Calcium Channel Blockers include -

Bepridil, Diltiazem, Felodipine, Isradipine, Nicardipine, Nifedipine,
 Nimodipine, Verapramil, Amlodipine, Nisodipine, Clevidipine, Lercandipine

 Refer verapramil-

Interacting drugs - summary

+  Cal. Channl Blockers -

Barbiturates + Verapramil
 Verapramil bioavailabilty decreased

Calcium salts + verapramil
 clinical effects & toxicities  of Verapramil reversed

Dantrolene + Verapramil
 hyperkalaemia and myocardial depression occur. 

Erythromycin  + felodipine
 pharmacologic and toxic effects of felodipine increased        

H2 antogonists + Diltiazem/Felodipine/ Nicradipine/Nifedipine / verapramil /
 cimetidine and ranitidine  increase the bioavailability
 of  diltiazem, felodipine, and nicradipine.
  Cimetidine  increase Verapramil's bioavailability                             
    
Hydantoin  + Felodipine/ Verapramil
serum felodipine and Verapramil levels increased

Quinidine  + Verapramil/Nifedipine
 Hypotension, bradycardia, ventricular arrhythmia,
  AV block  and  pulmonary edema occur.
 Use concomittantly only when no other alternatives  exist.                                                                                    

Rifampicin + verapramil
loss of clinical effect of oral Verapramil occur,
 IV verapramil  circumvent the interaction

Sulfinpyrazone + Verapramil
 increased clearance and decreased bioavailabilty
 of verapramil  occur

Vitamin D  + Verapramil 
 therapeutic efficacy of verapramil reduced

Nifedipine + Anticoagulants
rarely  increased prothrombin time.                                                

Verapramil, Diltiazem + Carbamazepine
 increased carbamazepine serum levels  with  toxicity occur.  Nifedipine does not appear to interact.
                                                                                  
                                           
Diltiazem/Nicardipine/verapramil  + cyclosporine 
 increased cyclosporine levels   with possible toxiciy  occur
  Verapramil may be nephroprotective when given  before cyclosporine. Monitor Cyclosporine levels

 Bepridil/ Diltiazem/Felodipine/ Nifedipine /Verapramil   + Digitalis  Glycosides    -   
  serum digitoxin levels  increased.                      
                     
Diltiazem + Encainide
serum encainide levels  increased           
                                        
Verapramil +  Etomide
 anesthetic effect of etomide  increased with   prolonged  respiratory depression and apnea

Cal chan Blckrs +   Fentanyl
 severe hypotension or increased fluid volume  occurred in patients  receiving nifedipine.

Verapramil/ Diltiazem  + lithium
 reduction in lithium levels causing decreased  antimaniac control,                            
                                          
Nifedipine +  Mag sulphate Parentral
neuromuscular blockade and hypotension occurred with coadmin.

Verapramil +  Non polarizing muscle relaxants
 muscle relaxant effects may be enhanced.   Respiratory depression  prolonged 

Verapramil +   Prazosin
prazosin serum concentrations increased with  increased sensitivity to prazosin.

Diltiazem/ Felodipine/ Nifedipine/Verapramil   + Theophylline 
 pharmacologic actions  of theophylline enhanced,  with  drug intoxication.
 Theophylline levels  slightly decreased.  
 

Angina

 Calcium Channel Blockers include -

Bepridil, Diltiazem, Felodipine, Isradipine, Nicardipine, Nifedipine, Nimodipine, Verapramil, Amlodipine, Nisodipine, Clevidipine, Leracandipine

Refer Verapramil

Adverse reactions summary

Generally not serious, rarely requires discontinuation or dosage adjustment

VERAPRAMIL
 

CNS

Dizziness/lightheadeness  4%, Headache   2.%,
Asthenia , Insomnia 2 %
Weakness/shakiness ,Jitteriness, Parathesia, Somnolence, Confusion  1 %

GASTROINTESTINAL -

Constipation  7%, Nausea   3% ,
Diarrhea , Abdominal discomfort, Dry mouth/ thirst 1 %

CARDIOVASCULAR -

Hypotension 3%, Periph.edema 2%, Bradycardia 2 %,
Congestive heart failure, Pulmonary edema 2%,
AV block  1,2,3 degree 1%,
Palpitation, Syncope, Myocardial infarction < 1 %

DERMATOLOGIC -  

Dermatitis/rash 1%, Erythema multiforme,  Stevens-Johnson synd  < 1%

HEMATOLOGIC -

Petechiae/ pupura/  bruising/  hematoma 1%

OTHER-  

Shortness of breath/ dyspepsia/wheezing  2%,
Sweating 1%,   Sexual difficultes,
Mituration disord,  polyuria/nocturia/ frequency, Muscle cramps/  pain/inflammation  1 %
  

Lab test abnormalities-
Positive direct coombs test with or without hemolytic anemia with nifedipine.
Isolated cases of decreased platelet counts and elevated non-fasting serum glucose ,
LDH, alkaline phosphatase and ALT have occured with nimodipine. ALT increase with bepridil.
Some elevated liver function tests have occured with isradipine  

Cardiogenic shock,2nd or 3rd degree,

AV Block.Severe Badycardia,sick sinus syndrome.

