Interacting drugs - summary

Amiodrone +

Anticoagulants

may increase the anticoagulant effects of Warfarin and amiodiorone due to inhibition of the anticoagulants hepatic metabolism. Risk of bleeding may be increased.

Beta blockers

 pharmacologic effects of metaprolol and possibly other beta blockers eliminated by hepatic may be increased.

 Calcium blockers

amiodarone inhibits AV conduction and decreases myocardial contractility, increased risk of AV blcok with verapramil or diltiazem or hypotension with any calcium blocker may occur.

 Cyclosporine

concomitant use has produced persistently elevated cyclosporine levels resulting in elevated creatinine despite reduction in dose of cyclosporine.

  Digoxin

serum levels of Digoxin increased, by as much as 70%, perhaps to the point of toxicity.

  Flecainide

plasma levels of Flecainide increased

Hydantoin

Hydantoin conc increased with symptoms of toxcicity. Also Amiodarone Amiodarone + decr serum levels may be decreased Hydantoin }

Hydantoin + Amiodarone

Decreased  serum levels of Hydantoin

 Lidocaine

seizure associated with increased lidocaine concentration was observed.

 Methotrexate

chronic use of oral amiodarone administration impairs metabolism of methotrexate.

  Procainamide

increased procainamide or NAPA serum levels, may occur

 Quinidine

 increased quinidine levels may occur with possible production of potentially fatal cardiac dysrhythmias

 Theophylline

Theophylline levels and toxicity increased.

+Amiodrone:

Cholestyramine

 increased enterohepatic elimination of amiodarone and reduced serum levels and half-life may occur.

 Cimetidine

 increased serum amiodarone levels may occur.

Oral- ventricular arrhythmias.

Reactions requiring discontinuation-

pulmonary infiltrates or fibrosis, paroxymal ventricular tachycardia, CHF, elevation of liver enzymes, visual disturbances, solar dermatitis, blue discolration of skin, hyperthyroidism, hypothyroidism

Cardiovascular- CHF, bradycardia, cardiac arrhythmias, SA node dysfunction

CNS- malaise, fatigue, tremor/abnormal invoulntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias, decreased libido,insomnia, headache, sleep disturbances, peripheral neurtopathy

Dermatologic- solar dermatitis, blue discoloration of skin, rash, spontaneous ecchymosis, alopecia

GI- nausea, vomiting, constipation, anorexia, abdominal pain, abnormal taste and smell, abnormal salivation.

Hepatic- abnormal liver function tests, nonspecific hepatic disorders, hepatitis, cholestatic hepaitis, cirrhosis.

Miscellaneous- pulmonary inflammation or fibrosis, hypothyroidism, edema, coagulation abnormalities, flushing, epididmitis, vaculitis,pseudomotor cerebri, thrombocytopenia Parentral.

Cardiovascular- atrial fibrillation, nodal arrhythmias, prolonged QT interval, sinus bradycardia Miscellaneous- abnormal kidney function, lung edema, increased ALT, increased AST, respiratory disorder, shock, stevens Johnson syndrome, thrombocytopenia

Thyroid disease,pregnancy,previous toxic effect of amiodarone.

Special precautions:

Initial therapy in hospital or under specialist supervision. Monitor thyroid,pulmonary & liver function,elderly,patients with disorders of sinus/A.V.node.

Opthalmologic effects-

Some patients develop photophobia and dry eyes. vision is rarely affected and drug discontinuation is rarely needed

Thyroid abnormalities- because of the slow ellimination of amiodarone and its metabolites,high plasma iodide levels, altered thyroid function and abnormal thyroid function tests may persist for several weeks or even months following amidarone withdrawal.

Hypothyroidism- has been reported in 2% to 10% of patients. However, therapyay be individualized and it may be necessary to discontinue amiodarone in some patients.

Hyperthyroidism- amiodarone induced hyperthyroidism usually poses a greater hazard to the patient than hypothyroidism because of the possibility of arrhythmia breakthrough or aggravation.

Electrolyte disturbances- give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomittant diuretics.

Photosentivity- amiodarone has induced photosentization in about 10% of patients. This is slowly and and occasionally incompletely reversible on discontinuation of drug butis of cosmetic importance only.

Warnings-

Potentially fatal toxicites with pulmoinary toxicity have occured with ventricular arrythmias and symptomless abnormal diffusion capacity has occcured in much higher percentages

Survival- there is no evidence that the use of amiodarone favorably affects survival

Hypersentivity pneumonitis- usually apears in the course of therapy Interstitial/aleveolar pneumonitis- may result from the releae of oxygen radicals of phospholipidosis and is characterized by findings of diffuse alveolar damage.

