous injection. If
a patient has stopped treatment with AMGEVITA and the signs and
symptoms of disease return, AMGEVITA may be
re-administered. Experience with re-administration of treatment
beyond 8 weeks after the previous dose is limited.
During
maintenance treatment, corticosteroids may be
gradually reduced in accordance with
clinical practice recommendations .
Some
patients in whom a decreased response to treatment with
AMGEVITA 40 mg every other week is observed may benefit
from an increase in the dose to AMGEVITA 40 mg every
week or 80 mg every other week.
Some
patients who have not responded to treatment at week 4 may
continue maintenance therapy until week 12.
Continuation of treatment should be carefully reconsidered in a
patient who has not responded within this time.

Ulcerative colitis

In
adult patients with moderate to
severe ulcerative colitis , the recommended induction regimen of AMGEVITA is
160 mg at week 0 (given as 4 injections of 40 mg
per day or 2 injections of 40 mg per day. day for two
consecutive days ) and 80 mg at week 2 (given as two
40 mg injections per day). After induction therapy, the
recommended dose is 40 mg every two weeks, by
subcutaneous injection.
During
maintenance treatment, corticosteroids may be
gradually reduced in accordance with
clinical practice recommendations .
Some
patients in whom a decreased response to treatment with
AMGEVITA 40 mg every two weeks is observed may
benefit from an increase in the dose to AMGEVITA 40 mg every
week or 80 mg every two weeks.
The
clinical response is usually achieved within 2 to 8 weeks of
treatment. Treatment with AMGEVITA should not be continued in
patients who have not responded within this time frame .

Uveitis

In
adult patients with uveitis, the recommended dose
of AMGEVITA is an initial dose of 80 mg followed by a dose of 40 mg
every two weeks starting one week after
the first dose. There
is limited experience with initiating treatment with adalimumab monotherapy. The
treatment can be started AMGEVITA in combination with
corticosteroids and / or other immunomodulatory therapies not
organic. The combined corticosteroid dose may be gradually
reduced in accordance with clinical practice, starting two weeks
after initiation of treatment with AMGEVITA.
An
annual reassessment of the benefits and risks associated
with long-term continuous therapy is recommended (see section 5.1).

Special populations

Older subjects

No dosage adjustment is necessary.

Renal and / or hepatic impairment

Adalimumab has not been studied in these patient populations. It is not possible to recommend dosages.

Pediatric population

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis from 2 years old

The
recommended dosage of AMGEVITA for patients with
polyarticular juvenile idiopathic arthritis from the age of 2 years depends
on body weight (Table 1). AMGEVITA is administered every two
weeks as a subcutaneous injection.

Table 1. Amgevita dosage in patients with polyarticular juvenile idiopathic arthritis

The
clinical response is usually achieved within 12 weeks of
treatment. Continuation of treatment should be carefully
reconsidered in a patient who has not responded within this time frame.
There is no relevant use of adalimumab in patients under 2 years of age in this indication.

Enthesitis-related arthritis

The
recommended dosage of AMGEVITA for patients with
enthesitis-related arthritis from the age of 6 years depends on body weight
(Table 2). AMGEVITA is administered every two weeks
as a subcutaneous injection.

Table 2. Dosage of AMGEVITA in Patients with Enthesitis-Related Arthritis

Adalimumab has not been studied in patients less than 6 years of age with arthritis related to enthesitis.

Plaque psoriasis in children and adolescents

The
recommended dosage of AMGEVITA for patients with
plaque psoriasis aged 4 to 17 years depends on body weight
(Table 3). AMGEVITA is administered by subcutaneous injection.

Table 3. Amgevita dosage in children and adolescents with plaque psoriasis

The
continuing treatment beyond 16 weeks should be carefully
reconsidered in a patient not responding within this time.
If
retreatment with AMGEVITA is indicated, the above recommendations
for dosage and duration of treatment should be followed.
The
safety of adalimumab in children and adolescents with
plaque psoriasis has been evaluated over a mean duration of 13 months.
There is no relevant use of AMGEVITA in children aged less than 4 years in this indication.

Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg)

There
is no clinical trial conducted with adalimumab in
adolescents with HS. The dosage of AMGEVITA in these patients
was determined from pharmacokinetic modeling and
simulation.
The
recommended dose of AMGEVITA is 80 mg at week 0 followed by
40 mg every two weeks from week 1 by subcutaneous injection.
In
adolescents with insufficient response to AMGEVITA 40 mg every
two weeks, an increase in the dosage to 40 mg every
week or 80 mg every other week may be considered.
If
necessary, antibiotics can be continued during
treatment with AMGEVITA. During treatment with AMGEVITA, it is
recommended that the patient cleanse his lesions daily with a
topical antiseptic.
The
continuing treatment beyond 12 weeks should be carefully
reconsidered in patients showing no improvement during
this period.
If treatment is interrupted, AMGEVITA could be reintroduced if necessary.
The
benefit and risk of continued long-term treatment should
be assessed regularly (see data in
adults under Pharmacodynamic properties).
There is no relevant use of AMGEVITA in children aged less than 12 years in this indication.

