1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Brand names, Trade names
   1.6 Manufacturers, Importers
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Properties of the substance
      3.3.2 Properties of the locally available formulation
   3.4 Other characteristics
      3.4.1 Shelf-life of the substance
      3.4.2 Shelf-life of the locally available formulation
      3.4.3 Storage conditions
      3.4.4 Bioavailability
      3.4.5 Specific properties and composition
   4.1 Indications
   4.2 Therapeutic dosage
      4.2.1 Adults
      4.2.2 Children
   4.3 Contraindications
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
   7.1 Mode of action
      7.1.1 Toxicodynamics
      7.1.2 Pharmacodynamics
   7.2 Toxicity
      7.2.1 Human data Adults Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   7.7 Main adverse effects
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material Simple Qualitative Test(s) Advanced Qualitative Confirmation Test(s) Simple Quantitative Method(s) Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens Simple Qualitative Test(s) Advanced Qualitative Confirmation Test(s) Simple Quantitative Method(s) Advanced Quantitative Method(s) Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis Blood, plasma or serum Urine Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
   8.6 References
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological CNS Peripheral nervous system Autonomic nervous system Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary Renal Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic Acid-base disturbances Fluid and electrolyte disturbances Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
   10.1 General principles
   10.2 Relevant laboratory analyses
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
      10.2.4 Other investigations
   10.3 Life supportive procedures and symptomatic/specific treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
12. Additional information
   12.1 Availability of antidotes
   12.2 Specific preventive measures
   12.3 Other
    1. NAME
     1.1 Substance
     1.2 Group
       Therapeutic group : calcium channel blockers; Class IV
            antiarrhythmic drugs
     1.3 Synonyms


       [3-[ [2-(3,4-dimethoxyphenyl) ethyl]-methylamino] propyl]-3,4- 
       dimethoxy- -(1-methylethyl)benzeneacetonitrile 

       isopropyl- -(N-methyl-N-Homoveratryl)- -aminopropyl]-
       Iproveratril, Isoptin, D 365, CP-16533-1

     1.4 Identification numbers
       1.4.1 CAS number
             52 - 53 - 9
       1.4.2 Other numbers
             NIOSH/RTECS : YV 8300 000
             UPDT : 7907
     1.5 Brand names, Trade names
       Calan (Searle); Cardibeltin (Pharma - Schwarz - Germany); 
       Cordilox (Knoll AG, Germany; Abbott); Cardimil; Dilacoron 
       (Knoll AG, Germany); Ikacor (Ikapharm, Israel); Isoptin (Knoll 
       AG, Germany; Isoptine (Biosédra, France); Manidon (Knoll AG, 
       Germany; Medinsa, Spain); Vasolan (Knoll AG, Germany); Veramil 
       (Yurtoglu, Turkey); Verapamil (Erco, Danemark; Orion, Finland)
       Generic products are also available
     1.6 Manufacturers, Importers
       See section 1.5
    2. SUMMARY
     2.1 Main risks and target organs
       The principal effects of verapamil are on the cardiovascular 
       system. It  decreases atrioventricular conduction and has a 
       negative inotropic effect.  It has a vasodilating action on 
       the vascular system.
     2.2 Summary of clinical effects
       Toxic effects occur usually after a delay of 1 to 5 hours 
       following  ingestion. After IV injection, symptoms appear 
       after a few minutes.
       The main cardiovascular symptoms are :
       bradycardia and atrioventricular block (in 82 % of cases)
       hypotension and cardiogenic shock (in 78 % of cases)
       cardiac arrest (in 18 % of cases)

       Pulmonary oedema may occur
       Impairement of consciousness and seizures may occur and are 
       related to a low  cardiac output.
       Nausea and vomiting may be observed.
     2.3 Diagnosis
       The principal symptoms are due to the effects of verapamil on 
       the  cardiovascula system.  They include bradycardia, 
       atrioventricular block,  hypotension, cardiogenic shock and 
       cardiac arrest. Pulmonary oedema,  impairment of consciousness 
       and seizures may also occur.
       ECG is the most relevant investigation in verapamil poisoning.
       Measurement of blood verapamil concentrations are not useful 
       for clinical  management.
       Therapeutic blood concentrations may vary from 50 to 350 
       Metabolic acidosis due to shock and hyperglycaemia may occur.
     2.4 First aid measures and management principles
       Patients with verapamil overdose should be closely monitored 
       preferably  in an Intensive Care Unit
       Monitor vital signs : ECG, blood pressure, respiration, 
       diuresis, central  venous pressure 
       Treatment may include :
       emesis, early gastric lavage and oral activated charcoal 
       correction of hypotension and shock by alpha or/and beta 
       sympathomimetic  agents
       correction of atrioventricular block by betamimetic agents or 
       ventricular  pacing
       artificial ventilation and treatment of metabolic acidosis in 
       case of  cardiogenic shock
       treatment of cardiac arrest 
     3.1 Origin of the substance
       Synthetic substance
     3.2 Chemical structure
       Molecular weight : 454.59
     3.3 Physical properties
       3.3.1 Properties of the substance
             Viscous, pale yellow oil

             Boiling point: 243-246°C
             Practically insoluble in water, sparingly 
             soluble in hexane,  soluble in benzene, ether, 
             freely soluble in the lower alcohols,  acetone, 
             ethylacetate, chloroform
             Verapamil hydrochloride:  C27H39ClN2O4
             Crystals, decompose at 138.5-140.5°C. The pH of 
             a 0.1 % aqueous  solution is 5.25. Sparingly 
             soluble in chloroform. Soluble in  ethanol, 
             isopropanol, acetone, ethyl acetate; freely 
             soluble in  methanol.
       3.3.2 Properties of the locally available formulation
     3.4 Other characteristics
       3.4.1 Shelf-life of the substance
       3.4.2 Shelf-life of the locally available formulation
             To be added by PCC.
       3.4.3 Storage conditions
             Store tablets and ampoules at room temperature. Protect  
             ampoules from light.
       3.4.4 Bioavailability
       3.4.5 Specific properties and composition
    4. USES
     4.1 Indications
       (Martindale, Goodman and Gillman, Drugdex)
       Paroxysmal supraventricular tachycardia (PSVT): 
       Verapamil is the drug of  choice for prevention and 
       treatment of PSVT.
       Angina: Verapamil has been shown to be effective in the
       treatment of angina pectoris.
       Hypertension: Verapamil may be used as an alternative 
       treatment for mild or  moderate hypertension. Verapamil 
       seems to be as effective as nifedipine or  nicardipine 
       and does not produce reflex tachycardia. There is no  
       contraindication in patients with bronchospastic 
     4.2 Therapeutic dosage
       4.2.1 Adults
             In arrhythmias
             The initial dose for supraventricular tachycardia, 
             atrial  fibrillation or atrial flutter is 5 to 10 mg 
             (0.075 to 0.15 mg/Kg)  given as an IV bolus over 2 
             minutes (3 minutes in the elderly). A  further dose of 5-
             10 mg may be administered after 30 minutes if no  
             response is observed.
             In angina pectoris
             The daily oral dose ranges between 240 and 360 mg (80 to 
             120 mg  three times daily). The half-life is prolonged 

