Infliximab (Remicade)

- only approved drug therapy specifically

indicated for the treatment of fistulizing
Crohn disease, an inflammation of the
intestine, rheumatoid arthritis and for
patients without response to methotrexate
therapy.
-This MAb binds and neutralizes one of the
primary
cytokines
that
propagate
inflammatory response
-It has been associated with hypersensitivity
reactions, including urticaria, dyspnea, and
hypotension, and should be discontinued in
case of a severe reaction

Muromonab-CD3 (Orthoclone OKT3)

- reacts with a T3 (CD3) molecule linked to
an antigen receptor on the surface
membrane of human T lymphocytes. It
blocks both generation and functions of the
T cells and is indicated for the treatment of
organ transplant rejection.
-Muromonab-CD3 injection is administered
by IV push over a period not less than
1 minute.
-For acute renal allograft rejection, it
is given IV at 5 mg per day for 10 to 14
days.
-To decrease the incidence of reactions
resulting from the first injection of
muromonab, methylprednisolone sodium
succinate 8 mg/kg should be administered
intravenously 1 to 4 hours beforehand.
-The patients temperature should not
exceed 37.8C
-it should be drawn into the syringe through
a lowprotein binding 0.2- to 0.22-mm filter.
-it must not be shaken.

Omalizumab (Xolair)
- is the first humanized therapeutic
antibody for the treatment of asthma and
first to target immunoglobulin E (IgE)
-Initially approved for treatment of moderate
to severe persistent asthma in patients
more than 12 years of age who demonstrate
a positive skin test to a perennial
aeroallergen
-for a patient who is inadequately
controlled with inhaled corticosteroids.

- administered subcutaneously
every 2 to 4 weeks. Dosing is based on
the patients body weight and IgE.
-Not more than 150 mg should be
injected into one site.

Palivizumab (Synagis)
-a humanized MAb
produced by rDNA technology
-It is a composite of human (95%) and
murine (5%) antibody sequences.
-is used to prevent serious lower respiratory
tract disease caused by RSV in children.
-The safety and efficacy of this drug were
established
in
infants
with
bronchopulmonary dysplasia (BPD) and
infants with a history of prematurity (35
gestational
weeks).
-The injection must be administered within 6
hours after reconstitution.
-The recommended dosage is 15 mg/kg
intramuscularly in the anterolateral aspect of
the thigh
-The use of gluteal muscle is not advocated
because of sciatic nerve damage risk.

Rituximab (Rituxan)
- first MAb approved to treat cancer
-Rituximab is used to treat patients with
relapsed or refractory low-grade or follicular
CD20-positive beta-cell NHL.
- The recommended dosage is 375 mg/m2
given as an intravenous infusion weekly for
four doses
-If hypersensitivity or infusion-related
reactions develop, the infusion is interrupted
or slowed.
-Because hypotension may
occur during infusion, it is suggested that
one
consider
withholding
any
antihypertensive medication 12 hours prior
to rituximab infusion.

Satumomab Pendetide (OncoScint

CR/OV Kit)
- a diagnostic imaging agent that
is indicated for determining the extent and

location of extrahepatic malignant disease

in patients with known ovarian carcinoma.
-Each kit contains all of the nonradioactive
ingredients necessary to produce a
singleunit dose of OncoScint CR/OV-In for
use as
-Proper aseptic technique and precautions
for handling radioactive materials should
be employed. Waterproof gloves should
be worn during radiolabeling.
-it should be administered within
8 hours after radiolabeling.

Tocilizumab (Actemra)
-first IL-6 receptor inhibiting MAb for the
treatment of rheumatoid arthritis
The resulting antibody has a longer half-life,
that is, 240 hours, achieved after the third
dose of 8 mg/kg in humans.
-The drug is administered as an IV infusion
every 4 weeks for 3 months.
-Because the drug is a humanized antibody,
infusion related adverse effects, that is,
hypersensitivity
reactions,
might
be
expected.

Trastuzumab (Herceptin)
- second MAb approved to treat cancer.
- for the treatment of metastatic breast
cancer or cancer that has spread beyond
the breast and lymph nodes
under the arm
-Specifically, trastuzumab is a chimeric
humanmurine MAb that binds to the
HER2 protooncogene
-In the case of metastatic breast cancer
cells, approximately 25% to 30% of tumors
overexpress excess mounts of HER2.
- Thus, only patients who
have tumors with this characteristic have
shown benefit from trastuzumab
- contains amblack box warning regarding
the risk of ventricular dysfunction and
congestive heart failure (CHF).
-Therecommended loading dose is 4 mg/kg
as a 90-minute intravenous infusion along
with 175 mg/m2/dose on day 1 of therapy

-should not be administered as an IV push

or
bolus.

