Dobisim 20, 50 & 300 20 mg, 50 mg & 300 mg Solution for injection

DOBISIM is used as a local anaesthetic in infiltration and field block anaesthesia. As a local anaesthetic it has an action of intermediate duration which can be increased by adding adrenaline (epinephrine).

Posology
It is recommended that a needle not larger than 21 gauge is used to reduce fragmentation of the rubber stopper. The dosage will depend on the area to be anaesthetised:
1. Infiltration anaesthesia: 0,5 u2013 1,0 % solution is used.
2. Field block anaesthesia: As for infiltration anaesthesia.
3. Epidural anaesthesia: Determined by the segmental level of anaesthesia required. The volume of anaesthetic required is determined by which nerve fibres are to be blocked, what level of anaesthesia is required and whether epinephrine (adrenaline) is used. The addition of epinephrine (adrenaline) 1:200 000 is often used to increase the duration of anaesthesia. The maximum 24-hour dose is 300 mg of DOBISIM.
Method of administration
DOBISIM is administered subcutaneously (SC) or intramuscularly (IM).

Hypersensitivity to lidocaine (lignocaine), other local anaesthetics of the amide type, or any other component of DOBISIM (see section 6.1)
DOBISIM should not be given to patients with:
u2022 Hypovolaemia
u2022 Heart block or other conduction disturbances
u2022 Bradycardia
u2022 Cardiac decompensation
u2022 Hypotension unrelated to treatable tachydysrhythmias
u2022 Myasthenia gravis

DOBISIM should not be given intravenously. In such case, the rapid absorption is likely to cause systemic toxic symptoms, such as hypotension, pallor, dysrhythmias, sweating, nausea, vomiting and muscular twitching. The local anaesthetic effect of DOBISIM may be reduced if the injection is administered into an inflamed area with a low tissue pH. DOBISIM is considered to be unsafe in patients with porphyria. DOBISIM should be used with caution in patients with:
u2022 Epilepsy
u2022 Congestive heart failure
u2022 Severe shock
u2022 Impaired respiratory function or impaired renal function with a creatinine clearance of less than 10 ml/minute.
u2022 DOBISIM is metabolised in the liver and it should be used with caution in patients with impaired hepatic function.
u2022 Hypokalaemia, hypoxia and disorders of acid-base balance should be corrected before treatment with DOBISIM begins.
u2022 Facilities for resuscitation should be available when administering local anaesthetics.
u2022 Intra-articular administration of DOBISIM may cause chondrotoxicity.
u2022 Central nerve blocks may cause cardiovascular depression, especially in the presence of hypovolaemia, and therefore epidural anaesthesia should be used with caution in patients with impaired cardiovascular function.
u2022 Epidural anaesthesia may lead to hypotension and bradycardia. This risk can be reduced by preloading the circulation with crystalloidal or colloidal solution. Hypotension should be treated promptly.
u2022 Retrobulbar injections may reach the cranial subarachnoid space causing serious/ severe reactions, including cardiovascular collapse, apnoea, convulsions and temporary blindness.
u2022 Retro- and peribulbar injections of local anaesthetics carry a low risk of persistent ocular motor dysfunction. The primary causes include trauma and/or local toxic effects on muscles and/ or nerves.
u2022 The severity of such tissue reactions is related to the degree of trauma, the concentration of the local anaesthetic and the duration of exposure of the tissue to the local anaesthetic. For this reason, as with all local anaesthetics, the lowest effective concentration and dose of local anaesthetic should be used.
u2022 Doses should be reduced in elderly and debilitated patients and in children.
u2022 DOBISIM is not recommended for use in neonates.
DOBISIM contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially u2018sodium - freeu2019.

Effects of DOBISIM on other medicines
u2022 DOBISIM should be used with caution in patients receiving other local anaesthetics or medicines structurally related to amide-type local anaesthetics (e.g., anti-dysrhythmics, such as mexiletine), since the systemic toxic effects are additive.
u2022 There may be an increased risk of enhanced and prolonged neuromuscular blockade in patients treated concurrently with other muscle relaxants (e.g., suxamethonium).
Effects of other medicines on DOBISIM
u2022 The clearance of lidocaine (lignocaine) may be reduced by beta-adrenoceptor blocking medicines (e.g., propranolol) and by cimetidine, requiring a reduction in the dosage of DOBISIM.
u2022 Increase in serum levels of lidocaine (lignocaine) may also occur with anti-viral medicines (e.g., amprenavir, atazanavir, darunavir, lopinavir).
u2022 There may be an increased risk of ventricular dysrhythmia in patients treated concurrently with antipsychotics which prolong or may prolong the QT interval (e.g., pimozide, sertindole, olanzapine, quetiapine, zotepine), or 5HT3 antagonists (e.g., tropisetron, dolasetron).
u2022 While epinephrine (adrenaline) when used in conjunction with DOBISIM might decrease vascular absorption, it greatly increases the danger of ventricular tachycardia and fibrillation if accidentally injected intravenously.
u2022 Concomitant use of quinupristin or dalfopristin should be avoided.
u2022 Hypokalaemia produced by acetazolamide, loop diuretics and thiazides may antagonize the effect of DOBISIM if administered concomitantly (see section 4.4).
u2022 Inhibition of CYP1A2 by fluvoxamine considerably reduces elimination of DOBISIM and increases the risk of DOBISIM toxicity. Concomitant use of both fluvoxamine and a CYP3A4 inhibitor such as erythromycin can further increase lidocaine (lignocaine) concentrations. Because lidocaine (lignocaine) possesses a narrow therapeutic window, doses of DOBISIM may need to be adjusted accordingly.
u2022 Phenytoin can also increase plasma concentrations of 1-acid glycoprotein and thereby reduce the free fraction of lidocaine in plasma.
u2022 Lidocaine (lignocaine) is markedly bound to 1-acid glycoprotein (AAG). AAG concentration may be reduced by oestrogens leading to a higher free fraction of lidocaine in women than in men and the free fraction is further increased during pregnancy and in women taking oral contraceptives or HRT.
u2022 Opioid-antiemetic combination sometimes used for sedation in children could reduce the convulsant threshold to lidocaine (lignocaine) and increase the CNS depressant effect.