             during chronic  treatment; smaller doses may therefore 
             be given after 3 to 5 days  of treatment (Shand 81, 
             Schwarz 82).
             In hypertension
             The initial recommended dose is one tablet (240 mg) of 
             sustained  release verapamil, once daily. If necessary, 
             the daily dose should  be increased to 480 mg.
             Dosage in renal failure
             No dosage adjustment is recommended in patients with 
             renal failure  (Hamann et al, 1984)
             Dosage in hepatic insufficiency
             Dose reductions are required in hepatic insufficiency. 
             Dosage  should be reduced to 20 - 30 % of the normal 
             oral dose (Drugdex;  Somogyi et al, 1981) Intravenous 
             single doses should be reduced by  half (Hamann et al, 
             Dosage in congestive heart failure
             Dosage may be reduced due to a decrease of liver blood 
       4.2.2 Children
             Infants up to 1 year
             The recommended initial dose is 0.1-0.2 mg/Kg given as 
             an IV bolus  under continuous ECG monitoring. This dose 
             may be repeated after 30  minutes if necessary.  The 
             oral maintenance dose is 4-8 mg/kg/day.
             Children 1-15 years
             An initial dose of 0.1-0.3 mg/kg/day given as an IV 
             bolus is  recommended.  Doses should not exceed 5 mg. A 
             second dose may be  administred after 30 minutes. The
             oral maintenance dose is 4-8 mg/kg/day.
     4.3 Contraindications
       - Severe heart failure
       - Second or third degree atrioventricular block
       - Cardiogenic shock
       - Severe hypotension
       - Sick sinus syndrome
       - Severe left ventricular dysfunction
       - Hypersensitivity to verapamil

     5.1 Oral
       Oral absorption is the most frequent cause of intoxication
     5.2 Inhalation
       Not relevant
     5.3 Dermal
       Not relevant
     5.4 Eye
       Not relevant
     5.5 Parenteral
       Cardiovascular toxicity was reported with IV doses much lower 
       than oral  toxic doses (Benaim et al, 1972, Vaughan-Neil et al,
        1972, Hattori et al,  1982, Lipman et al, 1982)
     5.6 Other
       Not relevant
     6.1 Absorption by route of exposure
       Oral: About 90 % of verapamil is absorbed from the 
       gastrointestinal  tract.  Absorption is rapid and the peak 
       plasma concentration is reached  30-120 minutes following an 
       oral dose. In a case of acute poisoning the  calculated
       half-time of absorption was 1.5 hours (Sauder et al, 1990).  
       Verapamil  undergoes extensive first-pass metabolism by the 
       liver.  Bioavailability  ranges from 20 to 35% (Eichelbaum et 
       al, 1981) but it may vary in patients  with underlying 
       disease: 13-14% in cardiac failure; 35 % in atrial  
       fibrillation; and 50-55% in cirrhosis (Drugdex; Somogyi et al, 
     6.2 Distribution by route of exposure
       Oral: The volume of distribution is 2.4-6.2 l/Kg (Schomerus et 
       al,  1976; Mc Allister et al, 1982).  In cirrhotic patients, 
       the apparent volume  of distribution is higher than in control 
       patients (9.17 vs 6.15 l/Kg)  (Somogyi et al, 1981)
       Parenteral: Volume of distribution is 2.5-6.76 l/Kg (Dominic 
       et al, 1981;  Mc.Allister et al, 1982; Eichelbaum et al, 1981) 
       in normal subjects, and  this doubles in patients with 
       cirrhosis (Somogyi et al, 1981).  90 % of  plasma verapamil is 
       bound to plasma protein. Verapamil crosses the placental  
       barrier and has also been found in breast milk.
     6.3 Biological half-life by route of exposure
       Parent Compound
       Oral: The mean elimination half-life following single oral 
       doses is 2.8-7.4  hours (Shomerus et al, 1976; Knoll 
       Pharmaceuticals, 1984). After repeated or  chronic doses,
       the half-life increases to 4.5-12.0 hours (Knoll 
       pharmaceuticals, 1984;  Schwartz et al, 1982; Shand et al, 
       1981). Sauder et al (1990) reported an   elimination half-life 
       of 7.9 and 13.2 hours in two cases of acute poisoning.
       Parenteral: Following IV administration, Dominic et al (1981) 
       reported a  distribution half-life of 3.5 minutes and an 
       elimination half-life of 110.5  minutes.

