Consumer medicine information

DELTAZINE 1:100,000

Articaine hydrochloride; Adrenaline (epinephrine) acid tartrate

BRAND INFORMATION

Brand name

Deltazine Injection

Active ingredient

Articaine hydrochloride; Adrenaline (epinephrine) acid tartrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DELTAZINE 1:100,000.

WHAT'S IN YOUR MEDICINE

Active ingredients
2.2 mL Cartridge:

Articaine hydrochloride 88.0 mg
Adrenaline (as acid tartrate) 22.0 µg

Active ingredients
1.7mL Cartridge:

Articaine hydrochloride 68.0 mg
Adrenaline (as acid tartrate) 17.0 µg

Other ingredients:
Sodium chloride, sodium metabisulfite, sodium hydroxide solution, water for injections.

Presentation:

Box of 50 cartridges single use, containing each 1.7 mL of solution
Box of 50 cartridges single use, containing each 2.2 mL of solution

WHAT IS YOUR MEDICINE USED FOR, AND HOW DOES IT WORK

DELTAZINE is given by injection to cause loss of feeling before and during dental procedures. It contains two active ingredients:
Articaine hydrochloride, a local anaesthetic to prevent the pain, and adrenaline tartrate, a vasoconstrictor, which makes it last longer (adrenaline narrows the blood vessels at the site of injection, which keeps the anaesthetic where it's needed for a longer time) and controls bleeding during the surgery.

ADVICE BEFORE USING THE MEDICINAL PRODUCT

In deciding to use a medicine, the risks of using the medicine must be weighed against the good it will do. This is a decision you and your dentist will make before treatment.

This product should not be used if any of the following apply to you:

  • You are allergic to adrenaline, articaine, or any local anaesthetic and any other ingredient included in the product.
  • You are asthmatic or have broncho-spasmic (difficulty in breathing) reactions to sulfites.
  • You have arterial hypertension (high blood pressure), coronary disease or valvular cardiac disease (heart or circulation problems).
  • You have an overactive thyroid gland, whether or not treated for this.
  • You have cerebral arteriosclerosis (hardening in the brain arteries).
  • You have an inflammation or infection in the region of the proposed injection.
  • You have diabetes.
  • Children under the age of 4 years old.

You must tell your dentist if you have the following conditions:

  • You have problems with your heart, blood vessels and heart rhythm.
  • You have epilepsy.
  • You have hepatic (liver) or renal (kidney) diseases.
  • You have malignant hyperthermia (history or experience of a rapid rise in body temperature to a dangerously high level brought on by general anaesthesia).
  • You have prostatic hypertrophy (enlarged prostate).
  • You are pregnant or breast-feeding. If Deltazine is used when you are breast-feeding you should not breast-feed for at least 48 hours following use of Deltazine .
  • You have any other medical conditions.

DELTAZINE MAY INTERACT WITH OTHER MEDICINES

It should not be used if you are taking:

  • Mono Amine Oxidase Inhibitors (MAOI) or tricyclic antidepressants (medicines used to treat depression), or have taken this type of medicine within the last two weeks..
  • Phenothiazines (medicines used to treat mental illnesses).
  • Vasopressor drugs (medicines used to elevate blood pressure).
  • Ergot type oxytocic drugs (medicines used to induce labour in pregnant women).

It should be used with caution if you are taking:

  • Beta-blockers or guanethidine (medicines used to lower high blood pressure and/or treat heart problems).
  • Hypoglycaemics (medicines used to treat high blood sugar).
  • Anti-arrhythmic drugs and amiodarone (medicines used to treat irregular heartbeats).
  • Antiepileptic drugs (medicines used to treat epilepsy).
  • Cardiac glycosides (medicines used to treat heart failure).
  • Cimetidine (medicine used to treat reflux and stomach or duodenal ulcers).
  • Thyroid hormone.
  • Inhalational anaesthetics.

Please make sure that you tell your dentist about all medicines which you are taking, whether prescribed or purchased over the counter.

