Case debrief

Allergic reactions happen and can be managed like any other side effects

In both of these cases, side effects were controlled by tapering off the medication and prescribing antihistamines

As both patients were doing a little better, the prescriber next tried to maintain the patients on the rash-prone, but initially effective medications (albeit different preparations), with one patient continuing to improve and the other patient doing worse again with rash-based side effects

Patient #2 was eventually placed on sertraline (Zoloft), which previously made her agitated prior to admission to the practice

• – However, this was started at the low dose of 12.5 mg/d and titrated much more slowly to avoid activating side effects

• – This approach was effective and she eventually was titrated up to 150 mg/d (a more therapeutic trial to the previous one), and has started a gradual response

Take-home points

All drugs may cause rashes

Providers should be aware that certain drugs carry greater risks

Providers have options on how to manage these

Often, maintaining a good clinical response is worth an attempt at trying the offending agent again

• – Treating and mitigating its side effects, such as rashes in these cases

  • Rash side-effect mitigation might be considered similar to treating extrapyramidal symptoms in psychotic patients with anticholinergics

Treating side effects often builds patient rapport and trust in that one is actively trying to improve their outcome and tolerability

Attempts to maintain patients on their initially effective medication may actually be of great importance as treatment resistance increases, as patients are tried on many short-term medication trials and then begin to run out of treatment options

Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – Rashes can be serious

• – Rechallenging patients who are rash sensitive should be done with a high degree of patient education and support

• – During a rechallenge, patients should be warned that any throat tightening, facial swelling, shortness of breath should trigger a call to the office or trip to the emergency room

Possible action items for improvement in practice

• – Try to minimize risk to the patient

• – There are many antidepressants available. It may have been easier (in Patient #2) to switch to an unrelated, chemically distinct, new antidepressant

Tips and pearls

Clinicians should be aware of drugs that have a higher tendency toward rashes. These drugs often contain dyes

Clinicians should be aware of all of the different preparations that a certain drug has, so that changing among them can be done if clinically warranted

Generics and brand name drugs may be pharmacokinetically “bioequivalent” within FDA-approved ranges, but may have different side-effect profiles

• – Depending on differing absorption rates

• – Depending upon the different dyes and fillers used

• – They may not be equal from a tolerability standpoint

Two-minute tutorial

What are the rules for being a generic drug?

A generic drug is comparable to the initial brand name drug product in dosage form, strength, route of administration, quality, and intended use

A generic must be bioequivalent to the original manufactured brand name drug

• – This is often measured by evaluating the time it takes the generic drug to reach the bloodstream as compared to the brand name drug

• – The generic drug’s absorption must deliver roughly the same amount (within 25% - see later) of active brand name drug product

• – The FDA requires the bioequivalence of the generic product to be between 80% and 125% of that of the parent branded product

• – Studies suggest that the average difference is often 3.5%

• – The Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Waxman–Hatch Act (now Public Law No: 98–417) set this standard into place

  • This Act allows generic drug makers to create their version of the product but without repeating similar human patient trials

  • It is assumed that a bioequivalent drug will be equally safe and effective as the brand name

  • The FDA does not demand a brand name versus generic trial to prove this, nor does it insist that the generic drug be studied against a placebo

  • This saves the generic manufacturer certain costs and they can place the generic product on the market for less as a result

  • When generic products become available, the market competition often leads to substantially lower prices for both the original brand name product and the generic forms

  • Often, multiple generic manufacturers will make their own version of the brand name product in question

  • This way, there are multiple versions of generics available for pharmacies to purchase and stock at any given time

  • This competition often lowers the generic drug’s price even further

The time it takes a generic drug to appear on the market varies

• – In the United States, drug patents give 20 years of protection

• – This patent is often filed when the drug molecule is discovered

• – It is tested in the bench-top laboratory, then preclinically in animal models, and finally in human trials of increasing complexity and size

• – By the time a brand name drug is available for patients to take, its remaining brand name life and patent protection is often between seven and 12 years

Diagnosing and treating rashes in clinical practice