FDA Classification of Drugs Used in Pregnancy and Its Criteria According to the standards of the U.S. Food and Drug Administration (FDA), the safety of drugs used in pregnancy is categorized into five classes: A, B, C, D, and X. Some drugs are categorized into two different hazard classes, one for commonly used dosages and the other for overdosages. The five classifications are described as follows: FDA-A: No risk to the fetus has been demonstrated in early pregnancy in women with controls (and no evidence of risk in middle and late pregnancy), and the potential harm to the fetus is minimal. FDA-B: No risk to the fetus has been demonstrated in animal reproduction tests, but there is no control group of pregnant women, or side effects (less severe than infertility) have been demonstrated in animal reproduction tests, but there is no certainty of side effects in a control group of women with early pregnancies (and no evidence of risk in mid- or late-term pregnancies). FDA-C: Fetal side effects (teratogenicity or embryonic lethality or other) have been demonstrated in animal studies, but there are no controls in women or no available information in women and animal studies. Drugs are given only when the benefits to the fetus are weighed against the harms. FDA-D: Positive evidence of risk to the human fetus, but despite the harm, a positive benefit to the pregnant woman is required for application (e.g., in cases of life-threatening or severe disease where a safer drug cannot be applied or where the drug is ineffective). FDA-X: The drug has been shown in animal or human studies to cause fetal abnormalities or is known to be dangerous to the fetus based on human experience, is harmful to humans or both, and the risks of the drug to a pregnant woman clearly outweigh any benefits. The drug is contraindicated in women who are or will be pregnant. A brief introduction to each classification of drugs 1, FDA – Class A drugs: Very rarely, vitamins belong to this type of drug, such as various vitamins B, C, etc., but in the normal range of doses of vitamin A is a class A drug, while large doses of vitamin A, a daily dose of 20,000 IU, can be teratogenic, and become a class X drug. 2, FDA – Class B drugs: also not many, commonly used antibiotics are such. Such as all the penicillin family and the vast majority of cephalosporins are B drugs, commonly used ampicillin, cefradine, cefotrizine (cefatrizine, trade name of the bacterium or called ROSFEN) and serious infections with rescue cefotaxime (cefatrizine, trade name of the Fudaxin) and so on is a class B drug. In addition, Zeomicin, Clindamycin, Erythromycin and Furotoxin are also class B drugs. In addition, metronidazole is known to be a treatment for trichomoniasis, but it is also an excellent treatment for anaerobic infections. Although in animal experiments, it can be teratogenic to rodents, but for humans, a large amount of clinical data accumulated over a long period of time has confirmed that the application of early pregnancy does not increase the rate of fetal teratogenicity, so in the FDA classification of drugs in pregnancy metronidazole is placed in Class B. Among antituberculosis drugs, ethambutol is a Class B drug. Among the commonly used antipyretic and analgesic drugs, indomethacin (anti-inflammatory), diclofenac (fitalin), and ibuprofen (fen-phen) are classified as Class B drugs. However, it should be noted that indomethacin may cause arterial stenosis or atresia in the fetus after 32 weeks of gestation, resulting in fetal death. indomethacin should not be taken after 32 weeks of gestation. Among the cardiovascular drugs, digitalis, digoxin, and silymarin C are class B drugs. Prednisone, an adrenocorticotropic hormone, also belongs to class B drugs, which is harmful to the fetus. 3. FDA-C class drugs: more. This class of drugs either has not been introduced for a long enough time or is seldom used in pregnant women, mainly in early pregnancy, whether it will cause damage to the fetus has not been reported, so it is difficult to have a more definite conclusion. To antibiotics quinolones, for example, this class of drugs in animal experiments found that ofloxacin damage to cartilage, in humans there have been reports of more than 6,000 cases of early pregnancy taking the drug, after delivery of the child’s growth period of 6 cases of pain in the legs and so on, but the symptoms disappeared soon after, none of the sequelae, so that the data of the argument, this drug is still safe. However, the clinic still has to wait for more reports to confirm its harmlessness. There are also prospective studies on the