HOW THIS MEDICINE WILL BE USED

Your dentist will explain to you why you are being treated with DELTAZINE and what dose you will be administered. Your dentist will inject Deltazine into your oral (mouth) cavity. This will result in an area of numbness at the site of the injection. One cartridge is usually sufficient but your dentist may give you a greater quantity. He will adjust the dosage according to your age, your health, your weight and the dental work to be performed. If only a portion of a cartridge is used the remainder must be discarded.

While you are using DELTAZINE

Things you must not do:

  • Do not eat or drink anything until the feeling has returned to your mouth. You may burn or bite yourself.

Things to be careful of:

  • Be careful driving or operating machinery until you know how DELTAZINE affects you. You may be drowsy and your reflexes may be slow.
  • Do not drink alcohol immediately before or after you are given DELTAZINE .

If you drink alcohol while you are being given DELTAZINE , your blood pressure may drop making you feel dizzy and faint.

Please talk to your dentist or pharmacist about these possibilities if you think they may bother you.

SIDE EFFECTS

DELTAZINE like most other medicines may cause side effects in some patients. Although not all of these side effects may occur, if they do occur they may need medical attention. While you are in your dentist's office, your dentist will carefully follow the effects of DELTAZINE . However, some effects may not be noticed or appear later. Check with your dentist if any of the following side effects occur:

Common reactions:

  • infection and pain in the injection site
  • tingling and numbness of the hand and feet or increased feeling or sensitivity of the skin
  • you are feeling nervous, nauseous or dizzy
  • you have a headache
  • you are trembling, have buzzing in the ears, blurred vision or have any abnormal feeling
  • your breathing is difficult
  • your heart is beating slowly or irregularly
  • you have facial swelling or inflammation of gums
  • you have skin rash, hives or itching
  • you may have a loss of sensation and muscle function following the injection of DELTAZINE. Resolution occurs generally within two weeks.

Very rare reactions:

There are some serious unwanted reactions, which may happen if DELTAZINE is given into the veins or you are very sensitive to it, it may cause:

  • Fits.
  • Unconsciousness.
  • Breathing problems.
  • Low blood pressure.
  • Slow heart beat.
  • Collapse.

If experiencing any of these, you may have had a serious (allergic) reaction to DELTAZINE . You may need urgent medical attention or hospitalisation.

Tell your dentist if you notice anything else that is making you feel unwell.

Some people may get other side effects while using DELTAZINE .

You may be hypersensitive to sulfites and therefore show allergic symptoms to DELTAZINE such as breathing difficulties and/or skin reactions.

If you have problems with your blood vessels, circulation or have high blood pressure, you may react exaggeratedly to the vasoconstrictor contained in DELTAZINE and develop a small injury at the site of injection.

IN CASE OF OVERDOSE

Your dentist will determine the amount of solution, which is needed to provide pain control during your treatment, and it is very unlikely that you would receive too much DELTAZINE . However, some persons tolerate articaine and adrenaline less well than others and the signs and symptoms of too much of these substances in your blood include: nervousness, dizziness, blurred vision, nausea, trembling, convulsions, slow or irregular heart beat, troubled breathing.

Tell your dentist immediately if you experience any of these symptoms during or shortly after your treatment.

STORAGE CONDITIONS

It is most unlikely that you will be asked to look after this medicine. Your dentist will keep it below 25°C and protected from light. He will not use this medicine after the expiry date printed on the package.

All medicines must be kept in a safe place out of the reach of children.

FURTHER INFORMATION

Only a dentist can administer this product. This leaflet provides only a summary of the information known about DELTAZINE . If you have any questions, want to know more about this medicine, or have some doubts, ask your dentist.

SPONSOR: Ato Zizine Pty Ltd, 14 Cliffbrook Crescent, Emu Plains, NSW 2750, Australia.

