Australian Drug Categories

From Embryology

Introduction

Therapeutic Goods Administration logo.

Legal drugs are classified, usually by each country's appropriate regulatory body, on the safety of drugs during pregnancy. In Australia, the Therapeutic Goods Authority (TGA) has classes (A, B1, B2, B3, C, D and X) to define legal drugs safety.

The Australian categorisation system differs from the US FDA categorisation. The categorisation of medicines for use in pregnancy does not follow a hierarchical structure.

  • Human data are lacking or inadequate for drugs in the B1, B2 and B3 categories
  • Subcategorisation of the B category is based on animal data
  • The allocation of a B category does not imply greater safety than a C category
  • Medicines in category D are not absolutely contraindicated during pregnancy (e.g.anticonvulsants)


The original Australian Drug Evaluation Committee (ADEC) formed in 1963 was replaced in 2010 by the Advisory Committee on Prescription Medicines (ACPM).


In the USA, drugs are classified by the Food and Drug Administration (FDA) into classes (A, B, C, D, and X) to define their safety. (More? USA Drug Categories)

The drug examples given on this current page are not a comprehensive list within the drug classification, and are derived from Prescribing medicines in pregnancy.[1]


This page also includes a brief generic description of current drug testing procedures.


Links: Australian Drug Categories | USA Drug Categories | Human Abnormal Development | Medicine BGD2 Tutorial - Applied Embryology and Teratology


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Pregnancy Category

Australian Drug Categories 
Legal drugs are classified, usually by each country's appropriate regulatory body, on the safety of drugs during pregnancy. In Australia, the Therapeutic Goods Authority has classes (A, B1, B2, B3, C, D and X) to define their safety. In the USA, drugs are classified by the Food and Drug Administration (FDA) into classes (A, B, C, D, and X) to define their safety. (More? Australian Drug Categories)


  • Pregnancy Category A - Have been taken by a large number of pregnant women and women of childbearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
  • Pregnancy Category B1 - Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.
  • Pregnancy Category B2 - Have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
  • Pregnancy Category B3 - Have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
  • Pregnancy Category C - Have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible.
  • Pregnancy Category D - Have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects.
  • Pregnancy Category X - Have such a high risk of causing permanent damage to the fetus that they should NOT be used in pregnancy or when there is a possibility of pregnancy.

Abnormal Development - Drugs

Pregnancy Category A

Have been taken by a large number of pregnant women and women of childbearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

Pregnancy Category B1

Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

Pregnancy Category B2

Have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.

Pregnancy Category B3

Have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

Pregnancy Category C

Have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible.

Pregnancy Category D

Have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects.

Examples: Angiotensin converting enzyme (ACE) inhibitors (captopril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril), Angiotensin II receptor antagonists (ARAs) (candesartan cilexetil, eprosartan, irbesartan, losartan, valsartan), Anticonvulsants / Antiepileptics (carbamazepine, phenytoin sodium, methylphenobarbitone, phenobarbitone, primidone, sodium valproate (valproic acid), lamotrigine, ethosuximide, methsuximide, phensuximide, sulthiame, vigabatrin), Antirheumatoid agents (hydroxychloroquine), Muscle relaxants (quinine), Endocrine system (estrogens conjugated, Dydrogesterone, hydroxyprogesterone, megestrol, norethisterone, Fluoxymesterone, methenolone, nandrolone, oxandrolone, oxymetholone, testosterone, Nafarelin, goserelin, Aminoglutethimide, Danazol, Gestrinone), Antimicrobials (Tetracyclines Demeclocycline, doxycycline, minocycline, tetracycline)

Pregnancy Category X

Have such a high risk of causing permanent damage to the fetus that they should NOT be used in pregnancy or when there is a possibility of pregnancy.

Examples: Misoprostol, Dienoestrol, Raloxifene, Finasteride, Ribavirin, Tretinoin (Oral), Isotretinoin, sodium phosphate P32

Prescribing Medicines in Pregnancy Database

The TGA database must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases.


Links: Prescribing Medicines in Pregnancy Database

Drug Testing

Typical testing of new drug compound today involves a lengthy series of animal and human studies.

Animal Studies

Usually tested in at least two mammalian species (rats and guinea pigs) using both single and repeated doses. For determining reproductive effects, tests on both male and female animals with dosing begins 4 weeks prior to mating are conducted to determine effects on fertility in both sexes, on embryogenesis, and on fetal malformation.