       The main metabolite is norverapamil which has an elimination 
       half-life very  similar to that of the parent compound, 
       ranging from 4 to 8 hours (Reynolds,  1982; Mc.Allister et al, 
       1982; Piotrowski et al, 1986; Barberi et al, 1985)
     6.4 Metabolism
       Verapamil undergoes an extensive hepatic metabolism. Due to a 
       large  hepatic first-pass effect, bioavailability does not 
       exceed 20 - 35% in  normal subjects. Twelve metabolites have 
       been described. The main metabolite  is norverapamil and the 
       others are various N- and 0-dealkylated metabolites  (Knoll 
       Pharmaceuticals, 1984; Shomerus et al, 1976).
     6.5 Elimination by route of exposure
       About 70% of the administered dose is excreted in urine within 
       5 days as  metabolites, of which 3-4% is excreted as unchanged 
       drug (Eichelbaum et al,  1979; Knoll Pharmaceuticals, 1984).
       About 16% of the ingested dose is excreted within 5 days in 
       faeces as  metabolites (Eichelbaum et al, 1979; Prod Info, 
       Breast milk
       Verapamil may appear in breast milk.
     7.1 Mode of action
       7.1.1 Toxicodynamics
             (Goodman and Gilman; Jaeger et al, 1990)
             Verapamil is a calcium channel blocker and inhibits the 
             entry of  calcium through calcium channels into 
             cardiovascular cells.  Verapamil reduces the magnitude 
             of the calcium current entry and  decreases the rate of 
             recovery of the channel. Channel blockade by  verapamil 
             is enhanced as the frequency of stimulation increases.  
             Its action on cardiac tissue results in antiarrythmic 
             and negative  inotropic effects.
             Verapamil slows the spontaneous firing of pacemaker 
             cells in the  sinus node in vitro. In vivo, this effect 
             is partially abolished by  an increase in the 
             sympathetic activity due to arterial dilatation.  
             Verapamil decreases the rate of phase 4 spontaneous
             depolarization in cardiac  Purkinje cells. The most 
             marked effect  of verapamil is a reduction in conduction 
             velocity through the A.V.  node and a significant 
             increase in the functional refractory  period.
             Verapamil decreases peripheral vascular and coronary 
             resistance but  it is a less potent vasodilator than 
             nifedipine. In contrast, its  cardiac effects are more 
             prominent than those of nifedipine. At  doses necessary 

             to produce arterial vasodilatation, verapamil has  much 
             greater negative chronotropic, dromotropic and inotropic 
              effects than nifedipine.  The intrinsic negative 
             inotropic effect  of verapamil is partially offset by 
             the decrease in afterload and  the reflex increase in 
             sympathic activity.
             At toxic doses, calcium channel inhibition by verapamil 
             results in  three principal effects: 
             hypotension due to arterial vasodilatation;
             cardiogenic shock secondary to a negative inotropic 
             bradycardia and atrio-ventricular block.
       7.1.2 Pharmacodynamics
             The therapeutic effects of verapamil on hypertension and 
              angina pectoris are due to arterial systemic and 
             coronary  vasodilatation. The antiarrhythmic activity of 
             verapamil is due to  a delay in impulse transmission 
             through the AV node by a direct  action.
     7.2 Toxicity
       7.2.1 Human data
                     (Kozlowski et al, 1988; Coaldrake et al, 1984; 
                     Mc  Millan et al, 1987; Immonen et al, 1981; 
                     Defaire et al,  1976; Hruby and Missliwetz 1985; 
                     Moroni et al, 1980;  Perkins 1978; Woie et al, 
                     1985; Madera and Wenger 1977;  Enyart et al, 
                     1983; Mayer et al, 1985; Da Silva et al,  1979; 
                     Candell et al, 1979; Terwee et al, 1985; Haegy 
                     et al,  1979; Grosch and Zweigle 1979; Eckert et 
                     al, 1988; Orr et  al, 1982; Gris et al, 1989; 
                     Hendren et al, 1989; Sauder et  al, 1990)
                     Toxicity may occur after ingestion of 1 g. 
                     Haemodynamic  disturbances are dose-dependent: 
                     hypotension or  cardiogenic shock occurred in 
                     45% of the cases when the  dose ingested was 2 g 
                     and in 100% of the cases when the  dose exceeded 
                     2 g (Sauder et al, 1990). Deaths have been  
                     reported after overdoses of 1.4., 2.4. and 2.8 g 
                     (Hendren  et al, 1989; Madera et al, 1977; Mayer 
                     et al, 1985).  Recovery has been reported with 
                     doses above 6 g (Immoney  et al, 1981, Mc Millan 
                     et al, 1988 : Coaldrake et al,  1984; Kozlowski 
                     et al, 1988).
                     No data available
       7.2.2 Relevant animal data
             Experimental IV intoxication has been described in rat, 
             dog  or cat models (Strubelt et al, 1984; Hamann et al, 
             1987; Gay et al,  1984; Jolly et al, 1987; Agoston et al,
             1984). In a dog  intoxication model, an IV bolus of 200 
             g/kg followed with an  infusion of 16 g/kg/min of verapamil 
             produced an hyperdynamic shock with severe  hypotension, a 

             decrease in vascular resistance and an increase of cardiac 
             output. Heart rate was significantly reduced as the PR
             interval increased. Higher doses in a similar protocol 
             (bolus of  720 g/kg and infusion dose of 110 g/kg/mn) 
             produced cardiogenic shock (Gay et al, 1984). These data 
             suggest that experimental overdosage in animal should 
             produce two different degrees of severity:
             the first degree appears at "low" toxic doses and is
             characterized by a cardiovascular collapse due to 
             decreased  vascular resistance eventually associated 
             with bradycardia and/or  atrioventricular block;
             the second degree appears when toxic doses are increased 
             (Gay et al,  1984) or when beta-blocking agents are 
             given in association  (Hamann et al, 1987; Jolly et al, 
             1987). This stage is  characterized by a predominent 
             negative inotropic effect responsible for a cardiogenic 
       7.2.3 Relevant in vitro data
             No data available.
     7.3 Carcinogenicity
       No data available.
     7.4 Teratogenicity
       Verapamil is classified as Category C (United States
       Pregnancy Classification) by the manufacturer (Knoll 
       Pharmaceuticals, 1987).
     7.5 Mutagenicity
       No data available.
     7.6 Interactions
       (Reynolds, 1982; Meyler; Drugdex)
       Beta-blockers:  Hypotension, atrioventricular block, left 
       ventricular failure and asystole have been reported after IV 
       administration of verapamil to patients receiving beta-
       blockers. Combined IV beta-blocker and IV verapamil
       therapy is contraindicated.  Although oral verapamil combined 
       with oral beta-blockers has been recommended in some cases of 
       angina, this combination should be avoided in patients with 
       impaired left ventricular function.
       Digoxin: Increase in digoxin half-life. Impairment of renal 
       and extra-renal clearance of digoxin.
       Amiodarone:    Sinus arrest and A-V block
       Calcium salts: Antagonism of the effects of calcium channel 
       Quinidine: Hypotension in patients with hypertrophic 
       Theophylline: Increase in serum theophylline levels may give 
       symptoms of toxicity.
       Disopyramide: Additive negative inotropic effects.

