Newer and Investigational Anti-Thyroid Drugs

Submitted by: Group-6 (Girls)

Maheen Adnan-45953 (Eprotirome)
Noor-ul-ain Ali-45480 (Teprotumumab)
Muntaha Noor- 46003 (Lanreotide)
Mizna Naz- 45585 (Lenvatinib)
Filza Arshad-45785 (Debio 1143)
Mahnoor Abdullah-38018(Selinexor)
Noor ul ain Ali- 45480
Teprotumumab
This medication is used to treat thyroid eye disease, also known as
Graves' eye disease. Teprotumumab belongs to a class of drugs
known as monoclonal anti-bodies.

Mechanism of Action
The mechanism of action of teprotumumab in patients with TED has
not been fully characterized. Teprotumumab-trbw binds to IGF-1R
and blocks its activation and signaling. IGF-1R, insulin-like growth
factor-1 receptor

Pharmacokinetics
 Absorption: After intravenous (IV) administration,
teprotumumab's pharmacokinetics show a two-compartment
model. The median time to maximum concentration (Tmax) is
about 2 hours.
 Distribution: The volume of distribution (Vd) of teprotumumab
is approximately 7.7 L, indicating that it distributes mainly in
the vascular compartment.
 Metabolism: Teprotumumab is a protein and is expected to be
degraded into smaller peptides and amino acids by proteolytic
enzymes, but specific metabolic pathways have not been
extensively studied.
 Elimination: The clearance (CL) of teprotumumab is
approximately 0.24 L/day, and the half-life (t1/2) is about 17
days. This indicates that teprotumumab is eliminated relatively
slowly from the body.

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 Administration
Administer the diluted solution intravenously over 90 minutes for
the first 2 infusions1: If well tolerated, the minimum time for
subsequent infusions can be reduced to 60 minutes. If not well
tolerated, the minimum time for subsequent infusions should remain
at 90 minutes.

Half-life
It is approximately 14 days, which supports the three-week dosing
interval, with the steady-state concentration achieved after the fifth
dose.

Side effects
 Hair loss
 Fatigue
 Diarrhea
 Deafness and nail disorder

Contraindications
 IBD
 Hyperglycemia
 Muscle spasm
 Pregnancy
 Head and neck malignant tumors

Toxicity
In recent reports teprotumumab shows deafness and tinnitus at
high dose.

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 Clinical indications
For the treatment of Thyroid Eye Disease regardless of Thyroid Eye
Disease activity or duration.

Muntaha Noor- 46003

Lanreotide
 Synthetic analogue of somatostatin.
 Used to treat conditions like acromegaly and neuroendocrine
tumours.
 Inhibits secretion of growth hormone, insulin-like growth factor
1 (IGF-1), and other hormones.
 Effective in controlling symptoms associated with hormone
excess and tumors growth.

Pharmacokinetics
 Administration: Typically administered via subcutaneous
injection.
 Absorption: Sustained absorption into the bloodstream.
 Distribution: Binds to somatostatin receptors, particularly
subtype
 Metabolism: Metabolized in tissues and plasma by proteolytic
enzymes.
 Elimination: Primarily excreted via the kidneys.

Half-life
Approximately 1.5 weeks, allowing for prolonged therapeutic
effects.

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 Pharmacodynamics
 Mechanism of Action
Acts as a somatostatin analogue, binding to somatostatin
receptors (SSTs) to inhibit secretion of growth hormone (GH),
insulin-like growth factor 1 (IGF-1), and other peptides.
 Somatostatin Receptor Affinity
Exhibits high affinity for somatostatin receptor subtypes 2
(SST2) and 5 (SST5), leading to inhibition of hormone secretion.
 Effects on Hormone Secretion
Reduces GH and IGF-1 levels, providing therapeutic benefit in
conditions like acromegaly. Inhibits secretion of other peptides
such as glucagon and insulin.

Clinical Applications
Used in the treatment of acromegaly and neuroendocrine tumors
(NETs) where hormonal control is necessary.

Duration of Action
Exhibits prolonged duration of action due to its sustained-release
formulation, requiring less frequent dosing compared to short-acting
somatostatin analogues.

Clinical indications
 Acromegaly: Lanreotide is indicated for the treatment of
acromegaly in patients who have had an inadequate response to
surgery or radiation therapy or for whom surgery or radiation
therapy is not an option.

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 Neuroendocrine Tumors (NETs): It's used for the treatment of
unresectable, well- or moderately differentiated, locally advanced
or metastatic gastro-enteropancreatic neuroendocrine tumours to
improve progression-free survival.
 Also indicated for the relief of symptoms associated with carcinoid
syndrome.

