Which drugs are safe for use in pregnant mares?
My pregnant mare is colicking … can I give her Banamine? She needs a laceration sutured … is it safe for her to get a sedative? What about her fall vaccines?
Which common drugs and medications are safe for use in pregnant mares is a huge topic with more questions than answers, says Margo Macpherson, DVM, MS, Dipl. ACT, professor of large animal reproduction at the University of Florida’s College of Veterinary Medicine, in Gainesville. This is primarily because very few drugs have been thoroughly evaluated and validated for use in this population.
“There is much we don’t know about drug safety in pregnant mares,” she says. “Safety studies are usually done in geldings rather than pregnant mares, and we can’t always extrapolate. Mainly all we have is anecdotal use that suggests the majority of commonly used drugs are relatively safe for use in pregnant mares.”
Why Does it Matter?
Pregnancy changes everything. Physiologic changes in the mare during pregnancy are enormous, says Macpherson, but little published information about them exists.
“Cardiac output is increased by about two-thirds,” she says. “The way blood flow is directed in the body, the way the kidneys operate (which is very different than in the nonpregnant female), etc., are all affected by pregnancy. There is a huge increase in fluid volume in pregnant women and pregnant animals.
“These changes all affect how drugs are distributed in the body and what the body does with them and the way they are cleared from the body,” she continues. “There are a number of metabolic pathways that these drugs undergo. Our database of information about some of the metabolic pathways and the way the drugs are handled in the liver and kidneys is very limited. We don’t know enough about some of the pharmacodynamics (effects and mechanism of action) of the drugs.”
Knowing so little about the physiologic changes mares go through during pregnancy affects veterinarians’ ability to not only predict certain drugs’ impact but also make proper dosing decisions.
Women and Mares Are Different
Veterinarians often look at human drug safety data when trying to determine if they should be concerned about using a drug in pregnant mares, says Peter Sheerin, DVM, of Nandi Veterinary Associates, in New Freedom, Pennsylvania. This is mainly due to the time, expense, and challenges associated with studying medications in broodmares.
“One issue with doing that, however, is that placentation (placental formation) in the human and horse is not the same, so the things that can cross the placenta and affect the fetus can be different,” he says.
Jennifer Linton, VMD, Dipl. ACT, assistant professor of clinical studies at the University of Pennsylvania School of Veterinary Medicine’s New Bolton Center, in Kennett Square, agrees that there are major differences between horse and human pregnancies: “The human has only three layers of tissue between the maternal bloodstream and the fetal bloodstream, so it’s easy for anything in the maternal bloodstream (bacteria, chemicals, etc.) to cross into the fetal bloodstream, whereas in the horse there are six layers,” she says. “The fetus is better protected in the horse.”
FDA Guidelines for Drug Use in Pregnant Women Categorized by Risk, as Adapted for Mares
|Category||FDA Definition||Examples of Equine Drugs|
|Category A||Adequate and well-controlled studies have failed to demonstrate risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters)||N/A|
|Category B||Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women||Azithromycin, erythromycin, penicillins, cephalosporins, metronidazole, amphotericin B, omeprazole, cimetidine, ranitidine|
|Category C||Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant the use of the drug in pregnant women despite potential risks||Clarithromycin, imipenem, gentamicin, fluoroquinolones, trimethoprim sulfadiazine, rifampin, fluconazole, itraconazole, ketoconazole, some non-steroidal anti-inflammatories (NSAIDs), butorphanol, dexamethasone, prednisolone, fluticasone, albuterol|
|Category D||There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant the use of the drug in pregnant women despite potential risks||Tetracyclines, aminoglycosides (except gentamicin), some NSAIDs, angiotensin-converting-enzyme inhibitors, diazepam, phenobarbital|
|Category E||Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits||Misoprostol|
To Administer or Not To Administer?
Safety data for commonly used equine drugs in pregnant mares is basically nonexistent. “The concerns when administering a drug to a pregnant mare are the risks to the developing fetus and risks to the mare,” says Macpherson. “The fetus is particularly at risk, given its poor ability to metabolize and eliminate most foreign compounds.”
