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Fateme Jahanshahifar MD
1
Presented By : Fateme
Jahanshahifar
Fateme Jahanshahifar MD
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Therapy monitoring in approved
therapeutics.Possible side effects.
Potential side
effects
Glatiramer
acetate
Flushing,
chest pain,
dyspnoea,
Palpitations,
urticaria,
skin necrosis
Recommended
monitoring
None
Flu-like symptoms,
injection-site necrosis, Liver enzymes
Interferon
beta
Depression,
Blood count
allergic reactions
Thryroid testing
Hepatic injury,
Neutralizing
neutropenia,
antibodies
Lipoatrophy
Fateme Jahanshahifar MD
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Therapy monitoring in approved
therapeutics.Possible side effects.
Potential side effects
Mitoxantrone
Recommended
monitoring
Congestion heart failure,
Left ventricular EF,
Urine colour blue-green,
ECG,
Birth deficiency,
differential blood
Sterility,
count,
Hair loss,
Liver enzymes,
nausea
pregnancy testing
PML,
fever,
Natalizumab
JC-virus,
joint pain,
Liver disease,
Melanoma,
Neutralizing
antibodies
Allergic reactions
Fateme Jahanshahifar MD
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Therapy monitoring in approved
therapeutics.Possible side effects.
Potential side effects
Recommended
monitoring
ECG,
Fingolimod
Bradycardia,
heart failure,
Fever,
diarrhoea,
liver disease
Macular oedema,
skin cancers,
Enzephalities
cardiological
evaluation,
Ophtalmological
evaluation,
VZV-antibodies,
liver enzymes
Teriflunomide
Hepatic injury,
Leukopenia,
elevated liver enzymes,
Infections(TB,…),
renal failure, skin reactions, hair
thinning, increase in BP
Polyneuropathy
Fateme Jahanshahifar MD
Liver enzymes,
pregnancy
testing,
white blood count
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Therapy monitoring in approved
therapeutics.Possible side effects.
Potential side effects
Recommended
monitoring
Autoimmune disorders
Alemtuzumab
(thyroid disorders, immune
thrombocytic purpura, renal &
dermatological ),
Complete monthly
blood counts,
infusion-related side
testing for
effects (urticaria, pyrexia &
autoimmunity
rigor)
Lymphopenia,
Dimethyl
fumarate
Flushing,
gastrointestinal side
White blood cell
count
effects,
PML
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FDA
pregnancy
category
Interpretation
A
Well-controlled trials in pregnant women
revealed no increased risk for fetus
B
No well-controlled trials, but animal
trials revealed no increased risk or wellcontrolled trials revealed no risk,
whereas animal trials have shown
adverse effects
Therapeutic agent
Glatiramer acetate
Interferon beta,
C
Animal studies have shown increased
risk for the fetus or have not been
conducted; no well-controlled trials in
pregnant women
natalizumab,
fingolimod,
alemtuzumab,
dimethyl fumarate
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FDA
pregnancy
category
Interpretation
Therapeutic agent
D
Studies have shown harm to the
fetus; however, the benefit may
outweigh risk under certain
circumstances
Mitoxantrone
X
Studies in animals or humans have
demonstrated fetal abnormalities
and/or there is positive evidence of
human fetal risk based on adverse
reaction data from investigational
or marketing experience, and the
risks involved in use of the drug in
pregnant women clearly outweigh
potential benefits
Teriflunomide
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GA (COPAXONE®)
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20 mg GA s.c daily
No laboratory monitoring
during pregnancy only if clearly needed
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IFN-Β
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Neutralizing antibodies are up to 7 times more prevalent in patients
receiving IFN-β-1b every other day or IFN-β-1a s.c. 3 times weekly,
when compared with IFN-β-1a i.m. once a week. Routine testing for
IFN-β neutralizing antibodies is currently not universally
recommended.
Testing for neutralizing antibodies might be recommended in the
setting of clinical disease progression under IFN-β treatment. If
testing is performed, the presence of high titres against IFN-β on
recurrent testing or the failure to induce interferon inducible protein
(MxA) should perhaps lead to the discontinuation of therapy and a
switch to a different class of drug
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MITOXANTRONE
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Mitoxantrone (Novantrone®) for rapidly worsening
RRMS or SPMS. Mitoxantrone is administered at doses
of 12 mg/m2 every 3 months intravenously (i.v.) as short
infusions.
Heart failure may occur during or after termination of therapy
with mitoxantrone. The risk correlates with accumulating
doses of mitoxantrone, and a cumulative dose of 140 mg/m2
should not be exceeded.
There seems to be no correlation between the applied
dose and the likelihood for lymphoma.
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Prior to initiation of therapy, (LVEF) should be obtained by
echocardiogram, multi-gated radionucleotide angiography
(MUGA) or MRI.
