Dose reduction of warfarin is as follows: 40% reduction if amiodarone dose is 400 mg daily, 35% reduction if amiodarone dose is 300 mg daily, 30% reduction if amiodarone dose is 200 mg daily, and 25% reduction if amiodarone dose is 100 mg daily. The effect of amiodarone on the warfarin concentrations can be as early as a few days after initiation of treatment; however, the interaction may not peak for up to seven weeks. Amiodarone inhibits the action of the cytochrome P450 isozyme family. This reduces the clearance of many drugs, including the following:

Ciclosporin
Digoxin
Flecainide
Procainamide
Quinidine
Sildenafil
Simvastatin
Theophylline
WarfarinIn 2015, Gilead Sciences warned health care providers about people that began taking the hepatitis C drugs ledipasvir/sofosbuvir or sofosbuvir along with amiodarone, who developed abnormally slow heartbeats or died of cardiac arrest. Metabolism
Amiodarone is extensively metabolized in the liver by cytochrome P450 3A4 and can affect the metabolism of numerous other drugs. It interacts with digoxin, warfarin, phenytoin, and others. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone. On 8 August 2008, the FDA issued a warning of the risk of rhabdomyolysis, which can lead to kidney failure or death, when simvastatin is used with amiodarone. This interaction is dose-dependent with simvastatin doses exceeding 20 mg. This drug combination especially with higher doses of simvastatin should be avoided. Excretion
Excretion is primarily via the liver and the bile duct with almost no elimination via the kidney and it is not dialyzable.
Netupitant/palonosetron, sold under the brand name Akynzeo, is a fixed-dose combination medication used for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. It is marketed and distributed by Helsinn Therapeutics. Netupitant is an NK1 receptor antagonist and palonosetron is a 5-HT3 receptor antagonist.The capsules contain netupitant and palonosetron hydrochloride. The intravenous version is a combination of fosnetupitant chloride hydrochloride and palonosetron hydrochloride. Contraindications
Netupitant/palonosetron may be contraindicated during pregnancy. Adverse effects
The most common side effects include headache, weakness, fatigue, upset stomach, constipation, and skin redness. The overall profile of adverse effects is comparable to that of palonosetron (see Palonosetron#Adverse effects); no common adverse effects can be attributed to netupitant. Interactions
Pharmacology
History
Netupitant/palonosetron was approved for use in the United States in October 2014. It was approved for use in the European Union in May 2015. The intravenous version, which contains the prodrug fosnetupitant in place of netupitant, was approved in the United States in April 2018. References
External links
"Netupitant mixture with palonosetron". Drug Information Portal. U.S. National Library of Medicine. "Fosnetupitant". Drug Information Portal. U.S. National Library of Medicine. "Fosnetupitant and Palonosetron (Professional Patient Advice)". Drugs.com.