Approved Drug Label (PDF)
4
Contraindications
Additions and revisions underlined:
TYGACIL is contraindicated for use in patients who have known hypersensitivity to tigecycline
or to any of the excipients.
5
Warnings and Precautions
5.11 Tetracycline-Class Adverse Effects
Additions and revisions underlined:
TYGACIL is structurally similar to tetracycline-class antibacterial drugs and may have similar
adverse effects. Such effects may include: photosensitivity, fixed drug
eruption, pseudotumor cerebri, and anti-anabolic action (which has led to increased
BUN, azotemia, acidosis, and hyperphosphatemia). Discontinue TYGACIL if any
of these adverse reactions are suspected.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.6 Monitoring of Blood Coagulation Parameters
(Newly added
subsection)
Hypofibrinogenemia
has been reported in patients treated with TYGACIL [see Adverse Reactions (6.2)]. Obtain baseline blood coagulation
parameters, including fibrinogen, and continue to monitor regularly during treatment
with TYGACIL.
6
Adverse Reactions
6.2 Postmarketing Experience
(Additions and/or
revisions underlined)
The
following adverse reactions have been identified during post-approval use of
TYGACIL. Because these reactions are reported voluntarily from a population of
uncertain size, it is not always possible to reliably estimate their frequency or
establish causal relationship to drug exposure.
anaphylactic
reactions
acute
pancreatitis
hepatic
cholestasis, and jaundice
severe
skin reactions, including Stevens-Johnson Syndrome
symptomatic
hypoglycemia in patients with and without diabetes mellitus
hypofibrinogenemia [see
Warnings and Precautions (5.6)]
7
Drug Interactions
7.2 Calcineurin Inhibitors
(Newly added
subsection)
Concomitant
use of TYGACIL and calcineurin inhibitors such as tacrolimus or cyclosporine may
lead to an increase in serum trough concentrations of the calcineurin
inhibitors. Therefore, serum concentrations of the calcineurin inhibitor should
be monitored during treatment with TYGACIL to avoid drug toxicity.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.6 Tooth Discoloration and Enamel Hypoplasia
(subsection
revised, additions underlined)
The
use of TYGACIL during tooth development (last half of pregnancy, infancy, and
childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during
long-term use of tetracyclines, but it has been observed following repeated short-term courses. Enamel
hypoplasia has also been reported.
Advise
the patient of the potential risk to the fetus if TYGACIL is used during the
second or third trimester of pregnancy.
5.7 Inhibition of Bone Growth
(new subsection
added)
The
use of TYGACIL during the second and third trimester of pregnancy, infancy and
childhood up to the age of 8 years may
cause reversible inhibition of bone
growth. All tetracyclines form a stable calcium complex in any bone-forming
tissue. A decrease in fibula growth rate has been observed in premature infants
given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was
shown to be reversible when the tetracycline was discontinued. Advise the
patient of the potential risk to the fetus if TYGACIL is used during the second
or third trimester of pregnancy.
8
Use in Specific Populations
8.1 Pregnancy
(PLLR
conversion)
Risk
Summary
TYGACIL,
like other tetracycline class antibacterial drugs, may cause permanent
discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the
second and third trimesters of pregnancy .There
are no available data on the risk of major birth defects or miscarriage
following the use of TYGACIL during
pregnancy. Administration of intravenous
tigecycline in pregnant rats and rabbits
during the period of organogenesis was associated with reduction in fetal
weights and an increased incidence of skeletal anomalies (delays in bone
ossification) at exposures of 5 and 1
times the human exposure at the recommended clinical dose in rats and rabbits,
respectively. Advise the patient of the potential risk to the fetus if TYGACIL
is used during the second or third trimester.
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 in clinically
recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Human Data
The
use of tetracycline-class antibacterial
drugs, that includes TYGACIL, during
tooth development (second and third trimester of pregnancy) may cause permanent
discoloration of deciduous teeth.
This
adverse reaction is more common during long-term use of tetracyclines but has been observed following repeated
short-term courses. TYGACIL may cause
reversible inhibition of bone growth
when administered during the second and third trimesters of pregnancy. A
decrease in fibula growth rate has been observed in premature infants given
oral tetracycline in doses of 25 mg/kg every 6 hours.
Animal Data
In
embryo-fetal development studies,
tigecycline was administered during the period of organogenesis at doses up to
12 mg/kg/day in rats and 4 mg/kg in rabbits or 5 and 1 times the systemic
exposure at the recommended clinical dose, respectively. In the rat study,
decreased fetal weight and fetal skeletal variations (reduced ossification of
the pubic, ischial, and supraoccipital bones and increased incidences of
rudimentary 14th rib) were observed in the presence of maternal toxicity at 12
mg/kg/day (5 times the recommended clinical dose based on systemic exposure).
In rabbits, decreased fetal weights were observed in the presence of maternal
toxicity at 4 mg/kg (equivalent to the human exposure at the recommended
clinical dose).
In
preclinical safety studies, 14C-labeled tigecycline crossed the placenta and was found in fetal
tissues.
8.2 Lactation
(PLLR
conversion)
Risk
Summary
There
are no data on the presence of tigecycline in human milk; however, tetracycline-class antibacterial
drugs are present in breast milk. It is not known whether tigecycline has an effect on the breastfed infant or on
milk production. Tigecycline has low
oral bioavailability; therefore, infant exposure is expected to be low.
Tigecycline is present in rat milk with little
or no systemic exposure to tigecycline
in nursing pups as a result of exposure via maternal milk. When a drug
is present in animal milk, it is likely that the drug will be present in human
milk.
The
developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for TYGACIL and any potential adverse effects
on the breastfed child from TYGACIL or from the underlying maternal
condition (see Clinical Considerations).
Clinical
Considerations
Because
of the theoretical risk of dental discoloration
and inhibition of bone growth,
avoid breastfeeding if taking TYGACIL for longer than three weeks. A lactating
woman may also consider interrupting breastfeeding and pumping and discarding
breastmilk during administration of TYGACIL and for 9 days (approximately 5 half-lives) after the last dose in order to
minimize drug exposure to a breastfed
infant.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(subsection
revised, additions underlined)
Tooth
Discoloration and Inhibit ion of Bone Growth
Advise
pregnant women that TYGACIL may cause permanent discoloration of deciduous teeth and reversible inhibition
of bone growth when administered during the second and third trimesters of
pregnancy.
Lactation
Advise
a woman not to breastfeed for longer than 3 weeks while taking TYGACIL because
of the lack of data on effects due to prolonged breastfeeding, and the
theoretical risk of dental discoloration
and inhibition of bone growth.
Women may also consider reducing infant exposure through pumping and discarding
breastmilk during and for 9 days after the last dose of tigecycline
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