Crohn’s disease in children and adolescents

The
recommended dosage of AMGEVITA for patients with
Crohn’s disease aged 6 to 17 years depends on body weight (Table
4). AMGEVITA is administered by subcutaneous injection.

Table 4. Dosage of AMGEVITA in Children and Adolescents with Crohn’s Disease

40 mg in week 0 and 20 mg in week 2
80 mg in week 0 and 40 mg in week 2
80 mg in week 0 and 40 mg in week 2
160 mg in week 0 and 80 mg in week 2

The
patients with an inadequate response to treatment is observed
may benefit from increasing the dosage:

<40 kg: 20 mg every week
≥ 40 kg: 40 mg every week or 80 mg every two weeks
Continuation of treatment should be carefully reconsidered in a patient who has not responded by week 12.
- There is no relevant use of adalimumab in children aged less than 6 years in this indication.

Uveitis in children and adolescents

The
recommended dose of AMGEVITA for children and adolescents
with uveitis from the age of 2 years depends on body weight
(Table 5). AMGEVITA is administered by subcutaneous injection.
In
uveitis in children and adolescents, no clinical trials have been
conducted with AMGEVITA without concomitant treatment with methotrexate.
Table 5. Dosage of AMGEVITA in Children and Adolescents with Uveitis
When initiating treatment with AMGEVITA, a loading dose of 40 mg for patients <
30 kg or 80 mg for patients ≥ 30 kg may be administered one
week before the start of maintenance therapy. No
clinical data are available from the use of a loading dose of
AMGEVITA in children less than 6 years of age .
There is no relevant use of AMGEVITA in children aged less than 2 years in this indication.
An
annual reassessment of the benefits and risks associated
with long-term continuous therapy is recommended.

Pediatric ulcerative colitis

The
safety and efficacy of adalimumab in children 4 to 17 years of age
have not been established. No data is available. There is no relevant
use of adalimumab in children aged less than
4 years in this indication.

Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis

There
is no relevant use of adalimumab in the population
pediatric in indications, ankylosing spondylitis and
psoriatic arthritis.

Administration mode

AMGEVITA is administered by subcutaneous injection. Full instructions for use are provided in the package leaflet.

Contraindications

Hypersensitivity adalimumab
Hamster protein hypersensitivity
Active tuberculosis
Severe infection
Stage III or IV heart failure
Pregnancy
Lack of effective female contraception

Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.

Active tuberculosis or other severe infections such as sepsis and opportunistic infections.

Moderate to severe heart failure (NYHA classes III / IV) .

amgevita Side Effects

Adalimumab has been studied in 9,506 patients in pivotal,
open- label, controlled trials of 60 months and longer duration. These trials included
patients with recent or old rheumatoid arthritis,
juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) or patients with axial spondyloarthritis (ankylosing spondylitis and
axial spondyloarthritis without radiographic evidence of AS ),
psoriatic arthritis, Crohn’s disease, ulcerative
colitis, psoriasis and hidradenitis suppurativa and uveitis. The
pivotal controlled studies involved 6,089 patients who received
adalimumab and 3,801 patients who received placebo or an
active comparator during the controlled phase.
The
percentage of patients who discontinued treatment due
to adverse reactions during the double-blind, controlled phase
of the pivotal studies was 5.9% in patients treated with
adalimumab and 5.4% in patients of the control group.
The
most frequently reported side effects are infections
(such as nasopharyngitis, upper
respiratory tract infections and sinusitis),
injection site reactions (erythema, itching, bleeding, pain or
swelling), headache and musculoskeletal pain.
Some
serious side effects have been reported with adalimumab. The
TNF antagonists, such qu’AMGEVITA affect the immune system
and their use may affect the defenses of the
body against infections and cancer.
Life-
threatening and fatal
infections (including sepsis, opportunistic infections and tuberculosis),
hepatitis B reactivations and various cancers (including leukemia, lymphoma and
hepatosplenic T-cell lymphoma) have also been reported
with use of adalimumab.
Severe
haematological, neurological and autoimmune effects have
also been reported. This includes rare cases of pancytopenia,
bone marrow anemia , cases of central and peripheral demyelination, and
cases of lupus, lupus-related events, and
Stevens-Johnson syndrome .

Pediatric population

In
general, the frequency and type of adverse events seen
in children and adolescents were comparable to those seen in
adult patients.

List of side effects

The
list of undesirable effects is based on clinical studies and
post-marketing experience and is presented by
system organ and frequency in Table 6 below: very
common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥
1 / 1,000 to <1/100); rare (≥ 1 / 10,000 to <1 / 1,000) and
not known (cannot be estimated from the
available data ).
Within each frequency grouping,
undesirable effects are presented in order of decreasing seriousness. The
highest frequency observed in the various indications was
included.
The presence of an asterisk (*) in the column “Class of
organ systems ”indicates that more information is
available under the sections Contraindications, Warnings and precautions for use and Undesirable effects.