safety of such drugs, such as Adam observed 0.1 a lla of pediatric 50 cases, po tartrazine acid 10-815d, dosage; 50mg/(kg-d), clinical observation and X-ray pickup are not abnormal, height has no effect. Another study found that the concentration of drugs in fetal cartilage was higher than fetal plasma drug concentration after PO CIX in pregnant women, although fetal cartilage gross observation and light microscopy pickup were not abnormal, but the ultrastructure of the same pathomorphological changes as animal cartilage, that is, the degeneration of chondrocytes and the loss of matrix. Caution should be exercised in the use of class C drugs, if there is an alternative drug available then the alternative drug is chosen, otherwise after weighing the pros and cons, the rationale for the choice of the drug is explained to the patient or the patient’s family. Take tuberculosis as an example: as commonly used anti-tuberculosis drugs only ethambutol a class B drug, and anti-tuberculosis treatment is often a number of drugs combined treatment, it is necessary to consider the application of p-amino salicylic acid sodium (sodium para-aminosalicylate), isoniazid (isoniazid) and other class C drugs, if the patient is in the early stages of pregnancy and the combination of pulmonary tuberculosis, it should be explained to the patient. The situation. Most of the antiviral drugs belong to category C, such as acyclovir (acyclovir) and zidovudine (zidovudine) for AIDS. Some antiepileptic drugs and tranquilizers such as ethosuximide, felbamate, barbiturates, and pentobarbital. Among the autonomic nervous system drugs, cholinergics and anticholinergics belong to class C. Some of the adrenergics belong to class C, such as epinephrine, ephedrine and dopamine. Methyldopa, prazosin and all commonly used vasodilators, such as phenamphetamine, amlazoline, pentylenetetrazol, belong to class C. Furosemide (tachycardia) and mannitol are class C diuretics. Among the adrenocorticotropic hormone drugs, betamethasone and dexamethasone are class C drugs. 4, FDA-D drugs: Because of the experimental and clinical evidence, the classification of drugs belonging to the D in pregnancy, especially in the early stages of pregnancy as far as possible not to use. In the antibiotic tetracycline family is a typical, tetracycline or oxytetracycline used in pregnancy, the destruction of fetal tooth enamel, to the adult teeth yellow, which is the consequence of the use of tetracycline drugs. Aminoglycosides, such as streptomycin, should not be used in pregnancy as much as possible, as they may damage the eighth pair of cranial nerves and cause hearing loss. As for antineoplastic drugs, almost all of them are class D drugs, take methotrexate (MTX) as an example, in the late 1940s, it was recognized that in leukemia combined with pregnancy application of MTX can occur chorionic villus necrosis and lead to miscarriage, so in the early 1950s, Hertz et al. developed the idea of treating chorionic villous carcinoma with MTX and achieved success, and to this day, MTX has been Nowadays, MTX has been widely used in the treatment of trophoblast-related diseases, such as ectopic pregnancy, placental implantation, etc.; other antitumor drugs, such as cisplatin, 5-fluorouracil, etc., have also joined the ranks. So antitumor drugs are contraindicated in pregnancy. In the central nervous system drugs in the analgesic, small doses of B drugs, large doses of D drugs, especially long-term application of harmful to the fetus, the main manifestation of fetal growth and development as well as addiction to drugs after delivery, restlessness, crying and so on. Many of the antiepileptic drugs are class D drugs, such as paracetamol (primidone), trimethadione (trimethadione), etc. have teratogenic effects, it is important to note that after pregnancy in epileptic patients, the malformation rate of the fetus is higher than that of the general population, and the use of antiepileptic drugs can increase the rate of malformations, especially when several types of antiepileptic drugs are used simultaneously in difficult to control seizures, then it is even more likely to increase the rate of fetal malformations. This is something that needs to be made clear to the patient and family when diagnosing and treating epilepsy in combination with pregnancy. Among the sedative and hypnotic drugs, diazepam (diazepam, valium), chlordiazepoxide (chlordiazepoxide, librium), meprobamate (meprobamate, sleep and pass), and nortriptyline (oxazepam) are class D drugs, which can not be given to pregnant women who have early pregnancy reactions and insomnia