DATE OF INFORMATION: May, 2004

AUST R: 101551 (50 cartridges of 1.7 mL

AUST R: 101552 (50 cartridges of 2.2 mL)

DELTAZINE 1:100,000

(Articaine hydrochloride 4% with adrenaline 1:100 000, solution for injection)

BRAND INFORMATION

Brand name

Deltazine Injection

Active ingredient

Articaine hydrochloride; Adrenaline (epinephrine) acid tartrate

Schedule

S4

 

Name of the medicine

Articaine hydrochloride 4% with adrenaline 1:100,000.

Excipients

See Table 1.

Description

Articaine hydrochloride.

Chemical name: (±)-4-methyl-3- [2-(propylamino)- propionamido]-2-thiophene- carboxylic acid, methyl ester hydrochloride. Molecular formula: C13H20N2O3S.HCl. MW: 320.84. CAS: 23964-57-0. Articaine hydrochloride is a local anaesthetic and is a racemic mixture. Articaine hydrochloride has a partition coefficient in n-octanol/ Soerensen buffer (pH: 7.35) of 17 and a pKa of 7.8. It is a white to almost white powder and odourless.

Adrenaline acid tartrate.

Chemical name: (R)-1-(3,4-di-hydroxyphenyl)- 2-methylamino-ethanol hydrogen tartrate. Molecular formula: C9H13NO3.C4H6O6. MW: 333.3. CAS: 51-42-3. A white or greyish white or light brownish grey, odourless, crystalline powder, which slowly darkens on exposure to air and light. Adrenaline acid tartrate 1.8 mg is approximately equivalent to adrenaline 1 mg.

Actions

Articaine hydrochloride is a local anaesthetic. Adrenaline acid tartrate is a vasoconstrictor.

Pharmacology

Pharmacodynamics.

Articaine is a local anaesthetic of the amide type. Preclinical pharmacodynamic studies show that the mechanism of action of articaine is similar to that of other commonly used anaesthetics (lidocaine, procaine, prilocaine). Inhibition of the generation and the conduction of the action potential but no change in resting potential is shown.
Articaine blocks sodium channels and, with lower sensitivity, potassium channels at neutral pH. Inhibition of muscle activation after nerve stimulation and depression of cardiac electrophysiological measurements demonstrate that articaine has the same pharmacological activities as other local anaesthetics. When injected close to sensitive nerve filaments, articaine has the reversible effect of blocking the conduction of painful sensations.
Adrenaline added to the solution reduces bleeding during surgery, slows down the passage of articaine into the general circulation and thus ensures the prolonged maintenance of an active tissue concentration.
Adrenaline acts on both adrenergic receptors of tissue innervated by sympathetic nerves, except for the sweat glands and arteries of the face. It is the most important α-receptor activator. Adrenaline stimulates the heart to increase output, raises the systolic blood pressure, lowers the diastolic blood pressure, relaxes bronchial spasm and mobilises liver glycogen, resulting in hyperglycaemia and possibly glycosuria.
The mean time to onset of anaesthesia after administration of articaine 4% with adrenaline 1:100,000 is about 3.5 minutes with a range of one to six minutes, and the mean duration of anaesthesia is about 68 minutes with a range of 20 to 175 minutes. The pulpal analgesia lasts 75 minutes and the bleeding during surgery is significantly reduced.

Pharmacokinetics

Absorption.

Following dental injection by the submucosal route of an articaine 4% solution containing adrenaline 1:200,000, articaine reaches peak blood concentration about 25 minutes after a single dose injection and 48 minutes after three doses. Peak plasma levels of articaine achieved after 68 minutes and 204 mg doses are 385 and 900 nanogram/mL, respectively.

Distribution.

Approximately 60 to 80% of articaine hydrochloride is bound to human serum albumin and γ-globulins at 37°C in vitro.

Metabolism.

