Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Serious Risks Related to Overtreatment or Undertreatment with Levothyroxine Sodium Tablets
Additions and/or revisions underlined:
Levothyroxine Sodium Tablets
have a narrow therapeutic index. Overtreatment or undertreatment with may
Levothyroxine Sodium Tablets have negative effects on growth and development,
cardiovascular function, bone metabolism, reproductive function, cognitive
function, gastrointestinal function, and glucose and lipid metabolism in
adult or pediatric patients.
In pediatric patients
with congenital and acquired hypothyroidism, undertreatment may adversely
affect cognitive development and linear growth, and overtreatment is associated
with craniosynostosis and acceleration of bone age [see Use in Specific
Populations (8.4)].
Titrate the dose of Levothyroxine
Sodium Tablets carefully and monitor response to titration to avoid these
effects [see Dosage and Administration (2.4)]. Consider the potential
for food or drug interactions and adjust the administration or dosage of Levothyroxine
Sodium Tablets as needed [see Dosage and Administration (2.1), Drug
Interactions (7.1, 7.9), and Clinical Pharmacology (12.3)].
6
Adverse Reactions
Additions and/or revisions underlined:
…
Pediatric Patients
Pseudotumor cerebri and slipped capital femoral epiphysis
have been reported in pediatric patients receiving levothyroxine therapy. Overtreatment
may result in craniosynostosis in infants who have not undergone complete
closure of the fontanelles, and in premature closure of the epiphyses in pediatric
patients still experiencing growth with resultant compromised adult
height.
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
Risk Summary
The clinical experience, including data from postmarketing
studies, in pregnant women treated with oral levothyroxine to maintain euthyroid
state have not reported increased rates of major birth defects,
miscarriages, or other adverse maternal or fetal outcomes. There are risks to the mother and
fetus associated with untreated hypothyroidism in pregnancy. Since TSH levels
may increase during pregnancy, TSH should be monitored and Levothyroxine Sodium
Tablets dosage adjusted during pregnancy (see
Clinical Considerations). Animal reproductive studies have not been conducted
with levothyroxine sodium. Levothyroxine Sodium Tablets should not be
discontinued during pregnancy and hypothyroidism diagnosed during pregnancy
should be promptly treated.
The
estimated background risk of major birth defects and miscarriage for the
indicated population is unknown. All pregnancies have a background risk of
birth defect, loss, or other adverse outcomes. In the U.S. general population,
the estimated background risk of major birth defects and miscarriage in
clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
…
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
Published
studies report that levothyroxine is present in human milk following
administration of oral levothyroxine. No adverse effects on the breastfed
infant have been reported and there is no information on the effects of
levothyroxine on milk production. Adequate levothyroxine treatment during
lactation may normalize milk production in hypothyroid lactating mothers with
low milk supply. The developmental and health benefits of breastfeeding should
be considered along with the mother’s clinical need for Levothyroxine Sodium
Tablets and any potential adverse effects on the breastfed infant from
Levothyroxine Sodium Tablets or from the underlying maternal condition.
8.4 Pediatric Use
Additions
and/or revisions underlined:
Levothyroxine
Sodium Tablets are indicated in patients from birth to less than 17 years of
age:
As a replacement therapy in primary (thyroidal), secondary
(pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.
As an adjunct to surgery and radioiodine therapy in the
management of thyrotropin-dependent well-differentiated thyroid cancer.
…
Approved Drug Label (PDF)
Boxed Warning
PLR conversion; newly added section:
WARNING: NOT FOR
TREATMENT OF OBESITY OR FOR WEIGHT LOSS
Thyroid hormones, including THYRO-TABS, either alone or with other
therapeutic agents, should not be used for the treatment of obesity or for
weight loss.
In euthyroid patients, doses within the range of daily hormonal
requirements are ineffective for weight reduction.
Larger doses may produce serious or even life threatening manifestations
of toxicity, particularly when given in association with sympathomimetic amines
such as those used for their anorectic effects.
4
Contraindications
PLR conversion; revised as below:
THYRO-TABS is contraindicated in patients
with uncorrected
adrenal
insufficiency.
5
Warnings and Precautions
PLR conversion; newly created subsections; please
refer to label for full information.
