A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Carbocaine Warnings, Precautions, Pregnancy, Nursing, Abuse - Mepivacaine
Carbocaine Warnings, Precautions, Pregnancy, Nursing, Abuse - Mepivacaine
WARNINGS
LOCAL ANESTHETICS SHOULD ONLY BE EMPLOYED BY CLINICIANS WHO ARE WELL VERSED
IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES
WHICH MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED, AND THEN ONLY AFTER INSURING
THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY
RESUSCITATIVE EQUIPMENT, AND THE PERSONNEL RESOURCES NEEDED FOR PROPER MANAGEMENT
OF TOXIC REACTIONS AND RELATED EMERGENCIES. (See also ADVERSE REACTIONS
and PRECAUTIONS
.) DELAY IN PROPER MANAGEMENT OF DOSE-RELATED
TOXICITY, UNDERVENTILATION FROM ANY CAUSE, AND/OR ALTERED SENSITIVITY MAY LEAD
TO THE DEVELOPMENT OF ACIDOSIS, CARDIAC ARREST AND, POSSIBLY, DEATH.
Local anesthetic solutions containing antimicrobial preservatives (ie, those
supplied in multiple-dose vials) should not be used for epidural or caudal anesthesia
because safety has not been established with regard to intrathecal injection,
either intentionally or inadvertently, of such preservatives.
It is essential that aspiration for blood or cerebrospinal fluid (where applicable)
be done prior to injecting any local anesthetic, both the original dose and
all subsequent doses, to avoid intravascular or subarachnoid injection. However,
a negative aspiration does not ensure against an intravascular or subarachnoid
injection.
Reactions resulting in fatality have occurred on rare occasions with the use
of local anesthetics.
Mepivacaine with epinephrine or other vasopressors should not be used concomitantly
with ergot-type oxytocic drugs, because a severe persistent hypertension may
occur. Likewise, solutions of mepivacaine containing a vasoconstrictor, such
as epinephrine, should be used with extreme caution in patients receiving monoamine
oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine
types, because severe prolonged hypertension may result.
Local anesthetic procedures should be used with caution when there is inflammation
and/or sepsis in the region of the proposed injection.
Mixing or the prior or intercurrent use of any local anesthetic with mepivacaine
cannot be recommended because of insufficient data on the clinical use of such
mixtures.
PRECAUTIONS
General
The safety and effectiveness of local anesthetics depend on proper dosage,
correct technique, adequate precautions, and readiness for emergencies. Resuscitative
equipment, oxygen, and other resuscitative drugs should be available for immediate
use. (See WARNINGS
and ADVERSE REACTIONS.) During major regional nerve blocks,
the patient should have IV fluids running via an indwelling catheter to assure
a functioning intravenous pathway. The lowest dosage of local anesthetic that
results in effective anesthesia should be used to avoid high plasma levels and
serious adverse effects. Injections should be made slowly, with frequent aspirations
before and during the injection to avoid intravascular injection. Current opinion
favors fractional administration with constant attention to the patient, rather
than rapid bolus injection. Syringe aspirations should also be performed before
and during each supplemental injection in continuous (intermittent) catheter
techniques. An intravascular injection is still possible even if aspirations
for blood are negative.
During the administration of epidural anesthesia, it is recommended that a
test dose be administered initially and the effects monitored before the full
dose is given. When using a "continuous" catheter technique, test doses should
be given prior to both the original and all reinforcing doses, because plastic
tubing in the epidural space can migrate into a blood vessel or through the
dura. When the clinical conditions permit, an effective test dose should contain
epinephrine (10 µg to 15 µg have been suggested) to serve as a warning of unintended
intravascular injection. If injected into a blood vessel, this amount of epinephrine
is likely to produce an "epinephrine response" within 45 seconds, consisting
of an increase of pulse and blood pressure, circumoral pallor, palpitations,
and nervousness in the unsedated patient. The sedated patient may exhibit only
a pulse rate increase of 20 or more beats per minute for 15 or more seconds.
Therefore, following the test dose, the heart rate should be monitored for a
heart rate increase. The test dose should also contain 45 mg to 50 mg of mepivacaine
hydrochloride to detect an unintended intrathecal administration. This will
be evidenced within a few minutes by signs of spinal block (eg, decreased sensation
of the buttocks, paresis of the legs, or, in the sedated patient, absent knee
jerk).