       Antibiotics: Reduction of verapamil concentrations in 
       tuberculous patients treated with rifampicin, isoniazid and 
       ethambutol. It is sugggested that the metabolism of verapamil 
       is enhanced by induction of hepatic enzymes by rifampicin. 
       Carbamazepine: Increase of plasma carbamazepine levels by 
       inhibition of carbamazepine metabolisation with subsequent 
       Cimeditine: Controversial data concerning effects on verapamil 
       bioavailability have been reported.
       Cyclosporin: Increase in serum cyclosporin concentrations due 
       to inhibition of cyclosporin metabolism.
       Dantrolene:    Hyperkalaemia and cardiac depression
       Lithium: Decrease of serum lithium concentration with 
       exacerbation of manic psychosis.
       Oral hypoglycaemic drugs: Improvement of glucose tolerance in 
       non-insulin dependent diabetes mellitus.
     7.7 Main adverse effects
       The following adverse reactions have been reported during 
       verapamil  treatment: 
       Hypotension is the most frequent side effect associated with
       intravenous verapamil injection; hypotension was also reported 
       after oral  administration of verapamil. 
       Heart failure has been reported in patients with impaired 
       cardiac function  and in patients treated with beta-blockers 
       and verapamil.
       Supraventricular tachycardia
       Heart block: atrioventricular block has been reported after 
       verapamil IV  injection in patients on digitalis treatment.  
       Ventricular fibrillation and  cardiac arrest: 5 cases of 
       cardiac arrest after IV verapamil injection in  patients with 
       Wolf-Parkison-White syndrome have been reported (Mac Govern et 
        al, 1986)
       Central nervous system
       Rare episodes of dizziness, headache, drowsiness and fatigue 
       have been  described after oral administration. One case of 
       dystonia with jerking  movements has been reported (Hicks and 
       Abraham, 1985). 
       Endocrine - metabolic
       Lipid abnormalities: an increase in triglycerides and VLDL-C 

       levels in  patients with hyperlipidemia.
       Gynaecomastia: 18 cases reported during prolonged verapamil
       Nausea, diarrhoea and constipation (6.3%) are sometimes 
       Transient elevation of SGOT and SGPT
       Rare cases of hepatotoxicity have been reported in patients 
       after 2-3 weeks  treatment
       In a series of 120 patients treated with verapamil for a
       cardiomyopathy, 8 developed pulmonary oedema with a fatal 
       outcome in 3  cases.
     8.1 Material sampling plan
       8.1.1 Sampling and specimen collection
    Toxicological analyses
    Biomedical analyses
    Arterial blood gas analysis
    Haematological analyses
    Other (unspecified) analyses
       8.1.2 Storage of laboratory samples and specimens
    Toxicological analyses
    Biomedical analyses
    Arterial blood gas analysis
    Haematological analyses
    Other (unspecified) analyses
       8.1.3 Transport of laboratory samples and specimens
    Toxicological analyses
    Biomedical analyses
    Arterial blood gas analysis
    Haematological analyses
    Other (unspecified) analyses
     8.2 Toxicological Analyses and Their Interpretation
       8.2.1 Tests on toxic ingredient(s) of material
    Simple Qualitative Test(s)
    Advanced Qualitative Confirmation Test(s)
    Simple Quantitative Method(s)
    Advanced Quantitative Method(s)
       8.2.2 Tests for biological specimens
    Simple Qualitative Test(s)
    Advanced Qualitative Confirmation Test(s)
    Simple Quantitative Method(s)
    Advanced Quantitative Method(s)
    Other Dedicated Method(s)
       8.2.3 Interpretation of toxicological analyses
     8.3 Biomedical investigations and their interpretation

       8.3.1 Biochemical analysis
    Blood, plasma or serum
                     Routine biomedical investigations, i.e. sodium,  
                     potassium, creatinine and/or urea, glucose.
    Other fluids
       8.3.2 Arterial blood gas analyses
             Should be performed.
       8.3.3 Haematological analyses
       8.3.4 Interpretation of biomedical investigations
             Hyperglycaemia has been reported.  Acidosis may occur in 
              shock.  Verapamil may be measured in biological fluids 
             but levels  are not useful or necessary for the 
             management of verapamil  poisoning. 
             Following chronic administration, therapeutic plasma
             concentrations of verapamil are 50-350  g/l.
             In 6 patients with acute verapamil poisoning, plasma 
             levels ranged  from 845 to 7,266  g/l (Enyart et al, 
             1983; Gris et al, 1989;  Kozlowski et al, 1988; Orr et 
             al, 1982; Ter Wee et al, 1985; Woie &  Storstein 1981). 
             Higher levels (up to 85,000  g/l) were measured in  
             fatal overdose.
             Verapamil concentrations in urine are 3,300-25,204 g/l 
             during the  first 24 hours after ingestion (Sauder et al,
              1990). The renal  clearance of verapamil is less than 
             2% of total body clearance  (Sauder et al, 1990)
             Tissue analyses in patients with fatal outcome show very 
             high  concentrations in the liver (29-400 mg/kg) and in 
             the kidney  (30-140 mg/kg) (Chan et al, 1987; Weller and 
             Wolf, 1984; Thompson  and Ranneil, 1981).
     8.4 Other biomedical (diagnostic) investigations and their 
     8.5 Overall Interpretation of all toxicological analyses and 
       toxicological investigations
     8.6 References
     9.1 Acute poisoning
       9.1.1 Ingestion
             Symptoms usually appear within 1 to 5 hours of ingestion 
             and  may include hypotension, bradycardia, 
             atrioventricular block,  cardiogenic shock, cardiac 
       9.1.2 Inhalation
             No data available.
       9.1.3 Skin exposure
             No data available.

