Figure 1. Saliva and gastric fluid have dissolved the outer pink coating, revealing the bilayer brown and yellow appearance of the Gastrointestinal Therapeutic System.
Figure 2. Procardia XL 30-mg tablet (Pfizer Inc, New York, NY).
Figure 3. The tablet's pink coating dissolves readily under tap water.
Figure 4. The nifedipine Gastrointestinal Therapeutic System.1
The nifedipine GITS is the key functional element in Pfizer's extended-release Procardia formulation.1 This proprietary technology was designed to provide zero-order delivery of the drug over a 24-hour period. The convenient dosing regimen is believed to have improved compliance with calcium channel blocker therapy in hypertensive patients.2 Many pediatricians may be unfamiliar with this product, encountering it only in the setting of a suspected poisoning. A review of the product's formulation design is necessary to understand the appearance of tablets after ingestion.
Nifedipine is poorly soluble in water. The GITS utilizes a "push-pull" osmotic pump process to control drug delivery.3 A 2-layer core is surrounded by a rigid cellulose acetate semipermeable membrane, allowing only water to enter.1 Osmotic forces move the drug from the lower "push" layer to the upper "pull" layer, where it is expelled through a precision laser-drilled hole (Figure 4).4 The tablet shell remains intact as it passes through the gastrointestinal tract, and ultimately, it appears in the stool. The manufacturer applies a thin, rapidly dissolving pink film over the surface of the tablet, obscuring the bilayer nature of the design.
After a single GITS dosage, plasma nifedipine concentrations begin to rise in 3 hours and reach a plateau at 6 hours.5 Concentrations begin to decline at 24 hours, at which time the patient is recommended to take a second therapeutic dose. Even in therapeutic doses, the time to peak plasma concentration is known to be highly variable, as late as 24 hours, and may be affected by other stomach contents.5,6 In supratherapeutic ingestions, high levels of the drug may persist for several days.
The main toxic effects of nifedipine and other calcium channel blocking agents are hypotension and bradycardia.7 Additional toxic effects include nausea, vomiting, confusion, and hyperglycemia. Therapeutic interventions in face of toxic effects are directed primarily at the cardiovascular effects. Hypotension may require intravenous fluids and pressor agents. Administration of calcium (10% calcium gluconate, 0.3-0.4 mL/kg) reverses depression of cardiac contractility.8 Glucagon, 0.15 mg/kg, and epinephrine may be useful when the hypotension is refractory.7
It is important to recognize that recovery of intact tablets reveals little about the quantity of the drug absorbed. Associated conditions that delay gastric emptying may result in the recovery of tablets from which a substantial portion of the drug has already been delivered. Physicians must be prepared to continue to monitor patients for toxic effects after ingesting these drugs.
Accepted for publication March 13, 1999.
Reprints: Karen M. Kreiling, MD, Office of Medical Education, Box 18, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
Thank you for submitting a comment on this article. It will be reviewed by JAMA Pediatrics editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Purchase Online Access to this article for 24 hours
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 2
Customize your page view by dragging & repositioning the boxes below.
and access these and other features:
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.