Commentary

To those of us who live and practice in the northeast, it comes as no surprise that the mortality rate for middle class whites is climbing. Obituaries in our local papers often include men and women in their forties “dying at home,” with no mention of cancer or chronic disease. Rarely, the family can bring itself to announce that their loved one has died of a drug overdose.

Deaths attributable to prescription opioid overdoses quadrupled in the decade from 1999 to 2010, and the trend shows little sign of abating as the number of prescriptions for opioids has risen tenfold over the last 20 years (“How Doctors Helped Drive the Addiction Crisis,” by Dr. Richard Friedman, New York Times, Nov. 7, 2015). Could physician behavior have contributed to outbreak of this deadly plague of addiction? That is like asking if something the zookeeper did or didn’t do could have been responsible for the escape of the man-eating tiger that is devouring the neighborhood children. Regardless of what other factors might be responsible for the epidemic of fatal prescription opioid overdoses, physicians must admit some culpability.

Until recently, I assumed that the problem of prescription opioids finding their way to addicts was unique to physicians treating adults. However, a study reported at the annual meeting of the American Society of Anesthesiologists reveals pediatricians and other clinicians prescribing for children must share in the blame.

Dr. Myron Yaster at Johns Hopkins University Hospital, Baltimore, has found that in a group of nearly 300 pediatric patients (average age, 11 years and average weight of 44 kg), overall the patients used only 42% of the prescribed amount of opioids. Almost half of the patients had a teenage sibling, a group that Dr. Yaster describes as the “target population of drug abuse.”

What’s going on here? Some of the problem dates back to the 1990s when physicians were urged to shift their focus toward the problem of inadequately treated pain. With the help of nurses armed with pain-rating schemes and smiley/grumpy face charts, the mantra became “no pain shall go unmedicated,” when the better response should have been “no pain shall go unmanaged.” But good pain management takes time. It requires that the physician and staff consider each patient as a unique individual. In many cases, reassurance and education can make a non–opioid medication or even no medication a better choice.

However, according to Dr. Yaster, “leftover medicine is the most important element in drug addiction.” Why did physicians prescribe 10 days of medication when his study revealed that most patients took the medication for only 5? It could just be a bad habit. Or it could be ignorance or inexperience. How many physicians ask at follow-up appointments “How long did you take your medication? Tell me the history of your pain.”

Or could it be that physicians are simply trying to prevent those annoying calls from patients who have run out of their medication? Dr. Yaster’s findings suggest that those calls would be few and far between. More careful thought into how much medication we prescribe also would mean that when a patient called for more medication that there was a problem. Either the patient’s recuperation has hit a worrisome bump in the road or possibly her medication is being diverted.

History tells us that physicians, even pediatricians, have been poor stewards of the powerful medications with which we have been entrusted. First, it was antibiotics and now opioids have joined the list.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at pdnews@frontlinemedcom.com.

To those of us who live and practice in the northeast, it comes as no surprise that the mortality rate for middle class whites is climbing. Obituaries in our local papers often include men and women in their forties “dying at home,” with no mention of cancer or chronic disease. Rarely, the family can bring itself to announce that their loved one has died of a drug overdose.

Deaths attributable to prescription opioid overdoses quadrupled in the decade from 1999 to 2010, and the trend shows little sign of abating as the number of prescriptions for opioids has risen tenfold over the last 20 years (“How Doctors Helped Drive the Addiction Crisis,” by Dr. Richard Friedman, New York Times, Nov. 7, 2015). Could physician behavior have contributed to outbreak of this deadly plague of addiction? That is like asking if something the zookeeper did or didn’t do could have been responsible for the escape of the man-eating tiger that is devouring the neighborhood children. Regardless of what other factors might be responsible for the epidemic of fatal prescription opioid overdoses, physicians must admit some culpability.

Until recently, I assumed that the problem of prescription opioids finding their way to addicts was unique to physicians treating adults. However, a study reported at the annual meeting of the American Society of Anesthesiologists reveals pediatricians and other clinicians prescribing for children must share in the blame.

Dr. Myron Yaster at Johns Hopkins University Hospital, Baltimore, has found that in a group of nearly 300 pediatric patients (average age, 11 years and average weight of 44 kg), overall the patients used only 42% of the prescribed amount of opioids. Almost half of the patients had a teenage sibling, a group that Dr. Yaster describes as the “target population of drug abuse.”

What’s going on here? Some of the problem dates back to the 1990s when physicians were urged to shift their focus toward the problem of inadequately treated pain. With the help of nurses armed with pain-rating schemes and smiley/grumpy face charts, the mantra became “no pain shall go unmedicated,” when the better response should have been “no pain shall go unmanaged.” But good pain management takes time. It requires that the physician and staff consider each patient as a unique individual. In many cases, reassurance and education can make a non–opioid medication or even no medication a better choice.

However, according to Dr. Yaster, “leftover medicine is the most important element in drug addiction.” Why did physicians prescribe 10 days of medication when his study revealed that most patients took the medication for only 5? It could just be a bad habit. Or it could be ignorance or inexperience. How many physicians ask at follow-up appointments “How long did you take your medication? Tell me the history of your pain.”

Or could it be that physicians are simply trying to prevent those annoying calls from patients who have run out of their medication? Dr. Yaster’s findings suggest that those calls would be few and far between. More careful thought into how much medication we prescribe also would mean that when a patient called for more medication that there was a problem. Either the patient’s recuperation has hit a worrisome bump in the road or possibly her medication is being diverted.

History tells us that physicians, even pediatricians, have been poor stewards of the powerful medications with which we have been entrusted. First, it was antibiotics and now opioids have joined the list.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at pdnews@frontlinemedcom.com.

To those of us who live and practice in the northeast, it comes as no surprise that the mortality rate for middle class whites is climbing. Obituaries in our local papers often include men and women in their forties “dying at home,” with no mention of cancer or chronic disease. Rarely, the family can bring itself to announce that their loved one has died of a drug overdose.

Deaths attributable to prescription opioid overdoses quadrupled in the decade from 1999 to 2010, and the trend shows little sign of abating as the number of prescriptions for opioids has risen tenfold over the last 20 years (“How Doctors Helped Drive the Addiction Crisis,” by Dr. Richard Friedman, New York Times, Nov. 7, 2015). Could physician behavior have contributed to outbreak of this deadly plague of addiction? That is like asking if something the zookeeper did or didn’t do could have been responsible for the escape of the man-eating tiger that is devouring the neighborhood children. Regardless of what other factors might be responsible for the epidemic of fatal prescription opioid overdoses, physicians must admit some culpability.

Until recently, I assumed that the problem of prescription opioids finding their way to addicts was unique to physicians treating adults. However, a study reported at the annual meeting of the American Society of Anesthesiologists reveals pediatricians and other clinicians prescribing for children must share in the blame.

Dr. Myron Yaster at Johns Hopkins University Hospital, Baltimore, has found that in a group of nearly 300 pediatric patients (average age, 11 years and average weight of 44 kg), overall the patients used only 42% of the prescribed amount of opioids. Almost half of the patients had a teenage sibling, a group that Dr. Yaster describes as the “target population of drug abuse.”

What’s going on here? Some of the problem dates back to the 1990s when physicians were urged to shift their focus toward the problem of inadequately treated pain. With the help of nurses armed with pain-rating schemes and smiley/grumpy face charts, the mantra became “no pain shall go unmedicated,” when the better response should have been “no pain shall go unmanaged.” But good pain management takes time. It requires that the physician and staff consider each patient as a unique individual. In many cases, reassurance and education can make a non–opioid medication or even no medication a better choice.

However, according to Dr. Yaster, “leftover medicine is the most important element in drug addiction.” Why did physicians prescribe 10 days of medication when his study revealed that most patients took the medication for only 5? It could just be a bad habit. Or it could be ignorance or inexperience. How many physicians ask at follow-up appointments “How long did you take your medication? Tell me the history of your pain.”

Or could it be that physicians are simply trying to prevent those annoying calls from patients who have run out of their medication? Dr. Yaster’s findings suggest that those calls would be few and far between. More careful thought into how much medication we prescribe also would mean that when a patient called for more medication that there was a problem. Either the patient’s recuperation has hit a worrisome bump in the road or possibly her medication is being diverted.

History tells us that physicians, even pediatricians, have been poor stewards of the powerful medications with which we have been entrusted. First, it was antibiotics and now opioids have joined the list.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at pdnews@frontlinemedcom.com.

“We are just statistics, born to consume resources.” –Horace

You know the winter is coming when rheumatologists spend their weekends writing appeal letters for sildenafil.

I inherited a scleroderma patient from a retired colleague. She has had severe Raynaud’s for which she’d been on sildenafil since 2013. On Nov. 23, 2015, I received a letter stating that the medication would no longer be covered because the patient did not meet criteria (in this case, pulmonary arterial hypertension).

I had to submit a letter of appeal, in which I explained how, despite maximum tolerated doses of nifedipine and pentoxifylline, she continued to have digital ischemia, and how, when she finally started the sildenafil, which they had approved prior, the problem went away. I continued to say:

“In the medical literature on this problem, the PDE-5 inhibitors, of which sildenafil is one, is typically recommended, after vasodilation, on the basis of Level I evidence (that is, evidence from high quality randomized controlled trials). Sildenafil has been shown to promote complete healing of digital ulcers and prevents the formation of new ulcers. Thought leaders in the field uniformly recommend this drug as an important part of therapy particularly in patients who have already had digital ulcers. I am happy to provide you with the literature upon request.

“I urge you to reconsider your decision. If you withhold this drug there is a chance that the patient will end up with ulcers again and this could potentially cost you even more. Not only would it impair the patient’s ability to work, which leads to loss of income for her, it would also cost you more in terms of paying for her health care.”

On Nov. 28, I received a second denial, no different than the first letter: “Your request was reviewed by a Medical Doctor specialized in Internal Medicine/Rheumatology. Upon review of the available information, it was determined that the previous decision should be upheld because the Prior Authorization criteria is not met. This determination was made based upon our review of your health condition in relation to the prior authorization criteria and/or guidelines listed below. You have CREST ... with Raynaud’s phenomenon which is not a covered diagnosis. You do not have Pulmonary Arterial Hypertension. Therefore the requested drug sildenafil citrate is not medically necessary according to plan criteria. The denial is therefore appropriate and consistent with your benefits.

“Sildenafil will be approved based on one of the following criteria:

(1) All of the following:

(A) Pulmonary arterial hypertension is symptomatic; AND

(B) Submission of medical records documenting diagnosis of pulmonary arterial hypertension that is confirmed by right heart catheterization; OR

(2) Patient is currently on any therapy for the diagnosis of pulmonary arterial hypertension.”

On Dec. 4, I fired off the following response:

“I received your decision letter dated 11/28/2015 in which you reiterate that your criteria for approval requires a diagnosis of pulmonary hypertension, as if you had not read my first letter at all. This request is not for pulmonary hypertension, it is to prevent limb-threatening gangrene and ischemia from Raynaud’s phenomenon. Please reconsider your decision. We do not want this young patient to lose any digits.”