Articaine HCl is rapidly metabolised by plasma carboxyesterase to its primary metabolite, articainic acid, which is inactive. Articainic acid concentration reaches its peak about 30 to 60 minutes following the peak in articaine concentration. In vitro studies show that the human liver microsome P450 isoenzyme system metabolises approximately 5 to 10% of the available articaine with nearly quantitative conversion to articainic acid.

Excretion.

The elimination half-life of articaine is about 1.8 hours and that of articainic acid is about 1.5 hours. Articaine is excreted primarily through urine with 53 to 57% of the administered dose eliminated in the first 24 hours following submucosal administration. Articainic acid is the primary metabolite in urine. A minor metabolite, articainic acid glucuronide, is also excreted in urine. Articaine constitutes only 2% of the total dose in excreted urine.

Special populations.

Effect of age.

No pharmacokinetic data are available in the following populations: elderly, children.

Race.

No pharmacokinetic data are available for different racial groups.

Renal and hepatic insufficiency.

No pharmacokinetic data are available for patients with hepatic or renal impairment.

Clinical Trials

Three randomised, double blind, active controlled studies were designed to evaluate effectiveness of Deltazine 1:100,000 as a dental anaesthetic. A total of 882 patients received Deltazine 1:100,000. Of these, 7% were between 4 and 16 years old, 87% were between 17 and 65 years old, and 6% were at least 65 years old. In addition, 53% of patients were female and 47% were male, with a racial/ ethnic distribution of 73% white, 11% Hispanic, 8% black, 5% Asian and 3% ‘other’ races/ ethnicities. These patients underwent simple dental procedures, single apical resections and single crown procedures, and complex dental procedures such as multiple extractions, multiple crowns and/or bridge procedures, multiple apical resections, alveolectomies, mucogingival operations and other surgical procedures on the bone. Deltazine 1:100,000 was administered as submucosal infiltration and/or nerve block. Efficacy was measured immediately following the procedure by having the patient and investigator rate the patient's procedural pain using a 10 cm visual analogue scale (VAS), in which a score of zero represented no pain, and a score of ten represented the worst pain imaginable. Mean patient and investigator VAS pain scores were 0.3 to 0.4 cm for simple procedures and 0.5 to 0.6 cm for complex procedures. These values are summarised in Table 2 below.
In clinical trials, 61 paediatric patients between the ages of 4 and 16 years received Deltazine 1:100,000. Among these paediatric patients, doses from 0.76 to 5.65 mg/kg (0.9 to 5.1 mL) were administered safely to 51 patients for simple procedures and doses between 0.37 and 7.48 mg/kg (0.7 to 3.9 mL) were administered safely to ten patients for complex procedures. However, there was insufficient exposure to Deltazine 1:100,000 at doses greater than 7.00 mg/kg in order to assess its safety in paediatric patients. No unusual adverse events were noted in these patients. Approximately 13% of these paediatric patients required additional injections of anaesthetic for complete anaesthesia.
In the clinical trials 54 patients between the ages of 65 and 75 years and eleven patients 75 years and over received Deltazine 1:100,000. Among all patients between 65 and 75 years, doses from 0.43 to 4.76 mg/kg (0.9 to 11.9 mL) were administered safely to 35 patients for simple procedures and doses from 1.05 to 4.27 mg/kg (1.3 to 6.8 mL) were administered safely to 19 patients for complex procedures. Among the eleven patients ≥ 75 years old, doses from 0.78 to 4.76 mg/kg (1.3 to 11.9 mL) were administered safely to seven patients for simple procedures and doses of 1.12 to 2.17 mg/kg (1.3 to 5.1 mL) were administered to four patients for complex procedures.

Indications

Local or regional anaesthesia for both simple and complex dental procedures in adults, adolescents and children 4 years of age and older.
Deltazine 1:100,000 is indicated only for dental procedures.

Contraindications

Articaine.

Specific allergies to articaine or to other anaesthetics of amide type, hypersensitivity to any local anaesthetic agent.

Vasoconstrictor.