Plasminogen Activators
- produced in small quantity by the inner
lining of blood vessels and by the muscular
wall of the uterus.
-They prevent abnormal blood clotting by
converting plasminogen to the enzyme
plasmin, which breaks down fibrin,
-artificially produced versions are used as
thrombolytic agents for blood dissolution
-They are used for conditions such as
heart attack, angina, and occluded arteries.
-they only act locally on the site of the clot

Recombinant Alteplase (Activase)

-A tPA (tissue Plasminogen Activator)
produced by rDNA, is used in
the management of acute myocardial
infarction (AMI), acute ischemic stroke, and
pulmonary embolism (PE).
-When administered, it initiates local
fibrinolysis with limited systemic proteolysis.
-There are no antibacterial preservatives
in the product, so it should be prepared just
before use.
-Because its molecule is large it must be
administered
parenterally,
usually
intravenously.
-Alteplase is stable for up to 8 hours and
should be administered within this time.

Recombinant Reteplase (Retavase)

-It is produced by rDNA in E. coli.
-Its mechanism of action is the
same as that of alteplase.
-Reteplase is indicated for management of
AMI in adults, improvement of ventricular
function following an AMI, reduction of the
incidence of CHF, and reduction in mortality
associated with an AMI.
- for intravenous administration
only.

-The second bolus is given 30 minutes after

initiation of the first bolus injection without
other drugs.
-The lyophilized powder for injection of
reteplase should be reconstituted only with
sterile water for injection and must be
allowed to stand after reconstitution since
bubbles might form.

Recombinant Tenecteplase
(TNKase)
-This thrombolytic agent is marketed with a
needleless administration set that can be
used to deliver the medication with just one
dose in only 5 seconds
-The agent is administered via an
intravenous line with saline, as dextrose
may
cause precipitation.
-Produced in Chinese hamster ovary cells
using rDNA technology
-The three letters in the name
derive from amino acid substitutions at three
regions of the tPA protein.
-To be effective, tenecteplase, like the
other clot busters, must be used within the
first hours of a heart attack.

Tyrosine Kinase Inhibitor

The Philadelphia (Ph) chromosome, a
truncated chromosome 22, was the first
consistent
chromosomal
abnormality
identified in human malignancy (27).
-The product of fusion gene is
a constitutively active tyrosine kinase with
markedly enzymatic activity when compared
to the Abl kinase.
-Because all of cell growth, adhesion,
proliferation depend on the increased
tyrosine kinase activity of the fusion protein,
it is apparent that inhibition of the enzymatic
activity of Bcr-Abl, which is present in
diseased patients, would be an effective
treatment of CML.

Imatinib Mesylate (Gleevec)

- demonstrates potent and selective

inhibitory activity
against Abl tyrosine kinases
-It does so without any significant effect on
normal cells or other cells affected by the
tyrosine oncogenes
-The chronic phase dosage is 400 to 600
mg daily. The accelerated phase or blast
crisis dosage ranges from 600 to 800 mg
daily.
-The patient should be instructed to take
this medication with food and a large glass
of water because of mild gastrointestinal
effects.
-Other common adverse effects include
edema, muscle cramps, hemorrhage,
and musculoskeletal pain

Nilotinib (Tasigna)
-a Bcr-Abl tyrosine kinase inhibitor and is
used for the treatment of chronic and
accelerated-phase CML in
adults resistant or intolerant to prior
therapies
-The dosage regimen
of nilotinib is 400 mg orally every 12 hours,
and the capsule dosage form should be
swallowed whole at least 2 hours after a
meal.
-Nilotinib can cause QT prolongation, and
patients are educated to be aware of
possible symptoms, for example, irregular
heartbeat and fainting.

Vaccines
-Genetically engineered vaccines use a
synthetic copy of the protein coat of a virus
to fool the bodys immune system into
mounting a protective response.
-it avoids the use of live viruses
-The first genetically engineered vaccine
for use in the United States for hepatitis B, a
widespread liver infection.