Injection of repeated doses of local anesthetics may cause significant increases
in plasma levels with each repeated dose due to slow accumulation of the drug
or its metabolites or to slow metabolic degradation. Tolerance to elevated blood
levels varies with the status of the patient. Debilitated, elderly patients,
and acutely ill patients should be given reduced doses commensurate with their
age and physical status. Local anesthetics should also be used with caution
in patients with severe disturbances of cardiac rhythm, shock, heart block,
or hypotension.
Careful and constant monitoring of cardiovascular and respiratory (adequacy
of ventilation) vital signs, and the patient's state of consciousness should
be performed after each local anesthetic injection. It should be kept in mind
at such times that restlessness, anxiety, incoherent speech, lightheadedness,
numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness,
blurred vision, tremors, twitching, depression, or drowsiness may be early warning
signs of central nervous system toxicity.
Local anesthetic solutions containing a vasoconstrictor should be used cautiously
and in carefully restricted quantities in areas of the body supplied by end
arteries or having otherwise compromised blood supply such as digits, nose,
external ear, penis. Patients with hypertensive vascular disease may exhibit
exaggerated vasoconstrictor response. Ischemic injury or necrosis may result.
Mepivacaine should be used with caution in patients with known allergies and
sensitivities.
Because amide-type local anesthetics such as mepivacaine are metabolized by
the liver and excreted by the kidneys, these drugs, especially repeat doses,
should be used cautiously in patients with hepatic and renal disease. Patients
with severe hepatic disease, because of their inability to metabolize local
anesthetics normally, are at greater risk of developing toxic plasma concentrations.
Local anesthetics should also be used with caution in patients with impaired
cardiovascular function because they may be less able to compensate for functional
changes associated with the prolongation of AV conduction produced by these
drugs.
Serious dose-related cardiac arrhythmias may occur if preparations containing
a vasoconstrictor such as epinephrine are employed in patients during or following
the administration of potent inhalation anesthetics. In deciding whether to
use these products concurrently in the same patient, the combined action of
both agents upon the myocardium, the concentration and volume of vasoconstrictor
used, and the time since injection, when applicable, should be taken into account.
Many drugs used during the conduct of anesthesia are considered potential triggering
agents for familial malignant hyperthermia. Because it is not known whether
amide-type local anesthetics may trigger this reaction and because the need
for supplemental general anesthesia cannot be predicted in advance, it is suggested
that a standard protocol for management should be available. Early unexplained
signs of tachycardia, tachypnea, labile blood pressure, and metabolic acidosis
may precede temperature elevation. Successful outcome is dependent on early
diagnosis, prompt discontinuance of the suspect triggering agent(s), and institution
of treatment, including oxygen therapy, indicated supportive measures, and dantrolene.
(Consult dantrolene sodium intravenous package insert before using.)
Use in Head and Neck Area
Small doses of local anesthetics injected into the head and neck area may produce
adverse reactions similar to systemic toxicity seen with unintentional intravascular
injections of larger doses. The injection procedures require the utmost care.
Confusion, convulsions, respiratory depression, and/or respiratory arrest,
and cardiovascular stimulation or depression have been reported. These reactions
may be due to intra-arterial injection of the local anesthetic with retrograde
flow to the cerebral circulation. Patients receiving these blocks should have
their circulation and respiration monitored and be constantly observed. Resuscitative
equipment and personnel for treating adverse reactions should be immediately
available. Dosage recommendations should not be exceeded.
Information for Patients
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.
Also, when appropriate, the physician should discuss other information including
adverse reactions listed in this package insert.
Clinically Significant Drug Interactions
The administration of local anesthetic solutions containing epinephrine or
norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic
antidepressants may produce severe, prolonged hypertension. Concurrent use of
these agents should generally be avoided. In situations when concurrent therapy
is necessary, careful patient monitoring is essential.
Concurrent administration of vasopressor drugs and of ergot-type oxytocic drugs
may cause severe, persistent hypertension or cerebrovascular accidents.