in the early stages of pregnancy. Among diuretics, hydrochlorothiazide (hydrochlorothiazide, dihydroclonidine), ethacrynic acid (ethacrynicacid, diuretic acid), and benzylserazine (benzthiazide) are class D drugs and should not be used during pregnancy. As for the antipyretic and analgesic drugs, aspirin, salicylic acid and sodium salicylate are class C drugs when they are used in small doses, but when they are taken in large doses over a long period of time, sometimes they are even addictive, which is unfavorable to the fetus and become class D drugs. In fact, there are thousands of medications available for people to use, and there are B, C, and D drugs in all of them, so people can choose B or C drugs instead of D drugs. FDA Classification of Drugs Used in Pregnancy and Its Criteria According to the standards of the U.S. Food and Drug Administration (FDA), the safety of drugs used in pregnancy is divided into five categories: A, B, C, D, and X. Some drugs have two different levels of risk, one is the level of commonly used dose, and the other is the level of exceedingly used dose. The five classes are described as follows: FDA-A: No risk to the fetus has been demonstrated in early pregnant women with controls (and no evidence of risk in mid- and late-term pregnancies), and possible harm to the fetus is minimal. Kaiyu Zhou, Department of Pediatric Cardiovascular Medicine, West China Second Hospital, Sichuan University, China FDA-B: No risk to the fetus in animal reproduction tests, but no control group of pregnant women, or side effects (less severe than infertility) in animal reproduction tests, but no certainty of side effects in a control group of women with early pregnancies (and no evidence of risk in intermediate or late pregnancies). FDA-C: Fetal side effects (teratogenicity or embryonic lethality or other) have been demonstrated in animal studies, but there are no controls in women or no available information in women and animal studies. Drugs are given only when the benefits to the fetus are weighed against the harms. FDA-D: Positive evidence of risk to the human fetus, but despite the harm, a positive benefit to the pregnant woman is required for application (e.g., in cases of life-threatening or severe disease where a safer drug cannot be applied or where the drug is ineffective). FDA-X: The drug has been shown in animal or human studies to cause fetal abnormalities or is known to be dangerous to the fetus based on human experience, is harmful to humans or both, and the risks of the drug to a pregnant woman clearly outweigh any benefits. The drug is contraindicated in women who are or will be pregnant. A brief introduction to each classification of drugs 1, FDA – Class A drugs: Very rarely, vitamins belong to this type of drug, such as various vitamins B, C, etc., but in the normal range of doses of vitamin A is a class A drug, while large doses of vitamin A, a daily dose of 20,000 IU, can be teratogenic, and become a class X drug. 2, FDA – Class B drugs: also not many, commonly used antibiotics are such. Such as all the penicillin family and the vast majority of cephalosporins are B drugs, commonly used ampicillin, cefradine, cefotrizine (cefatrizine, trade name of the bacterium or called ROSFEN) and serious infections with rescue cefotaxime (cefatrizine, trade name of the Fudaxin) and so on is a class B drug. In addition, Zeomicin, Clindamycin, Erythromycin and Furotoxin are also class B drugs. In addition, metronidazole is known to be a treatment for trichomoniasis, but it is also an excellent treatment for anaerobic infections. Although in animal experiments, it can be teratogenic to rodents, but for humans, a large amount of clinical data accumulated over a long period of time has confirmed that the application of early pregnancy does not increase the rate of fetal teratogenicity, so in the FDA classification of drugs in pregnancy metronidazole is placed in Class B. Among antituberculosis drugs, ethambutol is a Class B drug. Among the commonly used antipyretic and analgesic drugs, indomethacin (anti-inflammatory), diclofenac (fitalin), and ibuprofen (fen-phen) are classified as Class B drugs. However, it should be noted that indomethacin may cause arterial stenosis or atresia in the fetus after 32 weeks of gestation, resulting in fetal death. indomethacin should not be taken after 32 weeks of gestation. Among the cardiovascular drugs, digitalis, digoxin, and silymarin C are class B drugs. Prednisone, an adrenocorticotropic hormone, also belongs to class B drugs, which is harmful to the fetus. 