Arterial hypertension, coronary disease, valvular cardiac disease (particularly sequelae to acute rheumatic fever), thyrotoxicosis (untreated), known sensitivity to sympathomimetic amines.
Hypersensitivity to sulfites (sodium metabisulfite is present in the formula as an antioxidant).
Injection by intravenous route.
Inflammation or sepsis in the region of the proposed injection.
Patients who have experienced bronchospasm after administration of any product which contains sulfites should not be given Deltazine.
Hypersensitivity to any other component of Deltazine.
Patients who are known or who have a history which suggests a deficiency in plasma cholinesterase activity (see Actions, Pharmacokinetics).
Patients receiving monoamine oxidase inhibitors (or who have received such an agent within two weeks) or tricyclic antidepressants.
Patients in whom there is a possibility that general anaesthesia might be required to complete the procedure.
Do not use under 4 years of age.

Precautions

When any local anaesthetic agent is used, resuscitative equipment and resuscitative drugs, including oxygen, should be immediately available in order to manage possible adverse reactions involving the cardiovascular, respiratory or central nervous systems. Because of the possibility of hypotension and bradycardia following major blocks, an intravenous (IV) cannula should be inserted before the local anaesthetic is injected. Delay in proper management of dose related toxicity, under ventilation from any cause and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and death.
Injection should always be made slowly with frequent aspirations to avoid inadvertent intravascular injection, which can produce cerebral symptoms even at low doses.
Note, however, that the absence of blood in the syringe does not assure that intravascular injection will be avoided. There should be careful monitoring of cardiovascular and respiratory vital signs after each injection.
Intravascular injection is strictly contraindicated. An accidental injection into a blood vessel may be associated with systemic adverse effects due to the circulating levels of adrenaline and/or articaine. Therefore, it is imperative to ensure that the needle being used for the injection does not go into a vessel.
Since amide type local anaesthetics are also metabolised by the liver, Deltazine should be used with caution in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolise local anaesthetics normally, are at greater risk of developing toxic plasma concentration.
Due to the presence of adrenaline, the product is not advised for diabetic subjects and for patients with thyrotoxicosis.

Use with caution in the following circumstances.

The lowest dosage that results in effective anaesthesia should be used to avoid high plasma levels and serious adverse effects. Repeated doses may cause significant increases in blood levels with each repeated dose due to slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients and children should be given reduced doses commensurate with their age and physical condition. Deltazine should also be used with caution in patients with heart block.
Local anaesthetic solutions containing a vasoconstrictor should be used with caution in areas of the body supplied by end arteries or having otherwise compromised blood supply. Patients with peripheral vascular disease and those with hypersensitive vascular disease may exhibit exaggerated vasoconstrictor response. Ischaemic injury or necrosis may result. Deltazine containing a vasoconstrictor should be used with caution in patients during or following the administration of potent general anaesthetic agents, since cardiac arrhythmias may occur under such conditions.
Many drugs used during the conduct of anaesthesia are considered potential triggering agents for familial malignant hyperthermia. Since it is not known whether amide type local anaesthetics may trigger this reaction, and since the need for supplemental general anaesthesia cannot be predicted in advance, it is suggested that a standard protocol for management should be available.
Solutions containing adrenaline should be used with caution in patients with hypertension, cardiac disease and/or cerebrovascular insufficiency.
Prostatic hypertrophy.
Deltazine should be administered with caution to subjects with cardiovascular disease, abnormalities of cardiac conduction or a history of epilepsy.
Deltazine should not be used in patients with a deficiency of plasma cholinesterase activity.
Systemic absorption of local anaesthetics can produce effects on the central nervous and cardiovascular systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.
Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be accomplished after each local anaesthetic injection. It should be kept in mind at such times that restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness may be early warning signs of central nervous system toxicity.
In vitro studies show that about 5 to 10% of articaine is metabolised by the human liver microsomal P450 isoenzyme system. However because no studies have been performed in patients with liver dysfunction, caution should be used in patients with severe hepatic disease. Deltazine should also be used with caution in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of atrioventricular (AV) conduction produced by these drugs.
Small doses of local anaesthetics injected in dental blocks may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses. 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 anaesthetic with retrograde flow to the cerebral circulation. Patients receiving these blocks should be observed constantly. Resuscitative equipment and personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded.