       9.1.4 Eye contact
             No data available.
       9.1.5 Parenteral exposure
             The effects are similar to those observed after 
       9.1.6 Other
             No data available.
     9.2 Chronic poisoning
       9.2.1 Ingestion
       9.2.2 Inhalation
       9.2.3 Skin exposure
       9.2.4 Eye contact
       9.2.5 Parenteral exposure
       9.2.6 Other
     9.3 Course, prognosis, cause of death
       Course:  Symptoms appear within 1-5 hours after ingestion and 
       may  persist for up to 48 hours (Haegy et al, 1979)
       Prognosis is worse if: 
       the dose was higher than 2 g
       cardiogenic shock occurs 
       other cardiotoxic drugs, especially beta-blockers, have also 
       been ingested 
       there is an underlying cardiac insufficiency
       If the patient has not developed cardiac arrest or postanoxic 
       coma during  the 48 first hours, recovery is usual.
       Death may occur within a few hours after ingestion. It is 
       associated with  irreversible shock and/or atrioventricular 
       block (Madera et al, 1977; Meyer  et al, 1989; Orr et al, 
     9.4 Systematic description of clinical effects
       9.4.1 Cardiovascular
             Cardiovascular symptoms are dose-dependent; they occur 
             in 45% of  the cases when the dose ingested is less than 
             2 g, and in 100% of  the cases when the dose exceeds 2 g 
             (Sauder et al, 1990).
             Hypotension is due to arterial vasodilatation and the 
             negative  inotropic effect of verapamil. In a review of 
             28 cases of acute  verapamil poisoning in adults, 
             hypotension was present in 22 cases  (mean
             systolic arterial pressure 54 mmHg) (Sauder et al, 
             1990). In a  series of 21 cases (7 adults and 14 
             children) reported by  Schlagenhaufen and Keller (1987), 
             hypotension was present in 18  cases. 
             Cardiogenic shock
             In the cases reviewed by Sauder et al (1990), 11 of the 

             22 patients  who had hypotension developed cardiogenic 
             Sauder et al (1990) reported cardiogenic shock in 2 
             patients who  had ingested verapamil and beta-blockers. 
             A haemodynamic study  performed in one case showed a 
             strong decrease in cardiac index  (1.3 l/min/m›) despite 
             treatment with positive inotropic agents  (epinephrine 
             0.8  g/kg/min and isoproterenol
             0.2  g/kg/min). 
             Bradycardia is the commonest symptom and occurs within 
             the first  hour of ingestion. In the 28 cases reviewed 
             by Sauder et al (1990),  heart rate ranged between 30 
             and 100 beats/min with a mean of 55  beats/min.  
             Bradycardia is often associated with atrioventricular  
             Atrioventricular block
             Atrioventricular block, associated mainly with a 
             junctional rhythm,  is a frequent feature and is present 
             in 82% of cases (Sauder et al,  1990).  There is no 
             correlation between the ingested dose and  
             atrioventricular conduction disturbances which may be 
             seen with  doses lower than 1 g (Hruby et al, 1985; 
             Immoven et al, 1981;  Eckert et al, 1988).  Third degree 
             AV block occurred in 90% of  cases; first or second 
             degree AV block is less frequent (10% of the  cases). 
             Recovery of normal sinus rythm occurs between 5 and 48  
             Cardiac arrest
             In the cases reviewed by Sauder et al (1990), 5 patients 
             developed  cardiac arrest with a fatal outcome in 3 
             cases (Immonen et al,  1981; Madera et al, 1977; Mayer 
             et al, 1985; Hruby et al, 1985; Orr  1982). 
             Chronic: No data available.
       9.4.2 Respiratory
             Acute: Pulmonary oedema may occur and is due to
             cardiogenic shock. 
             Chronic: No data available.
       9.4.3 Neurological
                     Drowsiness and confusion have been reported. 
                     Coma due to  cerebral hypoxaemia may occur in 
                     severe shock.
                     Seizures occured in a child who had ingested 400 

                     mg  verapamil (Passel & Crespin, 1984). 
                     Chronic: No data available.
    Peripheral nervous system
                     No data available.
    Autonomic nervous system
                     No data available.
    Skeletal and smooth muscle
                     No data available.
       9.4.4 Gastrointestinal
             Acute: Nausea and vomiting are common.
             Chronic: No data available.
       9.4.5 Hepatic
             No data available.
       9.4.6 Urinary
                     No data available.
                     No data available.
       9.4.7 Endocrine and reproductive systems
             No data available.
       9.4.8 Dermatological
             No data available.
       9.4.9 Eye, ear, nose, throat: local effects
             No data available.
       9.4.10 Haematological
              No data available.
       9.4.11 Immunological
              No data available.
       9.4.12 Metabolic
     Acid-base disturbances
                       Acidosis may be seen in cardiogenic shock.
     Fluid and electrolyte disturbances
                       No data available.
                       Hyperglycaemia may occur but is rather rare 
                       (Mc  Millan et al, 1987; Enyart et al, 1983; 
                       Da Silva et al,  1979; Gris et al, 1989). 
       9.4.13 Allergic reactions
              No data available.
       9.4.14 Other clinical effects
              No data available.
       9.4.15 Special risks
              No data available.
     9.5 Other
       No data available.
     9.6 Summary
      10.1 General principles
         Patients with verapamil overdose should be closely monitored
         preferably in an intensive care unit. Monitor vital signs,
         including ECG, blood pressure, central venous pressure, 
         output and respiration.  

