Local anesthetic for periodontal administration
Not for injection.
(lidocaine and prilocaine periodontal gel) 2.5%/2.5%
INDICATIONS AND USAGE
Oraqix® is an amide local anesthetic indicated for adults who require localized
anesthesia in periodontal pockets during scaling and/or root planing.
Oraqix® is contraindicated in patients with a known history of hypersensitivity
to local anesthetics of the amide type or to any other component of the product.
Prilocaine can cause elevated methemoglobin levels particularly in conjunction
with methemoglobin-inducing agents. Methemoglobinemia has also been
reported in a few cases in association with lidocaine treatment. Patients with
glucose-6-phosphate dehydrogenase defciency or congenital or idiopathic
methemoglobinemia are more susceptible to drug-induced methemoglobinemia.
Oraqix® should not be used in those patients with congenital or idiopathic
methemoglobinemia and in infants under the age of twelve months who are
receiving treatment with methemoglobin-inducing agents. Signs and symptoms
of methemoglobinemia may be delayed some hours after exposure. Initial
signs and symptoms of methemoglobinemia are characterized by a slate grey
cyanosis seen in, e.g., buccal mucous membranes, lips and nail beds. In severe
cases symptoms may include central cyanosis, headache, lethargy, dizziness,
fatigue, syncope, dyspnea, CNS depression, seizures, dysrhythmia and shock.
Methemoglobinemia should be considered if central cyanosis unresponsive to
oxygen therapy occurs, especially if metHb-inducing agents have been used.
Calculated oxygen saturation and pulse oximetry are inaccurate in the setting
of methemoglobinemia. The diagnosis can be confrmed by an elevated
methemoglobin level measured with co-oximetry. Normally, metHb levels are
<1%, and cyanosis may not be evident until a level of at least 10% is present.
The development of methemoglobinemia is generally dose related. The
individual maximum level of metHb in blood ranged from 0.8% to 1.7% following
administration of the maximum dose of 8. 5 g Oraqix®.
Management of Methemoglobinemia: Clinically signifcant symptoms of
methemoglobinemia should be treated with a standard clinical regimen such as
a slow intravenous infection of methylene blue at a dosage of 1-2 mg/kg given
over a fve minute period.
Patients taking drugs associated with drug-induced methemoglobinemia
such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine,
chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin,
nitroglycerin, nitroprusside, pamaquine, para-aminosalicylic acid, phenacetin,
phenobarbital, phenytoin, primaquine, and quinine are also at greater risk for
developing methemoglobinemia. Treatment with Oraqix® should be avoided in
patients with any of the above conditions or with a previous history of problems
in connection with prilocaine treatment.
General: DO NOT INJECT Oraqix® should not be used with standard dental
syringes. Only use this product with the Oraqix® blunt-tipped applicator. Allergic
and anaphylactic reactions associated with lidocaine or prilocaine in Oraqix®
can occur. These reactions may be characterized by urticaria, angioedema,
bronchospasm, and shock. If these reactions occur they should be managed by
Oraqix® coming in contact with the eye should be avoided because animal
studies have demonstrated severe eye irritation. A loss of protective refexes may
allow corneal irritation and potential abrasion. If eye contact occurs, immediately
rinse the eye with water or saline and protect it until normal sensation returns.
In addition, the patient should be evaluated by an ophthalmologist, as indicated.
However, Oraqix® should be used with caution in patients with a history of drug
sensitivities, especially if the etiologic agent is uncertain. Patients with severe
hepatic disease are at greater risk of developing toxic plasma concentrations of
lidocaine and prilocaine.
Information for Patients: Patients should be cautioned to avoid injury to the
treated area, or exposure to extreme hot or cold temperatures, until complete
sensation has returned.
Drug Interactions: Oraqix® should be used with caution in combination with
dental injection anesthesia, other local anesthetics, or agents structurally
related to local anesthetics, e.g., Class 1 antiarrhythmics such as tocainide and
mexiletine, as the toxic effects of these drugs are likely to be additive and
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY:
Carcinogenesis - Long-term studies in animals have not been performed to
evaluate the carcinogenic potential of either lidocaine or prilocaine. Chronic
oral toxicity studies of o-toluidine, a metabolite of prilocaine, have shown that
this compound is a carcinogen in both mice and rats. The tumors associated
with o-toluidine included hepatocarcinomas/ adenomas in female mice,
multiple occurrences of hemangiosarcomas/hemangiomas in both sexes of
mice, sarcomas of multiple organs, transitional-cell carcinomas/papillomas of
urinary bladder in both sexes of rats, subcutaneous fbromas/fbrosarcomas and
mesotheliomas in male rats, and mammary gland fbroadenomas/adenomas
in female rats. These fndings were observed at the lowest tested dose of 150
mg/kg/day or greater over two years (estimated daily exposures in mice and
rats were approximately 6 and 12 times, respectively, the estimated exposure
to o-toluidine at the maximum recommended human dose of 8.5g of Oraqix®
gel on a mg/m2 basis). Complete conversion of prilocaine to its metabolite
otoluidine on a molar basis is assumed. This gives a conversion on a weight basis
of about 50% for prilocaine base (dependent on the molecular weights, i.e. 220
for prilocaine base and 107 for o-toluidine).