Prior to each infusion with mitoxantrone an ECG should be
performed. In addition, a quantitative re-evaluation of LVEF
should be performed before initiation of mitoxantrone, during
therapy with mitoxantrone and yearly after termination of
mitoxantrone using the same method utilized at baseline.
A significant reduction of LVEF (below 50%) is a
contraindication for initiation of therapy with mitoxantrone
and a reason for terminating therapy.
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administration of mitoxantrone is not recommended when
neutrophil numbers fall below 1500 mm3.
Patients with hepatic insufficiency with threefold elevated
liver enzymes should not be administered mitoxantrone
The application of other anti-neoplastic agents should be
avoided.
During therapy with mitoxantrone, vaccinations with live virus
vaccines should be avoided.
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If there are signs of extravasation, the infusion has to be
stopped immediately to avoid tissue necrosis
Patients who have not completed their family planning
should be informed that mitoxantrone may cause sterility.
As mitoxantrone may cause birth defects, contraception is
required during therapy.
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NATALIZUMAB
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Regular monitoring warrants for clinical signs for PML and
JCV testing should be repeated in negative patients every 6
months. Upon suspicion of PML, treatment with natalizumab
should be terminated immediately.
0 _ 6 m _ ...
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Persistent anti-idiotypic antibodies against natalizumab
(detected at two time-points) will prevent the drug from being
efficient. Thus, therapy has to be terminated.
In the case of anaphylaxis or allergic reaction, neutralizing
antibodies are typically detectable.
The prevalence of neutralizing antibodies appears higher in
patients in whom natalizumab therapy was stopped within 6
months of initiation and then restarted later.
Because of the risk of allergic reaction, post-infusion
observation for 1 h is recommended.
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FINGOLIMOD
(GILENYA®)
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Before the initiation of fingolimod …
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should be assessed
by a cardiologists
contraindicated
• patients who become
clinically symptomatic
during fingolimodrelated
bradyarrhythmias
• who take other
bradycardia-promoting
agents
• AV block II
• significant QT
prolongation
• symptomatic known
bradycardia
• history of syncope
• IHD
• CVA
• uncontrollable HTN
• congestive heart dis
Because of the first-dose cardiac side effects of fingolimod,
cardiac monitoring has to be repeated in all patients who
experience a treatment hiatus of 14 days or longer.
Additionally, it requires for repeated monitoring when the
treatment is interrupted for 1 day during the first 2 weeks of
treatment, or 7 days during week 3 and 4 of treatment
After termination of therapy, macular oedema usually
resolves spontaneously; therefore, evaluation of the fundus
has to be performed prior to initiation of therapy, within 4
months after onset of therapy and at any time of
decreased visual acuity
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Vaccination during therapy with fingolimod may be less effective.
Vaccination with live attenuated virus vaccines
should be avoided during, and 2 months after, fingolimod
therapy as it may carry the risk of infections.
In those without VZV antibodies VZV vaccination should be
considered before initiation. Vaccination is recommended
1 month prior to initiation with fingolimod therapy in order to
ensure immunization.
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TERIFLUNOMIDE
(AUBAGIO®)
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Teriflunomide is available in two doses: 7 or 14 mg once daily
Vaccinations with live vaccines are not recommended.
In the case of immunodeficiency teriflunomide should not be
administered.
Teriflunomide is contraindicated in patients with severe
hepatic injury.
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In the case of pregnancy, treatment with teriflunomide should
be terminated immediately and accelerated elimination with
cholestyramine for 11 days or with oral activated charcoal
powder for 11 days should be initiated.
Men with women who plan to become pregnant should not
take teriflunomide. As in female MS patients, effective birth
control is essential for men.
Teriflunomide will stay in the blood for up to 2 years
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ALEMTUZUMAB
(LEMTRADA®)
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12 mg in 1·2 ml (10 mg/ml) concentrate for solution
The risk of secondary autoimmunity should be explained to
the patient.
Regular monitoring includes monthly CBC.
Testing for thyroid disorders, renal and dermatological
disorders needs to be performed regularly even up to 5
years after termination of treatment
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DIMETHYL FUMARATE
(TECIFIDERA®)
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120-mg and 240-mg capsules
Dimethyl fumarate may cause lymphopenia.
Lymphocyte numbers in peripheral decrease by about 30% on
average during the first year, and then stabilize.
After termination of dimethyl fumarate, lymphocyte counts
increase but do not reach the baseline for a substantial period.
Flushing was reported in up to 40% of the treated patients. In
fewer than 1% of treated patients, flushing led to
hospitalization.
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Gastrointestinal side effects such as vomiting, abdominal pain,
diarrhoea and dyspepsia were more common. A transient
moderate increase during the first 2 months of treatment was
reported.
Recently, there were two reports of PML, one with psoriasis
and another with a diagnosis of MS, who received fumaric
acid preparations containing dimethyl fumarate . Prolonged
lymphopenia may have contributed to a higher risk for PML.
Another contributing risk factor may be a history of prior
immunosuppressant use
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Thank you for your attention!
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