How Do They Know Your Dose?
Doses differ for many reasons - find out how they're determined.

You take 7.5 milligrams (mg) of methotrexate once a week, while a friend in your arthritis support group takes 15 mg. The "standard" dosage of adalimumab (Humira) is 40 mg every two weeks, but some patients take 40 mg weekly. Why the differences?

The information a doctor uses to determine what and how much to prescribe evolves with time. The main information a doctor uses is the package labeling, says John Clough, MD, a rheumatologist and chairman of the Cleveland Clinic's Division of Health Affairs. With a few exceptions, doctors prescribe within the dosage range published on the label, which is determined by the manufacturer and approved by the FDA after years of testing for safety and effectiveness on both animals and people.

So how is that dosage range determined? Early studies take place to determine the safest range at which a drug is most effective, and those studies continue throughout testing before a drug is approved. For instance, a recent study showed that doubling the dose of an experimental drug helped people with rheumatoid arthritis (RA) improve by 34 percent.

Studies continue after a drug is approved, and reports of serious side effects at a certain dosage may prompt drug manufacturers to change the dosage on the label after the drug is approved and on the market, says Dr. Clough. For example, in 2002, the manufacturer of the COX-2 inhibitor rofecoxib (Vioxx) changed labeling after post-approval studies demonstrated cardiovascular risks of taking the drug at the highest recommended dosage. Subsequent studies confirming the risks ultimately led to the drug being removed from the market.

Factors that influence where within the published dosage range a doctor will prescribe include the following:

• Diagnosis. The same drug may be used at different dosages for different diagnoses. For example, 10 mg of prednisone daily may be sufficient to treat inflammation of RA, whereas much higher dosages of prednisone might be necessary to treat vasculitis or lupus nephritis (kidney inflammation).
• Disease severity. People with severe disease likely require higher or more frequent doses of medication than those with milder disease. The goal is to use as little medication as necessary to control your disease. As your disease becomes better controlled, your medication dosage may be lowered.
• Age. Naturally dosages are lower for children than for adults. They may also be lower for older adults than younger adults. As people grow older, their liver function and metabolism slows, so older people may need less of a drug or may need to take the drug more often. Reduced kidney function can also slow the elimination of drugs. As a result, dosages designed for younger adults may linger longer in the systems of older people (generally those older than 65) and cause increased effects - and side effects. Drugs that often require dosing modifications in older people include NSAIDs, narcotic analgesics and many of the drugs used for fibromyalgia, such as antidepressants and benzodiazepines.
• Possible drug interactions. If you are taking other medications to treat your disease, the dosage of a new drug being added to your regimen may differ. For example, the people who take 40 mg Humira weekly may do so only if they are not also taking methotrexate.
• Body size. The dosage of some drugs, particularly for children, is based on a measure of body size or weight. The biologic agent infliximab (Remicade), for example, has a dosage of 3 mg of drug for every kilogram (approximately 2.2 pounds) of body weight.
• Toxicity. If you experience side effects from a medication, your doctor may lower the dosage before taking you off the medication.

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