It’s quite ironic that on the same weekend that I wrote my first letter, a mentor and friend of mine who is a rheumatologist also wrote a letter of appeal to get a prescription for sildenafil approved for a scleroderma patient with Raynaud’s who failed previous medications. She got sildenafil approved. At her suggestion, I attached a copy of the 2005 study published in Circulation demonstrating the efficacy of sildenafil for Raynaud’s to support my letter after the second denial (Circulation. 2005 Nov 8;112[19]:2980-5). As of this writing, I still have not heard back.

Dr. Chan practices rheumatology in Pawtucket, R.I.

“We are just statistics, born to consume resources.” –Horace

You know the winter is coming when rheumatologists spend their weekends writing appeal letters for sildenafil.

I inherited a scleroderma patient from a retired colleague. She has had severe Raynaud’s for which she’d been on sildenafil since 2013. On Nov. 23, 2015, I received a letter stating that the medication would no longer be covered because the patient did not meet criteria (in this case, pulmonary arterial hypertension).

I had to submit a letter of appeal, in which I explained how, despite maximum tolerated doses of nifedipine and pentoxifylline, she continued to have digital ischemia, and how, when she finally started the sildenafil, which they had approved prior, the problem went away. I continued to say:

“In the medical literature on this problem, the PDE-5 inhibitors, of which sildenafil is one, is typically recommended, after vasodilation, on the basis of Level I evidence (that is, evidence from high quality randomized controlled trials). Sildenafil has been shown to promote complete healing of digital ulcers and prevents the formation of new ulcers. Thought leaders in the field uniformly recommend this drug as an important part of therapy particularly in patients who have already had digital ulcers. I am happy to provide you with the literature upon request.

“I urge you to reconsider your decision. If you withhold this drug there is a chance that the patient will end up with ulcers again and this could potentially cost you even more. Not only would it impair the patient’s ability to work, which leads to loss of income for her, it would also cost you more in terms of paying for her health care.”

On Nov. 28, I received a second denial, no different than the first letter: “Your request was reviewed by a Medical Doctor specialized in Internal Medicine/Rheumatology. Upon review of the available information, it was determined that the previous decision should be upheld because the Prior Authorization criteria is not met. This determination was made based upon our review of your health condition in relation to the prior authorization criteria and/or guidelines listed below. You have CREST ... with Raynaud’s phenomenon which is not a covered diagnosis. You do not have Pulmonary Arterial Hypertension. Therefore the requested drug sildenafil citrate is not medically necessary according to plan criteria. The denial is therefore appropriate and consistent with your benefits.

“Sildenafil will be approved based on one of the following criteria:

(1) All of the following:

(A) Pulmonary arterial hypertension is symptomatic; AND

(B) Submission of medical records documenting diagnosis of pulmonary arterial hypertension that is confirmed by right heart catheterization; OR

(2) Patient is currently on any therapy for the diagnosis of pulmonary arterial hypertension.”

On Dec. 4, I fired off the following response:

“I received your decision letter dated 11/28/2015 in which you reiterate that your criteria for approval requires a diagnosis of pulmonary hypertension, as if you had not read my first letter at all. This request is not for pulmonary hypertension, it is to prevent limb-threatening gangrene and ischemia from Raynaud’s phenomenon. Please reconsider your decision. We do not want this young patient to lose any digits.”

It’s quite ironic that on the same weekend that I wrote my first letter, a mentor and friend of mine who is a rheumatologist also wrote a letter of appeal to get a prescription for sildenafil approved for a scleroderma patient with Raynaud’s who failed previous medications. She got sildenafil approved. At her suggestion, I attached a copy of the 2005 study published in Circulation demonstrating the efficacy of sildenafil for Raynaud’s to support my letter after the second denial (Circulation. 2005 Nov 8;112[19]:2980-5). As of this writing, I still have not heard back.

Dr. Chan practices rheumatology in Pawtucket, R.I.

“We are just statistics, born to consume resources.” –Horace

You know the winter is coming when rheumatologists spend their weekends writing appeal letters for sildenafil.

I inherited a scleroderma patient from a retired colleague. She has had severe Raynaud’s for which she’d been on sildenafil since 2013. On Nov. 23, 2015, I received a letter stating that the medication would no longer be covered because the patient did not meet criteria (in this case, pulmonary arterial hypertension).

I had to submit a letter of appeal, in which I explained how, despite maximum tolerated doses of nifedipine and pentoxifylline, she continued to have digital ischemia, and how, when she finally started the sildenafil, which they had approved prior, the problem went away. I continued to say:

“In the medical literature on this problem, the PDE-5 inhibitors, of which sildenafil is one, is typically recommended, after vasodilation, on the basis of Level I evidence (that is, evidence from high quality randomized controlled trials). Sildenafil has been shown to promote complete healing of digital ulcers and prevents the formation of new ulcers. Thought leaders in the field uniformly recommend this drug as an important part of therapy particularly in patients who have already had digital ulcers. I am happy to provide you with the literature upon request.

“I urge you to reconsider your decision. If you withhold this drug there is a chance that the patient will end up with ulcers again and this could potentially cost you even more. Not only would it impair the patient’s ability to work, which leads to loss of income for her, it would also cost you more in terms of paying for her health care.”

On Nov. 28, I received a second denial, no different than the first letter: “Your request was reviewed by a Medical Doctor specialized in Internal Medicine/Rheumatology. Upon review of the available information, it was determined that the previous decision should be upheld because the Prior Authorization criteria is not met. This determination was made based upon our review of your health condition in relation to the prior authorization criteria and/or guidelines listed below. You have CREST ... with Raynaud’s phenomenon which is not a covered diagnosis. You do not have Pulmonary Arterial Hypertension. Therefore the requested drug sildenafil citrate is not medically necessary according to plan criteria. The denial is therefore appropriate and consistent with your benefits.

“Sildenafil will be approved based on one of the following criteria:

(1) All of the following:

(A) Pulmonary arterial hypertension is symptomatic; AND

(B) Submission of medical records documenting diagnosis of pulmonary arterial hypertension that is confirmed by right heart catheterization; OR

(2) Patient is currently on any therapy for the diagnosis of pulmonary arterial hypertension.”

On Dec. 4, I fired off the following response:

“I received your decision letter dated 11/28/2015 in which you reiterate that your criteria for approval requires a diagnosis of pulmonary hypertension, as if you had not read my first letter at all. This request is not for pulmonary hypertension, it is to prevent limb-threatening gangrene and ischemia from Raynaud’s phenomenon. Please reconsider your decision. We do not want this young patient to lose any digits.”

It’s quite ironic that on the same weekend that I wrote my first letter, a mentor and friend of mine who is a rheumatologist also wrote a letter of appeal to get a prescription for sildenafil approved for a scleroderma patient with Raynaud’s who failed previous medications. She got sildenafil approved. At her suggestion, I attached a copy of the 2005 study published in Circulation demonstrating the efficacy of sildenafil for Raynaud’s to support my letter after the second denial (Circulation. 2005 Nov 8;112[19]:2980-5). As of this writing, I still have not heard back.

Dr. Chan practices rheumatology in Pawtucket, R.I.

One of the most apparent and difficult-to-treat aspects of the aging eye is the descent of the eyebrow. The change in the orbital bone structure as well as fat loss and fat redistribution along the upper and lower eyelids and loss of skin elasticity contribute to the skeletonization of the periorbital area and a “drooping” of the eyebrow. Patients either have loss of volume across the entire brow, or primarily across the lateral and central brow creating what is known as an “a-frame” deformity.

Nonsurgical techniques that help lift the brow include a combination of relaxation of the orbicularis oculi muscle with neurotoxins, in addition to the injection of hyaluronic acid fillers along the brow margin and upper third of the face.

Small amounts of hyaluronic acid fillers injected with a 22- to 25-gauge cannula both above and below the eyebrow along the orbital rim provide an instantaneous lifting effect with long-lasting results. Hyaluronic acid and poly-L-lactic acid in dilute concentrations can also be injected with a cannula in the forehead, which creates a repletion of the volume in the upper face that is often lost with aging to create a lift of the eyebrows. Temple hollows can also be filled with calcium hydroxylapatite, poly-L-lactic acid and less often with hyaluronic acid to revolumize and create a lift of the lateral brow. Care should be taken as fillers used in these areas are off-label and need to be done by trained, expert injectors. The periorbital area is a danger zone with many vessels and nerves, and proper injection technique is crucial to avoid arterial blockage, nerve damage, and long-term complications.

Nonablative skin tightening with radiofrequency energy or ultrasound can be used for achieving a brow-lift. Although these techniques do provide collagen remodeling, multiple procedures are often necessary, and results are not always substantial. In a study of 36 patients undergoing ultrasound tightening of the face and neck, 86% showed a clinically significant brow-lift 90 days after treatment. The average brow elevation in this study was 1.7 mm.

In practice, however, patients are often more satisfied with the brow elevation they achieve with neurotoxins and fillers. Injectables provide a faster onset of results, fewer treatments, and minimal discomfort. Combination treatments provide the best overall results and although injectables in the periorbital area are technically difficult, patients are often very satisfied and return for repeat treatments.

References Aesthet Surg J. 2009;May-Jun;29(3):174-9.

J Am Acad Dermatol. 2010;Feb;62(2):262-9.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub.

One of the most apparent and difficult-to-treat aspects of the aging eye is the descent of the eyebrow. The change in the orbital bone structure as well as fat loss and fat redistribution along the upper and lower eyelids and loss of skin elasticity contribute to the skeletonization of the periorbital area and a “drooping” of the eyebrow. Patients either have loss of volume across the entire brow, or primarily across the lateral and central brow creating what is known as an “a-frame” deformity.

Nonsurgical techniques that help lift the brow include a combination of relaxation of the orbicularis oculi muscle with neurotoxins, in addition to the injection of hyaluronic acid fillers along the brow margin and upper third of the face.

Small amounts of hyaluronic acid fillers injected with a 22- to 25-gauge cannula both above and below the eyebrow along the orbital rim provide an instantaneous lifting effect with long-lasting results. Hyaluronic acid and poly-L-lactic acid in dilute concentrations can also be injected with a cannula in the forehead, which creates a repletion of the volume in the upper face that is often lost with aging to create a lift of the eyebrows. Temple hollows can also be filled with calcium hydroxylapatite, poly-L-lactic acid and less often with hyaluronic acid to revolumize and create a lift of the lateral brow. Care should be taken as fillers used in these areas are off-label and need to be done by trained, expert injectors. The periorbital area is a danger zone with many vessels and nerves, and proper injection technique is crucial to avoid arterial blockage, nerve damage, and long-term complications.

Nonablative skin tightening with radiofrequency energy or ultrasound can be used for achieving a brow-lift. Although these techniques do provide collagen remodeling, multiple procedures are often necessary, and results are not always substantial. In a study of 36 patients undergoing ultrasound tightening of the face and neck, 86% showed a clinically significant brow-lift 90 days after treatment. The average brow elevation in this study was 1.7 mm.