3. FDA-C class drugs: more. This class of drugs either has not been introduced for a long enough time or is seldom used in pregnant women, mainly in early pregnancy, whether it will cause damage to the fetus has not been reported, so it is difficult to have a more definite conclusion. To antibiotics quinolones, for example, this class of drugs in animal experiments found that ofloxacin damage to cartilage, in humans there have been reports of more than 6,000 cases of early pregnancy taking the drug, after delivery of the child’s growth period of 6 cases of pain in the legs and so on, but the symptoms disappeared soon after, none of the sequelae, so that the data of the argument, this drug is still safe. However, the clinic still has to wait for more reports to confirm its harmlessness. There are also prospective studies on the safety of such drugs, such as Adam observed 0.1 a lla of pediatric 50 cases, po tartrazine acid 10-815d, dosage; 50mg/(kg-d), clinical observation and X-ray pickup are not abnormal, height has no effect. Another study found that the concentration of drugs in fetal cartilage was higher than fetal plasma drug concentration after PO CIX in pregnant women, although fetal cartilage gross observation and light microscopy pickup were not abnormal, but the ultrastructure of the same pathomorphological changes as animal cartilage, that is, the degeneration of chondrocytes and the loss of matrix. Caution should be exercised in the use of class C drugs, if there is an alternative drug available then the alternative drug is chosen, otherwise after weighing the pros and cons, the rationale for the choice of the drug is explained to the patient or the patient’s family. Take tuberculosis as an example: as commonly used anti-tuberculosis drugs only ethambutol a class B drug, and anti-tuberculosis treatment is often a number of drugs combined treatment, it is necessary to consider the application of p-amino salicylic acid sodium (sodium para-aminosalicylate), isoniazid (isoniazid) and other class C drugs, if the patient is in the early stages of pregnancy and the combination of pulmonary tuberculosis, it should be explained to the patient. The situation. Most of the antiviral drugs belong to category C, such as acyclovir (acyclovir) and zidovudine (zidovudine) for AIDS. Some antiepileptic drugs and tranquilizers such as ethosuximide, felbamate, barbiturates, and pentobarbital. Among the autonomic nervous system drugs, cholinergics and anticholinergics belong to class C. Some of the adrenergics belong to class C, such as epinephrine, ephedrine and dopamine. Methyldopa, prazosin and all commonly used vasodilators, such as phenamphetamine, amlazoline, pentylenetetrazol, belong to class C. Furosemide (tachycardia) and mannitol are class C diuretics. Among the adrenocorticotropic hormone drugs, betamethasone and dexamethasone are class C drugs. 4, FDA-D drugs: Because of the experimental and clinical evidence, the classification of drugs belonging to the D in pregnancy, especially in the early stages of pregnancy as far as possible not to use. In the antibiotic tetracycline family is a typical, tetracycline or oxytetracycline used in pregnancy, the destruction of fetal tooth enamel, to the adult teeth yellow, which is the consequence of the use of tetracycline drugs. Aminoglycosides, such as streptomycin, should not be used in pregnancy as much as possible, as they may damage the eighth pair of cranial nerves and cause hearing loss. As for antineoplastic drugs, almost all of them are class D drugs, take methotrexate (MTX) as an example, in the late 1940s, it was recognized that in leukemia combined with pregnancy application of MTX can occur chorionic villus necrosis and lead to miscarriage, so in the early 1950s, Hertz et al. developed the idea of treating chorionic villous carcinoma with MTX and achieved success, and to this day, MTX has been Nowadays, MTX has been widely used in the treatment of trophoblast-related diseases, such as ectopic pregnancy, placental implantation, etc.; other antitumor drugs, such as cisplatin, 5-fluorouracil, etc., have also joined the ranks. So antitumor drugs are contraindicated in pregnancy. In the central nervous system drugs in the analgesic, small doses of B drugs, large doses of D drugs, especially long-term application of harmful to the fetus, the main manifestation of fetal growth and development as well as addiction to drugs after delivery, restlessness, crying and so on. Many of the antiepileptic drugs are class D drugs, such as paracetamol (primidone), trimethadione (trimethadione), etc. have teratogenic effects, it is important to note that after pregnancy in