Dr. Greene’s Answer:
Your concerns are quite valid. At the time of your question, Propulsid and Zantac were two of the most commonly used prescriptions for babies with gastroesophageal reflux – even though neither of them had been approved for this use by the FDA. Later research led to one of one of them gaining approval after being shown to be safe and effective. The other was recalled, after being found to be dangerous.
I’ll answer your question about side effects, discuss other treatment options, and address the important issue of using drugs that have not been approved by the FDA for children. But first a few words about reflux itself.
How do you spell relief?
If you’ve ever experienced heartburn or acid indigestion, you are familiar with the dull, burning ache produced when acid sloshes up out of the stomach into the esophagus. This sloshing is called gastroesophageal reflux.
Babyhood is a time of spit-upping. Since the sphincter at the top of the stomach is often loose, many babies spit up milk out of their mouths or noses. In otherwise healthy, happy babies who are growing well, the spit-up is mostly milk, rather than stomach acid, and nothing needs to be done (except a lot of laundry!).
In some babies, though, the acid makes the lining of the esophagus tender, red, and swollen. They might arch their backs in pain. The acid can also be inhaled into the lungs, irritating their sensitive linings. These children might not gain weight well, or might cry and cry from discomfort. Some might develop a chronic cough, wheezing, hoarse voice, or recurrent pneumonia. A few even stop breathing (apnea) to try to protect their lungs. All of these children deserve some relief from their reflux.
Usually the first place to start is with looking at how the baby is fed. Decreasing the volume and increasing the frequency of feedings is sometimes enough to deal with reflux. If the baby is already drinking from a bottle, thickening the feedings with rice cereal is an option to be discussed with your physician. This can mechanically reduce the amount of milk sloshed back up the esophagus. Some studies suggest that this decreases both spitting up and crying in babies with reflux. However, this does provide extra calories to your baby, and it may also make it harder for your baby to know when he or she has had enough to eat.
Food allergies may also cause reflux. The most common culprits are cow’s milk and soy proteins in formulas. Foods in mother’s diet can also affect breastfeeding babies. Cow’s milk is the most common cause of this, but other foods such as soy, egg, and peanuts could also be a problem. For most babies, I prefer briefly trying to feed the baby without these exposures to see if this solves the reflux problem before trying any medication. I suspect that tobacco, coffee, and caffeine in breastmilk and secondhand smoke in the air also worsen reflux in babies, but I have not seen proof of this.
Because reflux is usually a mechanical problem, and because babies can’t adjust their position as well as you and I can, positioning is an important part of reflux treatment. Sitting usually is the worst position for reflux. Minimizing the use of carriers and swings that keep small babies in a sitting position makes a big difference for some babies. When the baby is awake, carrying the baby upright (especially just after a meal) and encouraging spending time on the tummy are associated with the least reflux for most babies. Babies should not be put to sleep on their tummies, but tummy-time is great for babies when they are awake. Because of the angle of the connection between the esophagus and the stomach, both the upright and “tummy time” positions use the force of gravity to minimize the chances of food and acid refluxing up the esophagus.
A number of medicines have been used to treat reflux.
Antacids come quickly to mind. Although these seem gentle, those available in liquid form today usually rely on magnesium or aluminum. These silvery metals could cause diarrhea or constipation in babies, and their long-term effects are not well understood. If it is absolutely necessary to use one of these, I prefer magnesium to aluminum.
Another class of medicines, called H2RA’s (H2-Receptor Antagonists), decrease acid production in the stomach. Many of them are familiar because of their use in treating reflux or peptic ulcer disease in adults. They do not decrease the reflux itself, but make the sloshed liquid less acidic, and thus less likely to cause irritation. These medicines commonly used in children include cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), and one of the medicines you asked about, ranitidine (Zantac). Tagamet is not approved by the FDA for children under 16 and Axid is not approved by the FDA for children under 12. Pepcid and Zantac are now approved for children, even infants, although they were not at the time of your question. Zantac is a strong drug. It has brought relief to many babies. It is well tolerated by most children. Headaches, sometimes severe, are the most commonly reported side effects in those old enough to describe them. The most serious side effects, heart rhythm abnormalities, can be caused by any medicine in this class – but they are quite rare. Because there has been a lot of experience with these medications, they are usually the first to be used in babies with reflux.
Proton pump inhibiters are a more recent development. They are more powerful at blocking acid production. You might recognize some of the names from television ads. Those commonly used in children include esomeprazole (Nexium – the Purple Pill), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex). Protonix, and Aciphex are not approved by the FDA for use in children. Nexium is not approved by the FDA for use under 12 years. Prevacid and Prilosec are newly approved by the FDA for use in children as young as 1 year old.
Another class of medicines, called prokinetic agents, are supposed to help speed along whatever is in the stomach, and to tighten the valve at the top of the stomach so acid is less likely to slosh up. Propulsid falls into this category, but thankfully is no longer used. It was extremely popular for several years, but when looked at carefully was found to have killed 80 of those taking it. Other prokinetic medicines used in children include bethanechol (Urecholine), metoclopramide (Reglan), and the antibiotic erythromycin. Urecholine has not been approved by the FDA for use in children. Nor has Reglan been approved for use in children. in fact, caution is strongly recommended because of increased risk of neurological side effects in children. Erythromycin has been approved by the FDA for children, but not for treating reflux in them.
You will have noticed that many of these drugs have not been approved by the FDA for use in children. “Safety and effectiveness in children have not been established.” Do they really work? Are they really safe? We really don’t know. Most of what we do know about both drugs has been learned from their use in adults. This does not mean that your physician was wrong to prescribe them. Pediatricians routinely use many drugs which are not FDA approved for a particular use or patient population. Often, this is because the drugs have never been systematically studied in children, not because they are known to be especially dangerous to children.
Of the two unapproved drugs that your physician chose, Zantac went on to be approved after research in children found it to be both safe and effective; Propulsid was recalled after it was found to be dangerous.
As of the time of your question, of the 80 drugs most commonly used to treat newborns and infants, only 5 had been tested and approved for use in children! (American Medical News, June 2, 1997) The situation is now improving, but we still have a long way to go. Because children of each age represent a small market share, because tailoring trials to specific age groups is very expensive, because parents are understandably reluctant to let their children participate in clinical trials, because pharmaceutical companies are reluctant to risk liability for side effects, and because many of us don’t take little children and their needs seriously — our knowledge of the safety and effectiveness of drugs in small children is unconscionably inadequate.
In the current environment, prescribing unapproved drugs is common and often vital. But let’s not settle for the current environment. Let’s encourage the FDA and the pharmaceutical industry to learn more about the effects of commonly used drugs on children.
In the meantime, I would only use these excellent medications if the symptoms from the reflux are severe. Last week a baby I take care of was proven to have episodes of reflux that produced prolonged apnea spells (not breathing) and periods of slow heart rate. For this baby, the benefits of strong medicines clearly outweigh the risks. For most babies, though, the impact of reflux is much less serious
I’ve begun to hear about doctors who prescribe Zantac for almost any fussy baby. This is unwise. While side effects are uncommon, this is a strong drug that alters the normal secretions of the cells of the stomach wall. I agree with thoughtful use of Zantac. It should not be dispensed like candy.
The human body is amazing. Even as we consider the options for treating reflux, your baby is already busy doing the real work. Silently, the muscles mature and coordinate. The great majority of babies with reflux cure themselves, with nothing but a tincture of time and some thoughtful, gentle relief.