Approved Drug Label (PDF)
5
Warnings and Precautions
The following subsections created to
comply with Physician Labeling Rule (PLR), please refer to label for complete
information.
5.1 Dose-Related
Toxicity
5.2 Methemoglobinemia
5.3 Antimicrobial
Preservatives in Multiple-Dose Vials
5.4 Chondrolysis
with Intra-Articular Infusion
5.5 Risk
of Systemic Toxicities with Unintended Intravascular or Intrathecal Injection
5.6 Risk
of Systemic Toxicity in Patients with Hepatic and/or Renal Impairment
5.7 Risk
of Use in Patients with Impaired Cardiovascular Function
5.8 Risk
of Adverse Reactions with Use in Head and Neck Area
5.9 Risk
of Respiratory Arrest with Use in Ophthalmic Surgery
6
Adverse Reactions
Addition of the
following bulleted line listing:
…
Dose-Related Toxicity [see Warnings and
Precautions (5.1)]
Methemoglobinemia [see Warnings and Precautions
(5.2)]
Chondrolysis with Intra-Articular Infusion [see
Warnings and Precautions (5.4)]
Systemic Toxicities with Unintended Intravascular
or Intrathecal Injection [see Warnings and Precautions (5.5)]
…
7
Drug Interactions
Addition
of the following subsections, please refer to label for complete information:
7.1 Local Anesthetics
7.2 Drugs Associated with Methemoglobinemia
8
Use in Specific Populations
8.5 Geriatric Use
Additions
and/or revisions underlined:
Clinical
studies and other reported clinical experience indicate that use of the drug in
elderly patients requires a decreased dosage.
Mepivacaine
is metabolized primarily by the liver. Mepivacaine and mepivacaine metabolites
are known to be substantially excreted by the kidney. Therefore the risk of
adverse reactions including drug toxicities during use of this drug may
be greater in patients with impaired hepatic and/or renal function. Because
elderly patients are more likely to have decreased hepatic and/or renal
function, care should be taken in dose selection, and it may be useful to
monitor hepatic and/or renal function.
8.6 Hepatic Impairment
Newly
added subsection:
Amide-type
local anesthetics, such as mepivacaine, are metabolized by the liver. Patients
with severe hepatic impairment, because of their inability to metabolize local
anesthetics normally, are at a greater risk of developing toxic plasma
concentrations, and potentially local anesthetic systemic toxicity. Therefore,
consider reduced dosing and increased monitoring for local anesthetic systemic
toxicity in patients with moderate to severe hepatic impairment treated with
CARBOCAINE, especially with repeat doses [see
Warnings and Precautions (5.6), Use in Specific Populations (8.5), Clinical
Pharmacology (12.3)].
8.7 Renal Impairment
Newly added subsection:
Mepivacaine is known to be substantially excreted by
the kidney, and the risk of adverse reactions to this drug may be greater in
patients with renal impairment. Therefore, consider reduced dosing and
increased monitoring for local anesthetic systemic toxicity in patients with
moderate to severe renal impairment treated with CARBOCAINE, especially with
repeat doses [see Warnings and
Precautions (5.6), Use in Specific Populations (8.5), Clinical Pharmacology
(12.3)].
8.1 Pregnancy
PLLR conversion:
Risk Summary
Local anesthetics including mepivacaine rapidly
cross the placenta, and when used for epidural, paracervical, caudal, or
pudendal block anesthesia, can cause varying degrees of maternal, fetal, and
neonatal toxicity [see Clinical
Considerations, see Clinical Pharmacology (12.3)]. The incidence and degree
of toxicity depend upon the procedure performed, the type, frequency, and
amount of drug used, and the technique of drug administration. Available data
for mepivacaine use in pregnant women in early pregnancy are insufficient to
establish a drug associated risk of major birth defects or miscarriage.
Animal reproduction studies have not been conducted
with mepivacaine. Mepivacaine hydrochloride should be used during pregnancy
only if the potential benefit justifies the potential risk to the fetus (see Clinical Considerations).
The background risk of major birth defects and
miscarriage for the indicated population is unknown. All pregnancies have a
background risk of birth defects, 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.
Clinical Considerations
Labor or Delivery
Adverse reactions in the parturient, fetus, and
neonate involve alterations of the CNS, peripheral vascular tone, and cardiac
function. Epidural, paracervical, caudal, or pudendal anesthesia may alter the
forces of parturition through changes in uterine contractility or maternal expulsive
efforts. Epidural anesthesia has been reported to prolong the second stage of
labor by removing the parturient’s reflex urge to bear down or by interfering
with motor function. The use of obstetrical anesthesia may increase the need
for forceps assistance.