So when deciding whether to give a pregnant mare a certain drug, first consider whether she really needs it. “The second thing is that you can’t have a successful pregnancy and a live baby if you can’t keep the mare alive,” says Linton.
“For instance,” she says, “one group of antibiotics called tetracyclines (oxytetracycline, doxycycline, minocycline, etc.) is often used to treat Lyme disease, anaplasmosis, and Potomac horse fever. Anaplasmosis and Potomac horse fever cause high fevers and can make the mare very sick. Without appropriate treatment she might lose the pregnancy and possibly her life. We know tetracycline can damage … fetal bones. If the mare may die or lose the pregnancy from being sick, however, we use tetracycline and gamble on how it might affect the fetus.”
Let’s look at specific drug classes and how they might affect the mare and fetus.
Based on what research has been done in pregnant mares, we know some antibiotics cross the placenta and some don’t. “A lot of the first studies showing which ones do cross the placenta were done in research with placentitis (inflammation of the placenta),” says Sheerin, who notes that you need an antibiotic that will cross the placenta and address the infection causing the inflammation in such cases.
“But one thing to remember is that in mares with placentitis, the placenta is abnormal; effects of the antibiotic might be different than in a normal pregnancy,” he adds. “There is still a lot we don’t know.”
Antibiotics Linton says veterinarians have used without significant side effects in pregnant mares, particularly to treat placentitis, include sulfas or trimethoprim/sulfa combinations.
Macpherson, who’s done much of the research on these drugs in mares, agrees that these antibiotics, along with penicillin and gentamicin, “pass through the placenta and attain therapeutic concentrations for a period of time in the allantois fluid surrounding the fetus.”
Antibiotics that do not pass through the placenta well, say Macpherson, include ceftiofur sodium and ceftiofur crystalline free acid. Based on her research (TheHorse.com/111282), they produce almost undetectable concentrations in fetal fluids and fetal tissues and, thus, aren’t good treatment choices for placentitis.
“The ceftiofur drugs are still useful for treating conditions other than placentitis in pregnant mares,” she says, “as the pharmacokinetic profiles are not significantly altered in pregnancy.”
Other researchers are looking at the effects of the antibiotic enrofloxacin, which appears to have similar effects as gentamicin but isn’t as harsh on the kidneys, says Linton.
Many owners wonder whether sedation is safe for pregnant mares. “The common sedatives used in horses are α2 agonists (xylazine and detomidine),” says Linton. “Many people also use acepromazine, which is more of a calming agent (tranquilizer) than a sedative.”
While none of these are labeled for use in pregnant mares, she says they typically don’t cause serious side effects. Still, ask yourself why you are giving sedation and if it’s necessary. If it makes the mare more comfortable to have a laceration sutured, says Linton, you might want to use it. If it’s just to keep her calm because she doesn’t like being confined to a stall, come up with a medication-free way to keep her happy.
The downside to sedatives and tranquilizers are they can potentially affect the mare’s blood pressure and, therefore, blood flow to the fetus, says Sheerin. However, “used in moderation, they are probably fairly safe,” he says. “A one-time dose of the drugs we typically use for sedation or tranquilization would probably not cause a problem.”
Anesthesia—if your mare needs colic surgery, for instance—might be riskier. It can potentially decrease cardiac output, depress arterial pressures, and cause respiratory depression. If general anesthesia must be performed on a pregnant mare, researchers believe the safest window is Days 40-220 of gestation (TheHorse.com/156897).
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
The NSAIDs, including phenylbutazone (Bute), flunixin meglumine (Banamine), and firocoxib (Equioxx), also aren’t labeled for use in pregnant mares, but veterinarians often administer them in moderation without issue, says Sheerin. He says one conservative dose might be safe (if your pregnant mare is colicky, for instance, you can probably safely give her a dose of Banamine), whereas chronic administration might cause kidney problems or endanger the fetus.
There’s little research backing these drugs’ use in broodmares. “We have looked at flunixin meglumine and didn’t see whether or not it passed the placenta,” says Macpherson. “It may have been because the system we were using to measure it prevented it from passing, but we don’t know—we couldn’t detect it in fetal fluids.”