Table 6. Adverse reactions

* Further information is available under the sections Contraindications, Warnings and precautions for use and Adverse reactions.

** including open label extension studies.

1) including data from spontaneous notifications

Hidradenitis suppurativa (HS)

The
safety profile in patients with HS treated with
weekly adalimumab is consistent with the
known safety profile of adalimumab.

Uveitis

The
safety profile in patients with uveitis treated with
adalimumab every two weeks is consistent with the
known safety profile of adalimumab.

Description of selected adverse reactions

Injection site reactions

In
pivotal controlled trials in adults and children, 12.9% of
patients treated with adalimumab experienced
injection site reactions (erythema and / or pruritus, bleeding, pain or swelling)
versus 7 , 2% of patients receiving placebo or active comparator.
Injection site reactions generally did not require
stopping the drug.

Infections

In the pivotal controlled trials in adults and children, the frequency of infections was 1.51
per patient-year in the adalimumab group and 1.46 per
patient-year in the placebo group and the control group. . The
infections mainly consisted of nasopharyngitis,
upper respiratory tract infections and sinusitis. Most
patients continued with adalimumab after the infection cleared.
The incidence
of serious infections was 0.04 per patient-year in the
adalimumab group and 0.03 per patient-year in the placebo group and the
control group.
In
open-label, controlled studies with adalimumab in
adults and in the pediatric population, serious infections (
including fatal infections, which have rarely occurred)
have been reported including reports of tuberculosis. (including
miliary and extrapulmonary localizations) and
invasive opportunistic infections (eg disseminated
histoplasmosis or extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis,
pneumocystosis, candidiasis, aspergillosis and listeriosis). Most
cases of tuberculosis have occurred within the first eight months after
starting treatment and may reflect reactivation of
latent disease.

Malignant tumors and lymphoproliferative disorders

No
cases of cancer were observed in 249 pediatric patients
representing an exposure of 655.6 patient-years in studies of
adalimumab in patients with juvenile
idiopathic arthritis (polyarticular juvenile idiopathic
arthritis and arthritis related to enthesitis). In addition, no cases of cancer were
observed in 192 pediatric patients representing an exposure of
498.1 patient-years in studies with adalimumab in
pediatric Crohn’s disease. No cases of cancer were observed in 77
pediatric patients corresponding to an exposure of 80
patient-years in a study with adalimumab in psoriasis in
chronic pediatric plaques. No cases of cancer were observed in
60 pediatric patients representing an exposure of 58.4
patient-years in a study with adalimumab in
pediatric uveitis .
During
the controlled periods of pivotal adult clinical trials with
adalimumab lasting at least 12 weeks in patients
with moderately to severely active rheumatoid arthritis,
ankylosing spondylitis, axial spondyloarthritis without
radiographic evidence of AS , psoriatic arthritis, psoriasis,
hidradenitis suppurativa, Crohn’s disease, ulcerative
colitis and uveitis, a rate (95% confidence interval) of
cancers other than lymphomas or non-melanoma skin cancers,
6.8 (4.4 – 10.5) per 1,000 patient-years among the 5,291 patients
treated with adalimumab, was observed versus a rate of 6.3
(3.4 – 11.8) per 1000 patient-years among the 3444 patients in
the control group (the mean duration of treatment was 4.0 months for
patients treated with adalimumab and 3.8 months for patients
in the control group). The rate (95% confidence interval) of
non-melanoma skin cancer was 8.8 (6.0 – 13.0) per 1000
patient-years for patients treated with adalimumab and 3.2
(1.3 – 7.6) per 1000 patient years among patients in the
control group . In these skin cancers, squamous
cell carcinomas occurred at rates of 2.7 (1.4 – 5.4) per 1000
patient years in patients treated with adalimumab and 0.6 (0 , 1 –
4.5) per 1000 patient-years in patients in the control group
(95% confidence interval). The rate (95% confidence interval)
of lymphoma was 0.7 (0.2 – 2.7) per 1000 patient years in
patients treated with adalimumab and 0.6 (0.1 – 4, 5) per 1000 patient-years in patients in the control group.
By
combining the controlled periods of these trials
with the completed or ongoing open-label extension trials of adalimumab with an
average duration of approximately 3.3 years including 6,427 patients and more than 26,439
patient-years of treatment, the The observed rate of cancers, other than
lymphomas and non-melanoma skin cancers is approximately 8.5 per
1,000 patient-years. The observed rate of non-
melanoma skin cancer is approximately 9.6 per 1,000 patient-years and the
observed rate of lymphomas is approximately 1.3 per 1,000 patient-years.
In
post-marketing from January 2003 to December 2010, primarily in
patients with rheumatoid arthritis, the reported rate of
cancer is approximately 2.7 per 1,000 patient-years of
treatment. The reported rates for
non-melanoma skin cancer and lymphoma are approximately 0.2 and 0.3
per 1000 patient-years of treatment, respectively (see section 4.4).
In
post-marketing surveillance, rare cases of
hepatosplenic T-cell lymphoma have been reported in patients
treated with adalimumab.

