Septocaine and Epinephrine (Page 2 of 5)

5.3 Vasoconstrictor Toxicity

SEPTOCAINE contains epinephrine, a vasoconstrictor that can cause local or systemic toxicity and should be used cautiously. Local toxicity may include ischemic injury or necrosis, which may be related to vascular spasm. SEPTOCAINE should be used with caution in patients during and following the administration of potent general anesthetic agents, since cardiac arrhythmias may occur under such conditions. Patients with peripheral vascular disease and those with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response.

The American Heart Association has made the following recommendation regarding the use of local anesthetics with vasoconstrictors in patients with ischemic heart disease: “Vasoconstrictor agents should be used in local anesthesia solutions during dental practice only when it is clear that the procedure will be shortened or the analgesia rendered more profound. When a vasoconstrictor is indicated, extreme care should be taken to avoid intravascular injection. The minimum possible amount of vasoconstrictor should be used.” (Kaplan, 1986).

It is essential to aspirate before any injection to avoid administration of the drug into the blood stream.

5.4 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 central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue SEPTOCAINE 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.

5.5 Anaphylaxis and Allergic-Type Reactions

SEPTOCAINE contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

6 ADVERSE REACTIONS

Reactions to articaine are characteristic of those associated with other amide-type local anesthetics. Adverse reactions to this group of drugs may also result from excessive plasma levels (which may be due to overdosage, unintentional intravascular injection, or slow metabolic degradation), injection technique, volume of injection, or hypersensitivity or they may be idiosyncratic.

6.1 Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The reported adverse reactions are derived from clinical trials in the United States and the United Kingdom. Table 2 displays the adverse reactions reported in clinical trials where 882 individuals were exposed to SEPTOCAINE containing epinephrine 1:100,000. Table 3 displays the adverse reactions reported in clinical trials where 182 individuals were exposed to SEPTOCAINE containing epinephrine 1:100,000 and 179 individuals were exposed to SEPTOCAINE containing epinephrine 1:200,000.

Adverse reactions observed in at least 1% of patients:

Table 2: Adverse Reactions in Controlled Trials with an Incidence of 1% or Greater in Patients Administered SEPTOCAINE containing Epinephrine 1:100,000

Body System/Reaction	SEPTOCAINE containing epinephrine 1:100,000 (N=882) Incidence
Body as a whole
Face Edema	13 (1%)
Headache	31 (4%)
Infection	10 (1%)
Pain	114 (13%)
Digestive system
Gingivitis	13 (1%)
Nervous system
Paresthesia	11 (1%)

Table 3: Adverse Reactions in Controlled Trials with an Incidence of 1% or Greater in Patients Administered Septocaine containing Epinephrine 1:200,000 and Septocaine containing Epinephrine 1:100,000

Reaction	SEPTOCAINE with epinephrine 1:200,000 (N=179)Incidence	SEPTOCAINE with epinephrine 1:100,000 (N=182)Incidence
Any adverse reaction	33 (18%)	35 (19%)
Pain	11 (6.1%)	14 (7.6%)
Headache	9 (5%)	6 (3.2%)
Positive blood aspiration into syringe	3 (1.6%)	6 (3.2%)
Swelling	3 (1.6%)	5 (2.7%)
Trismus	1 (0.5%)	3 (1.6%)
Nausea and emesis	3 (1.6%)	0 (0%)
Sleepiness	2 (1.1%)	1 (0.5%)
Numbness and tingling	1 (0.5%)	2 (1%)
Palpitation	0 (0%)	2 (1.%)
Ear symptoms (earache, otitis media)	1 (0.5%)	2 (1%)
Cough, persistent cough	0 (0%)	2 (1%)

Adverse reactions observed in less than 1% of patients:

Table 4: Adverse Reactions in Controlled Trials with an Incidence of Less than 1% but Considered Clinically Relevant in Patients Administered SEPTOCAINE

Body System	Reactions
Body as a Whole	Asthenia; back pain; injection site pain; burning sensation above injection site; malaise; neck pain
Cardiovascular System	Hemorrhage; migraine; syncope; tachycardia; elevated blood pressure
Digestive System	Dyspepsia; glossitis; gum hemorrhage; mouth ulceration; nausea; stomatitis; tongue edemas; tooth disorder; vomiting
Hemic and Lymphatic System	Ecchymosis; lymphadenopathy
Metabolic and Nutritional System	Edema; thirst
Musculoskeletal System	Arthralgia; myalgia; osteomyelitis
Nervous System	Dizziness; dry mouth; facial paralysis; hyperesthesia; increased salivation; nervousness; neuropathy; paresthesia; somnolence; exacerbation of Kearns-Sayre Syndrome
Respiratory System	Pharyngitis; rhinitis; sinus pain; sinus congestion
Skin and Appendages	Pruritus; skin disorder
Special Senses	Ear pain; taste perversion