Cardiac effects- Proarrhythmias- amiodarone can cause serious exacerabation of the presentin arrhythmia, a risk that may be enhanced by concomittant antiarrhthmics.

Hypotension- is most common adverse effect seen with amiodarone IV.

Hepatic effects- Oral- elevated hepatic enzymes are frequent and inmost case asymtomatic

Parentral- elevations of blood hepatic enzyme values ALT, AST, and GST are seen commonly in patients with immediately life-threatening VT/VF

Elderly- healthy subjects > 65 years of age show lower clearance of amiodarone than younger subjects and increase in half-lfe (from 20 to 47 days).

Pregnancy- use only if the potential benefits outweigh the potential hazards to the fetus

Lactation- when amiodarone therapy is indicated advice the mother to discontinue nursing.

Children- safety and efficacy for use in children have not been established

Approved by FDA on December, 1985

Life threatening ventricular arrhythmias.

Dosage:

To be administered only by physicians with experience with life-threatning arrhythmias treatment and with facilities for monitoring effectiveness and side effects. Loading doses of 800 to 1600mg/day are required for 1 to 3 weeks or more until initial therapeutic response occurs.

Administer in divided doses with meals for total daily doses of 1000mg or when GI intolerance occurs. If side effects becomes excessive reduce the dose.

Overdosage-

Symptoms/ Treatment There have been a few reported cases of oral overdose

1. Usual supportive measures in which 3 to 8g of the drug was taken. There were no 2. Monitor the patients cardiac rhythm and blood deaths or permanent sequelae.

The most likely effects pressure of an inadvertant overdose of amiodarone are

3. If bradycardia occurs, use a beta adrenergic agonist hypotension, cardiogenic shock, bradycardia, AV block or a pace maker. and hepatotoxicity

4. Treat hypotensionwithinadequate tissue perfusion, by using positive inotropic or vasopressor agents.

5. Neither amiodarone nor its metabolite are dialyzable.

6. Cholestyramine may be useful inaccelrating the reversal of side effects of amiodarone by enhancing drug elimination, however it is known if this is beneficial in an overdose situation. 

Missed dose-

1. If you are using this medicine regularly and you miss a dose, use it as soon as possible.

2. Then use the remaining dose for that day at regularly spaced intervals. 3. Do not double doses.

List of entries

1.Congestive Heart Failure (CHF)

2.Atrial fibrillation

3.Atrial flutter

4. Heart Failure -

EVIDENCE BASED MEDICINE (MIMS March 2003)

Congestive Heart Failure (CHF)

Heart failure is charaterized by well known symptoms and physical signs.

Heart failure is coinsidered to be pathophysiological state in which an abnormal cardiac function is responsible for the failure of the heart to pump blood at a rate communsurate with the requirement of the metabolizing tissues.

Heart failure is frequently but not always caused by a defect in myocardial contraction, and then the term myocardial failure is appropiate,

. Increased cardiac output results in in diuresis and general amelioration of disturbances characteristic of fight heart failure (venous congestion, edema) and left heart failure ) dyspnea, orthopnea, cardiac asthma).

Digitalis is generaly most effective in "low output" failure and less effective in "high output " failure ) bronchopulmonary insufficiency, artriovenous fistula, anemia, hyperthyroidism.

Atrial fibrillation

This is a dysrhythmia in which the effective contraction of the atria is abolished and the AV node and the ventricles are bombarded with a very rapid and irregular series of stimuli. Many of these impulses are blocked at the AV node, but many are passed through, so that the ventricular contracrtions in the untreated patient are usually rapid and irregularly irregular.

Digitalis rapidly reduces ventricular rates and eliminates the pulse deficit. Palpitation,precordial distress or weakness are relieved and concomittant congestive failure ameliorated. Continue digitalis in doses necessary to maintain the desired ventricular rate, both ar rest and in response to excercise and other clinical effects

 Atrial flutter

The dysrhythmia is less common than artial fibrillation. There is a considerable controversy regarding its mechanism. A reciprocating rhythm or circus current movement is most likely. The atria contracts at a rate of 250 to 350 rates per minute. AV block is almost always present and its ratio is usually even numbered.