         Treatment may include correction of hypotension or shock, AV
         block and artificial ventilation.  Early gastric lavage
         and/or emesis is indicated in recent ingestion. Forced 
         diuresis and  extrarenal elimination are ineffective and not 
      10.2 Relevant laboratory analyses
         10.2.1 Sample collection
                Blood samples for verapamil analysis should be drawn 
                in  plastic tubes with heparin.
         10.2.2 Biomedical analysis
                A biochemical profile including glucose, BUN, 
                electrolytes,  creatinine, enzymes and blood gases 
                should be obtained on  admission.
         10.2.3 Toxicological analysis
                Verapamil analysis in biological fluids is not 
                necessary  for management of the poisoning. 
         10.2.4 Other investigations
      10.3 Life supportive procedures and symptomatic/specific 
         Observation and monitoring
         Monitor vital signs systematically, including ECG, blood 
         pressure and  central venous pressure. Insert a venous 
         catheter for hydration and drug  injection. If shock is 
         present, a haemodynamic study by a Swan Ganz catheter  may 
         be useful for guiding treatment.
         Hypotension and shock
         Experimental studies on verapamil intoxication showed that
         sympathomimetic agents are the drugs of choice for the 
         treatment of  haemodynamic and conduction disturbances. Beta 
         agonists reverse the negative  inotropic, dromotropic and 
         chronotropic effects.  However, beta agonists are  effective 
         in reversing hypotension only if they are combined with 
         alpha  agonists (Schomerus et al, 1976). Calcium salts 
         haemodynamic effects of verapamil but are ineffective in 
         A.V. block.  Drugs  which directly or indirectly enhance 
         intracellular calcium availability  should have a 
         complementary effect; these include calcium salts, glucagon, 
          phosphodiesterase III inhibitors (Amrinone, Enoximone, 
         Milrinone), beta  agonists (dobutamine, orciprenaline, 
         In an experimental model of verapamil toxicity, 4-
         increased the heart rate and the blood pressure (Shand et al,
         Apha and beta agonists (sympathomimetics)
         Alpha and beta sympathomimetic drugs such as dopamine or 
         epinephrine are  recommended at very high doses if 
         necessary. Dopamine should be given at a  dose of 10 
         g/kg/min and increased up to 20 - 30 g./kg/min if necessary. 

          Epinephrine is a better alternative and should be used at a 
         dose of 0.25  g/kg/min which should be increased up to 1 
         g/kg/min if needed (Sauder et al,  1990).
         It may be necessary to monitor haemodynamic parameters with 
         thermodilution Swan-Ganz catheter to evaluate the relative 
         importance of  arterial vasodilatation and of negative 
         inotropic effects. If arterial  vasodilatation is dominant, 
         it should be corrected with an alpha agonist  such as 
         norepinephrine, which should be given at high doses 
         sufficient to  restore the normal level of systemic vascular 
         resistance.  However, if  negative inotropic effects are 
         dominant, it is justifiable to increase the  dose of 
         epinephrine to normalize the cardiac output.
         Calcium salts
         Calcium gluconate 10% may be given at a dose of 0.2 to 0.5 
         ml/kg over 5 to  10 minutes and may be repeated as needed. 
         Calcium chloride 10% may be used  at a dose of 10 to 20 ml 
         in adults and 20 mg/kg in children.
         Glucagon has been used in some cases (Hruby et al, 1985)
         Amrinone was used successfully in one case (Sauder et al, 
         1990). An IV bolus  of 1 mg/kg over 5 minutes increased the 
         cardiac index significantly from  2.22 to 3.43 l/min/m›, and 
         the left ventricular stroke work index from 21 to  39 
         gm/m›/beat, in a patient who was treated with
         epinephrine 0.8 g/kg/min and with isoproterenol 1.3 
         Atrioventricular block
         Atropine is ineffective. Complete AV block should be treated 
         with high doses  of beta agonists such as isoproterenol. 
         Administer isoproterenol at a dose  of 0.3  g/kg/min and 
         increase in 0.2  g/kg/min increments as needed;  epinephrine 
         may also be effective. Calcium salts are not very effective 
         in  AV block. If the conduction disturbances do not respond 
         beta agonists, cardiac pacing may be necessary.
         Respiratory failure - pulmonary oedema
         Respiratory failure should be treated by artificial 
         ventilation.  Early  artificial ventilation is also 
         indicated in patients with cardiogenic shock.
      10.4 Decontamination
         Emesis is indicated in recent ingestion.
         Gastric lavage is indicated in recent ingestion and should 
         performed under strict ECG and blood pressure monitoring.

         The efficacy of activated charcoal has not been established. 
         However, it is  reportedly useful in diltiazem poisoning 
         (Jaeger et al, 1990a).  Repeated  doses of activated 
         charcoal may be useful in cases of poisoning with  verapamil 
         sustained-release forms.
      10.5 Elimination
         Forced diuresis is ineffective. Toxicokinetic studies show 
         that less  than 2% of the dose ingested is eliminated in the 
         urine (Sauder et al,  1990).
         Haemodialysis was ineffective in one case of acute verapamil
         poisoning (Ter Wee et al, 1985).
      10.6 Antidote treatment
         10.6.1 Adults
                The benefit of calcium salts has not been established 
                in  acute verapamil intoxication (See section 10.3.).
         10.6.2 Children
      10.7 Management discussion
         Patients with verapamil poisoning should be closely
         monitored, preferably in an intensive care unit as soon as 
         Outside of an intensive care unit
         Recent ingestion and no cardiotoxic symptoms:  perform 
         and/or gastric lavage and give oral activated charcoal
         Cardiotoxicity present: atrioventricular block - give
         isoproterenol; shock - treat with dopamine or epinephrine. 
         Transfer the patient to an intensive care unit.
         In the intensive care unit
         Monitor vital signs (ECG, blood pressure, central venous
         pressure, respiration) and biochemical parameters
         Gastric lavage and oral activated charcoal in recent 
         ingestion.  Symptomatic  treatment of respiratory distress.
         Atrioventricular block: give isoproterenol
         Hypotension, shock: give sympathomimetic drugs with alpha 
         beta agonists such as dopamine or preferably epinephrine.
         Calcium salts, glucagon or phosphodiesterase inhibitors may
         be given.  If the shock does not respond to these measures,
         perform a haemodynamic study in order to adapt the 
      11.1 Case reports from literature
         Schlagenhaufen and Keller (1987) reported a series of 21 
         cases of  acute verapamil poisoning (7 adults and 14 
         children) collected by the Swiss  Toxicological Information 
         Center. Hypotension was present in 18 cases, AV  block 
         occured in 11 cases, fatal outcome was reported in 2 cases.