Human Clinical Trials

Following animal studies to determine dose, efficacy and apparent safety, human studies can commence. Clinical trials are carried out under very strict conditions, set by international regulatory bodies in agreement with the principles espoused in the Declaration of Helsinki. There are four phases to the trials.

  • Phase I trials - conducted in small groups of 10 to 20 healthy young male volunteers. Designed to examine how the drug is absorbed, distributed, metabolised and excreted by the body and to establish the safe dose for phase II trials.
  • Phase II trials - conducted in 50 to 100 patients with the disease rather than healthy volunteers as in phase I. Designed to examine what effect the drug has on the body (heart rate, blood pressure and cognitive effects) depending on the disease the drug is being developed to treat.
  • Phase III trials - conducted in 100’s of patients (larger numbers) with a particular disease or condition and are generally randomised comparative double-blinded studies. Using a comparator of either placebo, another active drug already used, or both. Several phase III trials are usually required by the regulatory authorities. Note that even these studies may not identify uncommon adverse effects, until used widely in the community.
  • Phase IV trials - (post-registration) conducted in 1000’s of patients over several years, these trials are randomised controlled trials undertaken after the drug has been registered.

Government Regulatory Authorities

After phase I to III the pharmaceutical company compiles all study data for independent assessment by government regulatory authorities in each country:

  • Australia - Therapeutic Goods Administration (TGA)
  • Canada - Health Products and Food Branch (HPFB)
  • New Zealand - Medsafe in New Zealand
  • UK - Medicines & Healthcare products Regulatory Agency (MHRA)
  • USA - FDA


Declaration of Helsinki 
The Declaration of Helsinki was developed by The World Medical Association (WMA) as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data. The Declaration is intended to be read as a whole and each of its constituent paragraphs should not be applied without consideration of all other relevant paragraphs. It is widely regarded as the cornerstone document on human research ethics. It is named after the location of its initial adoption in Helsinki, Finland, in June 1964.

Australia - Advisory Committee on Prescription Medicines

The Australian Drug Evaluation Committee (ADEC) was established in 1963 following the thalidomide experience and in 2010 this committee was replaced by the Advisory Committee on Prescription Medicines (ACPM). The new ACPM advises and makes recommendations to the Therapeutic Goods Administration (TGA) on prescription medicines listed on the Australian Register of Therapeutic Goods (ARTG), established under the Therapeutic Goods Act 1989. There were approximately 54,000 products on the Australian Register of Therapeutic Goods as at 23 May 2008.

Advisory Committee on Prescription Medicines

  • inclusion of a prescription medicine on the Australian Register of Therapeutic Goods (the Register)
  • changes to an entry of a prescription medicine on the Register
  • removal or retention of a prescription medicine on the Register


Links: Advisory Committee on Prescription Medicines


Additional Notes

  1. Many herbal, illegal and recreational drugs do not fall into the above classifications and information about the affects on development can be found in research literature and in medical literature prepared for the general public.
  2. The placenta and fetal tissues may also deal with drugs differently from adult target tissues. In particular, drugs are "cleared", metabolised and excreted, at a different (lower) rate in both the fetus and in newborn infants.

References

Search PubMed: Australian Drug Categories | Drug Categories | teratogenic drugs


External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.


