Lidocaine

Generic name
Lidocaine
Brand name
ATC Code
N01BB02
Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

Lidocaine is metabolized primarily into monoethylglycinexylidide (MEGX) by oxidative N-desethylation by CYP1A2 and, to a lesser extent, by CYP3A4. CYP1A2 appears at 1-3 months of life, CYP3A4 appears during the first week of life. During this period, CYP3A4 is responsible for some of the transformations that normally would be performed by CYP3A4. After subsequent N-desethylation, glycinexylidide (GX) is formed, but to a lesser extent than MEGX. Less than 10% is excreted with the urine in unchanged form. Lidocaine is an anticonvulsant with a high hepatic extraction ratio (0.65-0.75) and therefore its clearance is related to hepatic blood flow. Therefore, hepatic flow during hypothermia is associated with decreased clearance by 21.8 – 24%. Normally, about 64 - 70% lidocaine is bound to alpha-1-glycoproteic acid (AAG). In neonates, AAG levels are low, and the free, biologically active, fraction of lidocaine is relatively high in neonates. The free fraction observed in children older than 1 year is similar to that measured in adults, i.e. ranging from 30% to 40% for lidocaine [[Mazoit 2004; van den Broek 2011; SmPC RVG 55119].

In infants and children (0.5 – 3 years), the following pharmacokinetic parameters were found after an IV bolus of 1 mg/kg during general anesthesia with no significant differences compared to adults [Finholt 1986]

Variables

Children (n=10)

Adults (n=8)

Age (yr)

0.5 – 3

18 – 51

Weight (kg)

4.5 – 14

48 – 82

T1/2 (min)

58 ± 19

43 ± 16

Vd (l/kg)

1.11 ± 0.34

0.71 ± 0.28

Cl (ml/kg/min)

11.1 ± 1.8

9.8 ± 1.4

(All) values represent mean ± SEM. Mean age and weight are unknown.

In neonates, infants and older children (0 – 18 years), the following pharmacokinetic parameters were found after an IV bolus of 1.5 mg/kg during general anesthesia with prolonged T1/2 in preterm and term neonates compared to older age groups [LeDez 1987]:

Variables

Preterm neonates (n=1)

Term neonates (n=5)

Infants (n=8)

Children (n=9)

Adolescents (n=6)

Age (yr)

NR

0.025 ± 0.043

0.35 ± 0.14

3.46 ± 0.78

15.33 ± 1.47

Weight (kg)

0.74

3.57 ± 0.6

6.63 ± 1.4

14.78 ± 2.53

58.97 ± 10.36

T1/2 (min)

191.4

145.3 ± 31.8

77.9 ± 31.7

52.5 ± 10.9

86.2 ± 28.2

(All) values represent mean ± SD. NR: not reported.

In preterm neonates, the following pharmacokinetic parameters were found after a subcutaneous injection of 1 – 2 mg/kg during local anesthesia with prolonged T1/2 in preterm neonates compared to adults [Mihaly 1978]:

Variables

Preterm neonates (n=4)

Adults (n=11)

Age

- Postpartum age (days)

- GA (weeks)

18.75 (5 – 42)

GA: 31.35 (26 – 38)

NR

Weight (kg)

2.03 (1.2 – 3.2)

NR

T1/2 (hr)

3.16 (3.03 – 3.30)

1.80 (1.22 – 2.23)

Vd (l/kg)

2.75 (1.44 – 4.99)

1.11 (0.58 – 1.91)

Cl (l/kg/h)

0.610 (0.307 – 1.141) 

0.550 (0.318 – 0.726)

All values represent mean and range. NR: not reported. GA: gestational age.

In children (3.5 – 9 years), the following pharmacokinetic parameters were found after an IV bolus of 5 mg/kg during caudal anesthesia with prolonged T1/2 in children compared to adults [Ecoffey 1984]:

Variables

Children (n=11)

Adults

Age

5.3 ± 0.5

Pharmacokinetics of lidocaine after caudal anaesthesia in children are similar to those reported in adults, except for T1/2, which is slightly longer in children. The longer T1/2 is attributed to a larger Vd in children because the Cl of lidocaine is similar in children to that in adults [Benowitz 1987; Tucker 1975]

Weight (kg)

19.5 ± 1.8

T1/2 (min)

155 ± 27

Vd (l/kg)

3.05 ± 0.40

Cl (ml/kg/min)

15.4 ± 1.2

All values represent mean ± SEM.