Hepatitis B Vaccine Recombinant

(Engerix-B, Recombivax HB)
-Recombinant hepatitis B vaccine has
demonstrated an ability to induce antibody
to hepatitis B surface antigen (anti-HBs) that

is comparable to antibody induced by the

plasma-derived hepatitis B vaccine.
-The vaccine should be administered by
intramuscular injection into the deltoid
muscle for immunization of adults and
older children and anterolateral thigh
for infants and younger children.
-For patients with a risk of hemorrhage
following intramuscular injection, the
vaccine
may
be
administered
subcutaneously

Haemophilus B Conjugate Vaccine

(HibTITER, Liquid PedvaxHIB, ActHIB)
-Haemophilus influenza type B (HIB) was
the most frequent cause of bacterial
meningitis and leading cause of serious
systemic bacterial disease among
children worldwide
-Haemophilus B is responsible for
numerous other invasive disease processes
(e.g., epiglottitis, sepsis, septic arthritis,
osteomyelitis, pericarditis).
-ActHIB is available as a lyophilized powder
for injection containing 10 mg purified
Haemophilus B capsular polysaccharide
and 24 mg tetanus toxoid/5 mL.
-This is available in single-dose vials with
7.5-mL vials of diphtheria and tetanus
toxoids and pertussis vaccine as diluents

Rasburicase (Elitek)
- a recombinant urate oxidase enzyme
produced by a genetically modified
S. cerevisiae strain.
Rasburicase catalyzes enzymatic oxidation
of uric acid into an inactive and soluble
metabolite, allantoin.
-it is indicated for initial management
of elevated plasma uric acid levels in
children with leukemia, lymphoma, and solid
tumor malignancies who are receiving
oncologic

Recombinant Human DNase I

(Pulmozyme)
-the discovery of the cystic fibrosis gene has
helped to lay the groundwork
for new therapies to treat this disease,
which is the most common inherited fatal

disease affecting whites.

-Because of a defective regulator in the
body a domino effect of chronic infection
and inflammation, followed by chronic lung
disease, pulmonary hypertension, and heart
failure occurs.
-DNase
(recombinant
human
deoxyribonuclease
I), or dornase alfa, is a DNA
enzyme indicated for the treatment of
symptoms of cystic fibrosis.
-Some nebulizers have been tested for the
administration of DNase
(examples of nebulizers)
-no other medication should be
mixed in the nebulizer system with this drug
because of the possibility that a pH change
could alter the DNase protein structure.
-The ampuls have an 18-month expiration
date when stored in the refrigerator at 2C
to 8 C and should be protected from strong
light.

The Future of Biotechnology

Products
The future will continue to demonstrate the
development
of
more
protein-based
pharmaceuticals as a result of modern
biotechnologic strategies.
Challenges:
-protein-based drugs have
intrinsic instability,
multifaceted metabolic properties, and
limited gastrointestinal absorption,
variable tissue penetration
(because of the size of the molecules)
and toxicity related to the stimulation of an
immune or allergic reaction.
Advantages:
-enhanced purity.
-Products
derived
from
recombinant
technology will not have co-extracted
contaminants.

new
methods
of
delivery
-Delivery systems being explored
include transdermal and nasal routes, other
forms of injectables, and oral tablets for
smaller proteins.
Problem
-instability of proteins in the strong acid
environment of the stomach and the low
systemic absorption through gastrointestinal
mucosa.
-To deliver regulatory proteins (e.g., insulin,
growth hormone) to distant organs or tissue
without
biotransformation.
Possible Solution
-nanotechnologic manipulation,
and manufacture of ultrasmall structures
made of as few as one molecule.
- Nanotechnology involves the control of
matter in the 1- to 100-nm dimension range.
-Nanotechnology can increase solubility,
deliver two or more drugs at the same time
to effect combination
Therapy.
nanoparticle-based products
-liposomal drugs
Liposomes
-These are water-filled vesicular structures
composed of several phospholipid layers

surrounding an aqueous core, with the outer

shell capable of providing direction to
specific target cells (e.g., tumors).
- concentrate the drug in cells of the
reticuloendothelial system of the liver and
spleen and reduce drug intake in the heart,
kidney, and gastrointestinal tract.
Others
Additional nanoscale systems for drug
delivery include phospholipid micelles,
pluronic micelles, drug nanoparticles, solid
nanoparticles, lipidbased nanoparticles,
nanogels, and dendrimer nanocomposites
for drug deliver.
Future Possibilities
-engineered protein complexes combined
with a transporting protein with one that
encodes the gene sequence to produce a
therapeutic protein in the target tissue,
decreasing delivery to an unintended
site.
-creation of more diagnostic products for inhome testing. These include products for
infectious disease processes
- MAb-based tests will be available to assay
blood or plasma concentrations
of a number of drugs, like digoxin,
phenytoin, and theophylline.