5.1 Cardiac Adverse Reactions
in the Elderly and in
Patients
with
Underlying
Cardiovascular Disease
5.2 Myxedema Coma
5.3 Acute Adrenal Crisis
in
Patients with Concomitant
Adrenal Insufficiency
5.4 Prevention of Hyperthyroidism or Incomplete Treatment of Hypothyroidism
5.5 Worsening of Diabetic Control
5.6 Decreased Bone Mineral Density Associated with Thyroid Hormone
Over-Replacement
6
Adverse Reactions
PLR Conversion; additions and/or revisions underlined:
Adverse reactions associated
with THYRO-TABS therapy are primarily those of hyperthyroidism due to
therapeutic overdosage. They include the following:
Central nervous system: headache,
hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia
Musculoskeletal: tremors, muscle weakness, muscle
spasm
Gastrointestinal: diarrhea, vomiting, abdominal
cramps, elevations in liver function tests
Dermatologic: hair loss, flushing, rash
Adverse Reactions
in Children
Pseudotumor
cerebri and slipped capital femoral epiphysis …
Hypersensitivity
Reactions
Hypersensitivity
reactions to inactive ingredients have occurred in patients treated with
thyroid hormone products. These include urticaria, pruritus, skin rash,
flushing, angioedema, various gastrointestinal symptoms (abdominal pain,
nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and
wheezing. Hypersensitivity to …
7
Drug Interactions
PLR conversion; additions and/or revisions underlined:
7.1 Drugs Known to Affect Thyroid Hormone
Pharmacokinetics
Many drugs can exert effects on thyroid hormone
pharmacokinetics and metabolism …
Table 2. Drugs
That May Decrease T4 Absorption (Hypothyroidism) Please refer to label for complete
information.
Table 3. Drugs
That May Alter T4 and Triiodothyronine (T3) Serum Transport Without
Affecting Free Thyroxine (FT4) Concentration (Euthyroidism) Please refer to label for complete
information.
Table 4. Drugs
That May Alter Hepatic Metabolism of T4 (Hypothyroidism) Please refer to label for complete
information.
Table 5. Drugs
That May Decrease Conversion of T4 to T3 Please
refer to label for complete information.
7.2 Antidiabetic Therapy
Addition of
THYRO-TABS therapy in patients with diabetes mellitus may worsen glycemic
control and result in increased antidiabetic agent or insulin requirements.
Carefully monitor glycemic control, especially when thyroid therapy is started,
changed, or discontinued.
7.3 Oral Anticoagulants
THYRO-TABS
increases the response …
7.4 Digitalis Glycosides
THYRO-TABS may
reduce the therapeutic effects of digitalis glycosides. Serum digitalis
glycoside levels may decrease …
7.5 Antidepressant Therapy
Concurrent use of
tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline)
antidepressants and THYRO-TABS may increase the therapeutic and toxic effects
of both drugs, possibly due to increased receptor sensitivity to
catecholamines. Toxic effects may include increased risk of cardiac arrhythmias
and central nervous system stimulation. THYRO-TABS may accelerate the onset of
action of tricyclics. Administration of sertraline in patients stabilized on
THYRO-TABS may result in increased THYRO-TABS requirements.
7.6 Ketamine
Concurrent use of
ketamine and THYRO-TABS may produce marked hypertension and tachycardia.
Closely monitor blood pressure and heart rate in these patients.
7.7 Sympathomimetics
Concurrent use of
sympathomimetics and THYRO-TABS may increase the effects of sympathomimetics or
thyroid hormone. Thyroid hormones may increase the risk of coronary
insufficiency when sympathomimetic agents are administered to patients with
coronary artery disease.
7.8 Tyrosine-Kinase Inhibitors
Concurrent use of
tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. Closely
monitor TSH levels in such patients.
7.9 Drug-Food Interactions
… decrease the
absorption of THYRO-TABS from the gastrointestinal tract. Grapefruit juice
may delay the absorption of levothyroxine and reduce its bioavailability.
7.10 Drug-Laboratory Test Interactions
Consider changes
in TBG concentration when interpreting T4 and T3 values …
8
Use in Specific Populations
8.1 Pregnancy
PLR and PLLR
conversion; as below:
Risk Summary
Experience with
levothyroxine use in pregnant women, including data from post-marketing
studies, have not reported increased rates of major birth defects or
miscarriages. There are risks to the
mother and fetus associated with untreated hypothyroidism in pregnancy. Since
TSH levels may increase during pregnancy, TSH should be monitored and
THYRO-TABS dosage adjusted during pregnancy. There are no animal studies
conducted with levothyroxine during pregnancy. THYRO-TABS should not be
discontinued during pregnancy and hypothyroidism diagnosed during pregnancy
should be promptly treated.
The estimated
background risk of major birth defects and miscarriage for the indicated
population is unknown. In the U.S. general population, the estimated background
risk of major birth defects and miscarriage in clinically recognized
pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical
Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
Maternal
hypothyroidism during pregnancy is associated with a higher rate of
complications, including spontaneous abortion, gestational hypertension,
pre-eclampsia, stillbirth, and premature delivery. Untreated maternal
hypothyroidism may have an adverse effect on fetal neurocognitive development.
Dose Adjustments During Pregnancy and the Postpartum
Period
Pregnancy may
increase THYRO-TABS requirements. Serum TSH levels should be monitored and the
THYRO-TABS dosage adjusted during pregnancy. Since postpartum TSH levels are
similar to preconception values, the THYRO-TABS dosage should return to the
pre-pregnancy dose immediately after delivery.
Data
Human Data
Levothyroxine is
approved for use as a replacement therapy for hypothyroidism. There is a long
experience of levothyroxine use in pregnant women, including data from
post-marketing studies that have not reported increased rates of fetal
malformations, miscarriages or other adverse maternal or fetal outcomes associated
with levothyroxine use in pregnant women.