Impaired hepatic function

See above.

Use in the elderly

No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Approximately 6% of patients between the ages of 65 and 75 years and none of the eleven patients 75 years of age or older required additional injections of anaesthetic for complete anaesthesia compared with 11% of patients between 17 and 65 years old who required additional injections.
See Actions, Clinical trials for description of studies in the elderly.

Carcinogenesis, mutagenesis, impairment of fertility

Studies to evaluate the carcinogenic potential of articaine hydrochloride in animals have not been conducted. Articaine was negative in bacterial and mammalian assays for gene mutation and a chromosomal aberration test in Chinese hamster ovary cells. In vivo clastogenicity (mouse micronucleous) assays with articaine alone and with adrenaline were negative at a low subcutaneous dose (same as the maximal recommended clinical dose on a mg/m2 basis).

Impairment of fertility.

No effects on male or female fertility were observed in rats given articaine hydrochloride with adrenaline subcutaneously from prior to mating until mating (males) or early gestation (females) at doses up to 80 mg/kg/day (approximately twice the maximum recommended human dose on a mg/m2 basis).

Use in pregnancy.

(Category B3)
No clinical experience of the use in pregnancy and lactating women is available. Safe use of local anaesthetics during pregnancy has not been established with respect to adverse effects on fetal development. The product should only be used in pregnancy when the benefits are considered to outweigh the risks.
No effects on embryofetal development were observed when articaine hydrochloride with adrenaline was administered subcutaneously throughout organogenesis at doses up to 40 mg/kg/day in rabbits and 80 mg/kg/day in rats (approximately two times the maximum recommended human dose on a mg/m2 basis). In rabbits, fetal death and increased fetal skeletal variations were observed at the maternotoxic dose of 80 mg/kg (approximately four times the maximum recommended human dose on a mg/m2 basis).
When articaine hydrochloride alone was administered subcutaneously to rats throughtout gestation and lactation, 80 mg/kg/day (approximately two times the maximum recommended human dose on a mg/m2 basis) increased the number of stillbirths, delayed eye opening and adversely affected passive avoidance, a measure of learning, in pups, along with maternal toxicity were observed. A dose of 40 mg/kg/day (approximately the maximum recommended human dose on a mg/m2 basis) did not produce these effects. A similar study using articaine hydrochloride with adrenaline produced maternal toxicity, but no effects on the offspring.

Use in lactation.

The excretion of articaine or its metabolites in human milk is unknown. As many drugs are excreted in human milk, caution should be exercised when Deltazine is administered to a breastfeeding woman. If administered, breastfeeding women should not breastfeed for at least 48 hours following anaesthesia with Deltazine.
For effects of articaine hydrochloride in rat pups being suckled see Use in pregnancy, above.

Use in children

Deltazine 1:100,000 should not be used in children younger than 4 years of age as safety and effectiveness have not been established in this age group.
See Actions, Clinical trials for description of studies in children and adolescents (4 to 16 years of age). See also Dosage and Administration.

Effect on ability to drive or operate machinery

In a controlled study on healthy volunteers articaine was shown to have no effect on the level of attentiveness, reaction time to visual stimulations or motor co-ordination.
Patients who experience systemic adverse effects during or immediately following administration of Deltazine should be advised to avoid driving or operating machinery until resolution of signs or symptoms.

Instructions to patients

The patient should be informed in advance of the possibility of temporary loss of sensation and muscle function following infiltration and nerve block injections.

