Unique Mydriatic Returns
The combination formula fosters patient flow efficiencies.
BY REBECCA LURCOTT, M.D.
Earlier this year, the FDA approved a unique mydriatic agent, Paremyd, which consists of hydroxyamphetamine 1% and tropicamide 0.25% ophthalmic solution. Hydroxyamphetamine is an indirect-acting sympathomimetic, while tropicamide acts as a parasympatholytic.
Paremyd was first introduced in 1993; however, it was removed from the commercial market in 1997 due to a shortage of the raw material necessary for its production. According to Bartlett, between 1993 and 1997, more than 165,000 units of Paremyd were sold. This potentially represents as many as 16,000,000 individual patient uses.
I recently conducted a review of the literature on Paremyd, which indicated that during those years it became a popular mydriatic agent because of its rapid onset of action, its reduced effect on accommodation and its early onset of recovery. What follows are other highlights from that review.
OF PARTICULAR INTEREST
Patient convenience, comfort and safety are attributes of Paremyd that are of particular interest:
Patient convenience and comfort. A study by Zeise and co-workers found that Paremyd appeared to be more comfortable for the patient compared with the routine instillation of tropicamide with phenylephrine. The study also showed that the pupillary dilation achieved with Paremyd was equivalent to that of the most commonly used clinical mydriatics: 0.5% tropicamide combined with 2.5% phenylephrine. Additionally, Paremyd appeared to produce less cycloplegia, particularly during the first hour after instillation, compared with tropicamide 0.5% and phenylephrine 2.5%. Therefore, Paremyd is not recommended as a cycloplegic agent; however, its reduced effect on patient accommodation may be better tolerated by those individuals who simply require a dilated fundus examination and a manifest refraction. The effects of Paremyd are also independent of iris color according to the authors.
Furthermore, although glare is a common complaint after pupillary dilation, in a study by Larkin most patients cited the post-dilatation cycloplegia as their primary concern. Larkin also noted that mydriasis and cycloplegia are directly related to the concentration of tropicamide.
Paremyd has also been shown to initiate the onset of mydriasis within 15 minutes, while phenylephrine generally requires 30 minutes to achieve mydriasis. And, according to Bartlett, patients have also noted a shorter duration of the cycloplegic effects with Paremyd, which permits a return to normal activities sooner. Reversing the effects can also be accomplished with a single drop of Dapiprazole (Rev-Eyes), as found by Anicho et al., in a randomized, masked, prospective clinical trial.
Patient safety. Paremyd, like other mydriatics, is known to potentially increase intraocular pressure. But the textbook Drug-Induced Ocular Side Effects (Fourth Ed.) states that "Some feel that [hydroxyamphetamine] may be the safest mydriatic to use with a shallow anterior chamber since it is slow-acting and possibly more easily counteracted by miotics."
Paremyd may also have a more favorable cardiovascular safety profile than either atropine or phenylephrine. In 1938 hydroxyamphetamine received FDA approval for use as a mydriatic. There were no reports of adverse reactions or significant side effects from hydroxyamphetamine or Paremyd recorded by the National Registry of Drug-Induced Ocular Side Effects until the mid-1990s.
Cooper and associates studied the effects of Paremyd compared with tropicamide and stated that the topical use of hydroxyamphetamine has not been associated with elevations in blood pressure but has been associated with the development of temporary eyelid elevation, secondary to the sympathetic activity of the hydroxyamphetamine. This effect was noted with other medications, including phenylephrine. Similarly, Gill and associates noted no increase (or decrease) in blood pressure in normotensive individuals with small divided doses of hydroxyamphetamine, even when the total daily dosage reached 400 mg. per day.
During the 5 years that Paremyd was previously commercially available, only five serious adverse events were reported to the FDA Med Watch Medical Products Reporting Program. Those cases involved:
- a female patient in her mid-50s who experienced chest pain and an elevated blood pressure. This patient had experienced similar episodes of hypertension, tachycardia, chest pain and profuse sweating in the past, unrelated to the use of Paremyd.
- a 50-year old male who experienced elevated blood pressure and tachycardia after administration of Paremyd.
- a 62-year old male who experienced ventricular fibrillation after administration of Paremyd. This patient had a history of ventricular dysfunction and coronary artery disease.
- a 45-year old female who developed hypotension, bradycardia and syncope after Paremyd administration.
- a 57-year old male who experienced a myocardial infarction and died 5 to 7 minutes after Paremyd was administered. This patient had a history of arthritis and hypertension, and his wife said he was experiencing "indigestion" earlier that day.
These adverse events serve to remind us of the known potential cardiovascular events that can be associated with sympathomimetic and parasympatholytic agents in this class.
But considering that more than 16,000,000 individual patient doses of Paremyd have been administered, its safety profile appears to be excellent compared with other drugs in its class.
Paremyd has an initial onset of 15 minutes and provides greater pupil diameter than either of its active ingredients alone.
AN OPTION WORTH CONSIDERING
The advantages of Paremyd in eye care are significant. They include a reduced effect on patient accommodation, possible reversal with miotics in cases of iatrogenic angle closure, convenient one-drop application, onset of action within 15 minutes and a slightly shorter duration of mydriasis.
These properties can help us to improve patient flow in the clinic and reduce patient waiting times. Therefore, this combination medication may afford the patient and the ophthalmologist a more convenient, more comfortable, and safer medical diagnostic tool.
Dr. Lurcott is the Cornea and Refractive Surgery fellow in the ophthalmology department of Henry Ford Health System in Detroit.