Autoantibodies

Repeated
autoantibody tests were performed on
serum samples from patients in the IV trials in rheumatoid
arthritis. In these trials,
initially negative antinuclear antibody titers were positive at week 24 in 11.9% of
patients treated with adalimumab and 8.1% of patients on placebo and
comparator. Two of the 3,441 patients treated with adalimumab in
all rheumatoid arthritis and
psoriatic arthritis studies exhibited clinical signs suggestive of a
new onset lupus-like syndrome . The condition of the patients
improved after stopping treatment. No patient presented
lupus nephritis or central nervous symptoms.

Hepato-biliary events

In
phase III controlled clinical trials of adalimumab in
rheumatoid arthritis and psoriatic arthritis with a
control period of 4 to 104 weeks, elevations of ALT ≥ 3 x N occurred in 3.7% of patients treated with adalimumab and in 1.6% of patients in the control group.
In
phase III controlled clinical trials of adalimumab in
patients with juvenile idiopathic polyarticular arthritis aged
4 to 17 years and patients with enthesitis-related arthritis
aged 6 to 17 years, elevations of ALT ≥ 3 x N occurred in
6.1% of patients treated with adalimumab and in 1.3% of patients
in the control group. Most of the elevations in ALT have occurred
with concomitant use of methotrexate. No
elevation of ALT ≥ 3 x N occurred in the phase
III trial of adalimumab in patients with
polyarticular juvenile idiopathic arthritis aged 2 to <4 years.
In
phase III controlled clinical trials of adalimumab in
patients with Crohn’s disease and ulcerative colitis
with a control period of 4 to 52 weeks, elevations of ALT
≥ 3 x N occurred in 0.9% of patients treated with adalimumab
and in 0.9% of patients in the control group.
In
the phase III clinical trial of adalimumab in children and
adolescents with Crohn’s disease that evaluated the efficacy and
safety profile of two
weight-based maintenance regimens following adjusted induction therapy by weight
up to 52 weeks of treatment, elevations of ALT ≥ 3 x N
occurred in 2.6% of patients (5/192), of whom 4 were
treated in combination with immunosuppressants at the start of the study .
In
phase III controlled clinical trials of adalimumab in
plaque psoriasis with a control period of 12 to 24 weeks,
elevations of ALT ≥ 3 x N occurred in 1.8% of patients
treated with adalimumab and in 1.8% of patients in the control group.
It
has not been observed ALT elevations ≥ 3 x N in the study
phase III adalimumab in pediatric patients with
plaque psoriasis.
In
controlled clinical trials of adalimumab (starting doses of 160 mg
at Week 0 and 80 mg at Week 2 followed by 40 mg each week
from week 4), in patients with
HS with a period of control from 12 to 16 weeks,
elevations of ALT ≥ 3 x N occurred in 0.3% of patients
treated with adalimumab and 0.6% of patients in the control group.
In
controlled clinical trials of adalimumab (starting dose 80 mg at
week 0 followed by 40 mg every two weeks from
week 1) in adult patients with uveitis for
up to 80 weeks , with a median duration of exposure of
166.5 days and 105.0 days for patients treated with
adalimumab and patients in the control group, respectively, elevations of ALT
≥ 3 x N occurred in 2.4% of patients treated with adalimumab
and 2.4% of patients in the control group.
In
clinical trials across all indications, patients with
elevated ALT were asymptomatic and in most cases the
elevations were transient and reversible upon continued
treatment. However, during post-marketing surveillance,
hepatic insufficiency as well as less
severe hepatic disorders , which may precede hepatic insufficiency, such as
hepatitis including autoimmune hepatitis, have been reported in
patients receiving l.adalimumab.

Concomitant administration of azathioprine / 6-mercaptopurine

In
studies in Crohn’s disease in adults, a
higher incidence of tumors and serious infections was observed with
the combination of adalimumab and azathioprine / 6-mercaptopurine
compared to adalimumab used alone.

Reporting of suspected adverse reactions

The
declaration of suspected adverse reactions after authorization of the
drug is important. It allows continuous monitoring of the
benefit / risk ratio of the medicinal product. Healthcare professionals
report any suspected adverse reactions via the national reporting system – see Annex V.

amgevita Interactions

Adalimumab has been studied in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and psoriatic arthritis taking adalimumab as monotherapy and in those taking methotrexate concomitantly. Antibody formation was lower when adalimumab was co-administered with methotrexate compared to its use as monotherapy. Administration of adalimumab without methotrexate resulted in increased antibody formation, increased clearance and reduced efficacy of adalimumab .
The combination of AMGEVITA and anakinra is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNFa”).
The combination of AMGEVITA and abatacept is not recommended (see section Warnings and precautions for use “Simultaneous administration of biological DMARDs and anti-TNFa”).