Pharmacokinetic data derived from PopPK studies in (preterm) neonates with seizures [van den Broek 2011, van den Broek 2013; Favié 2020 ]:

Variables

van den Broek et al. 2011 [2] (n=46)

van den Broek et al. 2013 [10] (n=26)

Favié et al. 2020 [11] (n=153)

Age (median/mean, range/SD)

- GA (weeks)

38 (25.0-42.7)

39.4 (34.1 – 42.7)

37.0 ± 4.84

Cl (l/h/kg)a

0.463d

0.523d,e

0.506d,f

Proportional effect of hypothermia on clearance (Cl)

 

0.760b

0782c

Vd (l/kg) a

2.963d

3.114d

2.663d

T1/2 during normothermia (hr)

 

4.1

 

T1/2 during hypothermia (hr)

 

5.5

 

GA: gestational age.

a Normothermic conditions.
b CI was reduced by 24% during hypothermia compared with normothermia.
c CI was reduced by 21.8% during hypothermia compared with normothermia.

d Body weight (BW) significantly affect Vd and Cl.

e Hypothermia (33.5°C) significantly affect Cl.

f Postmenstrual age (PMA) and hypothermia (33.5°C) significantly affect Cl.

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Go to:

Arrhythmias
  • Intravenous
    • 1 month up to 18 years
      [2] [18]
      • Initial dose: 0.5 - 1 mg/kg/dose over 1 minute. If necessary, repeat starting dose max. 2 times after 5 – 10 minutes. The max. cumulative dose of 3 mg/kg should not exceed.  .
      • Maintenance dose: 0.6 - 3 mg/kg/hour, continuous infusion.

      • On IV infusion lasting longer than 24 hours, the elimination rate may decrease. Decreasing the infusion rate can then be necessary.

        Treatment by or after consultations with a paediatric specialist (paediatric cardiologist) who has experience using lidocaine for this indication.
Local anaesthesia
  • Cutaneous
    • Salve
      • 1 month up to 18 years
        [24]
        • Max. 5 mg/kg/dose The minimum dosing interval is 8 hours..
  • Mucosal
    • 3 months up to 2 years
      [27] [40] [42]

      • Spray: Max. 1 – 3 mg/kg/dose

        In children < 2 years, the risk of overdose is high. Lower diluted concentrations of IV formulations can be used.

    • 2 years up to 18 years
      [12]

      • Spray: Max. 3-5 mg/kg/dose

  • Infiltration
    • Term neonate
      [9] [14] [21] [32] [33]
        • Without epinephrine: Max. 3 mg/kg:/dose, once. 
    • 1 month up to 1 year
      [14] [33]
        • Without epinephrine: Max. 3 mg/kg:/dose, once. 
        • Combined with epinephrine: Max. 5 mg/kg/dose, once. 
    • 1 year up to 18 years
      [34]
        • Without epinephrine: Max. 5 mg/kg:/dose, once. Max. total dose 400 mg
        • Combined with epinephrine: Max. 7 mg/kg/dose, once. Max. total dose 400 mg 
  • Oromucosal
    • 6 months up to 18 years
      [8] [20] [30]

      • Gel: Max. 16 mg/day in 4 doses
        Do not eat or drink within 45 minutes of application.
Neonatal epileptic seizures: Neonates WITHOUT hypothermia
  • Intravenous
    • Premature infants Gestational age ≥ 25 weeks and < 1.5 kg
      [3] [6] [15] [17] [29] [39]

      • Initial dose: 2 mg/kg in 10 min
        Maintenance dose: 5 mg/kg/hour for 4 hours, then phase out as follows:
        2.5 mg/kg/hour for 12 hours
        1.25 mg/kg/hour for 12 hours, then stop

      • Administer with ECG monitoring because of the possibility of arrhythmia occurring