Other Indications
Treatment of advanced neuroendocrine tumors of pancreatic origin
(pNETs) in adults.

Contraindications
 Hypersensitivity: Contraindicated in patients with a known
hypersensitivity to lanreotide or any of its components.
 Pregnancy: Not recommended during pregnancy as it may harm
the fetus based on animal data and its mechanism of action.
 Breastfeeding: Not recommended during breastfeeding due to
potential adverse effects on the infant

Drug Interaction of Lanreotide

Some notable interactions include:
 Insulin and Oral Antidiabetic Agents: Lanreotide can alter insulin
and glucose levels, requiring adjustments in the dosage of these
medications.
 Cyclosporine: Lanreotide may decrease the blood levels of
cyclosporine, potentially reducing its efficacy.
 Bromocriptine: Combining lanreotide with bromocriptine may
lead to decreased levels of both drugs, requiring careful
monitoring and possible dosage adjustments.

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 Beta-Blocker: Lanreotide can potentially enhance the effects of
beta-blockers, leading to symptomatic bradycardia.

Risks and side effects of Lanreotide

 Gastrointestinal Issues
 Injection Site Reactions
 Gallstones
 Blood Sugar Changes:

Maheen Adnan- 45953

Eprotirome
Eprotirome, also known as KB2115, is a synthetic thyroid hormone
receptor agonist. It was designed to mimic the effects of thyroid
hormones on metabolism, with the goal of reducing cholesterol
levels in the blood. By activating thyroid hormone receptors,
eprotirome was intended to increase the expression of genes
involved in cholesterol metabolism, leading to lower levels of LDL
cholesterol.

Pharmacodynamics
Eprotirome binds to thyroid hormone receptors, specifically the
thyroid hormone receptor beta (TRβ). Activation of TRβ by
eprotirome leads to changes in gene expression, ultimately affecting
metabolism, including lipid metabolism.

Pharmacokinetics

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 Absorption: Eprotirome was administered orally in clinical trials. It
was reported to be rapidly absorbed, with peak plasma
concentrations reached within 1 to 2 hours after dosing.
 Distribution: The volume of distribution of eprotirome was
reported to be approximately 6 to 8 L, suggesting distribution
mainly in the extracellular fluid.
 Metabolism: Eprotirome was primarily metabolized in the liver.
The main metabolites identified were glucuronide conjugates of
eprotirome and its derivatives. These metabolites were
considered to be inactive.
 Elimination: The elimination half-life of eprotirome was reported
to be approximately 20 to 24 hours in healthy individuals. The
primary route of elimination was through the feces, with a smaller
portion eliminated in the urine.

Dosage
The dosage of eprotirome that was being studied in clinical trials
varied depending on the specific study and the condition being
treated.
However, typical dosages ranged from 25 mg to 100 mg once daily
when used for the treatment of hypercholesterolemia and other
metabolic disorders.

Half-life
It takes about 20 to 24 hours for the concentration of eprotirome in
the bloodstream to decrease by half after administration.

Clinical Indications
 Treatment of hypercholesterolemia and other metabolic
disorders.

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 Lower LDL cholesterol level
 Potentially reduce the risk of cardiovascular disease.
 Expected to affect other metabolic processes regulated by thyroid
hormones, such as glucose metabolism and energy expenditure.

Contraindications
 Liver Dysfunction: Eprotirome was associated with liver toxicity in
clinical trials.
 Pregnancy and Breastfeeding: Thyroid hormones can have
significant effects on fetal development.
 Cardiovascular Disease: Thyroid hormones can affect
cardiovascular function.
 Thyroid Disorders: Eprotirome's effects on thyroid hormone
receptors could potentially interfere with the treatment of thyroid
disorders.

Drug Interactions
 Antithyroid Drugs: Eprotirome's effects on thyroid hormone
receptors could potentially interfere with the action of antithyroid
drugs used to treat hyperthyroidism.
 Thyroid Hormone Replacement Therapy: Eprotirome might have
interacted with thyroid hormone replacement therapy, potentially
altering the dose or effectiveness of thyroid hormones.
 Drugs Metabolized by the Liver: Since eprotirome was associated
with liver toxicity, it might have interacted with other drugs
metabolized by the liver, potentially affecting their metabolism
and clearance.
 Drugs Affecting Lipid Metabolism: Eprotirome was being
developed for its effects on lipid metabolism, so it might have
interacted with other drugs affecting lipid metabolism.