epileptic patients, the malformation rate of the fetus is higher than that of the general population, and the use of antiepileptic drugs can increase the rate of malformations, especially when several types of antiepileptic drugs are used simultaneously in difficult to control seizures, then it is even more likely to increase the rate of fetal malformations. This is something that needs to be made clear to the patient and family when diagnosing and treating epilepsy in combination with pregnancy. Among the sedative and hypnotic drugs, diazepam (diazepam, valium), chlordiazepoxide (chlordiazepoxide, librium), meprobamate (meprobamate, sleep and pass), and nortriptyline (oxazepam) are class D drugs, which can not be given to pregnant women who have early pregnancy reactions and insomnia in the early stages of pregnancy. Among diuretics, hydrochlorothiazide (hydrochlorothiazide, dihydroclonidine), ethacrynic acid (ethacrynicacid, diuretic acid), and benzylserazine (benzthiazide) are class D drugs and should not be used during pregnancy. As for the antipyretic and analgesic drugs, aspirin, salicylic acid and sodium salicylate are class C drugs when they are used in small doses, but when they are taken in large doses over a long period of time, sometimes they are even addictive, which is unfavorable to the fetus and become class D drugs. In fact, there are thousands of kinds of drugs available for people to apply, and there are B, C and D drugs in all kinds of drugs, so people can choose B or C drugs instead of D drugs. 5, FDA – X-class drugs: in common use of such drugs is not much, but because of the high rate of teratogenicity, or a great danger to the fetus, pre-pregnancy and pregnancy is prohibited. This is the most famous phthalaminopiperidone (thalidomide, reaction stop), in the late 1950s and early 1960s in Europe, near the allied positions of women in early pregnancy to take this drug to reduce the reaction to pregnancy, and later found that many fetuses are born with a short upper limb, the lower limb is combined with a seal-shaped so called seal-like deformity (sirenomelus), which is recognized in the early period of X drugs. This is a class X drug that has been recognized in earlier times. In the past, the commonly used sex hormone stilbestrol was used to treat preeclampsia in the early 50’s of the last century, and it was found that vaginal adenopathy or clear cell carcinoma of the vagina could occur in the offspring of females between the ages of 6 and 26 years old, and the consequences of this were serious, so it belonged to the X class of drugs. These are two famous cases of drug teratogenesis. Vitamin A can also be teratogenic when taken orally in large doses, which is also a class X drug, and retinoic acid, a derivative of vitamin A, is a kind of drug for treating skin diseases, which is also a class X drug. What is often overlooked is that heavy alcohol consumption, such as heavy drinking in early pregnancy, and the ingestion of large amounts of ethanol, 150 ml or more per day can cause fetal dysplasia or developmental malformations. Therefore, ethanol is categorized by the FDA as category D for small amounts of alcohol consumption and category X for large amounts. In addition, among the sedative drugs, flurazepam and flunitrazepam are classified as class X drugs, and the antitumor drug aminopterin is also classified as class X. In conclusion, the use of ethanol during pregnancy is not only a good choice for the pregnant women, but also a good choice for the pregnant women, as it can cause fetal dysplasia or malformation. In summary, the following points of attention are proposed for the use of drugs in pregnancy: (1) Avoid multiple drug prescriptions and choose A and B drugs as much as possible for the use of drugs in pregnancy. (2) Instead of thinking only about medication, focus on the disease, which can pose more risks to both mother and fetus. (3) Not only drugs can cause teratogenicity, but also various other teratogenic possibilities, which should be carefully explained to the patient when administering drugs. (4) It is important to note that early pregnancy is the stage of differentiation of fetal body parts and organs, drug teratogenesis is likely to occur in this stage, the safety of the use of drugs in the middle and late pregnancy increases, but some drugs, such as ethanol, the harm to the fetus, especially the nervous system, throughout the entire stage of pregnancy. In addition, it should be noted that: before the 28th week of pregnancy, almost all drugs can pass through the placenta to reach the fetus, fertilization of the egg 3 to 8 weeks of the risk of drugs for teratogenicity or kill the embryo to cause miscarriage. 