Interactions

No drug interaction studies have been performed.
Due to the possibility that clinically significant increases in circulating adrenaline concentrations may occur postinjection, Deltazine should be administered with caution to any patient receiving drugs with sympathomimetic properties or with agents whose therapeutic actions may be antagonised by adrenaline.
The administration of local anaesthetic solutions containing adrenaline to patients receiving monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants or phenothiazines may produce severe prolonged hypotension or hypertension. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of adrenaline. 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 ergot type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.
Deltazine should be administered with caution to patients under the following treatments.
Hypoglycaemics. Adrenaline induced hyperglycaemia may lead to loss of blood sugar control in diabetic patients treated with hypoglycaemics.
Antiarrhythmic agents (e.g. procainamide, mexilitine, disopyramide).
Antiepileptic skeletal muscle relaxant.
Cardiac glycosides (e.g. digoxin). Adrenaline may interact with cardiac glycosides resulting in cardiac arrhythmias.
Adrenergic neuron blocking agents (e.g. guanethidine) since the product contains adrenaline.
Quinidine. Combination with adrenaline may lead to cardiac arrhythmias.
Cimetidine.
Amiodarone.
Phenytoin and other antiepileptic drugs such as phenobarbitone, primidone and carbamazepine.
Inhalational anaesthetics. Serious cardiac arrhythmias may occur if preparations containing adrenaline are employed in patients following the administration of inhalational anaesthetics.
β-Adrenoreceptor antagonists. Propranolol and metoprolol, timolol. Administration of adrenaline may result in dose dependent hypertension and bradycardia with possible heart block.
Thyroid hormones may potentiate the actions of adrenaline.
Incompatibilities. None reported.

Adverse Effects

Articaine and adrenaline may reach sufficient concentrations in blood to provoke systemic adverse effects. Reactions to Deltazine are characteristic of those associated with other amide type local anaesthetics. 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.

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 Deltazine. See Table 3.
The following list includes adverse and concurrent events that were recorded in one 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.

Haemorrhage, migraine, syncope, tachycardia.

Digestive system.

Constipation, diarrhoea, dyspepsia, glossitis, gum haemorrhage, mouth ulceration, nausea, stomatitis, tongue oedemas, tooth disorder, vomiting.

Haemic and lymphatic system.

Ecchymosis, lymphadenopathy.

Metabolic and nutritional system.

Oedema, thirst.

Musculoskeletal system.

Arthralgia, myalgia, osteomyelitis.

Nervous system.

Dizziness, dry mouth, facial paralysis, hyperaesthesia, increased salivation, nervousness, neuropathy, paraesthesia, somnolence.

Respiratory system.

Pharyngitis, rhinitis.

Skin and appendages.

Pruritus, skin disorder.

Special senses.

Ear pain, taste perversion.

Urogenital system.

Dysmenorrhoea.

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 the following.

Symptoms showing effects on the central nervous system.

Nervousness, shaking, yawning, trembling, apprehension, nystagmus, logorrhoea, headache, nausea, buzzing in 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 (paraesthesia, hypoaesthesia and dysaesthesia) may appear after articaine administration. Resolution usually occurs within two weeks.

Uncommon ≥ 0.1% and < 1%.

Nausea.

Other adverse reactions.

Serious adverse experiences following the administration of articaine are similar in nature to those observed with other amide local anaesthetic agents. These adverse experiences are, in general, dose related and may result from high plasma levels caused by excessive dosage, rapid absorption, unintended intravascular injection or may result from hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported.

Central nervous system.

Central nervous system (CNS) manifestations are excitatory and/or depressant and may be characterised by lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, agitation, difficulty in swallowing and slurred speech, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest which are less common.
The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest.

Cardiovascular system.

Cardiovascular manifestations are usually depressant and are characterised by bradycardia, hypotension and cardiovascular collapse, which may lead to cardiac arrest. Signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position.
Less commonly, they may result from a direct effect of the drug. Failure to recognise the premonitory signs such as sweating, a feeling of faintness, changes in pulse or sensorium may result in progressive cerebral hypoxia and seizure or serious cardiovascular catastrophe. Management consists of placing the patient in the recumbent position and ventilation with oxygen. Supportive treatment of circulatory depression may require the administration of intravenous fluids and resuscitative drugs as directed by the clinical situation.