In the absence of a compatibility study, this medicinal product must not be mixed with other medicinal products.

Drive and use machines

Amgevita may have a minor effect on the ability to drive and use machines. Dizziness and visual disturbances may occur after administration of Amgevita ( see Undesirable effects ).

Warnings and Precautions

Traceability

In order
to improve the traceability of biological medicinal products, the name
of the medicinal product (see section 1) and the batch number of the
administered product must be clearly recorded.

Infections

The
patients receiving TNF-antagonists are more susceptible to
serious infections. Impaired lung function can increase the
risk of developing infections. Patients should therefore be
carefully monitored for infections (including
tuberculosis) before, during and after treatment with AMGEVITA. As the
duration of elimination of adalimumab may be up to four months,
monitoring should be continued throughout this period.
The
treatment AMGEVITA should not be initiated in patients with
active infections, including chronic infections or
localized, are not controlled. In patients who have been exposed
to tuberculosis or who have traveled to areas at high risk for
tuberculosis or endemic mycoses, for example histoplasmosis,
coccidioidomycosis or blastomycosis, the risks and benefits of
treatment with AMGEVITA should be considered before
initiation. treatment (see Opportunistic infections).
The
Patients who develop a new infection during
treatment with AMGEVITA must be monitored
carefully and complete diagnostic workup should be practiced.
If
a serious new infection or sepsis
develops, administration of AMGEVITA should be discontinued and
appropriate antimicrobial or antifungal therapy should be started until
the infection is controlled.
Caution should be exercised by the physician before using AMGEVITA in patients with a
history of recurrent infection or with
underlying conditions which may predispose them to infections, including
concomitant treatment with immunosuppressive drugs.

Serious infections

Of
serious infections, including sepsis due to infections
bacterial, mycobacterial, invasive fungal, parasitic,
viral, or other opportunistic infections such as listeriosis,
legionellosis and pneumocystis have been reported in patients
treated with adalimumab.
The
other serious infections seen in clinical trials include
pneumonia, pyelonephritis, septic arthritis and septicemia. There have been reports
of infections requiring hospitalization or with fatal outcome.

Tuberculosis

Of
TB cases, including cases of TB reactivation
and primary infection tuberculosis have been reported for patients
receiving adalimumab. Cases of pulmonary and
extra-pulmonary (i.e. disseminated) tuberculosis have been reported.
Before
initiating treatment with AMGEVITA, all patients should
be tested for active or non-active (“
latent”) tuberculosis infection . This assessment should include a detailed medical evaluation
in patients with a history of tuberculosis or
possible previous exposure to patients with active tuberculosis and / or
current or past immunosuppressive therapy. Appropriate
screening tests (eg tuberculin skin test and
chest x-ray) should be performed in all patients
(according to local recommendations). It is advisable to note
the performance and the results of these tests in the
patient monitoring. Prescribers are reminded that
the tuberculin skin test can give false negatives, especially in
seriously ill or immunosuppressed patients.
If active tuberculosis is diagnosed, treatment with AMGEVITA should not be initiated.
In
all the situations described below,
the benefit / risk ratio of the treatment should be assessed very carefully.
In
case of suspicion of latent tuberculosis, consulting a
specialist, qualified in the treatment of tuberculosis
should be considered.
In
case of diagnosis of latent tuberculosis, prophylactic
tuberculosis appropriate and in accordance with local recommendations
must be implemented before the start of treatment with AMGEVITA.
A
TB prophylaxis should also be considered before
introducing AMGEVITA in patients with factors
multiple risk or tuberculosis despite a significant test
screening for tuberculosis negative and in patients with
a history of latent or active tuberculosis in that the administration
of an appropriate anti-tuberculosis treatment cannot be confirmed.
The
case of reactivation of tuberculosis despite treatment
prophylactic occurred in patients treated with
adalimumab. Some patients who had been successfully treated
for active tuberculosis developed the disease again during
treatment with adalimumab.
The
patients should be advised that they will need their doctor
in case of occurrence of symptoms suggestive signs or infection
tuberculosis (eg persistent cough, wasting / loss of
weight, low grade fever, listlessness), during or after treatment AMGEVITA.

Other opportunistic infections

Of
opportunistic infections, including invasive fungal infections,
have been observed in patients treated with adalimumab. These
infections were not always detected in patients receiving
TNF antagonists, resulting in delayed initiation of
appropriate therapy, sometimes with fatal outcome.
In
patients who present with signs and symptoms such as fever,
malaise, weight loss, sweating, cough, dyspnea and / or
pulmonary infiltrates or other serious systemic disease with or without
concomitant shock , an invasive fungal infection should be suspected; in
this case, the administration
of AMGEVITA should be stopped immediately . Diagnosis and
initiation of empiric antifungal therapy in these patients should be made in
consultation with a physician experienced in the management of
patients with invasive fungal infections.