In practice, however, patients are often more satisfied with the brow elevation they achieve with neurotoxins and fillers. Injectables provide a faster onset of results, fewer treatments, and minimal discomfort. Combination treatments provide the best overall results and although injectables in the periorbital area are technically difficult, patients are often very satisfied and return for repeat treatments.

References Aesthet Surg J. 2009;May-Jun;29(3):174-9.

J Am Acad Dermatol. 2010;Feb;62(2):262-9.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub.

One of the most apparent and difficult-to-treat aspects of the aging eye is the descent of the eyebrow. The change in the orbital bone structure as well as fat loss and fat redistribution along the upper and lower eyelids and loss of skin elasticity contribute to the skeletonization of the periorbital area and a “drooping” of the eyebrow. Patients either have loss of volume across the entire brow, or primarily across the lateral and central brow creating what is known as an “a-frame” deformity.

Nonsurgical techniques that help lift the brow include a combination of relaxation of the orbicularis oculi muscle with neurotoxins, in addition to the injection of hyaluronic acid fillers along the brow margin and upper third of the face.

Small amounts of hyaluronic acid fillers injected with a 22- to 25-gauge cannula both above and below the eyebrow along the orbital rim provide an instantaneous lifting effect with long-lasting results. Hyaluronic acid and poly-L-lactic acid in dilute concentrations can also be injected with a cannula in the forehead, which creates a repletion of the volume in the upper face that is often lost with aging to create a lift of the eyebrows. Temple hollows can also be filled with calcium hydroxylapatite, poly-L-lactic acid and less often with hyaluronic acid to revolumize and create a lift of the lateral brow. Care should be taken as fillers used in these areas are off-label and need to be done by trained, expert injectors. The periorbital area is a danger zone with many vessels and nerves, and proper injection technique is crucial to avoid arterial blockage, nerve damage, and long-term complications.

Nonablative skin tightening with radiofrequency energy or ultrasound can be used for achieving a brow-lift. Although these techniques do provide collagen remodeling, multiple procedures are often necessary, and results are not always substantial. In a study of 36 patients undergoing ultrasound tightening of the face and neck, 86% showed a clinically significant brow-lift 90 days after treatment. The average brow elevation in this study was 1.7 mm.

In practice, however, patients are often more satisfied with the brow elevation they achieve with neurotoxins and fillers. Injectables provide a faster onset of results, fewer treatments, and minimal discomfort. Combination treatments provide the best overall results and although injectables in the periorbital area are technically difficult, patients are often very satisfied and return for repeat treatments.

References Aesthet Surg J. 2009;May-Jun;29(3):174-9.

J Am Acad Dermatol. 2010;Feb;62(2):262-9.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub.

We have actively avoided benchmarks in medicine since time immemorial. There is a strong argument that rote, one-size-fits-all parameters for care medicine are bad for our patients, and obviously they interfere with our flexibility in dealing with complex obscure diseases. This flexibility is critical in dermatology, where we deal with over 3,000 diseases, and there truly is more art than science involved in treating some of them.

Nonetheless, here come the benchmarks. Since we have not provided them, they have been provided for us. Look no further than United Health Care’s Optum program, or Cigna’s star ratings, both of which rank on average costs, without regard to subspecialty or intensity of disease.

Benchmarks have proven useful in industry and have improved quality there. I expect they will be most annoying to practicing physicians. There are also great variations in practice patterns we must make sure are accounted for. A pediatric dermatologist, for example, does radically fewer skin biopsies than a Mohs surgeon, and diagnoses many fewer malignancies. However, some things are inexplicable, even after opening two standard deviations, and you need to be aware they may be coming.

The Medicare data release was an eye opener for many. This information is readily available on multiple web sites in numeric and graphic display. You should look yourself and your “peers” up on the Wall Street Journal or ProPublicaweb sites. For example, it is hard to fathom how every closure can be a flap, or how every Mohs case is four stages. Or even more bizarre, how you can do Mohs and never have a second stage. It is hard to understand how most dermatologists have a certain number of skin biopsies or shave excisions per patient encounter and others ten times as many. With this in mind, I encourage all of you to look at your own ratios of procedures compared to your peers. Recall that Medicare data lag two years before publication. Areas that could be under scrutiny include:

• Number of skin biopsies per encounter.

• Number of repeat patient encounters per year.

• Number of lesion destructions per patient.

• Ratio of first to additional layers of Mohs.

• Number of Mohs procedures on trunk and extremities, compared with head and neck.

• Percentage of closures done with adjacent tissue transfers.

• Number of shave excisions per patient.

• Number of complex closures, compared with layered closures, particularly on the trunk and extremities.

• Number of diagnostic frozen sections.

• Frequency of use of special stains on pathology specimens.

We need to be actively involved in the development of these so that we are not forced into a one size fits all mold. I expect this will start with the private insurers, including Medicare advantage plans, since they have real time data analysis, and a keen desire to save money. These “benchmarks” will be a work in progress and will infuriate some of you. They are, however, more credible, and better, than the current state of affairs, where insurance companies rank you by simply averaging your costs under your tax identification number.

So heads up, benchmarks are coming your way. Review your own public data, compared with your peers and see if you are an outlier, and if so, ponder the reason why. It is not too late to take corrective action.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Reach him at dermnews@frontlinemedcom.com.

We have actively avoided benchmarks in medicine since time immemorial. There is a strong argument that rote, one-size-fits-all parameters for care medicine are bad for our patients, and obviously they interfere with our flexibility in dealing with complex obscure diseases. This flexibility is critical in dermatology, where we deal with over 3,000 diseases, and there truly is more art than science involved in treating some of them.

Nonetheless, here come the benchmarks. Since we have not provided them, they have been provided for us. Look no further than United Health Care’s Optum program, or Cigna’s star ratings, both of which rank on average costs, without regard to subspecialty or intensity of disease.

Benchmarks have proven useful in industry and have improved quality there. I expect they will be most annoying to practicing physicians. There are also great variations in practice patterns we must make sure are accounted for. A pediatric dermatologist, for example, does radically fewer skin biopsies than a Mohs surgeon, and diagnoses many fewer malignancies. However, some things are inexplicable, even after opening two standard deviations, and you need to be aware they may be coming.

The Medicare data release was an eye opener for many. This information is readily available on multiple web sites in numeric and graphic display. You should look yourself and your “peers” up on the Wall Street Journal or ProPublicaweb sites. For example, it is hard to fathom how every closure can be a flap, or how every Mohs case is four stages. Or even more bizarre, how you can do Mohs and never have a second stage. It is hard to understand how most dermatologists have a certain number of skin biopsies or shave excisions per patient encounter and others ten times as many. With this in mind, I encourage all of you to look at your own ratios of procedures compared to your peers. Recall that Medicare data lag two years before publication. Areas that could be under scrutiny include:

• Number of skin biopsies per encounter.

• Number of repeat patient encounters per year.

• Number of lesion destructions per patient.

• Ratio of first to additional layers of Mohs.

• Number of Mohs procedures on trunk and extremities, compared with head and neck.

• Percentage of closures done with adjacent tissue transfers.

• Number of shave excisions per patient.

• Number of complex closures, compared with layered closures, particularly on the trunk and extremities.

• Number of diagnostic frozen sections.

• Frequency of use of special stains on pathology specimens.

We need to be actively involved in the development of these so that we are not forced into a one size fits all mold. I expect this will start with the private insurers, including Medicare advantage plans, since they have real time data analysis, and a keen desire to save money. These “benchmarks” will be a work in progress and will infuriate some of you. They are, however, more credible, and better, than the current state of affairs, where insurance companies rank you by simply averaging your costs under your tax identification number.

So heads up, benchmarks are coming your way. Review your own public data, compared with your peers and see if you are an outlier, and if so, ponder the reason why. It is not too late to take corrective action.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Reach him at dermnews@frontlinemedcom.com.

We have actively avoided benchmarks in medicine since time immemorial. There is a strong argument that rote, one-size-fits-all parameters for care medicine are bad for our patients, and obviously they interfere with our flexibility in dealing with complex obscure diseases. This flexibility is critical in dermatology, where we deal with over 3,000 diseases, and there truly is more art than science involved in treating some of them.

Nonetheless, here come the benchmarks. Since we have not provided them, they have been provided for us. Look no further than United Health Care’s Optum program, or Cigna’s star ratings, both of which rank on average costs, without regard to subspecialty or intensity of disease.

Benchmarks have proven useful in industry and have improved quality there. I expect they will be most annoying to practicing physicians. There are also great variations in practice patterns we must make sure are accounted for. A pediatric dermatologist, for example, does radically fewer skin biopsies than a Mohs surgeon, and diagnoses many fewer malignancies. However, some things are inexplicable, even after opening two standard deviations, and you need to be aware they may be coming.

The Medicare data release was an eye opener for many. This information is readily available on multiple web sites in numeric and graphic display. You should look yourself and your “peers” up on the Wall Street Journal or ProPublicaweb sites. For example, it is hard to fathom how every closure can be a flap, or how every Mohs case is four stages. Or even more bizarre, how you can do Mohs and never have a second stage. It is hard to understand how most dermatologists have a certain number of skin biopsies or shave excisions per patient encounter and others ten times as many. With this in mind, I encourage all of you to look at your own ratios of procedures compared to your peers. Recall that Medicare data lag two years before publication. Areas that could be under scrutiny include:

• Number of skin biopsies per encounter.

• Number of repeat patient encounters per year.

• Number of lesion destructions per patient.

• Ratio of first to additional layers of Mohs.

• Number of Mohs procedures on trunk and extremities, compared with head and neck.

• Percentage of closures done with adjacent tissue transfers.

• Number of shave excisions per patient.

• Number of complex closures, compared with layered closures, particularly on the trunk and extremities.

• Number of diagnostic frozen sections.

• Frequency of use of special stains on pathology specimens.

We need to be actively involved in the development of these so that we are not forced into a one size fits all mold. I expect this will start with the private insurers, including Medicare advantage plans, since they have real time data analysis, and a keen desire to save money. These “benchmarks” will be a work in progress and will infuriate some of you. They are, however, more credible, and better, than the current state of affairs, where insurance companies rank you by simply averaging your costs under your tax identification number.

So heads up, benchmarks are coming your way. Review your own public data, compared with your peers and see if you are an outlier, and if so, ponder the reason why. It is not too late to take corrective action.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Reach him at dermnews@frontlinemedcom.com.

I was taught—and still believe—that obtaining a thorough history can direct you to a good working diagnosis. About 20 years ago, while in the Navy, I had a patient who showed me that I should not be fooled by a history that does not fit the current presentation.

The patient was a 34-year-old sailor with right-side knee pain, occurring intermittently for a long time but worsening in recent months. The pain did not prevent him from running, performing in the Navy’s semi-annual fitness test, or participating in departmental physical fitness activities.

However, his pain worsened after he was assigned to a ship, which required him to ascend and descend the steep shipboard stairs or ladders. He also complained of some intermittent buckling or “giving out.” But he was quite clear when he stated that he had sustained no recent injury to explain his condition.

