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Actually, technically, the destination *URL* doesn't have to match - but the actual *destination* has to match. That is, you can use a site that redirects to the destination - say, if you want to gather analytics.
Anyway, the domain name in the display URL needs to match the domain name of the web site that the user winds-up on.
It's a tough game, because only one ad per merchant will be shown on a page. You might be duking it out with 10 or 100 other affiliates, and only one ad is going to be displayed.
There is no profit in this. There is too much competition.
The only people I've heard say that are other PPC affiliates trying to guard their market share. It's very competitive, and you need deep pockets (or a very understanding credit card company) to break into competitive markets, but there can be good money in it.
For drugs, you need a square trade ID or soemthing like that.
You need the PharmacyChecker ID for US/Canada; outside of those, Google disallow med ads, but herbal products (which are not classified as medicines in the UK, assume it's the same elsewhere) are fine.