Reactivation of hepatitis B

A
reactivation of hepatitis B occurred in patients who received
a TNF antagonist including adalimumab and who were carriers
chronic of this virus (that is to say surface antigen positive – Ag
positive HBs) . Some cases have had a fatal outcome. Patients
should be screened for HBV infection before
initiating treatment with AMGEVITA. For patients who
test positive for hepatitis B, it is
recommended to consult a doctor specializing in the treatment of
hepatitis B.
In
HBV carriers who require treatment with AMGEVITA,
careful monitoring of signs and symptoms of active
HBV infection should be observed throughout treatment and for several months after
discontinuation. There are insufficient data available regarding
the treatment of patients with HBV treated with antiviral drugs to
prevent HBV reactivation and treated with a TNF antagonist.
In patients who develop HBV reactivation, AMGEVITA
should be discontinued and effective antiviral therapy and
appropriate additional therapy should be initiated.

Neurological events

The
TNF blockers, including adalimumab, have been associated in rare
circumstances the onset or exacerbation of symptoms
clinical and / or radiographic evidence of demyelinating disease of the
central nervous system including multiple sclerosis,
Optic neuritis and peripheral demyelinating disease, including
Guillain-Barré syndrome.
Prescribers are advised with caution before treating patients with pre-existing or recently-occurring
central or peripheral nervous system demyelinating disease with AMGEVITA ; Discontinuation of
treatment with AMGEVITA should be considered in the event of any
of these troubles. The association between intermediate uveitis and
demyelinating diseases of the central nervous system is known.
Aneurological assessment should be performed in patients with
non-infectious intermediate uveitis before initiating
treatment with AMGEVITA, and repeated regularly during
treatment to look for any system demyelinating disease of
preexisting or progressive CNS.

Allergic reactions

In
clinical trials, serious allergic reactions associated
with adalimumab were rarely reported and
non-serious allergic reactions associated with adalimumab were uncommon. Cases of
severe allergic reactions, including anaphylactic reactions
have been reported after administration of adalimumab. If
an anaphylactic or other
severe allergic reaction occurs, administration of AMGEVITA should be
stopped immediately and appropriate treatment initiated.

Dry natural rubber

The
needle cap of the pre-filled pen contains
dry natural rubber (a derivative of latex), which may cause
allergic reactions .

Immunosuppression

In
a study of 64 patients with rheumatoid
arthritis treated with adalimumab, there was no evidence
of delayed-type hypersensitivity depression,
decreased immunoglobulin levels. or a change in the
count of effector T and B lymphocytes, NK lymphocytes,
monocytes / macrophages and neutrophilic granulocytes.

Malignant tumors and lymphoproliferative disorders

In
the controlled part of the adalimumab clinical trials with anti-TNF drugs,
more cases of cancer including lymphomas were observed in
patients treated with an anti-TNF agent than in patients in the
control group . However, the incidence has been rare. During
post-marketing surveillance, cases of leukemia have been reported in
patients treated with anti-TNF. In addition, there is a background of
increased risk of lymphoma and leukemia in patients with
old, inflammatory and highly
active rheumatoid arthritis , which complicates the estimation of risk. In the current state of
knowledge, the possibility of a risk of developing lymphomas,
leukemia or other malignant diseases in patients treated
with anti-TNF cannot be excluded.
Of
malignancies, some fatal, have been reported
postmarketing in children, adolescents and
young adults (up to age 22 years) treated with TNF antagonists
(initiation of therapy before age 18), including
adalimumab. About half of these cases were lymphomas. The
other cases corresponded to other types of malignant tumors among
which rare cancers generally associated with a context
of immunosuppression. The risk of developing malignant tumors can
not be excluded in children and adolescents treated with anti-TNF.
In the
course of the post-marketing surveillance, rare cases of lymphoma
hepatosplenic T-cell lymphoma have been identified in patients
treated with adalimumab. This rare form of T-cell lymphoma
has a very aggressive course and is often fatal. Some of these
hepatosplenic T-cell lymphomas seen with adalimumab
have occurred in young adults who were concomitantly treated
with azathioprine or 6-mercaptopurine used in
inflammatory bowel disease. The potential risk of combining
azathioprine or 6-mercaptopurine with AMGEVITA should be
carefully considered. A risk of developing
hepatosplenic T-cell lymphoma in patients treated with
AMGEVITA cannot be excluded.
There
are no studies in patients with a history of
malignancies or in whom treatment with adalimumab is continued
after the development of cancer. Therefore, additional caution
should be observed when considering treatment of these patients
with AMGEVITA.
All
patients, especially those with a history of
intense immunosuppressive therapy or with psoriasis and a
history of puvatherapy, should be screened for
non-melanoma skin cancer before and during treatment with
AMGEVITA. Cases of melanoma and Merkel cell carcinoma have
also been reported in patients treated with anti-TNF inhibitors
including adalimumab.
In
a prospective clinical study evaluating the use of another
anti-TNF agent , infliximab, in patients with
moderate to severe chronic obstructive pulmonary disease (COPD),
more cancers, especially of the lung, were reported. head and neck,
among patients treated with infliximab compared to patients
in the control group. All patients had a history of
heavy smoking. For this reason, care should be
taken in the use of an anti-TNF in patients with COPD,
and also in patients at risk for cancer due to
heavy smoking .
Based
on current data, it is not known whether treatment with
adalimumab influences the risk of developing dysplasia or
colon cancer. All patients with ulcerative colitis
who are at high risk of dysplasia or colon cancer (for
example, patients with old ulcerative colitis or
primary sclerosing cholangitis) or who have a history of
dysplasia or colon cancer should do
regularly screened for dysplasia before treatment and
throughout the course of their disease. This assessment should include
colonoscopy and biopsies according to local recommendations.