Maternal Adverse Reactions
Maternal hypotension has resulted from regional
anesthesia. The supine position is dangerous in pregnant women at term because
of aortocaval compression by the gravid uterus. Therefore, during treatment of
systemic toxicity, maternal hypotension or fetal bradycardia following regional
block, the parturient should be maintained in the left lateral decubitus
position if possible, or manual displacement of the uterus off the great
vessels be accomplished. Elevating the patient’s legs will also help prevent
decreases in blood pressure. The recommended maximum dose of the local
anesthetic should not be exceeded. Injection should be made slowly and with
frequent aspiration. Allow a five-minute interval between sides.
Fetal/Neonatal Adverse Reactions
There have been reports of fetal and neonatal deaths
associated with administration of mepivacaine for paracervical and/or pudendal
nerve blocks in pregnant women during delivery. Adhere to recommended dosages
and proper administration techniques for these blocks. There have also been
reports of fetal bradycardia, neonatal respiratory depression, and neonatal
seizures after maternal administration of mepivacaine during delivery.
Inadvertent direct injection into the fetus at delivery with serious outcomes,
including death, have been described. The fetal heart rate should be monitored
continuously, and electronic fetal monitoring is highly advisable.
Failure to achieve adequate analgesia with
recommended doses should arouse suspicion of intravascular or fetal
intracranial injection.
The use of some local anesthetic drug products
during labor and delivery may be followed by diminished muscle strength and
tone for the first day or two of life. The long-term significance of these observations
is unknown.
8.2 Lactation
PLLR conversion:
Risk Summary
There are no available data on the presence of
mepivacaine in human milk, the effects on the breastfed infant, or the effect
on milk production. Mepivacaine is structurally similar to bupivacaine;
available data from case series and a case report demonstrate that bupivacaine
is found in human milk at low levels. The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need for
CARBOCAINE and any potential adverse effects on the breastfed child from
CARBOCAINE or from the underlying maternal condition.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Newly
added section to comply with Physician
Labeling Rule (PLR):
Allergic-Type
Reactions
Assess
if the patient has had allergic-type reactions to amide-type local anesthetics
or to other formulation ingredients, such as the antimicrobial preservative
methylparaben contained in multiple-dose vials [see Contraindications (4), Adverse Reactions (6)].
Methemoglobinemia
Inform
patients that use of local anesthetics may cause methemoglobinemia, a serious
condition that must be treated promptly. Advise patients or caregivers to seek
immediate medical attention if they or someone in their care experience the
following signs or symptoms: pale, gray, or blue colored skin (cyanosis);
headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue [see Warnings and Precautions (5.2)].
Temporary
Loss of Sensation and Motor Activity After Caudal or Epidural Anesthesia
When
appropriate, patients should be informed in advance that they may experience
temporary loss of sensation and motor activity, usually in the lower half of
the body, following proper administration of caudal or epidural anesthesia.
This
product’s labeling may have been updated. For the most recent prescribing
information, please visit www.pfizer.com.
Other
Physician
Labeling Rule (PLR) Conversion.
Approved Drug Label (PDF)
5
Warnings and Precautions
WARNINGS
(additions
underlined)
…
Methemoglobinemia
Cases of methemoglobinemia have been reported
in association with local anesthetic use. Although all patients are at risk for
methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency,
congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise,
infants under 6 months of age, and concurrent exposure to oxidizing agents or
their metabolites are more susceptible to developing clinical manifestations of
the condition. If local anesthetics
must be used in these patients, close monitoring for symptoms and signs of
methemoglobinemia is recommended.
Signs of methemoglobinemia may occur
immediately or may be delayed some hours after exposure, and are characterized
by a cyanotic skin discoloration and/or abnormal coloration of the blood.
Methemoglobin levels may continue to rise;
therefore, immediate treatment is required to avert more serious CNS and
cardiovascular adverse effects, including seizures, coma, arrhythmias, and
death.
Discontinue CARBOCAINE and any other
oxidizing agents. Depending on the severity of the signs and symptoms, patients
may respond to supportive care, i.e., oxygen therapy, hydration. A more severe
clinical presentation may require treatment with methylene blue, exchange
transfusion, or hyperbaric oxygen.
…
7
Drug Interactions
Clinically Significant Drug Interactions
(additions
underlined)
…
Patients who are administered local
anesthetics are at increased risk of developing methemoglobinemia when
concurrently exposed to the following drugs, which could include other local
anesthetics:
Examples of Drugs
Associated with Methemoglobinemia:
(please
refer to label to view examples)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Information for Patients
(additions
underlined)
…
Inform patients that use of local anesthetics
may cause methemoglobinemia, a serious condition that must be treated promptly.
Advise patients or caregivers to seek immediate medical attention if they or
someone in their care experience the following signs or symptoms: pale, gray,
or blue colored skin (cyanosis); headache; rapid heart rate; shortness of
breath; lightheadedness; or fatigue.
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