This case safety report describes an adverse reaction in a 78-year-old male patient taking amiodarone who experienced cerebral hemorrhage, epistaxis, mouth hemorrhage, and pyrexia, and died. The patient was also taking warfarin, colace, dulcolax, and morphine. There were major interactions between amiodarone and warfarin that can increase the effects of warfarin and risk of bleeding. The report recommends monitoring patients closely when amiodarone is added to an anticoagulant regimen and potentially reducing the anticoagulant dosage. It also discusses interactions between amiodarone and the laxatives as well as side effects of the various drugs

1.  Case safety report
 Drug : amiodarone
 Improved REMS
 D. Ibrahim Mahamoud
 Presented at : AAPS ,Toronto ,Canada
 21/ March /2014

2. 2 1 / 3 / 2 0 1 3
Amiodarone Adverse Reaction

3. Adverse reaction report number :000168147
Health Canada
 78 years old male patient
 Outcome : Death
 Date : 24/2/2004
 Reporter type : non health professional


4. Suspect :
amiodarone 400 mg once daily
Concomitant :
 colace (Docusate sodium) (stool softeners)
 dulcolax
 morphine
 warfarin

5. Adverse reaction
 Cerebral haemorrhage
 Epistaxis
 Mouth haemorrhage
 Pyrexia

6. Interactions between your selected drugs
 amiodarone ↔ warfarin ...............major
 Applies to: amiodarone, warfarin
 MONITOR CLOSELY: Amiodarone may increase the pharmacologic effects of
warfarin by inhibiting CYP450 2C9 hepatic metabolism of S-warfarin. Similar
effects may also occur with other oral anticoagulants, resulting in significant hypo
prothrombinemia and bleeding.
 When amiodarone is added to an anticoagulant regimen, increased anticoagulant
effects may become apparent within one to several weeks and may persist for
months after the amiodarone is discontinued.
 The effects of this interaction are highly variable - while some patients are
asymptomatic, serious and life-threatening bleeding complications have been
reported in others.

MANAGEMENT: An empiric 30% to 50% reduction in anticoagulant dosage has
been recommended, in addition to frequent monitoring of the patient and the
prothrombin time or International Normalized Ratio (INR).
 Patients should be advised to notify their physician promptly if they experience any
signs of excessive anticoagulation such as unusual or prolonged
bleeding, bruising, vomiting, change in stool or urine color, headache, dizziness, or
weakness.

7.  amiodarone ↔ bisacodyl ................... moderate
 Applies to: amiodarone, Dulcolax (bisacodyl)
 MONITOR: Bowel cleansing as well as overuse of certain laxatives may cause
electrolyte loss and increase the risk of torsade de pointes ventricular arrhythmia
in patients treated with drugs that prolong the QT interval.
 Electrolyte disturbances including hypokalemia and hypomagnesemia have been
reported with laxative abuse and are known risk factors for torsade de pointes
associated with QT interval prolongation.
MANAGEMENT: Patients treated with drugs that prolong the QT interval should
exercise caution when self-medicating with laxatives.
 The recommended dosage and duration of use should not be exceeded.
 Patients treated with lactulose for more than six months should be monitored
periodically for electrolyte imbalance. Patients should be advised to seek prompt
medical attention if they experience symptoms that could indicate the occurrence of
torsade de pointes such as
dizziness, lightheadedness, fainting, palpitation, irregular heart
rhythm, shortness of breath, or syncope.

8.  http://www.drugs.com/
 Drug Interactions Checker

9. warfarin
 Monitoring INR
 Diet
 Interaction
Dabigatran
 first oral direct thrombin inhibitor

11. Morphine Side Effects
 Gastrointestinal side effects - These include
nausea, vomiting, abdominal cramps and
constipation.
 Opioid receptors for morphine are present in the
gastrointestinal tract and their activation may lead to
a slowing of gut movement, leading to constipation.
Long-term use leads to severe constipation.

 Sedation –
 Respiratory depression –

12. Pyrexia
 Sepsis
 Disseminated intravascular coagulation (DIC)

13. summery
 Drug- drug Interaction
 Education ( medical staff, patient, care giver )
 To choose safer medication if possible
 Proper (clinical , Lab. Test) follow up of the patient.
 Other possibility ( sepses, DIC)
 Morphine ?

14. Thank you