    • Premature infants Gestational age ≥ 25 weeks and 1.5 up to 2.5 kg
      [15] [17] [29] [39]

      • Initial dose: 2 mg/kg in 10 min
        Maintenance dose: 6 mg/kg/hour for 4 hours, then phase out as follows:
        3 mg/kg/hour for 12 hours
        1.5 mg/kg/hour for 12 hours, then stop

      • Administer with ECG monitoring because of the possibility of arrhythmia occurring

    • Neonates Gestational age ≥ 25 weeks and ≥ 2.5 kg
      [3] [15] [17] [29] [39]

      • Initial dose: 2 mg/kg in 10 min
        Maintenance dose: 7 mg/kg/hour for 4 hours, then phase out as follows:
        3,5 mg/kg/hour for 12 hours
        1,75 mg/kg/hour for 12 hours, then stop

      • Administer with ECG monitoring because of the possibility of arrhythmia occurring
Neonatal epileptic seizures: Neonates WITH hypothermia
  • Intravenous
    • Neonates Gestational age ≥ 35 weeks and < 2.5 kg
      [15] [29] [39]

      • Initial dose: 2 mg/kg in 10 min
        Maintenance dose: 6 mg/kg/hour for 3,5 hours, then phase out as follows:
        -  3 mg/kg/hour for 12 hours
        - 1,5 mg/kg/hour for 12 hours, then stop

      • Administer with ECG monitoring because of the possibility of arrhythmia occurring

         

    • Neonates Gestational age ≥ 35 weeks and ≥ 2.5 kg
      [3] [15] [29] [39]

      • Initial dose: 2 mg/kg in 10 min
        Maintenance dose: 7 mg/kg/hour for 3,5 hours, then phase out as follows:
        -  3.5 mg/kg/hour for 12 hours
        - 1.75 mg/kg/hour for 12 hours, then stop

      • Administer with ECG monitoring because of the possibility of arrhythmia occurring

         
Teething pain
  • Oromucosal
    • Solution for dental use
      • 1 month up to 18 years
        [4]
        • 0.38% solution: 2 - 3 drop(s)/dose, as required, max. 4x daily.  Apply to the painful areas using a cotton bud.
        • Directions for administration:

          Do not eat or drink within 45 minutes after application.

    • Gel for dental user
      • 1 month up to 18 years

        • Gel 3,4 mg/g (+150,0 mg/g tincture of camomile flowers+3,2 mg/g Macrogollaurylether): apply a pea-size amount to painful areas 2-3 times daily

          Gel 20 mg/g: a maximum of one pea-size piece 4 times a day

          • Apply with clean fingers or using a cotton bud.
          • After meals or before going to bed.
Peripheral nerve block
  • Perineural
    • 1 month up to 1 year
      [14] [31] [33] [37] [38]
        • Without epinephrine: Max. 3 mg/kg:/dose, once. 
        • Combined with epinephrine: Max. 5 mg/kg/dose, once. 
    • 1 year up to 18 years
      [34]
        • Without epinephrine: Max. 5 mg/kg:/dose, once. max 400 mg
        • Combined with epinephrine: Max. 7 mg/kg/dose, once. max 400 mg
Epidural anaesthesia
  • Thoracal
    • 1 month up to 1 year
      [14] [31] [33] [37] [38]
        • Without epinephrine: Max. 3 mg/kg:/dose, once. 
        • Combined with epinephrine: Max. 5 mg/kg/dose, once. 
    • 1 year up to 18 years
      [34]
        • Without epinephrine: Max. 5 mg/kg:/dose, once. max 300 mg
        • Combined with epinephrine: Max. 7 mg/kg/dose, once. max 300 mg
  • Caudal, lumbal
    • 1 month up to 1 year
      [14] [31] [33] [37] [38]
        • Without epinephrine: Max. 3 mg/kg:/dose, once. 
        • Combined with epinephrine: Max. 5 mg/kg/dose, once. 
    • 1 year up to 18 years
      [34]
        • Without epinephrine: Max. 5 mg/kg:/dose, once. max 500 mg
        • Combined with epinephrine: Max. 7 mg/kg/dose, once. max 500 mg
Pre-existing chronic pain; sickle cell crisis
  • Intravenous
    • 1 year up to 18 years
      [11] [13] [36] [41]
      • Initial dose: 2 mg/kg/dose, bolus. Max: 80 mg/dose.
      • Maintenance dose: 1.5 mg/kg/hour, continuous infusion. Max: 300 mg/hour.

