4% ASTRACAINE DENTAL WITH EPINEPHRINE

1 Dosing Considerations As with all local anesthetics, the dosage varies and depends upon the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, individual tolerance and the technique of anesthesia.

The lowest dosage needed to provide effective anesthesia should be administered. To prevent the serious systemic adverse reactions associated with high plasma concentrations of local anesthetics or epinephrine, procedures to avoid intravascular injection should be used.

The lowest dose that results in effective anesthesia should be used. Injections should be made slowly or in incremental doses, with frequent aspirations before and during the injection to avoid intravascular injection. After each injection, the patient’s cardiovascular and respiratory (adequacy of ventilation) vital signs, and state of consciousness should be monitored.

The blood levels of articaine or its metabolites may accumulate significantly with repeated dosing. Tolerance to elevated blood levels varies with the status of the patient. 5 ml or 7 cartridges. 175 ml of solution per kg. 4 40-216 The above-suggested volumes serve only as a guide for normal healthy adults.

Other volumes may be used provided that the total maximum recommended dose is not exceeded. The duration of the anaesthesia during which an operation can be performed is about one hour (pulpal analgesia) depending on the technique used, and on the procedure.

Lower dose is recommended in patients with severe hepatic/renal insufficiency. Pediatric (4-17 years of age) Dosages in pediatric should be reduced commensurate with their age and weight. Experience in pediatric younger than 4 years of age has not been documented.

The dosage should not exceed 5 mg/kg body weight in pediatric between the ages of 4 and 12 with a maximum dose of 275 mg articaine for a healthy child of 55 kg body weight. 5 - 2 ml. 005 mg/mL) in pediatric under the age of 4 years is not recommended.

Geriatrics (>65 years of age) Consider dose adjustment (minimum quantity for sufficient anaesthesia) in older and frail patients as the clearance and volume of distribution of articaine after infiltration anaesthesia are significantly lower than in healthy adult patients.

1 Adverse Reaction Overview Adverse Reactions from Clinical Trials: The reported adverse events are derived from clinical trials in the US and UK. Of the 1,325 patients treated in the primary clinical trials, 882 were exposed to articaine hydrochloride 4% (40 mg/mL) with epinephrine (adrenaline) 1:100,000 injection.

Adverse events in controlled trials with an incidence of 1% or greater in patients administered articaine hydrochloride 4% (40 mg/mL) with epinephrine (adrenaline) 1:100,000 injection Body system Articaine hydrochloride 4% with adrenaline 1:100,000 injection N (%) Number of patients 882 (100%) Body as whole Face oedema Headache Infection Pain 13 (1%) 31 (4%) 10 (1%) 114 (13%) Digestive system Gingivitis 13 (1%) Nervous system Paraesthesia 11 (1%) The following list includes adverse and concurrent events that were recorded in 1 or more patients, but occurred at an overall rate of less than 1%, and were considered clinically relevant.

 Body as a Whole - abdominal pain, accidental injury, asthenia, back pain, injection site pain, malaise, neck pain.  Cardiovascular System - hemorrhage, migraine, syncope, tachycardia.  Digestive System - constipation, diarrhea, 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, paraesthesia, somnolence.

 Respiratory System - pharyngitis, rhinitis.  Skin and Appendages - pruritis, skin disorder.  Special Senses - ear pain, taste perversion.  Urogenital System - dysmenorrhea.

Adverse Reactions Due to Articaine:

Toxic reactions (showing an abnormally high concentration of local anaesthetic in the blood) may appear either immediately, by accidental intravascular injection or later, by true overdose following an injection of an excessive quantity of anaesthetic solution.

Symptoms include:  Symptoms showing effects on the central nervous system: nervousness, shaking, yawning, trembling, apprehension, nystagmus, logorrhoea, headache, nausea, buzzing in Page 12 of 26 the ears. These signs, when they appear, require rapid corrective measures to prevent possible worsening.