The pain did not prevent him from running, performing in the Navy's semi-annual fitness test, or participating in departmental activities.

His history was notable for an injury he sustained six years earlier, while running. Although he could not remember the exact mechanism of injury, he recalled that his knee hurt and was swollen the next day. He was seen in medical, where he was given crutches, modified duty, and ibuprofen for a few days. After a relatively short time, his activity returned to normal.

I had seen a lot of knee pain on board ship, mostly of the patellar tendonitis or patellofemoral syndrome types, that could often be treated conservatively with temporary duty modification to avoid aggravating activity. More serious injuries—such as meniscal, collateral, or cruciate ligament tears—were associated with recent or acute injuries and a history including a suspicious mechanism of injury.

This patient’s complete knee exam was largely unremarkable, except his anterior drawer test seemed to have no distinct endpoint. When I compared the results with his asymptomatic left knee, I could not appreciate any difference.

So I relayed to him my thought process: If he had done something serious to his knee six years ago, it probably would have manifested sooner. As other clinicians did previously, I treated him conservatively with duty limitations and advised him that if he failed to improve soon, I would refer him to an orthopedist for a second opinion.

Well, he did not improve soon. Since he was still concerned, I provided the referral, without obtaining an MRI.

To perhaps everyone’s surprise—but most definitely mine—the patient was diagnosed with a complete ACL tear by the orthopedist (again, without MRI). He was scheduled for surgery at a later date.

What surprised me most was that someone could perform the way he was required to perform in the Navy for six years with a torn ACL. As a result of this case, I have not let a remote history of injury cloud my judgment since!

I was taught—and still believe—that obtaining a thorough history can direct you to a good working diagnosis. About 20 years ago, while in the Navy, I had a patient who showed me that I should not be fooled by a history that does not fit the current presentation.

The patient was a 34-year-old sailor with right-side knee pain, occurring intermittently for a long time but worsening in recent months. The pain did not prevent him from running, performing in the Navy’s semi-annual fitness test, or participating in departmental physical fitness activities.

However, his pain worsened after he was assigned to a ship, which required him to ascend and descend the steep shipboard stairs or ladders. He also complained of some intermittent buckling or “giving out.” But he was quite clear when he stated that he had sustained no recent injury to explain his condition.

The pain did not prevent him from running, performing in the Navy's semi-annual fitness test, or participating in departmental activities.

His history was notable for an injury he sustained six years earlier, while running. Although he could not remember the exact mechanism of injury, he recalled that his knee hurt and was swollen the next day. He was seen in medical, where he was given crutches, modified duty, and ibuprofen for a few days. After a relatively short time, his activity returned to normal.

I had seen a lot of knee pain on board ship, mostly of the patellar tendonitis or patellofemoral syndrome types, that could often be treated conservatively with temporary duty modification to avoid aggravating activity. More serious injuries—such as meniscal, collateral, or cruciate ligament tears—were associated with recent or acute injuries and a history including a suspicious mechanism of injury.

This patient’s complete knee exam was largely unremarkable, except his anterior drawer test seemed to have no distinct endpoint. When I compared the results with his asymptomatic left knee, I could not appreciate any difference.

So I relayed to him my thought process: If he had done something serious to his knee six years ago, it probably would have manifested sooner. As other clinicians did previously, I treated him conservatively with duty limitations and advised him that if he failed to improve soon, I would refer him to an orthopedist for a second opinion.

Well, he did not improve soon. Since he was still concerned, I provided the referral, without obtaining an MRI.

To perhaps everyone’s surprise—but most definitely mine—the patient was diagnosed with a complete ACL tear by the orthopedist (again, without MRI). He was scheduled for surgery at a later date.

What surprised me most was that someone could perform the way he was required to perform in the Navy for six years with a torn ACL. As a result of this case, I have not let a remote history of injury cloud my judgment since!

I was taught—and still believe—that obtaining a thorough history can direct you to a good working diagnosis. About 20 years ago, while in the Navy, I had a patient who showed me that I should not be fooled by a history that does not fit the current presentation.

The patient was a 34-year-old sailor with right-side knee pain, occurring intermittently for a long time but worsening in recent months. The pain did not prevent him from running, performing in the Navy’s semi-annual fitness test, or participating in departmental physical fitness activities.

However, his pain worsened after he was assigned to a ship, which required him to ascend and descend the steep shipboard stairs or ladders. He also complained of some intermittent buckling or “giving out.” But he was quite clear when he stated that he had sustained no recent injury to explain his condition.

The pain did not prevent him from running, performing in the Navy's semi-annual fitness test, or participating in departmental activities.

His history was notable for an injury he sustained six years earlier, while running. Although he could not remember the exact mechanism of injury, he recalled that his knee hurt and was swollen the next day. He was seen in medical, where he was given crutches, modified duty, and ibuprofen for a few days. After a relatively short time, his activity returned to normal.

I had seen a lot of knee pain on board ship, mostly of the patellar tendonitis or patellofemoral syndrome types, that could often be treated conservatively with temporary duty modification to avoid aggravating activity. More serious injuries—such as meniscal, collateral, or cruciate ligament tears—were associated with recent or acute injuries and a history including a suspicious mechanism of injury.

This patient’s complete knee exam was largely unremarkable, except his anterior drawer test seemed to have no distinct endpoint. When I compared the results with his asymptomatic left knee, I could not appreciate any difference.

So I relayed to him my thought process: If he had done something serious to his knee six years ago, it probably would have manifested sooner. As other clinicians did previously, I treated him conservatively with duty limitations and advised him that if he failed to improve soon, I would refer him to an orthopedist for a second opinion.

Well, he did not improve soon. Since he was still concerned, I provided the referral, without obtaining an MRI.

To perhaps everyone’s surprise—but most definitely mine—the patient was diagnosed with a complete ACL tear by the orthopedist (again, without MRI). He was scheduled for surgery at a later date.

What surprised me most was that someone could perform the way he was required to perform in the Navy for six years with a torn ACL. As a result of this case, I have not let a remote history of injury cloud my judgment since!

Question: Oral contraceptives are prescription drugs sold with highly specific manufacturer instructions on how and when to take them, because the sequence of pill ingestion is critical to their anovulatory efficacy.

Suppose a manufacturing mishap resulted in improper labeling and sequencing of the pills, and some women, relying on the product, became pregnant. In a lawsuit against the manufacturer, which of the following choices is best?

A. This is a case of product liability.

B. Affected plaintiffs should consider filing a class-action lawsuit.

C. Mothers can sue for wrongful pregnancy.

D. Children can sue for wrongful life.

E. All are possible legal causes of action.

Answer: E. This hypothetical is adapted from a recent report that the use of mispackaged oral contraceptives had resulted in more than 100 women becoming pregnant. The prescription drugs, available in blister packs, were erroneously sequenced such that the daily use of active or inactive drug was asynchronous with the woman’s ovulatory cycle, thus foiling the drug’s pregnancy prevention efficacy.

Typically, each packet of oral contraceptives comes with 28 days’ worth of color-coded pills, with the first 21 containing the active principle to inhibit ovulation, followed by 7 inert pills. Each monthly pack begins with the same strict pill sequence.

In 2011, the manufacturer of several brands of oral contraceptives recalled half a million such packs when it was discovered that some of them had the pill sequence reversed. Foreseeably, this debacle resulted in a number of unplanned pregnancies – and live births. Legal action soon followed.

▶ Product liability: A simple negligence lawsuit would typically cover a situation in which a wrongdoer has breached the requisite standard of care, as appears to be the case here. However, when a product such as a prescription drug leads to “harm,” an injured party, using the law of product liability, can sue the manufacturer that had placed it into the stream of commerce. This allows the plaintiff to rely on legal theories other than negligence, including breach of warranty and strict liability.

Under the latter legal theory, there is no need to prove fault or contractual breach, and the significant part of the complaint is whether the product is both defective and unreasonably dangerous. “Defective” is usually defined as product quality that is less than what a reasonable consumer expects, and “unreasonably dangerous” is a conclusion that the risks that result from its condition outweigh the product’s advantages.

Although the medication itself in this case is not defective or unreasonably dangerous, the assembly and labeling fiasco would suffice to keep the lawsuit within the product liability category. According to Section 102(2) of the Uniform Product Liability Act, product liability includes “all claims or action brought for personal injury, death, or property damage caused by the manufacture, design, formula, preparation, assembly, installation, testing, warnings, instructions, marketing, packaging, or labeling of any product.”

▶ Class action: A class action lawsuit, governed by Rule 23 of the Federal Rules of Civil Procedure, describes a legal cause of action where a representative plaintiff asserts claims on behalf of a large class of similarly injured members, who then give up their rights to pursue an individual lawsuit. It confers several advantages upon the plaintiffs, including the potential of higher damages.

However, four prerequisites must be present before a lawsuit can be certified a class action: numerosity, commonality, typicality, and adequacy.

Although there is the possibility of going forward with a class action suit, a federal judge in Georgia refused to certify class action status in the 2011 recall case. The judge stated that only 53 of the half-million recalled blister packs had the pills arranged in reverse order, and each woman’s case should be individually adjudicated given the controlling laws in her state, the need to prove use of the product, and whether she became pregnant and carried the pregnancy to term.

▶ Wrongful life: Strictly speaking, tort issues in this case can be divided into two categories: wrongful pregnancy (sometimes confusingly referred to as wrongful birth) alleged by the mother, and wrongful life by the child. Unfortunately, these claims are frequently lumped together under the rubric of wrongful life.

The women affected by this mix-up are reportedly seeking damages for lost income, medical costs, and, in some cases, the cost of raising their children, including the cost of college. However, the common law has traditionally barred a wrongful life action, although state laws have evolved over the years. So, court decisions and statutes in each state should be carefully consulted for any individual case.

The prime reason for disallowing a wrongful life action is that life, even if imperfect, is always preferable to non-life. Besides, it will be impossible to assess the quantum of damages, because this necessarily requires placing a monetary worth on human existence.

The seminal case is the 1967 New Jersey decision of Gleitman v. Cosgrove (227 A.2d 689 [N.J. 1967]), but the state’s position has since changed. In Berman v. Allan (404 A.2d 8 [N.J. 1979]), the court allowed damages for maternal emotional distress, though not for medical and other expenses of raising the child.

Overall, the law of wrongful life appears to be increasingly willing to award damages to the mother for the physical, emotional, and financial costs of pregnancy and delivery, but not the cost associated with the normal rearing of a healthy child.

The legal situation is quite different for a lawsuit filed by the child, who in essence is arguing that he/she should not have been born at all. Courts continue to refuse a claim brought by a healthy infant for wrongful life, adopting the reasoning in Berman that the infant has not suffered any damage cognizable at law by being brought into existence. Even an infant with birth disabilities will not prevail in the majority of jurisdictions, with California being a notable exception.

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

Question: Oral contraceptives are prescription drugs sold with highly specific manufacturer instructions on how and when to take them, because the sequence of pill ingestion is critical to their anovulatory efficacy.