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

In general: drowsiness, paresthesia and dizziness. Overdose may initiate drowsiness, paresthesia and dizziness with further effects such as agitation, blurred vision, cold sweats, speech disturbances, tremors, convulsions, respiratory depression, anorexia, hearing en swallowing disturbances, impaired electrical conduction (bradycardia, reentry arrhythmias, atrioventricular (AV) block) and impaired cardiac muscle contractility (hypotension). , arrhythmias (AV block) and cardiovascular collapses. Toxic reactions occur at lidocaine concentrations starting at 5 – 9 mcg/ml. This also depends on the route of administration and risk factors of the patient. In general, therapeutic levels tend to be between 1 (1.5) – 5 mcg/ml. However, for the treatment of neonatal convulsions, a therapeutic range of 6 to 7 mcg/ml is aimed after completion of the initial infusion dose. IV doses should not exceed plasma levels of 9 mcg/ml [van den Broek 2013; Favié 2020; Donald 2004; Berde 2002; Takasaki 1984; NVZA 2022; Kituu 2012].
Neonates undergoing therapeutic hypothermia might be even less susceptible to cardiotoxicity compared to normothermic neonates, since the baseline frequency is already reduced hypothermia itself [van den Broek 2013; Favié 2020;]

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications in children

In application for neonatal seizures: hypo- and hyperkalemia, (suspected) cardiomyopathy (e.g. in diabetic mother), complex congenital heart defect. Avoid combination with phenytoin use Favié 2020; Weeke 2015]. Phenytoin has an additive effect on the cardiac depressant action of lidocaine.

 

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

As an antiarrhythmic: To correct existing hypokalaemia prior to treatment. In particular with persistent ventricular tachycardia or ventricular fibrillation, after a recent heart attack, liver or kidney impairment, structural heart disease and/or poor left ventricular function, arrhythmia may worsen. Caution is also needed in the elderly, those in poor general condition, with sinus node dysfunction, AV conduction disorders, convulsions, severe respiratory depression, bradycardia, cardiac failure and hypotension. If malignant hyperthermia is suspected, do not use amide-type local anaesthetics. Allowances should be made for cross-sensitivity with other amide-type local anaesthetics. Allergic reactions (asthma attacks, bronchial spasms, anaphylactic shock) can occur as a result of the intravenous administration of sulphite. Asthma patients in particular area a high-risk group. Ventilation equipment must be present. To avoid side effects, the following precautions are recommended: 1. Use the minimum effective dose as far as possible and do not exceed the maximum dose. 2. Administer the injection slowly and aspirate in infiltration or conduction anaesthesia several times to prevent intravascular injection.

In neonatal seizures:
Apply only in the NICU under careful ECG monitoring. In case of changes in ECG complexes and/or heart rhythm, discontinue lidocaine immediately.
Use only low concentrations (< 20 mg/ml). Always taper off according to schedule. Effect often not immediately visible on seizures, but effect seen on EEG < 6 hours after start of treatment. A waiting period of 30-60 minutes to observe the effect is recommended, after which the need for additional therapy should be assessed.

Obesity:
Due to higher body weight (increase of absolute volume of distribution) in obese children, loading doses should be calculated based on total body weight and continuous infusion rates on ideal body weight [Ross 2015; Heath 2022].

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

ANESTHETICS, LOCAL

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Amides
N01BB01

References

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  3. Smit LS et al, Richtlijnen voor behandeling van neonatale epileptische aanvallen, Nederlands Vlaamse Werkgroep Neonatale Neurologie van de sectie Neonatologie van de NVK en van de Nederlandse Vereniging voor Kinderneurologie, Nieuwe aangepaste versie juni 2012
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Changes

Therapeutic Drug Monitoring


Overdose