Terms

Drug Terms  
  • adverse reaction - (adverse event) An unwanted effect caused by the administration of drugs. Onset may be sudden or develop over time (See Side Effects).
  • approved drugs - In the U.S., the Food and Drug Administration (FDA) must approve a substance as a drug before it can be marketed. The approval process involves several steps including pre-clinical laboratory and animal studies, clinical trials for safety and efficacy, filing of a New Drug Application by the manufacturer of the drug, FDA review of the application, and FDA approval/rejection of application (See Food and Drug Administration).
  • AUC - acronym for Area Under the plasma concentration versus time Curve is an important parameter when determining drug effects, both therapeutic and teratogenic.
  • clinical trial - A research study to answer specific questions about vaccines or new therapies or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people. Trials are in four phases: Phase I tests a new drug or treatment in a small group; Phase II expands the study to a larger group of people; Phase III expands the study to an even larger group of people; and Phase IV takes place after the drug or treatment has been licensed and marketed. (See Phase I, II, III, and IV Trials).
  • cohort - In epidemiology, a group of individuals with some characteristics in common.
  • contraindication - A specific circumstance when the use of certain treatments could be harmful.
  • double-blind study - A clinical trial design in which neither the participating individuals nor the study staff knows which participants are receiving the experimental drug and which are receiving a placebo (or another therapy). Double-blind trials are thought to produce objective results, since the expectations of the doctor and the participant about the experimental drug do not affect the outcome; also called double-masked study. See Blinded Study, Single-Blind Study, and Placebo.
  • drug clearance - measured as the volume of blood or plasma from which a compound is irreversibly removed per unit time.
  • drug distribution - movement of a drug from one location in the body to another, generally by passive diffusion down the concentration gradient.
  • drug-drug interaction - A modification of the effect of a drug when administered with another drug. The effect may be an increase or a decrease in the action of either substance, or it may be an adverse effect that is not normally associated with either drug.
  • drug metabolism - (drug biotransformation)
  • efficacy - Referring to a drug or treatment, the maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed. In the procedure mandated by the FDA, Phase II clinical trials gauge efficacy, and Phase III trials confirm it (See Food and Drug Administration (FDA), Phase II and III Trials).
  • Food and Drug Administration - (FDA) The U.S. Department of Health and Human Services agency responsible for ensuring the safety and effectiveness of all drugs, biologics, vaccines, and medical devices, including those used in the diagnosis, treatment, and prevention of HIV infection, AIDS, and AIDS-related opportunistic infections. The FDA also works with the blood banking industry to safeguard the nation's blood supply. Internet address: http://www.fda.gov/.
  • informed consent - The process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the study to provide information for participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study.
  • oral bioavailability - refers to the percentage of the oral dose of that drug that ends up in the systemic circulation, few drugs have complete oral bioavailability.
  • orphan drugs - An FDA category that refers to medications used to treat diseases and conditions that occur rarely. There is little financial incentive for the pharmaceutical industry to develop medications for these diseases or conditions. Orphan drug status, however, gives a manufacturer specific financial incentives to develop and provide such medications.
  • pharmacokinetics - The processes (in a living organism) of absorption, distribution, metabolism, and excretion of a drug or vaccine.
  • Phase I trials - Initial studies to determine the metabolism and pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness; may include healthy participants and/or patients.
  • Phase II trials - Controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks.
  • Phase III trials - Expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide and adequate basis for physician labeling.
  • Phase IV trials - Post-marketing studies to delineate additional information including the drug's risks, benefits, and optimal use.
  • placebo - A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment's effectiveness. (See Placebo Controlled Study).
  • placebo controlled study - A method of investigation of drugs in which an inactive substance (the placebo) is given to one group of participants, while the drug being tested is given to another group. The results obtained in the two groups are then compared to see if the investigational treatment is more effective in treating the condition.
  • placebo effect - A physical or emotional change, occurring after a substance is taken or administered, that is not the result of any special property of the substance. The change may be beneficial, reflecting the expectations of the participant and, often, the expectations of the person giving the substance.
  • plasma proteins - can bind drugs, acidic drugs bind to albumin, basic drugs bind to lipoproteins or to alpha-1 acid glycoprotein.
  • Preclinical - Refers to the testing of experimental drugs in the test tube or in animals - the testing that occurs before trials in humans may be carried out.
  • side effects - Any undesired actions or effects of a drug or treatment. Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental drugs must be evaluated for both immediate and long-term side effects (See Adverse Reaction).
  • statistical significance - The probability that an event or difference occurred by chance alone. In clinical trials, the level of statistical significance depends on the number of participants studied and the observations made, as well as the magnitude of differences observed.
  • toxicity - An adverse effect produced by a drug that is detrimental to the participant's health. The level of toxicity associated with a drug will vary depending on the condition which the drug is used to treat.
  • treatment IND - Investigational New Drug (IND) application, which is part of the process to get approval from the FDA for marketing a new prescription drug in the U.S. It makes promising new drugs available to desperately ill participants as early in the drug development process as possible. Treatment INDs are made available to participants before general marketing begins, typically during Phase III studies. To be considered for a treatment IND a participant cannot be eligible to be in the definitive clinical trial.
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Cite this page: Hill, M.A. (2018, December 17) Embryology Australian Drug Categories. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Australian_Drug_Categories

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G