Mutagenesis - o-Toluidine, metabolite of prilocaine, was positive in Escherichia
coli DNA repair and phage-induction assays. Urine concentrates from rats treated
orally with 300 mg/kg otoluidine were mutagenic to Salmonella typhimurium
in the presence of metabolic activation. Several other tests on o-toluidine,
including reverse mutations in fve different Salmonella typhimurium strains with
or without metabolic activation, and single strand breaks in DNA of V79 Chinese
hamster cells, were negative.
USE IN PREGNANCY:
Teratogenic Effects: Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. Because
animal reproduction studies are not always predictive of human response,
Oraqix® should be used during pregnancy only if the benefts outweigh the
Nursing Mothers: Lidocaine and, possibly, prilocaine are excreted in breast milk.
Caution should be exercised when Oraqix® is administered to nursing women.
Pediatric Use: Safety and effectiveness in pediatric patients have not been
established. Very young children are more susceptible to methemoglobinemia.
There have been reports of clinically signifcant methemoglobinemia in infants
and children following excessive applications of lidocaine 2.5% topical cream
Geriatric Use: In general, dose selection for an elderly patient should be cautious,
usually starting at the low end of the dosing range, refecting the greater
frequency of decreased hepatic, renal, or cardiac function, and of concomitant
disease or other drug therapy.
A causal relationship between the reported adverse reactions and Oraqix®
could neither be established nor ruled out.
Following SRP treatment with Oraqix® in 391 patients, the most frequent
adverse events were local reactions in the oral cavity. These events, which
occurred in approximately 15% of patients, included pain, soreness, irritation,
numbness, vesicles, ulcerations, edema and/or redness in the treated area. Of
the 391 patients treated with Oraqix®, fve developed ulcerative lesions and two
developed vesicles of mild to moderate severity near the site of SRP. In addition,
ulcerative lesions in or near the treated area were also reported for three out
of 168 patients who received placebo. Other symptoms reported in more than
one patient were headache, taste perversion, nausea, fatigue, fu, respiratory
infection, musculoskeletal pain and accident/injury.
Local anesthetic toxicity emergency: If other local anesthetics are administered
at the same time as Oraqix, e.g. topically or by injection, the toxic effects are
thought to be additive and could result in an overdose with systemic toxic
reactions. There is generally an increase in severity of symptoms with increasing
plasma concentrations of lidocaine and/or prilocaine. Systemic CNS toxicity may
occur over a range of plasma concentrations of local anesthetics. CNS toxicity
may typically be found around 5000 ng/mL of lidocaine, however a small
number of patients reportedly may show signs of toxicity at approximately 1000
ng/mL. Pharmacological thresholds for prilocaine are poorly defned. Central
nervous system (CNS) symptoms usually precede cardiovascular manifestations.
The plasma level of lidocaine observed after the maximum recommended dose
( 5 cartridges) of Oraqix® in 11 patients exposed over 3 hours ranged from 157-
552 ng/mL with a mean of 284 ng/mL ± 122 SD. The corresponding fgure for
prilocaine was 53-181 ng/mL with a mean of 106 ± 45 SD.
Clinical symptoms of systemic toxicity include CNS excitation and/or depression
(lightheadedness, hyperacusis, visual disturbances, muscular tremors, and
general convulsions). Lidocaine and/or prilocaine may cause decreases in cardiac
output, total peripheral resistance and mean arterial pressure. These changes
may be attributable to direct depressant effects of these local anesthetic
agents on the cardiovascular system. Cardiovascular manifestations may include
hypotension, bradycardia, arrhythmia, and cardiovascular collapse.
Management of Local Anesthetic Emergencies: Should severe CNS or
cardiovascular symptoms occur, these may be treated symptomatically by, for
example, the administration of anticonvulsive drugs, respiratory support and/or
cardiovascular resuscitation as necessary.
DO NOT FREEZE. Some components of Oraqix® may precipitate if cartridges
are frozen. Cartridges should not be used if they contain a precipitate. Do not
use dental cartridge warmers with Oraqix®. The heat will cause the product to
York, PA 17404 USA
By: Recipharm Karlskoga AB Karlskoga Sweden