Women of childbearing potential/Contraception in males and females
u2022 Lidocaine (lignocaine) is markedly bound to 1-acid glycoprotein (AAG).
u2022 AAG concentration may be reduced by oestrogens leading to a higher free fraction of lidocaine (lignocaine) in women than in men and the free fraction is further increased during pregnancy and in women taking oral contraceptives or HRT (see section 4.5)
Pregnancy
DOBISIM crosses the placenta and blood-brain barrier and should not be administered during early pregnancy. DOBISIM given by epidural or paracervical block, especially in large doses, or by local perineal infiltration prior to delivery crosses rapidly into the foetal circulation. Elevated lidocaine (lignocaine) levels may persist in the newborn for at least 48 hours after delivery. Foetal bradycardia or neonatal bradycardia, hypotonia or respiratory depression may occur.
Breastfeeding
Small amounts of DOBISIM are secreted into breast milk and possibility of an allergic reaction in the infant, albeit remote, should be bored in mind when using DOBISIM in nursing mothers.

When outpatient anaesthesia affects areas of the body involved in driving or operating machinery, patients should be advised to avoid these activities until normal function is fully restored.

a. Summary of the safety profile
Adverse reactions to DOBISIM are infrequent and are usually the result of raised plasma concentrations due to accidental intravascular injection, excessive dosage or rapid absorption from highly vascular areas, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Systemic toxicity mainly involves the central nervous system and/ or the cardiovascular system (see section 4.9). Following regional blockade as when DOBISIM is injected intrathecally or extradurally, hypotension, hypoventilation, Homers Syndrome and hypoglycaemia may be seen. The degree of these effects will depend on the dose and the height of the block. Urinary Retention may occur following sacral or lumbar epidural block. It should not outlast the duration of the block. Apnoea and hemiparesis may occur following stellate ganglion block. The probable cause is a direct injection of DOBISIM into the vertebral or carotid arteries.
b. Tabulated list of adverse reactions
Blood and lymphatic system disorders
Frequency not known Methaemoglobinaemia.
Immune system disorders
Frequency not known Hypersensitivity reactions (allergic or anaphylactic reaction, anaphylactic shock)
Nervous system disorders
Frequency not known Stimulation of the central nervous system (CNS), (manifested by yawning, restlessness, excitement, nervousness, dizziness, light-headedness, tremor, circumoral paraesthesia, blurred vision, nausea, vomiting, muscle twitching and convulsions). Excitation of the central nervous system may be transient, followed by depression, with drowsiness, respiratory failure and coma. Seizures have also been reported after excessive doses administered subcutaneously. Numbness of the tongue and perioral region is an early sign of systemic toxicity.
Eye disorders
Frequency not known Blurred vision, diplopia and transient amaurosis may be signs of lidocaine toxicity. Bilateral amaurosis may also be a consequence of accidental injection of the optic nerve sheath during ocular procedures. Orbital inflammation and diplopia have been reported following retro-or peribulbar anaesthesia (see section 4.4).
Ear and labyrinth disorders
Frequency not known Tinnitus, hyperacusis
Cardiac disorders
Frequency not known Depression of the cardiovascular system (characterised by pallor, sweating and hypotension, dysrhythmias, bradycardia or cardiac arrest).
Respiratory, thoracic and mediastinal disorders
Frequency not known Dyspnoea, bronchospasm, respiratory depression, respiratory arrest
Gastrointestinal disorders
Frequency not known Drowsiness, vomiting
Skin and subcutaneous tissue disorders
Frequency not known Rash, urticaria, oedema

Symptoms of acute systemic toxicity
Central nervous system toxicity presents with symptoms of increasing severity. Patients may present initially with circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis and tinnitus. Visual disturbance and muscular tremors or muscle twitching are more serious and precede the onset of generalised convulsions (see section 4.8). These signs must not be mistaken for neurotic behaviour. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and hypercapnia occur rapidly following convulsions due to increased muscular activity, together with the interference with normal respiration and loss of the airway. In severe cases, apnoea may occur. Acidosis increases the toxic effects of local anaesthetics. Effects on the cardiovascular system may be seen in severe cases. Hypotension, bradycardia, dysrhythmia and cardiac arrest may occur as a result of high systemic concentrations, with potentially fatal outcome. Recovery occurs as a consequence of redistribution of the local anaesthetic medicine from the central nervous system, and metabolism and may be rapid unless large amounts of the medicine have been injected.
Treatment
Symptomatic and supportive