8.2 Lactation
PLR and PLLR conversion; as below:
Risk Summary
Limited published
studies report that levothyroxine is present in human milk. However, there is
insufficient information to determine the effects of levothyroxine on the
breastfed infant and no available information on the effects of levothyroxine
on milk production. Adequate levothyroxine treatment during lactation may
normalize milk production in hypothyroid lactating mothers. The developmental and
health benefits of breastfeeding should be considered along with the mother’s
clinical need for THYRO-TABS and any potential adverse effects on the breastfed
infant from THYRO-TABS or from the underlying maternal condition.
8.4 Pediatric Use
PLR conversion; as below:
The initial
dose of THYRO-TABS
varies with
age and body weight.
Dosing adjustments
are
based on an assessment
of the individual patient's clinical
and laboratory parameters.
In children in whom
a diagnosis
of permanent
hypothyroidism has
not been established,
discontinue THYRO-TABS
administration for a trial
period, but only after the child
is at least 3 years of
age. Obtain serum T4
and TSH levels at
the end of the trial period, and
use
laboratory test results
and clinical assessment to guide diagnosis and
treatment, if warranted.
Congenital Hypothyroidism
Rapid restoration
of normal serum T4
concentrations is essential
for
preventing the adverse effects of congenital hypothyroidism
on intellectual development
as well
as on overall physical
growth
and maturation. Therefore, initiate
THYRO-TABS therapy immediately upon
diagnosis. Levothyroxine
is generally continued for life in
these patients.
Closely monitor
infants during the first
2 weeks of THYRO-TABS therapy for
cardiac overload,
arrhythmias,
and aspiration from
avid suckling.
Closely monitor
patients to avoid undertreatment or overtreatment. Undertreatment may have deleterious
effects on intellectual development and linear growth.
Overtreatment
is associated with craniosynostosis
in infants, may adversely affect
the tempo of brain maturation, and
may accelerate the bone age and
result in premature epiphyseal closure and compromised
adult stature.
Acquired Hypothyroidism
in Pediatric Patients
Closely monitor
patients to avoid undertreatment
and overtreatment. Undertreatment may result
in poor school performance Overtreatment may accelerate the bone age and
result in premature epiphyseal
closure and compromised adult
stature …
8.5 Geriatric Use
PLR conversion; as
below:
Because of the increased prevalence of cardiovascular disease among the
elderly, initiate THYRO-TABS at less than the full replacement dose. Atrial
arrhythmias can occur in elderly patients. Atrial fibrillation is the most
common of the arrhythmias observed with levothyroxine overtreatment in the
elderly.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
PLR conversion; newly added section:
Inform the patient
of the following information to aid in the safe and effective use of
THYRO-TABS:
Instruct
patients to take THYRO-TABS only as directed by their healthcare provider.
Instruct
patients to take THYRO-TABS as a single dose, preferably on an empty stomach,
one- half to one hour before breakfast.
Inform
patients that agents such as iron and calcium supplements and antacids can
decrease the absorption of levothyroxine. Instruct patients not to take
THYRO-TABS tablets within 4 hours of these agents.
Instruct
patients to notify their healthcare provider if they are pregnant or
breastfeeding or are thinking of becoming pregnant while taking THYRO-TABS.
Important Information
Inform
patients that it may take several weeks before they notice an improvement in
symptoms.
Inform
patients that the levothyroxine in THYRO-TABS is intended to replace a hormone
that is normally produced by the thyroid gland. Generally, replacement therapy
is to be taken for life.
Inform
patients that THYRO-TABS should not be used as a primary or adjunctive therapy
in a weight control program.
Instruct
patients to notify their healthcare provider if they are taking any other
medications, including prescription and over-the-counter preparations.
Instruct
patients to notify their physician of any other medical conditions they may
have, particularly heart disease, diabetes, clotting disorders, and adrenal or
pituitary gland problems, as the dose of medications used to control these
other conditions may need to be adjusted while they are taking THYRO-TABS. If
they have diabetes, instruct patients to monitor their blood and/or urinary
glucose levels as directed by their physician and immediately report any
changes to their physician. If patients are taking anticoagulants, their
clotting status should be checked frequently.
Instruct
patients to notify their physician or dentist that they are taking THYRO-TABS
prior to any surgery.
Adverse Reactions
Instruct
patients to notify their healthcare provider if they experience any of the
following symptoms: rapid or irregular heartbeat, chest pain, shortness of
breath, leg cramps, headache, nervousness, irritability, sleeplessness,
tremors, change in appetite, weight gain or loss, vomiting, diarrhea, excessive
sweating, heat intolerance, fever, changes in menstrual periods, hives or skin
rash, or any other unusual medical event.
Inform
patients that partial hair loss may occur rarely during the first few months of
THYRO- TABS therapy, but this is usually temporary.
Get Email Alerts |
Guide
