A CDER conversation with Sharon Hertz, M.D., Director, Division of Anesthesia, Analgesia, and Addiction Products, Office of New Drugs, Center for Drug Evaluation and Research, FDA.

Thankfully, not many children experience the types of cancer pain, extensive trauma or surgeries that require long-term pain management. However, few pain management products have specific information in their label about their safety and effectiveness in pediatric patients. This even includes several new pain medications that have been approved for use in adults. To manage pain in pediatric patients, physicians often have to rely on their own experience to interpret and translate adult data into dosing information for pediatric patients.

To give health care providers more information on the safe use of drugs in pediatric patients, FDA can use its authority to ask manufacturers of drug products to conduct studies to obtain pediatric-specific information. We requested the manufacturer of the pain management drug OxyContin perform studies evaluating safety and other important information about oxycodone and OxyContin when used in pediatric patients. These studies supported a new pediatric indication for OxyContin in patients 11 to 16 years old, and provided prescribers with helpful information about the use of OxyContin in pediatric patients.

First, what is OxyContin, and how is it different than other drugs in its class?

OxyContin is an extended-release version of the opioid medicine, oxycodone. Opioids are powerful medications that can help manage pain when they are prescribed and used properly. Most oral opioid products are also available as extended-release versions.

As you would expect, immediate-release oxycodone products are usually taken every 4-6 hours, while extended-release oxycodone products are usually taken every 12 hours. So you can imagine that it can be difficult to manage severe pain that lasts for weeks, months or longer, using immediate-release products because patients would need to take the medicine many times during the day and night.

Due to problems with the abuse and misuse of opioid pain medications, we have encouraged drug companies to make extended-release medications more resistant to misuse and abuse. OxyContin is different from most other drugs in its class because it has been reformulated to better resist being crushed or dissolved to discourage abuse by nasal or intravenous (IV) routes.

What is OxyContin used to treat?

In adults, OxyContin is approved for the management of pain that is severe enough to require daily, around-the-clock, long-term opioid treatment. In the U.S., extended-release opioids are used to manage chronic pain in adults; from low back pain to osteoarthritis to cancer-related pain.

FDA recently approved the use of OxyContin in certain pediatric patients 11 years and older. Similar to adults, OxyContin is approved for use in these patients to manage pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate.

The major difference is that all pediatric patients that are considered for pain management with OxyContin should already have been treated with an opioid pain medicine. This way, their health care providers know that these pediatric patients can be treated safely with OxyContin.

What information did FDA need to support the approval of OxyContin for pediatric patients?

There's not a lot of opioid use in children, so when we planned this pediatric program for OxyContin, we had to carefully identify how these drugs were being used and also what information would be useful for prescribers.

But before I get into the program, I’ll back up a step and mention the Best Pharmaceuticals for Children Act (BPCA) of 2002. Among other provisions, this Act provides incentives to drug companies that study medications in pediatric patients. Under BPCA, we issued a Pediatric Written Request to ask the makers of OxyContin to study oxycodone and OxyContin in pediatric patients.

One of these studies evaluated the safety of OxyContin and its pharmacokinetic profile - briefly, how the drug moves through the body - in pediatric patients likely to receive OxyContin from their doctors. Pediatric patients don’t usually have the same kind of chronic pain conditions as adults, so patients in the study were prescribed OxyContin in situations where they were expected to require pain management with an opioid for many weeks - for example, after extensive trauma, or after major spinal surgery or other types of major surgery to correct of birth defects.

The studies supported the addition of a pediatric indication to the OxyContin label for patients 11 to 16 years old, and provided the much-needed data to health care providers.The new study data and resulting pediatric indication for OxyContin give doctors more specific information on how to safely manage pain in their pediatric patients following these types of surgery or traumas.

What is the difference between adult and pediatric approved uses of OxyContin?

Both adults and pediatric patients 11 to 16 years old may be prescribed OxyContin for pain. However, as I mentioned, pediatric patients, unlike adults, must already be responding to, and tolerating a minimum opioid dose equal to at least 20 mg of oxycodone per day before they can be prescribed an equivalent dose of OxyContin.