 Respiratory symptoms: tachypnoea, then bradypnoea, which could lead to apnoea.  Cardiovascular signs: reduction in the contractile power of the myocardium, lowering of heart rate and drop in blood pressure. Common ≥ 1% and <10% Headache, facial oedema, gingivitis.

Disruption of nerve transmission (para-, hypo- and dysaesthesia) may appear after articaine administration. Resolution usually occurs within two weeks. 1% and <1% Nausea General disorders and administration site conditions Adverse reactions to 4% ASTRACAINE® Dental (articaine hydrochloride) with Epinephrine (epinephrine bitartrate) are characteristic of those associated with amide-type local anesthetics and/or vasoconstrictors.

Adverse reactions may result from high plasma levels due to excessive dosage, rapid absorption or inadvertent intravascular injection, or may also result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.

Such reactions are systemic in nature and involve the central nervous system and/or the cardiovascular system. Local swelling, injection site pain, ulceration, exfoliation and necrosis may occur as a result of injection site tissue trauma.

Soft tissue injuries may occur whilst the area remains anesthetized. Local reactions may also include ischaemic injury or necrosis, which may be related to vascular spasm. Central Nervous System CNS manifestations are excitatory and/or depressant, and may be characterized by nausea, vomiting, headache, anxiety, restlessness, nervousness, dizziness, vertigo, blurred vision and tremors at the onset and then followed by drowsiness, convulsions, unconsciousness and possibly respiratory arrest.

The excitatory reactions may be very brief or may not occur at all, in which case, the initial manifestations of toxicity may be drowsiness, merging into unconsciousness and respiratory arrest. Swelling and persistent paresthesia of the lips and oral tissues have been reported after blocking of the inferior alveolar nerve.

Cardiovascular System Cardiovascular reactions are depressant, and may be characterized by hypotension, myocardial depression, vasodilatation, vasoconstriction, hypertension, bradycardia, tachycardia, hypotension, palpitations, atrioventricular block, circulatory collapse and possibly cardiac arrest.

Allergic Allergic and hypersensitivity reactions are characterized by erythema, chills, abdominal pain, bronchospasm, dyspnea, skin rashes, cutaneous lesions, urticaria, pruritus , edema or anaphylactoid reactions with circulatory collapse.

Allergic reactions to sodium metabisulfite are Page 13 of 26 rare; they are more common in patients with steroid-dependent asthma, and can range from mild asthma attacks to fatal anaphylactic shock. The detection of sensitivity by skin testing is of doubtful value.

2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. 3 Postmarketing Experience Persistent paresthesias of the lips, tongue, and oral tissues have been reported with use of articaine hydrochloride, with slow, incomplete, or no recovery.

These post-marketing events have been reported chiefly following nerve blocks in the mandible and have involved the trigeminal nerve and its branches.

General The safety and effectiveness of local anesthetics depend upon proper dosage, correct administration technique, adequate precautions and readiness for management of emergencies. Local anaesthetics should only be used by clinicians trained in the diagnosis and management of dose-related toxicity and other acute emergencies which may arise from their use.

Resuscitative drugs and equipment should be immediately available before local anesthetic is used (see ADVERSE REACTIONS AND OVERDOSAGE). Patients should be advised to exert caution in order to avoid inadvertent trauma to oral and buccal soft tissue from chewing or biting until normal sensation returns.

Persistent paresthesia of oral structures has been reported with slow, incomplete, or no recovery following nerve blocks. Cardiovascular As with other local anesthetics combined with epinephrine, excessive plasma levels can depress the myocardium, which may lead to heart block, cardiac arrhythmia, tachycardia, bradycardia, blood pressure changes (usually hypotension) and possibly fatal cardiac arrest.

005 mg/mL) is not recommended in patients with impaired cardiovascular function (see CONTRAINDICATIONS). ) (see CONTRAINDICATIONS). 005 mg/mL) should be used cautiously in  patients with peripheral vascular disease  patients currently or recently receiving drugs known to produce blood pressure alterations (for example phenothiazines), as either severe and sustained hypotension or hypertension may occur The medical history of the patients should be checked for certain conditions in which the drug is contraindicated.