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 Drugs Affecting Cardiovascular Function: Thyroid hormones can
affect cardiovascular function, so eprotirome might have
interacted with drugs affecting cardiovascular function.

Side Effects
 Elevated Liver Enzymes: Can be a sign of liver damage.
 Muscle Toxicity: Can manifest as muscle weakness or pain.
 Cardiovascular Effects: Thyroid hormones can affect
cardiovascular function for potential effects.
 Other Effects: It might have been associated with other side
effects related to thyroid hormone imbalance, such as changes in
weight, heart rate, or mood.

Toxicity
 Liver Toxicity

Mahnoor Abdullah- 38018

Selinexor
Selinexor, marketed under the brand name Xpovio, is a
medication used in the treatment of certain types of cancer or for
tumor treatment. It is an oral selective inhibitor of nuclear export
and it works by blocking the protein exportin 1 (XPO1). This action
leads to the accumulation of tumor suppressor proteins within the
nucleus, which in turn promotes the death of cancer cells.
Uses

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 Selinexor has been approved for use in the treatment of multiple
myeloma, a type of blood cancer, and diffuse large B-cell
lymphoma (DLBCL), which is a type of non-Hodgkin lymphoma. Its
approval often comes with specific indications, such as its use in
patients who have received several prior therapies or when the
disease has relapsed or is refractory.

Side Effects
 Fatigue
 Nausea
 Decreased appetite
 Low blood cell counts (like anemia and thrombocytopenia)
 Increased risk of infections.

Mechanism of Action
Selinexor is an anti-cancer drug that inhibits exportin-1 (XPO1), a
protein responsible for transporting certain molecules from the
nucleus to the cytoplasm. By blocking XPO1, selinexor causes
tumor suppressor proteins like p53 to accumulate in the nucleus,
leading to cell cycle arrest and apoptosis (programmed cell death).
This mechanism can disrupt cancer cell growth and survival,
making selinexor a valuable treatment for certain cancers like
multiple myeloma and diffuse large B-cell lymphoma (DLBCL).

Pharmacokinetics
Selinexor is an orally administered anticancer drug with a
bioavailability of about 60%, reaching peak plasma concentration
4 hours after ingestion. It has a high volume of distribution,
indicating broad tissue penetration, and binds extensively to
plasma proteins. Selinexor undergoes hepatic metabolism mainly
via hydrolysis and glucuronidation, not involving the cytochrome

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 P450 system, which reduces its potential for certain drug
interactions. The primary route of excretion is through feces
(approximately 60%), with a smaller fraction (10%-15%) excreted
via urine. This pharmacokinetic profile provides a foundational
understanding of how selinexor behaves in the body, informing
dosing and potential drug interaction considerations.

Half life
The half-life of selinexor is approximately 6 to 8 hours. This
duration indicates how long the drug's effects might last and helps
in determining dosing frequency. The half-life can vary based on
individual factors such as age, liver function, and drug
interactions.

Contraindications
 Hypersensitivity: If a patient has a known allergy or
hypersensitivity to selinexor or any of its components, it should
not be used.
 Pregnancy: Selinexor may cause fetal harm; it is contraindicated
during pregnancy.
 Severe Thrombocytopenia or Neutropenia: In patients with pre-
existing severe thrombocytopenia or neutropenia, the risk of
complications from low blood counts is heightened, and selinexor
may exacerbate these conditions.

Drug Interactions
 CYP3A Modulators: Drugs that induce or inhibit the CYP3A enzyme
can alter selinexor's metabolism, impacting its blood levels. Avoid
strong CYP3A inhibitors like ketoconazole, as they can increase

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 selinexor exposure, and strong inducers like rifampin, which can
reduce its effectiveness.
 Corticosteroids: Concurrent use may increase the risk of side
effects like immunosuppression, though corticosteroids are
sometimes used to manage selinexor associated side effects.
 Anticoagulants: Selinexor can increase the risk of bleeding, so
caution is needed when used with blood thinners or
anticoagulants.

Filza Arshad-45785

Debio 1143

Debio-1143, also known as Xevinapant is a small molecule

inhibitor of inhibitor of apoptosis aProteins (IAPs). IAPs are a
group of proteins that prevent apoptosis or programmed cell
death, which is a natural process that eliminates damaged or
abnormal cell. By inhibiting these proteins, Debio1143 aims to
promote apoptosis in cancer cells, potentially making them more
vulnerable to treatment.

Mechanism of Action
This is designed to target inhibitor of apoptosis protein (IAPs). It is
involved in inhibiting of anti-apoptotic activity of IAPs.