Haematological reactions

From
Rare reports of pancytopenia including aplastic anemia have been
reported with TNF antagonists. Adverse effects of the blood system
including medically significant cytopenias (eg
, thrombocytopenia, leukopenia) have been observed with adalimumab. It
should be recommended for all patients seek immediate
medical advice if they have signs or symptoms suggestive of
blood disorders (eg, persistent fever, bruising,
bleeding, pallor) while AMGEVITA. Discontinuation of treatment with AMGEVITA
should be considered for patients in whom
significant blood abnormalities are confirmed.

Vaccinations

Similar
antibody responses to the
standard 23-valence pneumococcal vaccine and to the trivalent influenza vaccine were
observed in a study in 226 adults with rheumatoid
arthritis treated with adalimumab or placebo. There are no
data available on the secondary transmission of infection from
live vaccines in patients receiving adalimumab.
In
children and adolescents, it is recommended, if possible, that
all immunizations be up to date according to current
immunization guidelines before initiating treatment with AMGEVITA.
The
patients AMGEVITA may receive multiple vaccines
simultaneously, except in respect of live vaccines.
Administration of live vaccines (eg, BCG vaccine) to
infants who have been exposed to AMGEVITA in utero is not
recommended for 5 months after the last injection of AMGEVITA
in the mother during pregnancy.

Congestive heart failure

In
a clinical trial with another TNF antagonist,
worsening congestive heart failure and
increased mortality from congestive heart failure were observed . Of
cases of congestive heart failure worsening have also been
reported in patients receiving adalimumab. AMGEVITA should be
used with caution in patients with
mild heart failure (NYHA classes I / II). AMGEVITA is contraindicated in
moderate to severe heart failure (see section 4.3). Treatment with AMGEVITA should be stopped in patients who experience new symptoms or worsening of their symptoms of congestive heart failure.

Autoimmune processes

The
treatment AMGEVITA may cause antibody formation
autoimmune. The impact of long-term treatment with AMGEVITA on the
development of autoimmune diseases is unknown. If a patient
develops lupus-like symptoms following
treatment with AMGEVITA and exhibits a positive anti-
double-stranded DNA reaction , treatment with AMGEVITA should not be continued.

Simultaneous administration of biological DMARDs or anti-TNF

Some
serious infections were seen in clinical studies in
the concurrent use of anakinra and another TNF antagonist,
etanercept, with no added clinical benefit compared to
etanercept alone. Due to the nature of the side effects
seen with treatment with etanercept and anakinra,
similar side effects may also result from the combination
of anakinra and other TNF blockers. Therefore the combination
of AMGEVITA and anakinra is not recommended (see section Interactions with other medicinal products and other forms of interactions).
Co- administration of AMGEVITA with other biologic DMARDs
(e.g. anakinra and abatacept) or with other TNF blockers is not
recommended due to the possible increased risk
of infections, including serious infections, and other
potential pharmacological interactions (see section Interactions with other medicinal products and other forms of interactions).

Surgery

There is limited experience
with safety during surgical procedures in
patients treated with adalimumab. The long half-life of
adalimumab should be taken into account if surgery
is planned. A patient treated with AMGEVITA requiring
surgery should be carefully monitored for
infections and appropriate actions should be taken.
There
is limited experience with the safety of adalimumab in patients undergoing arthroplasty.

Hail Occlusion

In
Crohn’s disease, treatment failure may indicate the presence of
fixed fibrous strictures that may require surgical treatment.
The available data suggest that adalimumab does not worsen or
cause strictures.

Older subjects

The
frequency of serious infections in subjects treated with
adalimumab over 65 years of age (3.7%) is higher than in
patients under 65 years of age (1.5%). Some cases have had a fatal outcome. Particular attention should be paid to the risk of infection when treating the elderly.