Phenothiazines and butyrophenones may reduce or reverse the pressor effect
of epinephrine.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term studies in animals of most local anesthetics including mepivacaine
to evaluate the carcinogenic potential have not been conducted. Mutagenic potential
or the effect on fertility have not been determined. There is no evidence from
human data that mepivacaine may be carcinogenic or mutagenic or that it impairs
fertility.
Pregnancy Category C
Animal reproduction studies have not been conducted with mepivacaine. There
are no adequate and well-controlled studies in pregnant women of the effect
of mepivacaine on the developing fetus. Mepivacaine hydrochloride should be
used during pregnancy only if the potential benefit justifies the potential
risk to the fetus. This does not preclude the use of mepivacaine at term for
obstetrical anesthesia or analgesia. (See Labor and Delivery .)
Mepivacaine has been used for obstetrical analgesia by the epidural, caudal,
and paracervical routes without evidence of adverse effects on the fetus when
no more than the maximum safe dosages are used and strict adherence to technique
is followed.
Labor and Delivery
Local anesthetics 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 Pharmacokinetics CLINICAL PHARMACOLOGY
.) The incidence and degree of toxicity depend upon the procedure performed,
the type and amount of drug used, and the technique of drug administration.
Adverse reactions in the parturient, fetus, and neonate involve alterations
of the central nervous system, peripheral vascular tone, and cardiac function.
Maternal hypotension has resulted from regional anesthesia. Local anesthetics
produce vasodilation by blocking sympathetic nerves. Elevating the patient's
legs and positioning her on her left side will help prevent decreases in blood
pressure. The fetal heart rate also should be monitored continuously and electronic
fetal monitoring is highly advisable.
Epidural, paracervical, caudal, or pudendal anesthesia may alter the forces
of parturition through changes in uterine contractility or maternal expulsive
efforts. In one study, paracervical block anesthesia was associated with a decrease
in the mean duration of first stage labor and facilitation of cervical dilation.
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.
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.
Fetal bradycardia may occur in 20 to 30 percent of patients receiving paracervical
block anesthesia with the amide-type local anesthetics and may be associated
with fetal acidosis. Fetal heart rate should always be monitored during paracervical
anesthesia. Added risk appears to be present in prematurity, postmaturity, toxemia
of pregnancy, and fetal distress. The physician should weigh the possible advantages
against dangers when considering paracervical block in these conditions. Careful
adherence to recommended dosage is of the utmost importance in obstetrical paracervical
block. Failure to achieve adequate analgesia with recommended doses should arouse
suspicion of intravascular or fetal intracranial injection.
Cases compatible with unintended fetal intracranial injection of local anesthetic
solution have been reported following intended paracervical or pudendal block
or both. Babies so affected present with unexplained neonatal depression at
birth which correlates with high local anesthetic serum levels and usually manifest
seizures within six hours. Prompt use of supportive measures combined with forced
urinary excretion of the local anesthetic has been used successfully to manage
this complication.
Case reports of maternal convulsions and cardiovascular collapse following
use of some local anesthetics for paracervical block in early pregnancy (as
anesthesia for elective abortion) suggest that systemic absorption under these
circumstances may be rapid. 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.
It is extremely important to avoid aortocaval compression by the gravid uterus
during administration of regional block to parturients. To do this, the patient
must be maintained in the left lateral decubitus position or a blanket roll
or sandbag may be placed beneath the right hip and the gravid uterus displaced
to the left.
Nursing Mothers
It is not known whether local anesthetic drugs are excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
local anesthetics are administered to a nursing woman.
Pediatric Use
Guidelines for the administration of mepivacaine to pediatric patients are
presented in DOSAGE AND ADMINISTRATION .
Geriatric Use
Clinical studies and other reported clinical experience indicates that use
of the drug in elderly patients requires a decreased dosage. (See CLINICAL PHARMACOLOGY
, PRECAUTIONS
, General , and DOSAGE AND ADMINISTRATION).
Mepivacaine and mepivacaine metabolites are known to be substantially excreted
by the kidney, and the risk of toxic reactions to this drug may be greater in
patients with impaired renal function. Because elderly patients are more likely
to have decreased renal function, care should be taken in dose selection, and
it may be useful to monitor renal function.
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