Suppose a manufacturing mishap resulted in improper labeling and sequencing of the pills, and some women, relying on the product, became pregnant. In a lawsuit against the manufacturer, which of the following choices is best?

A. This is a case of product liability.

B. Affected plaintiffs should consider filing a class-action lawsuit.

C. Mothers can sue for wrongful pregnancy.

D. Children can sue for wrongful life.

E. All are possible legal causes of action.

Answer: E. This hypothetical is adapted from a recent report that the use of mispackaged oral contraceptives had resulted in more than 100 women becoming pregnant. The prescription drugs, available in blister packs, were erroneously sequenced such that the daily use of active or inactive drug was asynchronous with the woman’s ovulatory cycle, thus foiling the drug’s pregnancy prevention efficacy.

Typically, each packet of oral contraceptives comes with 28 days’ worth of color-coded pills, with the first 21 containing the active principle to inhibit ovulation, followed by 7 inert pills. Each monthly pack begins with the same strict pill sequence.

In 2011, the manufacturer of several brands of oral contraceptives recalled half a million such packs when it was discovered that some of them had the pill sequence reversed. Foreseeably, this debacle resulted in a number of unplanned pregnancies – and live births. Legal action soon followed.

▶ Product liability: A simple negligence lawsuit would typically cover a situation in which a wrongdoer has breached the requisite standard of care, as appears to be the case here. However, when a product such as a prescription drug leads to “harm,” an injured party, using the law of product liability, can sue the manufacturer that had placed it into the stream of commerce. This allows the plaintiff to rely on legal theories other than negligence, including breach of warranty and strict liability.

Under the latter legal theory, there is no need to prove fault or contractual breach, and the significant part of the complaint is whether the product is both defective and unreasonably dangerous. “Defective” is usually defined as product quality that is less than what a reasonable consumer expects, and “unreasonably dangerous” is a conclusion that the risks that result from its condition outweigh the product’s advantages.

Although the medication itself in this case is not defective or unreasonably dangerous, the assembly and labeling fiasco would suffice to keep the lawsuit within the product liability category. According to Section 102(2) of the Uniform Product Liability Act, product liability includes “all claims or action brought for personal injury, death, or property damage caused by the manufacture, design, formula, preparation, assembly, installation, testing, warnings, instructions, marketing, packaging, or labeling of any product.”

▶ Class action: A class action lawsuit, governed by Rule 23 of the Federal Rules of Civil Procedure, describes a legal cause of action where a representative plaintiff asserts claims on behalf of a large class of similarly injured members, who then give up their rights to pursue an individual lawsuit. It confers several advantages upon the plaintiffs, including the potential of higher damages.

However, four prerequisites must be present before a lawsuit can be certified a class action: numerosity, commonality, typicality, and adequacy.

Although there is the possibility of going forward with a class action suit, a federal judge in Georgia refused to certify class action status in the 2011 recall case. The judge stated that only 53 of the half-million recalled blister packs had the pills arranged in reverse order, and each woman’s case should be individually adjudicated given the controlling laws in her state, the need to prove use of the product, and whether she became pregnant and carried the pregnancy to term.

▶ Wrongful life: Strictly speaking, tort issues in this case can be divided into two categories: wrongful pregnancy (sometimes confusingly referred to as wrongful birth) alleged by the mother, and wrongful life by the child. Unfortunately, these claims are frequently lumped together under the rubric of wrongful life.

The women affected by this mix-up are reportedly seeking damages for lost income, medical costs, and, in some cases, the cost of raising their children, including the cost of college. However, the common law has traditionally barred a wrongful life action, although state laws have evolved over the years. So, court decisions and statutes in each state should be carefully consulted for any individual case.

The prime reason for disallowing a wrongful life action is that life, even if imperfect, is always preferable to non-life. Besides, it will be impossible to assess the quantum of damages, because this necessarily requires placing a monetary worth on human existence.

The seminal case is the 1967 New Jersey decision of Gleitman v. Cosgrove (227 A.2d 689 [N.J. 1967]), but the state’s position has since changed. In Berman v. Allan (404 A.2d 8 [N.J. 1979]), the court allowed damages for maternal emotional distress, though not for medical and other expenses of raising the child.

Overall, the law of wrongful life appears to be increasingly willing to award damages to the mother for the physical, emotional, and financial costs of pregnancy and delivery, but not the cost associated with the normal rearing of a healthy child.

The legal situation is quite different for a lawsuit filed by the child, who in essence is arguing that he/she should not have been born at all. Courts continue to refuse a claim brought by a healthy infant for wrongful life, adopting the reasoning in Berman that the infant has not suffered any damage cognizable at law by being brought into existence. Even an infant with birth disabilities will not prevail in the majority of jurisdictions, with California being a notable exception.

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

Question: Oral contraceptives are prescription drugs sold with highly specific manufacturer instructions on how and when to take them, because the sequence of pill ingestion is critical to their anovulatory efficacy.

Suppose a manufacturing mishap resulted in improper labeling and sequencing of the pills, and some women, relying on the product, became pregnant. In a lawsuit against the manufacturer, which of the following choices is best?

A. This is a case of product liability.

B. Affected plaintiffs should consider filing a class-action lawsuit.

C. Mothers can sue for wrongful pregnancy.

D. Children can sue for wrongful life.

E. All are possible legal causes of action.

Answer: E. This hypothetical is adapted from a recent report that the use of mispackaged oral contraceptives had resulted in more than 100 women becoming pregnant. The prescription drugs, available in blister packs, were erroneously sequenced such that the daily use of active or inactive drug was asynchronous with the woman’s ovulatory cycle, thus foiling the drug’s pregnancy prevention efficacy.

Typically, each packet of oral contraceptives comes with 28 days’ worth of color-coded pills, with the first 21 containing the active principle to inhibit ovulation, followed by 7 inert pills. Each monthly pack begins with the same strict pill sequence.

In 2011, the manufacturer of several brands of oral contraceptives recalled half a million such packs when it was discovered that some of them had the pill sequence reversed. Foreseeably, this debacle resulted in a number of unplanned pregnancies – and live births. Legal action soon followed.

▶ Product liability: A simple negligence lawsuit would typically cover a situation in which a wrongdoer has breached the requisite standard of care, as appears to be the case here. However, when a product such as a prescription drug leads to “harm,” an injured party, using the law of product liability, can sue the manufacturer that had placed it into the stream of commerce. This allows the plaintiff to rely on legal theories other than negligence, including breach of warranty and strict liability.

Under the latter legal theory, there is no need to prove fault or contractual breach, and the significant part of the complaint is whether the product is both defective and unreasonably dangerous. “Defective” is usually defined as product quality that is less than what a reasonable consumer expects, and “unreasonably dangerous” is a conclusion that the risks that result from its condition outweigh the product’s advantages.

Although the medication itself in this case is not defective or unreasonably dangerous, the assembly and labeling fiasco would suffice to keep the lawsuit within the product liability category. According to Section 102(2) of the Uniform Product Liability Act, product liability includes “all claims or action brought for personal injury, death, or property damage caused by the manufacture, design, formula, preparation, assembly, installation, testing, warnings, instructions, marketing, packaging, or labeling of any product.”

▶ Class action: A class action lawsuit, governed by Rule 23 of the Federal Rules of Civil Procedure, describes a legal cause of action where a representative plaintiff asserts claims on behalf of a large class of similarly injured members, who then give up their rights to pursue an individual lawsuit. It confers several advantages upon the plaintiffs, including the potential of higher damages.

However, four prerequisites must be present before a lawsuit can be certified a class action: numerosity, commonality, typicality, and adequacy.

Although there is the possibility of going forward with a class action suit, a federal judge in Georgia refused to certify class action status in the 2011 recall case. The judge stated that only 53 of the half-million recalled blister packs had the pills arranged in reverse order, and each woman’s case should be individually adjudicated given the controlling laws in her state, the need to prove use of the product, and whether she became pregnant and carried the pregnancy to term.

▶ Wrongful life: Strictly speaking, tort issues in this case can be divided into two categories: wrongful pregnancy (sometimes confusingly referred to as wrongful birth) alleged by the mother, and wrongful life by the child. Unfortunately, these claims are frequently lumped together under the rubric of wrongful life.

The women affected by this mix-up are reportedly seeking damages for lost income, medical costs, and, in some cases, the cost of raising their children, including the cost of college. However, the common law has traditionally barred a wrongful life action, although state laws have evolved over the years. So, court decisions and statutes in each state should be carefully consulted for any individual case.

The prime reason for disallowing a wrongful life action is that life, even if imperfect, is always preferable to non-life. Besides, it will be impossible to assess the quantum of damages, because this necessarily requires placing a monetary worth on human existence.

The seminal case is the 1967 New Jersey decision of Gleitman v. Cosgrove (227 A.2d 689 [N.J. 1967]), but the state’s position has since changed. In Berman v. Allan (404 A.2d 8 [N.J. 1979]), the court allowed damages for maternal emotional distress, though not for medical and other expenses of raising the child.

Overall, the law of wrongful life appears to be increasingly willing to award damages to the mother for the physical, emotional, and financial costs of pregnancy and delivery, but not the cost associated with the normal rearing of a healthy child.

The legal situation is quite different for a lawsuit filed by the child, who in essence is arguing that he/she should not have been born at all. Courts continue to refuse a claim brought by a healthy infant for wrongful life, adopting the reasoning in Berman that the infant has not suffered any damage cognizable at law by being brought into existence. Even an infant with birth disabilities will not prevail in the majority of jurisdictions, with California being a notable exception.

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

A number of drugs are available for ophthalmic use. This review focuses on single drug products and, although combination drug products are not discussed, these formulations typically include the drugs reviewed here.

Since it appears that ophthalmic medications are commonly used for a wide range of conditions and ages, one would expect to see numerous reports of their use in the eyes of pregnant or breastfeeding patients. Unfortunately, the opposite is true. The majority of the drugs have no human pregnancy or lactation data. When there are human data, it invariably involves the systemic use of the drug for other indications, rather than its ophthalmic use. Moreover, the animal reproduction data are usually not relevant because they involve systemic drugs (e.g., IV or oral). Consequently, determining the level of risk an ophthalmic drug presents to an embryo and/or fetus is primarily based on time and dose, the two cardinal principles of teratology.

Avoiding exposure during organogenesis – the period when a drug can cause developmental toxicity (altered growth, structural anomalies, functional and/or behavioral deficits, or death) – is usually best, but may not be possible in some cases, including glaucoma, eye infections, and eye surgery. Fortunately, the systemic concentrations of drugs applied topically to the eye are typically thought to be low, even though the levels of most drugs have not been studied. Thus, the risk to the embryo and/or fetus in most cases can be considered low and the drug classified as compatible in pregnancy and breastfeeding.

If a topical eye drug must be used during pregnancy or lactation, teach the patient how to decrease the amount of drug reaching the systemic circulation. This involves placing pressure over the tear duct in the corner of the eye for 1 minute or more, then removing any excess solution with absorbent tissue.