9 weeks into the fetal stage, the risk of drugs is toxicity to injure the function of organs. Therefore, if the mother’s disease to make the fetus infected should be selected safe, the fetus and amniotic fluid drug concentration and the mother close to the drug, in order to achieve the mother and child with the treatment; pregnant women do not casually use over-the-counter medicines, drugs should be taken under the direction of a doctor before use; drugs should be used in the smallest amount of the minimum effective amount of the shortest effective course of treatment, to avoid blindly large doses, long-term use; non-disease needs, try to avoid using drugs in the early stages of pregnancy. In the commonly used drugs in this kind of drug is not much, but because of the high rate of teratogenicity, or on the fetus is very harmful, pre-pregnancy and pregnancy is prohibited. The most famous of these is phthalidomide (thalidomide, reaction stop), in the late 1950s and early 1960s in Europe, near the allied positions of women in early pregnancy to take this drug to reduce the reaction to pregnancy, and later found that many of the fetus was born with a short upper limb, lower limb merger and the seals were called seal-like deformity (sirenomelus), which is recognized in the earlier This is a class X drug that has been recognized in earlier times. In the past, the commonly used sex hormone stilbestrol was used to treat preeclampsia in the early 50’s of the last century, and it was found that vaginal adenopathy or clear cell carcinoma of the vagina could occur in the offspring of females between the ages of 6 and 26 years old, and the consequences of this were serious, so it belonged to the X class of drugs. These are two famous cases of drug teratogenesis. Vitamin A can also be teratogenic when taken orally in large doses, which is also a class X drug, and retinoic acid, a derivative of vitamin A, is a kind of drug for treating skin diseases, which is also a class X drug. What is often overlooked is that heavy alcohol consumption, such as heavy drinking in early pregnancy, and the ingestion of large amounts of ethanol, 150 ml or more per day can cause fetal dysplasia or developmental malformations. Therefore, ethanol is categorized by the FDA as category D for small amounts of alcohol consumption and category X for large amounts. In addition, among the sedative drugs, flurazepam and flunitrazepam are classified as class X drugs, and the antitumor drug aminopterin is also classified as class X. In conclusion, the use of ethanol during pregnancy is not only a good choice for the pregnant women, but also a good choice for the pregnant women, as it can cause fetal dysplasia or malformation. In summary, the following points of attention are proposed for the use of drugs in pregnancy: (1) Avoid multiple drug prescriptions and choose A and B drugs as much as possible for the use of drugs in pregnancy. (2) Instead of thinking only about medication, focus on the disease, which can pose more risks to both mother and fetus. (3) Not only drugs can cause teratogenicity, but also various other teratogenic possibilities, which should be carefully explained to the patient when administering drugs. (4) It is important to note that early pregnancy is the stage of differentiation of fetal body parts and organs, drug teratogenesis is likely to occur in this stage, the safety of the use of drugs in the middle and late pregnancy increases, but some drugs, such as ethanol, the harm to the fetus, especially the nervous system, throughout the entire stage of pregnancy. In addition, it should be noted that: before the 28th week of pregnancy, almost all drugs can pass through the placenta to reach the fetus, fertilization of the egg 3 to 8 weeks of the risk of drugs for teratogenicity or kill the embryo to cause miscarriage. 9 weeks into the fetal stage, the risk of drugs is toxicity to injure the function of organs. Therefore, if the mother’s disease to make the fetus infected should be selected safe, the fetus and amniotic fluid drug concentration and the mother close to the drug, in order to achieve the mother and child with the treatment; pregnant women do not casually use over-the-counter medicines, drugs should be taken under the direction of a doctor before use; drugs should be used in the smallest amount of the minimum effective amount of the shortest effective course of treatment, to avoid blindly large doses, long-term use; non-disease, try to avoid the use of drugs in the early stages of pregnancy.