Hypersensitivity.

One may observe manifestations of hypersensitivity to articaine as rash, pruritus, urticaria or anaphylaxis.
The administration of large doses of articaine may produce methaemoglobinaemia in patients with subclinical methaemoglobinaemia.

Allergic reactions.

Allergic reactions are characterised by cutaneous lesions, urticaria, oedema or anaphylactoid reactions.

Allergic reaction to sulfites.

Allergic type reactions may occur in patients with bronchial asthma due to hypersensitivity to the sulfite component and may be manifested by dermatological reactions, oedema, urticaria and other allergy symptoms.

Dosage and Administration

One or more cartridges should be used on a single patient on one occasion only during each session of treatment. If only a portion of a cartridge is used, the remainder must be discarded.

Use in adults.

Table 4 summarises the recommended volumes and concentrations of Deltazine for various types of anaesthetic procedures. For most common operations, one infiltration with Deltazine 1.7 mL is sufficient. In all cases, the injection must be done slowly (about 1 mL/minute). For an infiltration in the interdental septum, a quantity of 0.3 to 0.5 mL is generally sufficient. Higher volumes should rarely be required.
Maximum recommended dose for normal healthy adults of articaine hydrochloride administered by submucosal infiltration and/or nerve block should not exceed 7 mg/kg of bodyweight. This corresponds, for a subject weighing 60 kg, to six standard 1.7 mL cartridges or five standard 2.2 mL cartridges (doses of 7 mg/kg were not exceeded in clinical trials). Anaesthesia is obtained rapidly (one to six minutes).
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.

Use in children.

Safety and effectiveness in paediatric patients below the age of 4 years have not been established. Dosages in paediatric patients (over 4 years) should be reduced, commensurate with age, bodyweight and physical condition. See Table 5, below. Use of Deltazine in children under 4 years of age is not recommended due to the absence of safety and efficacy data.
Maximum recommended dose for normal healthy children must not exceed 7 mg/kg of bodyweight.
For single patient use only. Contains no antimicrobial agent. Discard unused contents after use.

Overdosage

The most serious effects of articaine intoxication are on the CNS and cardiovascular system. The type of toxic reaction is unpredictable and depends on such factors as dosage, rate of absorption and clinical status of the patient. Two types of reactions that effect stimulation and/or depression of the central cortex and medulla may result from systemic absorption.

Symptoms.

Slow onset symptoms following overdose include stimulation leading to nervousness, dizziness, blurred vision, nausea, tremors, convulsions, hypotension, cardiovascular depression and respiratory arrest.
Rapid onset symptoms following overdose include depression, leading primarily to respiratory arrest, cardiovascular collapse and cardiac arrest. Since cardiac arrest symptoms may occur rapidly and with little warning, treatment should be readily available.

Treatment.

For all symptoms.

If acute toxicity occurs the injection should be stopped immediately. A patent airway should be established and maintained, oxygen should be administered, and assisted or controlled ventilation should be provided as required.

Circulatory collapse.

Toxic cardiovascular reactions can include peripheral vasodilation, hypotension, bradycardia and cardiac arrest. Immediately resuscitate with oxygen and commence cardiovascular resuscitation procedures as appropriate.

Convulsions.

Appropriate medication for the management of convulsions should be used.
If not treated immediately, both convulsions and cardiovascular depression may result in hypoxia, acidosis, bradycardia, arrhythmia and cardiac arrest.
Supportive treatment should be given; standard cardiopulmonary resuscitative therapy, including respiratory support, may be required to counter adverse effects on the cardiovascular and/or respiratory systems and to control convulsions. There is no specific antidote.

Presentation

Injection (sterile, aqueous solution, cartridge) 1.7 mL: 50's; 2.2 mL: 50's.

Storage

Store below 25°C.

Poison Schedule

S4.