Other Colic Medications
Sheerin advises against administering more than one moderate dose of the anti-spasmodic and anti-cholinergic (blocks parasympathetic nerve signals) drug N-butylscopolammonium bromide (Buscopan) off-label to pregnant mares to treat spasmodic and gas colic. “The fear is that it might relax the cervix,” he says.
Steroids—both endogenous (produced naturally by the mare) and exogenous (administered by a human)—can affect the fetus. Examples of endogenous steroids include testosterone and progesterone.
Some breeders administer the progestin altrenogest (e.g., Regu-Mate) to mares in early pregnancy to prevent pregnancy loss associated with placentitis or low progesterone levels. The theory is it causes the cervix to remain closed and the uterus firm. While many veterinarians consider it safe for use in at-risk mares (e.g., those with a history of repeated pregnancy loss), they don’t advocate for its use in healthy pregnant mares.
“It is commonly used as a supplement for progesterone during pregnancy but may alter the local immune system and result in a decreased immune response in the mare,” says Linton.
Other exogenous steroids include those administered in joint injections, to treat hives or other allergic responses, or to treat shock. “They’re the best anti-inflammatory we have,” says Linton. “Yet steroids can also trigger labor, because labor is stimulated by a big steroid release from the fetus when it’s ready to be born.”
If you’re considering having your veterinarian inject your pregnant mare’s joints, first ask yourself if she really needs it. “If she has hock arthritis and is so uncomfortable she won’t lie down, and she’s really lame, we might decide that giving her a hock injection would improve her overall clinical condition enough that it would be better for the fetus,” says Linton. “On the other hand, if you are simply routinely giving hock injections every six months, you might hold off on those while she is pregnant.”
A small amount of steroid injected into a joint might be less likely to cause systemic issues and affect the fetus than steroids given systemically, however, because less would enter the bloodstream.
Sheerin says veterinarians have administered ophthalmic ointments containing low doses of corticosteroids for multiple days without much adverse effect.
One risk when giving steroids, however, is the potential for developing laminitis, says Linton. “If a pregnant mare has something similar to gestational diabetes, she is already at risk for developing laminitis,” she says. “A low dose of steroids that ordinarily would not cause laminitis could push her over that edge.”
Taking these factors and more into consideration, your veterinarian will weigh steroid administration in the pregnant mare on a case-by-case basis.
Most dewormers are labeled as safe for use in pregnant mares at the appropriate dose. An overdose of praziquantel or ivermectin (both safe for broodmares), says Linton, can be toxic, but typically only in very high doses—more than 10 times the weight dose of ivermectin, for instance.
“With dewormers, the biggest thing is to read labels,” says Sheerin, noting that even with those approved for use in pregnant mares, many vets warn against giving them within 30 days of foaling and advise waiting until after the mare foals.
If you have a good parasite control program, trying to keep the environment relatively free of parasite eggs, doing fecal egg counts, and deworming horses as needed, the mare might not need to be dewormed while pregnant. “You can probably wait until after she foals and have a strategy and management plan to help avoid having to give dewormers frequently,” says Sheerin.
Other drugs given to pregnant mares include anti-ulcer medications such as omeprazole (e.g., GastroGard), even though the label says safety for use in pregnant mares has not been determined. In the absence of data during pregnancy and lactation, veterinarians warn against administering GastroGard in pregnant and lactating mares, says Sheerin.
“Anti-ulcer medications have not been shown to have negative effects in the fetus, but should only be used when gastric ulcers have been definitively diagnosed by a veterinarian,” Linton says.
One drug that is safe is the dopamine antagonist domperidone, labeled to prevent fescue toxicosis in pregnant mares. Ingesting tall fescue infected with endophyte—a fungus that produces harmful alkaloids—is toxic to pregnant mares, particularly in the third trimester. If a mare can’t be removed from an affected pasture in late pregnancy, veterinarians might prescribe domperidone to block the toxin.
Giving medications to pregnant mares is never without risk and should always be discussed with your veterinarian.
“Even then, owners can’t expect their veterinarian to have a wealth of information on this topic because we don’t have that much data,” says Macpherson.
Horse owners and vets try to make the best decisions possible—in the interest of the mare and foal’s health—with the information available, but there is still a lot of research to be done. When in doubt, consider with your vet whether your mare really needs a certain medication.