Pharmacokinetics
 Absorption: Debio-1143 is typically administered orally. After oral
administration, it is rapidly absorbed, with peak plasma
concentrations usually reached within 2 to 4 hours.

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 Distribution: Debio-1143 has a moderate volume of distribution,
indicating that it is distributed fairly evenly throughout the body's
tissues. It is known to penetrate the blood-brain barrier.
 Metabolism: Debio-1143 is metabolized in the liver primarily by
the cytochrome P450 (CYP) enzyme CYP3A4. The primary
metabolite formed is M1, which is also active.
 Elimination: The elimination half-life of Debio-1143 is
approximately 10 to 20 hours. It is primarily eliminated through
the feces (about 70-80%), with the remainder excreted in the
urine.

Drug interactions
Debio-1143 has the potential to interact with drugs that are
metabolized by CYP3A4, as well as drugs that inhibit or induce this
enzyme. Caution should be exercised when co-administering
Debio-1143 with such drugs.

Administration
It has IV route of administration. This route of administration allows
for ease of dosing and patient compliance and making it convenient
for study participants and potentially for future patients if the drug is
approved for broader use.

Half life
The half-life of a drug refers to the time it takes for its plasma
concentration to reduce by half. Knowing the half-life is crucial in
determining dosing intervals and understanding the
pharmacokinetics of drug.

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 Side effects
 Fatigue
 Blood count change
 Skin reaction
 Gastro-intestinal issues
 Liver enzyme elevations

Clinical indications
 Head and Neck Cancer: Debio-1143 has been studied in the
context of head and neck squamous cell carcinoma (HNSCC).
Clinical trials have focused on its use in combination with chemo-
radiotherapy to evaluate its ability to improve treatment
outcomes and reduce tumor resistance.
 Other Solid Tumors: While head and neck cancer is a key focus,
Debio-1143's mechanism of action—targeting inhibitors of
apoptosis proteins (IAPs)—suggests that it may have broader
applications in treating various solid tumors. Studies are exploring
its effectiveness in combination with other cancer treatments.
 Combination Therapy: Debio-1143 is primarily studied in
combination with standard cancer treatments like chemotherapy
and radiotherapy. Its role is to sensitize tumor cells to these
treatments, potentially leading to improved response rates and
longer-term outcomes.

Contraindications
 Allergies or hypersensitivity
 Concurrent medications
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 Underlying health conditions
 Pregnancy and breast feeding

Toxicity
 Nausea
 Vomiting
 Diarrhea
 Increase toxins in liver

Mizna Naz-45585
Lenvatinib
Lenvatinib is a potent medication used in the treatment of various
cancers, notably thyroid cancer and renal cell carcinoma (kidney
cancer). It belongs to a class of drugs called tyrosine kinase
inhibitors (TKIs), which work by blocking signals within cancer cells
that help them grow and divide.

Mechanism of Action
Lenvatinib inhibits multiple receptor tyrosine kinases (RTKs),
including vascular endothelial growth factor (VEGF) receptors,
fibroblast growth factor (FGF) receptors, and others. By targeting
these pathways, it inhibits angiogenesis (the formation of new blood
vessels) and tumor cell proliferation, ultimately suppressing tumor
growth.

Clinical Uses

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 Thyroid Cancer: Lenvatinib is approved for the treatment of locally
recurrent or metastatic, progressive, radioactive iodine-refractory
differentiated thyroid cancer (DTC).
 Renal Cell Carcinoma: It is also approved for the treatment of
advanced renal cell carcinoma (RCC) following one prior anti-
angiogenic therapy.

Dosage and Administration

Lenvatinib is typically taken orally, usually once a day. The dosage
can vary depending on the type and severity of cancer being treated,
as well as individual patient factors. It’s important for patients to
follow their healthcare provider’s instructions carefully regarding
dosing and administration.

Side Effects
 Hypertension (high blood pressure)
 Fatigue
 Diarrhea
 Decreased appetite
 Weight loss
 Nausea and vomiting.
 It can also cause more serious side effects such as liver problems,
heart problems, bleeding, and blood clots.

Monitoring
Patients taking lenvatinib typically require regular monitoring by
their healthcare team to assess for both the effectiveness of the
medication and any potential side effects. This may include blood
tests, imaging studies, and other assessment

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 Conclusion
Lenvatinib represents an important advance in the treatment of
certain cancers, providing new options for patients who may not
have responded well to other therapies. However, like all cancer
treatments, it comes with potential risks and side effects, and should
be used under the guidance of a qualified healthcare provider.

Drugs available

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