In the sections below, drugs are shown by indication or by pharmacologic class. The term “human eye data” refers to the use of the drug in pregnancy and/or lactation.

Glaucoma

If you are caring for a pregnant patient who is being treated for glaucoma, two recent reviews may be helpful: Surv Ophthalmol. 2011 Jul-Aug;56(4):324-35 and Curr Opin Ophthalmol. 2014 Mar;25(2):93-7.

Sympathomimetics (alpha-adrenergic agonists) include apraclonidine (Iopidine), which has no human eye data, and brimonidine (Alphagan P), which has one case report in pregnancy and breastfeeding showing no fetal or nursing infant harm.

Four of the five beta-adrenergic blockers have no human eye data: betaxolol (Betoptic), carteolol (Ocupress), levobunolol (Betagan), and metipranolol, but there are two case reports for timolol (Betimol, Istalol, Timoptic, Timoptic-XE) showing no fetal harm in one newborn and growth restriction in the other.

Among the miotics, there are limited human eye data for pilocarpine (Isopto Carpine) and no fetal harm was observed. For echothiophate iodide (Phospholine Iodide), there is one case report of a normal full-term infant whose mother was treated with the agent up to 32 weeks’ gestation and then with pilocarpine for 8 weeks (Arch Ophthalmol. 1968 Mar;79[3]:283-5).

Fuse/Thinkstock.com

Carbonic anhydrase inhibitors include brinzolamide (Azopt), which has no human eye data, and dorzolamide (Trusopt), which has growth restriction in one case treated with fixed combination of dorzolamide and timolol. There are no human eye data for unoprostone isopropyl (Rescula), a synthetic docosanoid.

Of the four prostaglandin analogs, three have no human eye data, bimatoprost (Lumigan), tafluprost (Zioptan), and travoprost (Travatan Z). There were 11 pregnancies exposed to latanoprost (Xalatan). The outcomes of these cases were one lost to follow-up, one miscarriage, and nine infants without congenital anomalies (Am J Ophthalmol. 2004 Aug;138[2]:305-6).

Mitomycin (Mitosol) is an antimetabolite that is given topically to the surgical site of glaucoma filtration surgery. No reports of its use in pregnant humans have been located. According to the manufacturer, clinically significant systemic concentrations are not expected.

Antiseptics

Povidone-iodine (Betadine) is indicated for prepping of the periocular region. There does not appear to be any risk to the embryo-fetus or nursing infant from this indication.

Antihistamines

The four ophthalmic agents in this class are alcaftadine (Lastacaft), azelastine (Optivar), emedastine (Emadine), and epinastine (Elestat). There are no human eye data for these agents but, like antihistamines given systemically, they are probably compatible in pregnancy and lactation.

Antihistamine-mast cell stabilizers

There are no human eye data for bepotastine (Bepreve), ketotifen (Alaway), and olopatadine (Pataday, Patanol). Peak plasma concentrations of bepotastine were 5.1-7.3 ng/mL for 1-2 hours after instillation and were less than 2 ng/mL at 24 hours. It appears that these drugs can also be classified as compatible in pregnancy and lactation.

Anti-infectives

Ten anti-infectives are available for topical treatment of eye infections (systemic concentrations if known): besifloxacin (Besivance) (0.43 ng/mL), ciprofloxacin (less than 2.5 ng/mL), gentamicin, gatifloxacin (Zymaxid) (less than 5 ng/mL), levofloxacin (Iquix) (10.9 ng/mL), moxifloxacin (Vigamox) (2.7 ng/mL), ofloxacin (1.9 ng/mL), sulfacetamide (Isopto Cetamide), and tobramycin. The tenth agent, natamycin (Natacyn), is an antifungal. According to the manufacturer, systemic absorption is not expected.

None of these agents have human eye data, but they are usually considered compatible in pregnancy and breastfeeding when systemic formulations are used, so they should be compatible when used in the eye.

Antivirals

Ganciclovir (Zirgan) has no human eye data but, according to the manufacturer, the daily ophthalmic dose is about 0.04% and 0.1% of the oral and IV doses, respectively. Thus, minimal systemic exposure is expected. Trifluridine (Viroptic) also has no eye human data. As reported in the product information, detectable blood concentrations of the drug were not found in healthy normal subjects indicating that systemic absorption was negligible.

Corticosteroids

Among the nine corticosteroid products, six are suspensions or ointments, one is an injection, and two are implants. In most nonpregnant patients receiving the dexamethasone (Ozurdex) intravitreal implant, plasma dexamethasone concentrations were undetectable (less than 50 pg/mL) but, in some, ranged from 52 pg/mL to 102 pg/mL. There is only one case report describing the use of topical dexamethasone suspension (Maxidex) in pregnancy. In that case, dexamethasone and clindamycin were given in the first and second trimesters and the woman eventually gave birth to a normal full term infant (Int Ophthalmol. 1998-1999;22[2]:85-8).

For the fluocinolone (Retisert) ocular implant, systemic absorption of detectable amounts of the drug have not been observed. In a second report, a patient who had type 1 diabetes and was 6 months pregnant received a 2-mg intravitreal injection of triamcinolone (Triesence) in both eyes. No adverse effects in the mother or fetus were noted (Clin Ophthalmol. 2011;5:439-41).

There are no human eye data for five topical corticosteroids: difluprednate (Durezol), fluorometholone (Flarex, Fluor-OP, FML), loteprednol (Alrex, Lotemax), prednisolone (Econopred), and rimexolone (Vexol). Only two of the five drugs had information about systemic absorption. For difluprednate, blood levels were below the quantification limit (50 ng/mL). Extremely low levels were detected after the use of rimexolone with a mean serum concentration of 130 pg/mL (range less than 80-470 pg/mL).

Cycloplegics-mydriatics

This class includes four anticholinergic agents: atropine, cyclopentolate (Cyclogyl), homatropine, and tropicamide (Mydriacyl). Systemic absorption has not been studied for these drugs and there are no reports of their use in pregnancy or lactation.

Cystine-depleting agents

There are no reports describing the use of cysteamine (Cystaran) in human pregnancy or lactation. Since the drug is given as one drop in each eye every waking hour, transfer to the systemic circulation should be expected, but the amount, if it occurs, has not been reported.

Immunologics

There are no reports on the use of cyclosporine (Restasis) eye drops in human pregnancy or during breastfeeding. However, data for the systemic use of the drug during these conditions has shown it to be low risk. After long term ophthalmic use, blood concentrations of the drug were below the quantitation limit of 0.1 ng/mL.

Local anesthetics

The three drugs in this class are lidocaine, proparacaine (Alcaine), and tetracaine (Altacaine, Tetravisc). There is no information regarding the use of these agents in pregnancy or lactation. Since they are used for brief periods, the risk to an embryo or nursing infant appears to be nil.

Mast cell stabilizers

There are three drugs in this class that can be used topically in the eye: cromolyn, lodoxamide (Alomide), and nedocromil (Alocril). There are no human eye data for these agents. Systemic concentrations of lodoxamide were below the detection limit of 2.5 ng/mL.

Miotics

The two miotics are acetylcholine (Miochol E) and carbachol (Carbastat, Miostat). Both are used immediately before eye surgery. The amount, if any, in the systemic circulation is unknown. No reports of human eye use in pregnancy or lactation have been found.

NSAIDs

The five drugs in this class are bromfenac (Xibrom), diclofenac (Voltaren), flurbiprofen (Ocufen), ketorolac, and nepafenac (Nevanac). Although it has not been studied, the estimated plasma level for bromfenac is less than 50 ng/mL. For diclofenac, the plasma concentration was below the limit of quantification (10 ng/mL). In a study conducted with ketorolac, only 5 of 26 subjects had detectable plasma concentrations (10.7 to 22.5 ng/mL). These levels were about 2% of the peak plasma levels after oral dosing. For nepafenac, the peak plasma concentrations of the parent drug and active metabolite were 0.3 and 0.4 ng/mL, respectively. These data suggest that the risk to the embryo-fetus or a nursing infant are nil.

Photodynamic therapy

Verteporfin (Visudyne) is given intravenously. Three reports have described its use in three pregnancies. In all cases, the infants were healthy at birth and had normal growth (Acta Ophthalmol Scand. 2004 Oct;82[5]:623-4, Eye [Lond]. 2009 Jun;23[6]:1479, and Aust N Z J Obstet Gynaecol. 2009 Apr;49[2]:236-7).

Proteolytic enzymes

No human eye data were found for ocriplasmin (Jetrea), an agent given as an intravitreal injection. Although it was not studied, detectable levels of the drug in the systemic circulation are not expected, according to the manufacturer.

Selective vascular endothelial growth factor antagonists

There are three agents in this class: aflibercept (Eylea), pegaptanib (Macugen), and ranibizumab (Lucentis). There are no human eye data for these drugs. All are given as intravitreal injection. The systemic concentrations of the three drugs were a mean 0.02 mcg/mL; 80 ng/mL (after a dose of 10 times the recommended dose); and an estimated minimum 0.22 ng/mL, respectively. These data suggest that the risk to the embryo-fetus or a nursing infant is nil.

Sympathomimetics (decongestants)

There are four ophthalmic agents in this class and none have human eye data. Naphazoline (Naphcon, Vasocon) is the only one of the four that requires a prescription. No reports describing the systemic absorption, if any, have been found. The other three agents are available over the counter. They are oxymetazoline (Visine L.R.), phenylephrine, and tetrahydrozoline (Opti-Clear). Although the amount reaching the systemic circulation was not provided by the manufacturers for these three agents, a caution was placed on phenylephrine stating that systemic absorption, although rare, might cause alpha-adrenergic effects, such as a rise in blood pressure and reflex atropine-sensitive bradycardia.

The risk to the embryo-fetus or nursing infant from ophthalmic drugs appears to be low, with the possible exception of phenylephrine. Nevertheless, if any of these agents are used in pregnancy or during breastfeeding, careful assessment of the embryo-fetus and nursing infant should be conducted. Moreover, research on the potential effects of ophthalmic drugs on the embryo-fetus and nursing infant are desperately needed.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco; and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.

A number of drugs are available for ophthalmic use. This review focuses on single drug products and, although combination drug products are not discussed, these formulations typically include the drugs reviewed here.

Since it appears that ophthalmic medications are commonly used for a wide range of conditions and ages, one would expect to see numerous reports of their use in the eyes of pregnant or breastfeeding patients. Unfortunately, the opposite is true. The majority of the drugs have no human pregnancy or lactation data. When there are human data, it invariably involves the systemic use of the drug for other indications, rather than its ophthalmic use. Moreover, the animal reproduction data are usually not relevant because they involve systemic drugs (e.g., IV or oral). Consequently, determining the level of risk an ophthalmic drug presents to an embryo and/or fetus is primarily based on time and dose, the two cardinal principles of teratology.

Avoiding exposure during organogenesis – the period when a drug can cause developmental toxicity (altered growth, structural anomalies, functional and/or behavioral deficits, or death) – is usually best, but may not be possible in some cases, including glaucoma, eye infections, and eye surgery. Fortunately, the systemic concentrations of drugs applied topically to the eye are typically thought to be low, even though the levels of most drugs have not been studied. Thus, the risk to the embryo and/or fetus in most cases can be considered low and the drug classified as compatible in pregnancy and breastfeeding.