         Korlowski et al (1988) reported a case of acute poisoning 
         with 9.6 g of  sustained-release verapamil. The patient 
         developed cardiogenic shock (blood  pressure 40 mmHg) and 
         3rd degree atrioventricular block. Peak serum  verapamil 
         concentration was 2,814  g/l. Supportive treatment included  
         isoprenaline, dopamine, calcium salts and ventricular 
         pacing. The patient  recovered. 
         Mayer et al (1985) reported a case of fatal poisoning with
         2.4 g of a substained-release form of verapamil in a 60 year-
         old woman.  Haemodynamic study showed 2 stages: first, a 
         hyperdynamic state with  decreased systemic vascular 
         resistance; then cardiogenic shock with  decreased 
         contractility which became rapidly unresponsive to inotropic 
         Passal and Crespin (1984) reported a case of accidental 
         intoxication with  400 mg of verapamil in a 11 month-old 
         girl. She developed coma, seizures,  respiratory depression, 
         bradycardia and hypotension. She was successfully  
         resuscitated with intravenous calcium chloride, 
         isoproterenol and dopamine. 
      11.2 Internally extracted data on cases
         Sauder et al (1990) reported six cases of verapamil 
         poisoning with  doses of 1.2-9.6 g. Cardiogenic shock was 
         present in two cases and AV block  in four cases. The two 
         patients who presented with cardiogenic shock had  also 
         ingested beta-blockers. All patients recovered without any  
         A toxicokinetic study was performed in two cases and showed 
         peak serum  levels of 951 and 185  g/l; serum half-lives of 
         7.9 and 13.2 hours, total  body clearances of 425 and 298 
         ml/min, respectively. Only 2% of the ingested  dose was 
         eliminated in urine.
         A haemodynamic study performed in one patient with 
         cardiogenic shock showed  a marked decrease in cardiac index 
         (1.3 l/min/m2) and in left ventricular  stroke work index 
         (11 gm/m2/beat). Haemodynamic parameters improved with  
         treatment with high doses of epinephrine, isoproterenol, 
         amrinone and  calcium salts.
      11.3 Internal cases
         To be added by the PCC.
    12. Additional information
      12.1 Availability of antidotes
      12.2 Specific preventive measures
      12.3 Other
    Agoston S, Maestrone E, Hezik EJ, Ket JM, Houwertjes MC, Uges DRA 
    (1984).   Effective treatment of verapamil intoxication with 4-
    aminopyridine in the cat.  J  Clin Invest 73: 1291-1296 
    Candell J, Volle V, Soller M, Rius J (1979). Acute intoxication 
    with verapamil.  Chest 75: 200-201

    Chan LFT, Chuy LH, Crowley RJ (1987).  Verapamil tissue 
    concentrations in fatal  cases.  J Analytical Toxicol 11: 171-174
    Coaldrake LA (1984).  Verapamil overdose.  Anaesthesia and 
    Intensive Care 12: 174-175
    Da Silva OA, De Melo RA, Filho JPJ (1979). Verapamil acute self-
    poisoning.  Clin  Toxicol 14: 361-367
    De Faire U, Lundman T (1977).  Attempted suicide with verapamil.
    Eur J Cardiol 6: 195-198
    Drugdex (1989). Verapamil. Micromedex Inc. 
    Dukes MNG. Side effects of drugs.  Excerpta Medica
    Eckert S, Mertens HM, Mannebach H, Gleischmann U (1988).  
    Bradycardia factitia.  Dtsch Med Wschr 113: 469-471
    Enyeart JJ, Price WA, Hoffman DA, Woods L  (1983). Profound 
    hyperglycemia and  metabolic acidosis after verapamil overdose.  
    J Amer Coll Cardiol 2:  1228-1231
    Gay RG, Alego SS, Appelton C, Olajos M, Morkin E, Goldman S 
    (1984). Pharmacological  treatment of the effects of verapamil 
    toxicity in conscious dogs.  Clin Res 32: 6A
    Goodman LS, Gilman AG, Rall JW, Murad F (1985). Goodman and 
    Gilman's Pharmacological Basis of Therapeutics,  7th Ed. New York, 
    Gris P, Coffernils M, Alame T, Kimbimbi TP (1989). Intoxication 
    volontaire au  Vérapamil. A propos d'un cas.  Revue de la 
    littérature. Sem Hop Paris 65: 435-438
    Grosch E, Zweigle HP (1978). Kasuistische Beiträge zur 
    Intoxikation mit  antiarrhythmischen Substanzen (Verapamil und 
    Prajmaliumbitartrat). Therapiewoche 28:  3252-3264
    Haegy JM, Hasselmann M, Faller JP, Jaeger A, Tempe JD  (1979). 
    Intoxication aiguë par  le vérapamil.  J Med Strasbourg 10: 157-160
    Haraphat SR, Kates RE  (1979). Rapid high pressure liquid 
    chromatographic analysis of  verapamil in blood and plasma.  J 
    Chromatogr 170: 385-390
    Haraphat SR, Kates RE  (1980). High performance liquid 
    chromatographic Analysis of  verapamil II Simultaneous 
    quantitation of verapamil and its active metabolite,  
    norverapamil.  J Chromatogr 181, 484-489

    Hariman RJ, Mangiardi LM, McAllister RG, Surawicz B, Shabetai R, 
    Kishida H (1979).  Reversal of the cardiovascular effects of 
    verapamil by calcium and sodium :  differences between 
    eletrophysiologic and hemodynamic responses.  Circulation 59:  
    Hattori VT, Mandel WJ, Peter D (1982). Calcium for myocardial 
    depression from  verapamil (letter).  New Eng J Med 306: 238
    Hendren WG, Schieber RS, Garrettson LK (1989). Extracorporeal 
    bypass for the  treatment of verapamil poisoning.  Ann Emerg Med 
    18: 984-987
    Hese HG  (1979). Gas chromatographic determination of verapamil 
    in plasma and urine.  Arznei Forsch 29: 1681-1684
    Hicks CB, Abraham K  Verapamil and myoclonic dystonia (letter)  
    (1985). Ann Intens  Med 103: 154
    Hruby K, Missliwetz J (1985). Poisoning with oral antiarrhythmic 
    drugs.  Int J Clin  Pharmacol Ther Toxicol 23: 253-257
    Immoven P, Linkola A, Waris E (1981). Three cases of severe 
    verapamil poisoning.  Int J Cardiol: 101-105
    Jaeger A, Sauder Ph, Bianchetti G, Kopferschmitt J, Dahlet M, 
    Tritsch L, Flesch F  (1990).  Intoxications aiguës par le 
    Diltiazem.  Etude cinétique et hémodynamique.  J  Toxicol Clin 
    Exp 10: 243-249
    Jaeger A, Berton Ch, Sauder Ph, Kopferschmitt J (1990). Toxicité 
    des inhibiteurs calciques.  J Toxicol Clin Exp 10: 219-229
    Jolly SR, Kipnis JN, Lucchesi BR (1987). Cardiovascular 
    depression by verapamil: reversal by glucagon and interactions with 
    propranolol. Pharmacology 35: 249-255
    Knoll Pharmaceutical Co (1984), Product information : Isoptin SR (R)
    Knoll Pharmaceutical Co (1987), Product information : Isoptin SR (R)
    Kozlowski JH, Kozlowski JA, Schuller D (1988). Poisoning with
    substained-release verapamil.  Am J Med 85: 127
    Lignan H, Lheureux Ph, Fontaine J, Askenasi R  (1987). Effet du 
    calcium sur les  modifications électrocardiographiques et 
    tensionnelles induites par l'intoxication  aiguë par le vérapamil 
    chez le chien.  Réan Soins Intens Med Urg 3: 63-65
    Lipman J, Jardine I, Roos C, Dreosti L (1982). Intravenous 
    calcium chloride as an  antidote to verapamil-induced 