Uncompensated heart failure. Acute phase of MI.

Special precautions:

1st degree AV block.Control poor cardiac reserve with digitalis and diuretics.

Bradycardia, conduction disturbances,atrial flutter/fibrillation with an accessory pathway. Hepatic impairment.

Pregnancy

Defective platelet function/thrombocytopenia.

Acute hepatic injury- in rare cases symptoms consistent with acute hepatic injury as well as significant elevations in enzymes such as alkaline phosphatae , CPK,LDH, AST, and ALT, have occured with diltiazem, and nifedipine.

Cholestatis with or without jaundice has occured with nifedipine. Rare instances of allergic hepatitis also occured with nifedipine

Warnings- Hypotension- carefully monitor blood pressure during initial administration and titration, closely monitor patients already taking hypertensives.

Congestive heart failure- CHF- has developed rarely, in patients receiving a beta-blocker after beginning nifedipine.

 Use diltiazem, nicardipine, isradipine, felodipine, amlodipine and bepridil with caution in CHF patients

Antiplatelet effects- nifedipine decreases platelet aggregation in vitro.

Withdrawal syndrome- abrupt withdrawal of calcium channel blockers may cause increased frequency and duration of chest pain.Caution is warranted when discontinuing these drugs.

B-blocker withdrwal/nifediine- patients recently withdrawn from beta blockers may develop a withdrawal syndrome with increased angina,

Nicardipine- gradually reduce beta blocker dose over 8 to 10 days with coadministration.

Hepatic function impairment- the pharmocokinetics, bioavailability and patient response to verapramil and nifedipine may be significantly affected by hepatic cirrhosis

  Renal function impairment- caution is adviced in use of these agents in such patients.

 Elderly- verapramil, nifedipine and felodipine may cause a greater hypotensive effect than seen in younger patients, probably due to age-related changes in drug disposition.

Pregnancy- use during pregnancy only when clearly needed and when potential benefits outweigh potential hazards to the fetus.

Lactation- decidewhether to discontinue nursing or discontinue the drug while these agents are being used.

Children- Safety and efficacy of diltiazem, bepridil, felodipine, amlodipine and nifadipine have not been established.

Indications:

Angina,.arrhythmias,essential htpertension.

Dosage:

Angina- oral - initial dose 80 to 120 mg 3 times a day.

Overdosage- Symptoms

Nausea, weakness, dizzines, drowsiness, confusion and slurred speech. Marked and prolonged hypotension and bradycardia both of which may result in decreased cardiac output.

Death has occured. 

Treatment

1. If the patient is shortly after oral ingestion employ emetics or lavage and carthartics

2. Beta-adrenergic agonists and IV calcium have been used effectively.

3. Treat cardiac failure with inotropic agents (isoproterenol, dopamine or dobutamine) and may not always reverse electrophysiologic toxicity.

4. Monitor cardiac and respiratory function, elevate the extremities.

5. Since these agents are highly protein bound dialysis is not likely to help. 6. Verapramil vannot be removed by dialysis

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

SPECIFIC INFORMATION-

Notify physician if any of following occur- Irregular heart beat, shortness of breath, swelling of the hands and feet, pronounced dizziness, constipation, nausea, or hypotension.

GENERAL

1.Take the medicine exactly as directed by the physician.

2.Swallow the tablet whole,without crushing or chewing it. However if advised by the doctor, you may break into half.

3.Take the medicine with food or milk.

4. Allergies- tell your if you ever had any allergic reactions to beperidil, diltiazem, felodipine,flunarizine, isradipine, nicardipine, nifedipine ,nimodipine or verapramil Tell your doctor if you are allergic to to any other substances such as foods, preservatives or dyes.

5. Pregnancy- calcium channel blockers have not been studied on pregnat women. Studies in animals have shown that large doses f calcium channel blockers cause birth defects , prolonged pregnacy poor bone development and stillbirth.

6. Breast feeding- pass into breast milk and cause problems to nursing babies

7. Children- no specific inforamtion available. Not expected to cause different side effects in children

8. Other medicines- Your Doctor should know what othher medicines  to  if you are taking so that he can advice you accordingly.

9. Other medical problems- Your doctor should be aware of  your  other medical problems. Heart rhythm problems - bepridil can cause serious heart rhythm problems Kidney disease or Liver disease -efects of calcium channel blockers may be increased .

10. Missed dose- If you miss a dose of this medicine take it as soon as possible. However, if it is almost time for the next dose skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Food may slow the rate but not the extent of nifedipine absorption

Administration of bepridil after a meal results in insignificant delay in time to peak concentration

Admin of isradipine with food significantly increases the time to peak by about an hour, but no effect on bioavailability

Admin of sustained release verapramil, with food increases time to peak, but bioavailability not affected Bioavailability of felodipine is affected by food

Bioavailabilty of amlodipine is not affected by food.

Pregnancy:

Use only when clearly needed.

Lactation:

Observe caution and decide whether to discontinue nursing or discontinue the drug.

Children:

Safety and efficacy have not been established.