If a topical eye drug must be used during pregnancy or lactation, teach the patient how to decrease the amount of drug reaching the systemic circulation. This involves placing pressure over the tear duct in the corner of the eye for 1 minute or more, then removing any excess solution with absorbent tissue.

In the sections below, drugs are shown by indication or by pharmacologic class. The term “human eye data” refers to the use of the drug in pregnancy and/or lactation.

Glaucoma

If you are caring for a pregnant patient who is being treated for glaucoma, two recent reviews may be helpful: Surv Ophthalmol. 2011 Jul-Aug;56(4):324-35 and Curr Opin Ophthalmol. 2014 Mar;25(2):93-7.

Sympathomimetics (alpha-adrenergic agonists) include apraclonidine (Iopidine), which has no human eye data, and brimonidine (Alphagan P), which has one case report in pregnancy and breastfeeding showing no fetal or nursing infant harm.

Four of the five beta-adrenergic blockers have no human eye data: betaxolol (Betoptic), carteolol (Ocupress), levobunolol (Betagan), and metipranolol, but there are two case reports for timolol (Betimol, Istalol, Timoptic, Timoptic-XE) showing no fetal harm in one newborn and growth restriction in the other.

Among the miotics, there are limited human eye data for pilocarpine (Isopto Carpine) and no fetal harm was observed. For echothiophate iodide (Phospholine Iodide), there is one case report of a normal full-term infant whose mother was treated with the agent up to 32 weeks’ gestation and then with pilocarpine for 8 weeks (Arch Ophthalmol. 1968 Mar;79[3]:283-5).

Fuse/Thinkstock.com

Carbonic anhydrase inhibitors include brinzolamide (Azopt), which has no human eye data, and dorzolamide (Trusopt), which has growth restriction in one case treated with fixed combination of dorzolamide and timolol. There are no human eye data for unoprostone isopropyl (Rescula), a synthetic docosanoid.

Of the four prostaglandin analogs, three have no human eye data, bimatoprost (Lumigan), tafluprost (Zioptan), and travoprost (Travatan Z). There were 11 pregnancies exposed to latanoprost (Xalatan). The outcomes of these cases were one lost to follow-up, one miscarriage, and nine infants without congenital anomalies (Am J Ophthalmol. 2004 Aug;138[2]:305-6).

Mitomycin (Mitosol) is an antimetabolite that is given topically to the surgical site of glaucoma filtration surgery. No reports of its use in pregnant humans have been located. According to the manufacturer, clinically significant systemic concentrations are not expected.

Antiseptics

Povidone-iodine (Betadine) is indicated for prepping of the periocular region. There does not appear to be any risk to the embryo-fetus or nursing infant from this indication.

Antihistamines

The four ophthalmic agents in this class are alcaftadine (Lastacaft), azelastine (Optivar), emedastine (Emadine), and epinastine (Elestat). There are no human eye data for these agents but, like antihistamines given systemically, they are probably compatible in pregnancy and lactation.

Antihistamine-mast cell stabilizers

There are no human eye data for bepotastine (Bepreve), ketotifen (Alaway), and olopatadine (Pataday, Patanol). Peak plasma concentrations of bepotastine were 5.1-7.3 ng/mL for 1-2 hours after instillation and were less than 2 ng/mL at 24 hours. It appears that these drugs can also be classified as compatible in pregnancy and lactation.

Anti-infectives

Ten anti-infectives are available for topical treatment of eye infections (systemic concentrations if known): besifloxacin (Besivance) (0.43 ng/mL), ciprofloxacin (less than 2.5 ng/mL), gentamicin, gatifloxacin (Zymaxid) (less than 5 ng/mL), levofloxacin (Iquix) (10.9 ng/mL), moxifloxacin (Vigamox) (2.7 ng/mL), ofloxacin (1.9 ng/mL), sulfacetamide (Isopto Cetamide), and tobramycin. The tenth agent, natamycin (Natacyn), is an antifungal. According to the manufacturer, systemic absorption is not expected.

None of these agents have human eye data, but they are usually considered compatible in pregnancy and breastfeeding when systemic formulations are used, so they should be compatible when used in the eye.

Antivirals

Ganciclovir (Zirgan) has no human eye data but, according to the manufacturer, the daily ophthalmic dose is about 0.04% and 0.1% of the oral and IV doses, respectively. Thus, minimal systemic exposure is expected. Trifluridine (Viroptic) also has no eye human data. As reported in the product information, detectable blood concentrations of the drug were not found in healthy normal subjects indicating that systemic absorption was negligible.

Corticosteroids

Among the nine corticosteroid products, six are suspensions or ointments, one is an injection, and two are implants. In most nonpregnant patients receiving the dexamethasone (Ozurdex) intravitreal implant, plasma dexamethasone concentrations were undetectable (less than 50 pg/mL) but, in some, ranged from 52 pg/mL to 102 pg/mL. There is only one case report describing the use of topical dexamethasone suspension (Maxidex) in pregnancy. In that case, dexamethasone and clindamycin were given in the first and second trimesters and the woman eventually gave birth to a normal full term infant (Int Ophthalmol. 1998-1999;22[2]:85-8).

For the fluocinolone (Retisert) ocular implant, systemic absorption of detectable amounts of the drug have not been observed. In a second report, a patient who had type 1 diabetes and was 6 months pregnant received a 2-mg intravitreal injection of triamcinolone (Triesence) in both eyes. No adverse effects in the mother or fetus were noted (Clin Ophthalmol. 2011;5:439-41).

There are no human eye data for five topical corticosteroids: difluprednate (Durezol), fluorometholone (Flarex, Fluor-OP, FML), loteprednol (Alrex, Lotemax), prednisolone (Econopred), and rimexolone (Vexol). Only two of the five drugs had information about systemic absorption. For difluprednate, blood levels were below the quantification limit (50 ng/mL). Extremely low levels were detected after the use of rimexolone with a mean serum concentration of 130 pg/mL (range less than 80-470 pg/mL).

Cycloplegics-mydriatics

This class includes four anticholinergic agents: atropine, cyclopentolate (Cyclogyl), homatropine, and tropicamide (Mydriacyl). Systemic absorption has not been studied for these drugs and there are no reports of their use in pregnancy or lactation.

Cystine-depleting agents

There are no reports describing the use of cysteamine (Cystaran) in human pregnancy or lactation. Since the drug is given as one drop in each eye every waking hour, transfer to the systemic circulation should be expected, but the amount, if it occurs, has not been reported.

Immunologics

There are no reports on the use of cyclosporine (Restasis) eye drops in human pregnancy or during breastfeeding. However, data for the systemic use of the drug during these conditions has shown it to be low risk. After long term ophthalmic use, blood concentrations of the drug were below the quantitation limit of 0.1 ng/mL.

Local anesthetics

The three drugs in this class are lidocaine, proparacaine (Alcaine), and tetracaine (Altacaine, Tetravisc). There is no information regarding the use of these agents in pregnancy or lactation. Since they are used for brief periods, the risk to an embryo or nursing infant appears to be nil.

Mast cell stabilizers

There are three drugs in this class that can be used topically in the eye: cromolyn, lodoxamide (Alomide), and nedocromil (Alocril). There are no human eye data for these agents. Systemic concentrations of lodoxamide were below the detection limit of 2.5 ng/mL.

Miotics

The two miotics are acetylcholine (Miochol E) and carbachol (Carbastat, Miostat). Both are used immediately before eye surgery. The amount, if any, in the systemic circulation is unknown. No reports of human eye use in pregnancy or lactation have been found.

NSAIDs

The five drugs in this class are bromfenac (Xibrom), diclofenac (Voltaren), flurbiprofen (Ocufen), ketorolac, and nepafenac (Nevanac). Although it has not been studied, the estimated plasma level for bromfenac is less than 50 ng/mL. For diclofenac, the plasma concentration was below the limit of quantification (10 ng/mL). In a study conducted with ketorolac, only 5 of 26 subjects had detectable plasma concentrations (10.7 to 22.5 ng/mL). These levels were about 2% of the peak plasma levels after oral dosing. For nepafenac, the peak plasma concentrations of the parent drug and active metabolite were 0.3 and 0.4 ng/mL, respectively. These data suggest that the risk to the embryo-fetus or a nursing infant are nil.

Photodynamic therapy

Verteporfin (Visudyne) is given intravenously. Three reports have described its use in three pregnancies. In all cases, the infants were healthy at birth and had normal growth (Acta Ophthalmol Scand. 2004 Oct;82[5]:623-4, Eye [Lond]. 2009 Jun;23[6]:1479, and Aust N Z J Obstet Gynaecol. 2009 Apr;49[2]:236-7).

Proteolytic enzymes

No human eye data were found for ocriplasmin (Jetrea), an agent given as an intravitreal injection. Although it was not studied, detectable levels of the drug in the systemic circulation are not expected, according to the manufacturer.

Selective vascular endothelial growth factor antagonists

There are three agents in this class: aflibercept (Eylea), pegaptanib (Macugen), and ranibizumab (Lucentis). There are no human eye data for these drugs. All are given as intravitreal injection. The systemic concentrations of the three drugs were a mean 0.02 mcg/mL; 80 ng/mL (after a dose of 10 times the recommended dose); and an estimated minimum 0.22 ng/mL, respectively. These data suggest that the risk to the embryo-fetus or a nursing infant is nil.

Sympathomimetics (decongestants)

There are four ophthalmic agents in this class and none have human eye data. Naphazoline (Naphcon, Vasocon) is the only one of the four that requires a prescription. No reports describing the systemic absorption, if any, have been found. The other three agents are available over the counter. They are oxymetazoline (Visine L.R.), phenylephrine, and tetrahydrozoline (Opti-Clear). Although the amount reaching the systemic circulation was not provided by the manufacturers for these three agents, a caution was placed on phenylephrine stating that systemic absorption, although rare, might cause alpha-adrenergic effects, such as a rise in blood pressure and reflex atropine-sensitive bradycardia.

The risk to the embryo-fetus or nursing infant from ophthalmic drugs appears to be low, with the possible exception of phenylephrine. Nevertheless, if any of these agents are used in pregnancy or during breastfeeding, careful assessment of the embryo-fetus and nursing infant should be conducted. Moreover, research on the potential effects of ophthalmic drugs on the embryo-fetus and nursing infant are desperately needed.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco; and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.

A number of drugs are available for ophthalmic use. This review focuses on single drug products and, although combination drug products are not discussed, these formulations typically include the drugs reviewed here.

Since it appears that ophthalmic medications are commonly used for a wide range of conditions and ages, one would expect to see numerous reports of their use in the eyes of pregnant or breastfeeding patients. Unfortunately, the opposite is true. The majority of the drugs have no human pregnancy or lactation data. When there are human data, it invariably involves the systemic use of the drug for other indications, rather than its ophthalmic use. Moreover, the animal reproduction data are usually not relevant because they involve systemic drugs (e.g., IV or oral). Consequently, determining the level of risk an ophthalmic drug presents to an embryo and/or fetus is primarily based on time and dose, the two cardinal principles of teratology.