    hypotension.  Intens Care Med 8: 55-57
    Madera F, Wenger R (1977). Zur Frage von Vergiftung mit Isoptin S
    (Verapamil + Pentobarbital).  Intensivmed 14: 373-377
    Mayer U, Buhl N, Sachs H, Sigel H  (1985). Tödliche Vergiftung 
    mit verapamil in retard-form.  Dtsch Med Wschr 110: 1293-1296
    McAllister RG, Howell SM  (1976). Fluorometric assay of verapamil 
    in biological fluids and  tissues.  J Pharm Sci 65: 431-432
    McAllister RG, Kirsten EB  (1982). The pharmacology of verapamil. 
    IV Kinetic and dynamic effects after single intravenous and oral 
    doses.  Clin Pharmacol  Ther 31: 418-426
    McGovern B, Garan H, Ruskin JN  (1986). Precipitation of cardiac 
    arrest by verapamil  in patients in Wolff-Parkinson-White 
    syndrome.  Ann Intens Med 104: 791-794
    McIlhenny HM  (1971). Metabolism of "C Verapamil".  J Med Chem 
    14: 1178-1184 
    McMillan R  (1988).  Management of acute severe verapamil 
    intoxication.  J Emerg Med  6: 193-196
    Moroni F, Mannaioni PF, Dolara A, Ciaccheri M  (1980). Calcium 
    gluconate and  hypertonic sodium chloride in a case of massive 
    verapamil poisoning Clin Toxicol 17:  395-400
    Needleman P, Corr PB, Johnson Jr EM  (1985). Drugs used for the 
    treatment of angina :  organic nitrates, calcium channel blockers,
    and B-adrenergic antagonists  In :  "Pharmacological basis of 
    therapeutics". Goodman A, Gilman LS, Goodman TW, Rall F,  eds. 
    McMillan. 7th Edition, New York. p 806-826
    Orr GM, Bodansky HJ, Dymond DS, Taylor M  (1982). Fatal verapamil 
    overdose.  Lancet  ii: 1218-1219
    Passal DB and Crespin FH Jr (1984). Verapamil poisoning in an
    infant.  Pediatrics 73:  543-545
    Perkins CM  (1978). Serious verapamil poisoning : treatment with
    intravenous calcium gluconate.  Br Med J: 1127
    Reynolds JEF (1982), ed. Martindale,  The Extra Pharmacopoeia. 
    Pharmaceutical Press, 28th Ed, London; p 351
    Ryall JE (1978). Verapamil, oxprenolol and digoxin combination.
    TIAFT Personnal communication. 
    Sauder Ph, Kopferschmitt J, Dahlet M, Tritsch L, Flesch F, Siard 
    Ph, Mantz JM, Jaeger  A  (1990). Les intoxications aiguës par le 

    Vérapamil A propos de 6 cas Revue de la  littérature.  J Toxicol 
    Clin Exper 10: 261-271
    Schlaginhaufen G, Keller B  (1987). Vergiftungen mit verapamil.  
    Schweiz Rundschau  Med (Praxis) 76: 199-203
    Schomerus M, Spiegelhalder B, Slieren B, Eichelbaum M (1976). 
    Physiological disposition of verapamil in man.  Cardiovasc Res 
    10: 605-612
    Shand DG, Hammill SC, Aanonsen L, Pritchett ELC (1981). Reduced 
    verapamil clearance  during long-term oral administration.  Clin 
    Pharmacol Ther 30:  701-703
    Somogyi A, Albrecht M, Kliems G, Schafer K, Eichelbaum M (1981).
    Pharmacokinetics, bioavailability and ECG response of verapamil 
    in patients with  liver cirrhosis.  Br J Clin Pharmac 12: 51-60
    Spielgelhalder B, Eichelbaum M  (1977). Determination of 
    verapamil in human plasma by  mass fragmentography using stable 
    isotope-tabelled verapamil as internal standard.   Arzneim Forsch 
    27: 94-97
    Strubelt O (1984). Antidotal treatment of the acute 
    cardiovascular toxicity of  verapamil.  Acta Pharmacol Toxicol 
    55: 231-237
    Ter Wee PM, Kremer Hovinga TK, Uges DRA, Van Der Geest S (1985).
    4-aminopyridine and haemodialysis in the treatment of verapamil
    intoxication.  Human Toxicol 4: 327-329
    Thomson BM, Pannell LK  (1981). The analysis of verapamil in 
    postmortem specimens by  HPLC and GC.  J Analyt Toxicol 5: 105-109
    Weller JP, Wolf M (1984). Eine tödliche verapamil-Vergiftung  
    Beitr Gerichtl Med 44: 271-275
    Woie L, Storstein L (1981). Successful treatment of suicidal 
    verapamil poisoning with  calcium gluconate.  Eur Heart J 2: 239-242
    Authors:  Sauder Ph, Kopferschmitt J, Flesch F, Jaeger A
              Service de Réanimation Médicale et Centre Anti-Poisons
              CHU, Pavillon Pasteur
              67091 Strasbourg Cedex
              Tel:  33-88161144
              Fax: 33-88161330
    Date:  27 March 1991
    Peer Review: Adelaide, Australia, April 1991

    See Also:
       Toxicological Abbreviations