Digitalis slows the heart; normal sinus rhythm appear. Digitalis slows the ventricular rate, by decreasing the degree of AV block, and commonly converts flutter to fibrillation. When the drug is withdrawn , the atrial flutter will frequently revert spontaneosuly to normal sinus rhythm. If this not occur quinidine may be employed to restore sinus rhythm.

Heart failure

EVIDENCE BASED MEDICINE (MIMS March 2003)

Beneficial

ACE inhibitors such as captopril, enalapril,lisonopril,and perindopril

Digoxin

Appropriate use of beta-blockers Spironolactoone in severe cases

Likely to be beneficial

Multidisciplinary intereventions (nutrition, counselling)

Excercise

Angiotensin II receptor blockers

Amiiodarone

Implatable cardiac defibrillators

Unlikely to be beneficial

Calcium channel blockers

Likely to be ineffective or harmful

Positive inotropes(non-digitalis)

Non-amiodarone antiarrhythmic drugs

Key Points

1. There is conflicting evidence of the efficacy of multidisciplinary approach

2. Pescribed excercise training improves functional capacity and quality of life and reduces the rate of adverses cardiac events

3. Ace inhibitors reduce mortality, admission to hospital for heart failue and ischaemic events in patients with heart failure but are still under-used.

4. One critical trial has found that angiotensin II receptor blockers are at least as effective as ACE inhibitors for reducing clinical events(death or admission to hospitals). They confer no advantage over ACE inhibitors but can be useful if ACE inhibitors are not tolerated

5. Positve inotropic drugs improve symptoms but do not reduce mortality

6. Adding beta-blocker to ACE inhibitors decreases the rate of death and admission to hospitals

7. One clinical trial has found that in severe heart failure, adding an aldosterone receptor antagonist to an ACE inhibitor reduces mortality compared with ACE inhibitors alone.

8. ACE inhibitors delay the onset of symptoms and reduce cardiovascular events in patients with asymtomatic left ventricular systolic dysfunction

Amiodarone

1. Individual allergy

Tell your doctor if you have ever had any unusual or allergic reaction to amiodarone. Also tell your doctor if you are allergic to any other substances, such as foods, preservatives.

2. Pregnancy

Amiodarone has been shown to cause thyroid problems in babies whose mothers took amidarone when pregnant. Discuss with your doctor before taking this medicine.

3. Breast feeding

Although amiodarone passes into breast milk, it has not been shown to cause problems in nursing babies. Make sure you have discussed the risks and benefits with your doctor.

4. Children

Amiodrane can cause serious side efects in any patient. Discuss with your doctor before administering to children

5. Older adults

Elderly patients are more likey to get thyroid problems with this medicine. Also difficluty in walking and numbness, tingling, trembling, or weakness in hands or feet are more likely to occur in elderly.

 6.Other medicines

Certain medicines should not be used together at all, due interactions. Tell your doctor if you are taking anticoagulants or medicines for heart ailments or phenytoin- effects may be increased.

6. Other medical problems

Make sure that you tell your doctor if you have other medical problems- Liver disease- effects may be increased because of slower removal from the body Thyroid problems- risk of overactive or underactive thyroid is increased.

7. Dose

The dose of amiodarone is different for different patients. Follow the instructions of your doctor.

8. Missed dose - If you miss a dose of this medicine, do not take the missed dose and do not double the next dose. Instead, go back to your regular dosing schedule. If you miss two or more doses in a row, check with your doctor.

9. Storage - Keep out of reach of children. Store away from heat and direct light. Do not store in the bath room or near the kitchen sink. Moisture or heat may cause the medicine to break down. Do not keep outdated medicines or medicine no longer in use. Make sure you keep all discarded medicines out of reach of children

10. Side effects - Check with your doctor, if any of the side efects occur- cough, painful breathing, shortness of breath.

11.Food- Take consistently with or without meals. Take with meals if high dose or to reduce GI discomfort

Pharmacolgy:

Amiodarone prolongs the myocardial cell action potential duration and refractory period and non competitive alpha and beta adrenergic inhibition.

Pharmacokinetics:

Amiodarone is slowly and variably absorbed.Bioavailability is about 50% between(35 to 65%). Maximum plasma concentration are attained 3 to 7 hours,after a single dose. despite this the onset of action may occur in 2 to 3 days,but more commonly takes 1 to 3 weeks even with loading doses.

Take consistently with or without meals. Take with meals if high dose or to reduce GI discomfort

Pregnancy:

Use during pregnancy only if needed.

Lactation:

When amiodarone therapy is indicated advice the mother to discontinue nursing.

Children:

Safety and efficacy for use in children have not been established