Avoiding exposure during organogenesis – the period when a drug can cause developmental toxicity (altered growth, structural anomalies, functional and/or behavioral deficits, or death) – is usually best, but may not be possible in some cases, including glaucoma, eye infections, and eye surgery. Fortunately, the systemic concentrations of drugs applied topically to the eye are typically thought to be low, even though the levels of most drugs have not been studied. Thus, the risk to the embryo and/or fetus in most cases can be considered low and the drug classified as compatible in pregnancy and breastfeeding.

If a topical eye drug must be used during pregnancy or lactation, teach the patient how to decrease the amount of drug reaching the systemic circulation. This involves placing pressure over the tear duct in the corner of the eye for 1 minute or more, then removing any excess solution with absorbent tissue.

In the sections below, drugs are shown by indication or by pharmacologic class. The term “human eye data” refers to the use of the drug in pregnancy and/or lactation.

Glaucoma

If you are caring for a pregnant patient who is being treated for glaucoma, two recent reviews may be helpful: Surv Ophthalmol. 2011 Jul-Aug;56(4):324-35 and Curr Opin Ophthalmol. 2014 Mar;25(2):93-7.

Sympathomimetics (alpha-adrenergic agonists) include apraclonidine (Iopidine), which has no human eye data, and brimonidine (Alphagan P), which has one case report in pregnancy and breastfeeding showing no fetal or nursing infant harm.

Four of the five beta-adrenergic blockers have no human eye data: betaxolol (Betoptic), carteolol (Ocupress), levobunolol (Betagan), and metipranolol, but there are two case reports for timolol (Betimol, Istalol, Timoptic, Timoptic-XE) showing no fetal harm in one newborn and growth restriction in the other.

Among the miotics, there are limited human eye data for pilocarpine (Isopto Carpine) and no fetal harm was observed. For echothiophate iodide (Phospholine Iodide), there is one case report of a normal full-term infant whose mother was treated with the agent up to 32 weeks’ gestation and then with pilocarpine for 8 weeks (Arch Ophthalmol. 1968 Mar;79[3]:283-5).

Fuse/Thinkstock.com

Carbonic anhydrase inhibitors include brinzolamide (Azopt), which has no human eye data, and dorzolamide (Trusopt), which has growth restriction in one case treated with fixed combination of dorzolamide and timolol. There are no human eye data for unoprostone isopropyl (Rescula), a synthetic docosanoid.

Of the four prostaglandin analogs, three have no human eye data, bimatoprost (Lumigan), tafluprost (Zioptan), and travoprost (Travatan Z). There were 11 pregnancies exposed to latanoprost (Xalatan). The outcomes of these cases were one lost to follow-up, one miscarriage, and nine infants without congenital anomalies (Am J Ophthalmol. 2004 Aug;138[2]:305-6).

Mitomycin (Mitosol) is an antimetabolite that is given topically to the surgical site of glaucoma filtration surgery. No reports of its use in pregnant humans have been located. According to the manufacturer, clinically significant systemic concentrations are not expected.

Antiseptics

Povidone-iodine (Betadine) is indicated for prepping of the periocular region. There does not appear to be any risk to the embryo-fetus or nursing infant from this indication.

Antihistamines

The four ophthalmic agents in this class are alcaftadine (Lastacaft), azelastine (Optivar), emedastine (Emadine), and epinastine (Elestat). There are no human eye data for these agents but, like antihistamines given systemically, they are probably compatible in pregnancy and lactation.

Antihistamine-mast cell stabilizers

There are no human eye data for bepotastine (Bepreve), ketotifen (Alaway), and olopatadine (Pataday, Patanol). Peak plasma concentrations of bepotastine were 5.1-7.3 ng/mL for 1-2 hours after instillation and were less than 2 ng/mL at 24 hours. It appears that these drugs can also be classified as compatible in pregnancy and lactation.

Anti-infectives

Ten anti-infectives are available for topical treatment of eye infections (systemic concentrations if known): besifloxacin (Besivance) (0.43 ng/mL), ciprofloxacin (less than 2.5 ng/mL), gentamicin, gatifloxacin (Zymaxid) (less than 5 ng/mL), levofloxacin (Iquix) (10.9 ng/mL), moxifloxacin (Vigamox) (2.7 ng/mL), ofloxacin (1.9 ng/mL), sulfacetamide (Isopto Cetamide), and tobramycin. The tenth agent, natamycin (Natacyn), is an antifungal. According to the manufacturer, systemic absorption is not expected.

None of these agents have human eye data, but they are usually considered compatible in pregnancy and breastfeeding when systemic formulations are used, so they should be compatible when used in the eye.

Antivirals

Ganciclovir (Zirgan) has no human eye data but, according to the manufacturer, the daily ophthalmic dose is about 0.04% and 0.1% of the oral and IV doses, respectively. Thus, minimal systemic exposure is expected. Trifluridine (Viroptic) also has no eye human data. As reported in the product information, detectable blood concentrations of the drug were not found in healthy normal subjects indicating that systemic absorption was negligible.

Corticosteroids

Among the nine corticosteroid products, six are suspensions or ointments, one is an injection, and two are implants. In most nonpregnant patients receiving the dexamethasone (Ozurdex) intravitreal implant, plasma dexamethasone concentrations were undetectable (less than 50 pg/mL) but, in some, ranged from 52 pg/mL to 102 pg/mL. There is only one case report describing the use of topical dexamethasone suspension (Maxidex) in pregnancy. In that case, dexamethasone and clindamycin were given in the first and second trimesters and the woman eventually gave birth to a normal full term infant (Int Ophthalmol. 1998-1999;22[2]:85-8).

For the fluocinolone (Retisert) ocular implant, systemic absorption of detectable amounts of the drug have not been observed. In a second report, a patient who had type 1 diabetes and was 6 months pregnant received a 2-mg intravitreal injection of triamcinolone (Triesence) in both eyes. No adverse effects in the mother or fetus were noted (Clin Ophthalmol. 2011;5:439-41).

There are no human eye data for five topical corticosteroids: difluprednate (Durezol), fluorometholone (Flarex, Fluor-OP, FML), loteprednol (Alrex, Lotemax), prednisolone (Econopred), and rimexolone (Vexol). Only two of the five drugs had information about systemic absorption. For difluprednate, blood levels were below the quantification limit (50 ng/mL). Extremely low levels were detected after the use of rimexolone with a mean serum concentration of 130 pg/mL (range less than 80-470 pg/mL).

Cycloplegics-mydriatics

This class includes four anticholinergic agents: atropine, cyclopentolate (Cyclogyl), homatropine, and tropicamide (Mydriacyl). Systemic absorption has not been studied for these drugs and there are no reports of their use in pregnancy or lactation.

Cystine-depleting agents

There are no reports describing the use of cysteamine (Cystaran) in human pregnancy or lactation. Since the drug is given as one drop in each eye every waking hour, transfer to the systemic circulation should be expected, but the amount, if it occurs, has not been reported.

Immunologics

There are no reports on the use of cyclosporine (Restasis) eye drops in human pregnancy or during breastfeeding. However, data for the systemic use of the drug during these conditions has shown it to be low risk. After long term ophthalmic use, blood concentrations of the drug were below the quantitation limit of 0.1 ng/mL.

Local anesthetics

The three drugs in this class are lidocaine, proparacaine (Alcaine), and tetracaine (Altacaine, Tetravisc). There is no information regarding the use of these agents in pregnancy or lactation. Since they are used for brief periods, the risk to an embryo or nursing infant appears to be nil.

Mast cell stabilizers

There are three drugs in this class that can be used topically in the eye: cromolyn, lodoxamide (Alomide), and nedocromil (Alocril). There are no human eye data for these agents. Systemic concentrations of lodoxamide were below the detection limit of 2.5 ng/mL.

Miotics

The two miotics are acetylcholine (Miochol E) and carbachol (Carbastat, Miostat). Both are used immediately before eye surgery. The amount, if any, in the systemic circulation is unknown. No reports of human eye use in pregnancy or lactation have been found.

NSAIDs

The five drugs in this class are bromfenac (Xibrom), diclofenac (Voltaren), flurbiprofen (Ocufen), ketorolac, and nepafenac (Nevanac). Although it has not been studied, the estimated plasma level for bromfenac is less than 50 ng/mL. For diclofenac, the plasma concentration was below the limit of quantification (10 ng/mL). In a study conducted with ketorolac, only 5 of 26 subjects had detectable plasma concentrations (10.7 to 22.5 ng/mL). These levels were about 2% of the peak plasma levels after oral dosing. For nepafenac, the peak plasma concentrations of the parent drug and active metabolite were 0.3 and 0.4 ng/mL, respectively. These data suggest that the risk to the embryo-fetus or a nursing infant are nil.

Photodynamic therapy

Verteporfin (Visudyne) is given intravenously. Three reports have described its use in three pregnancies. In all cases, the infants were healthy at birth and had normal growth (Acta Ophthalmol Scand. 2004 Oct;82[5]:623-4, Eye [Lond]. 2009 Jun;23[6]:1479, and Aust N Z J Obstet Gynaecol. 2009 Apr;49[2]:236-7).

Proteolytic enzymes

No human eye data were found for ocriplasmin (Jetrea), an agent given as an intravitreal injection. Although it was not studied, detectable levels of the drug in the systemic circulation are not expected, according to the manufacturer.

Selective vascular endothelial growth factor antagonists

There are three agents in this class: aflibercept (Eylea), pegaptanib (Macugen), and ranibizumab (Lucentis). There are no human eye data for these drugs. All are given as intravitreal injection. The systemic concentrations of the three drugs were a mean 0.02 mcg/mL; 80 ng/mL (after a dose of 10 times the recommended dose); and an estimated minimum 0.22 ng/mL, respectively. These data suggest that the risk to the embryo-fetus or a nursing infant is nil.

Sympathomimetics (decongestants)

There are four ophthalmic agents in this class and none have human eye data. Naphazoline (Naphcon, Vasocon) is the only one of the four that requires a prescription. No reports describing the systemic absorption, if any, have been found. The other three agents are available over the counter. They are oxymetazoline (Visine L.R.), phenylephrine, and tetrahydrozoline (Opti-Clear). Although the amount reaching the systemic circulation was not provided by the manufacturers for these three agents, a caution was placed on phenylephrine stating that systemic absorption, although rare, might cause alpha-adrenergic effects, such as a rise in blood pressure and reflex atropine-sensitive bradycardia.

The risk to the embryo-fetus or nursing infant from ophthalmic drugs appears to be low, with the possible exception of phenylephrine. Nevertheless, if any of these agents are used in pregnancy or during breastfeeding, careful assessment of the embryo-fetus and nursing infant should be conducted. Moreover, research on the potential effects of ophthalmic drugs on the embryo-fetus and nursing infant are desperately needed.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco; and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.