Close monitoring for symptoms of cardiovascular collapse should be recommended. Driving and Operating Machinery Due caution should be exercised when driving or operating a vehicle or potentially dangerous machinery. 005 mg/mL) is contraindicated in patients with thyrotoxicosis (see CONTRAINDICAT IONS).

005 mg/mL) should be used with extreme caution in patients whose medical history and physical evaluation suggest the existence of diabetes who are on oral hypoglycemics (see DRUG INTERACTION). Use of articaine hydrochloride with epinephrine in hyperthyroid states may cause additive cardiac effects (tachycardia, arrhythmia, increased cardiac output, and cardiac ischemia.

Hematologic Articaine hydrochloride, like other local anesthetics, has the potential to cause methemoglobinemia. There is an increased risk observed with epidural anesthesia, but the incidence is rare in dental procedures when used as directed.

Methemoglobinemia values of less than 20% usually do not produce any clinical symptoms. The most common clinical sign of methemoglobinemia is cyanosis of the nail beds and lips. Methemoglobinemia can be rapidly reversed by intravenous administration of 1-2 mg/kg body weight of methylene blue over a 5-minute period.

005 mg/mL) is contraindicated in patients with severe hepatic/renal insufficiency (see CONTRAINDICAT IONS). Lower dose is Page 9 of 26 recommended in these patients (see DOSAGE AND ADMINISTRATION). 005 mg/mL) is contraindicated in patients with bronchial asthma (see CONTRAINDICATIONS).

The sodium metabisulphite component can precipitate hypersensitivity reactions in such patients (see CONTRAINDICAT IONS). 005 mg/mL) is contraindicated in patients who are taking certain drugs (MAO-inhibitors etc) (see CONTRAINDICATIONS).

Neurologic As with other local anesthetics combined with epinephrine, excessive plasma levels cause systemic reactions involving the central nervous system, characterized by excitation and/or depression (see OVERDOSAGE). Intravascular injection of even small doses in the head and neck area may cause CNS toxicity.

Patients with acidosis and/or hypoxia are at an increased risk of CNS and cardiovascular toxicity. Early neurological features include perioral tingling, tinnitus, and slurred speech. Lightheadedness and tremor may also occur, as may a change in mental status with confusion or agitation.

However, LAST can occur without these characteristic premonitory signs. The excitatory neurological phase culminates in generalized convulsions. This may lead to the depressive phase of coma and respiratory depression. The immediate management involves the general safety and resuscitation measures that are crucial in any emergency.

First, stop injecting the LA and secure airway, breathing, and circulation. If the patient is in cardiac arrest, cardiopulmonary resuscitation (CPR) must commence. Alternatively, if the patient still has a cardiac output, 100% oxygen should be administered and the airway secured as necessary.

V. access needs to be confirmed or established. Seizures should be addressed quickly and treatment options include a benzodiazepine or thiopental. Unintentional or inadvertent intravascular administration can be fatal. Aspiration to […]

005 mg/mL) is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container and in patients with a known hypersensitivity to sulphite especially in steroid-dependent asthma patients who may develop bronchospasm and anaphylactic shock.

For a complete listing, see Dosage Forms, Strengths, Composition and Packaging. As with all vasoconstrictors, epinephrine is contraindicated in:  children under 4 years of age  the use of a vasoconstrictor (epinephrine) is contraindicated for anaesthesia of fingers, toes, tip of nose, ears and penis due to risk of ischemia (necrosis).

g. propranolol),(due to the risk of hypertensive crisis or severe bradycardia)  patients with pheochromocytoma  patients with thyrotoxicosis  patients currently or recently receiving treatment with tricyclic antidepressants or Monoamino oxidase (MAO) inhibitors  patients taking ergot type drugs, inhalation type drugs such as halothane.

 patients with severe hepatic/renal insufficiency  patients with bronchial asthma. They should also not be used when there is inflammation and/or sepsis in the region near the proposed injection site. Intravascular use is contraindicated.