This way, the doctor knows that their patient tolerates and responds appropriately to opioids and knows the amount of opioid treatment needed to manage the patient’s pain. When appropriate, the doctor can then convert their patient over to an OxyContin dose that is tailored to their individual needs.

So, will OxyContin be given to pediatric patients only in the hospital?

If there's a need for ongoing treatment with an opioid after discharge from the hospital, pediatric patients 11-16 years old can be prescribed OxyContin and their parents and caregivers can get the medication at a pharmacy and administer the medicine as directed at home.

Parents and caregivers should follow all the usual safeguards for storing powerful medications when OxyContin is in their home. Briefly, make sure the medications are stored securely so young children never have direct access and also so that no one else in the household such as older children, siblings, friends, or other visitors have direct access. Also, it is extremely important to safely and properly dispose of unused OxyContin as soon as it is no longer needed. As with all opioid drugs, OxyContin shouldn't be kept casually in the bathroom medicine cabinet; it should always be secured.

Are there any other opioids approved for pediatric uses?

There are not many extended-release, long-acting products specifically approved for pediatric use. Duragesic (fentanyl) and OxyContin are the only extended-release opioid products with FDA-approved labeling regarding pediatric use. There are also some immediate-release opioid medicines that have some pediatric information in their labels.

What are the dangers of extended-release opioids and when should these powerful drugs be used in children?

We are always concerned about the safety of our children, particularly when they are ill and require medications and when they are in pain. OxyContin is not intended to be the first opioid drug used in pediatric patients, but the data show that changing from another opioid drug to OxyContin is safe if done properly.

Children are not treated with opioids very often and usually it's only for a limited period of time with close supervision by health care professionals. In pediatric patients who require opioid treatment to manage pain, extended-release opioids may be a useful alternative because they are taken only once or twice per day rather than every 4 to 6 hours.

Fewer daily doses may free patients for physical therapy appointments, allow them to go home from the hospital sooner, and may help them to sleep through the night without waking up from pain. So from that perspective it's very useful.

Do extended-release opioid drugs have more serious warnings and precautions for children?

The warnings and precautions for pediatric patients are the same as for adults.

It’s very important for the medical team to pay attention to any other medications that may be added to the patient’s treatment regimen. In particular, the team should be careful not to add any medicines that will slow the body’s breakdown of oxycodone, or add to its sedating effects.

When the decision is made to stop the medication, it should be done slowly and carefully to avoid withdrawal symptoms. Conversations between the medical team and parents should take place well in advance of the day when pediatric patients are discharged from the hospital or taken off their medications. Parents and caregivers should be educated about the risks and what to watch for at home – What does it mean if the pediatric patient is asking for more pain medicine? Is the underlying pain the problem or something else? – and bring their concerns to the attention of the care team.

The care of pediatric patients treated with an opioid analgesic has to be properly coordinated by a health care team experienced in opioid treatment. Discussions with parents and the patients are critical. The patients should be able to participate to some extent in the discussion of the benefits, the risks and the rules for how to use the medicine safely and also how to communicate their needs. Really, that’s the same thing we want for adult patients as well.

What was the public health need? Why did FDA take this action?

First, I must stress that this program was not intended to expand or otherwise change the pattern of use of extended-release opioids in pediatric patients. Prior to this action, doctors had to rely on adult clinical data to shape their decision-making in treating pediatric patients. This program was intended to fill a knowledge gap and provide experienced health care practitioners with the specific information they need to use OxyContin safely in pediatric patients.

Who from CDER was involved in the decision to approve the use of OxyContin in children?

As with most regulatory decisions, this was a team effort involving the combined expertise from several fields - there were physicians, clinical pharmacologists, statisticians, ethicists and of course pediatricians and opioid experts. Folks from each discipline provided their knowledge for the study design and review processes.

We worked closely with CDER’s Division of Pediatric and Maternal Health to review the data when it became available and to help us properly label this new indication so that it meets regulatory requirements and the needs of pediatric care providers.

Quite a few of the newer opioid drugs have pediatric studies underway to gather the data that will help prescribers use them safely. I expect that our teams will be working together a lot more in future to make sure that new pediatric pain management options continue to be safe for children in the U.S.

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