Pediatric population

See Vaccinations above.

Excipients with known effect

This
medicine contains less than 1 mmol sodium (23 mg) per 0.8
mL dose , that is to say essentially ‘sodium free’.

PREGNANCY & BREAST-FEEDING & FERTILITY

Women of childbearing age

Women of childbearing potential should consider using effective contraception during treatment with Amgevita and continue to use it for at least five months after the last administration of Amgevita.

Pregnancy

A large number (approximately 2,100) of pregnancies exposed to adalimumab for which data were collected prospectively, resulting in a live birth with a known course to term, including more than 1,500 pregnancies exposed to adalimumab in the first trimester , does not reveal any increase in the rate of malformations in newborns.
In a prospective cohort study, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab at least during the first trimester and 120 women with untreated RA or CD by adalimumab were included. The prevalence at birth of major congenital anomalies was the primary endpoint. The rate of pregnancies resulting in at least one living newborn with a major birth defect was 6/69 (8.7%) in women treated with adalimumab with RA and 5/74 (6.8 %) in untreated women with RA (unadjusted OR: 1.31, 95% CI: 0.38-4.52), and 16/152 (10.5%) in women treated with ‘adalimumab with CD and 3/32 (9, 4%) in untreated women with CD (unadjusted OR: 1.14, 95% CI: 0.31-4.16). The adjusted OR (considering baseline differences) was 1.10 (95% CI: 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. 31-4,16). The adjusted OR (considering baseline differences) was 1.10 (95% CI: 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. 31-4,16). The adjusted OR (considering baseline differences) was 1.10 (95% CI: 0.45-2.73) for RA and CD combined. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. No notable difference was reported between women treated with adalimumab and women not treated with adalimumab for secondary endpoints of spontaneous abortion, minor congenital anomalies, preterm delivery, height. at birth and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. birth size and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design. birth size and serious or opportunistic infections, and stillbirth or malignancy. Interpretation of the data may be affected due to methodological limitations of the study, including the small sample size and the non-randomized study design.
In a developmental toxicity study performed in monkeys, there were no signs of possible maternal toxicity, embryotoxicity or teratogenic potential. There are no preclinical data on the postnatal toxicity of adalimumab ( see Preclinical Safety ).
Due to its inhibitory effect on TNFα, adalimumab administered during pregnancy may affect the normal immune responses of the newborn. Amgevita should be used during pregnancy only if needed.
In women treated with adalimumab during pregnancy, adalimumab can cross the placenta and pass into the blood of their child. As a result, these children may have an increased risk of infections. The administration of live vaccines (eg BCG vaccine) to children who have been exposed to adalimumab in utero is not recommended for 5 months after the mother’s last injection during pregnancy.

Feeding with milk

Limited data from the published literature indicate that adalimumab is excreted in human milk at very low concentrations, with adalimumab being present in human milk at concentrations equivalent to 0.1% -1% of maternal serum levels. .
When administered orally, immunoglobulin G proteins undergo intestinal proteolysis and exhibit low bioavailability. No effects on breastfed newborns / infants are expected. Therefore, Amgevita can be used during breast-feeding.

Fertility

Preclinical data on the effects of adalimumab on fertility are not available.

What happens if I overdose from amgevita ?

No dose related toxicity was observed in clinical trials. The highest dose evaluated consisted of repeated doses of 10 mg / kg IV, which is approximately 15 times the recommended dose.

What is Forms and Composition ?

SHAPES and PRESENTATIONS

20 mg solution for injection (SC injection) (clear, colorless to slightly yellow) :

0.4 mL pre-filled single-dose syringe, with needle and needle protective cap, pack of 1.

Solution for injection (SC injection) (clear, colorless to slightly yellow) 40 mg:

0.8 mL single-dose pre-filled syringe, with needle and needle shield, packs of 1, 2 and 6 (3 x 2). 0.8 mL pre-filled single-dose pen^*(SureClick), with protectiveneedlecap^**, packs of 1, 2 and 6 (3 x 2).
^* The pen is a disposable, portable, single-use mechanical injection device.
^** The needle cap of the pre-filled pen contains dry natural rubber (a derivative of latex) ( see Warnings and Precautions for use ).

COMPOSITION

	p ser 0.4 mL	p ser or pen 0.8 mL
Adalimumab ^*	20 mg	40 mg

Excipients: glacial acetic acid, sucrose, polysorbate 80, sodium hydroxide (to adjust pH), water for injections.
Each mL contains 50 mg of adalimumab.
^* Adalimumab is a recombinant human monoclonal antibody produced in Chinese hamster ovary cells.

NOT’s

Edrug-online contains comprehensive and detailed information about drugs available in the medical field, and is divided into four sections:

general information:

Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

It treats possible side effects and drug interactions that require attention and its effect on continuous use.
The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.

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