Drugs with narrow therapeutic index ntidrugs are drugs with small differences between therapeutic and toxic doses. Therapeutic drug monitoring kieran hand consultant pharmacist antiinfectives the objectives of this section are. The related terms therapeutic window or safety window refer to a range of doses which optimize between efficacy and toxicity, achieving the. Understanding the significance of therapeutic index. Therapeutic window an overview sciencedirect topics. Generic drugs are essential in oncology because some anticancer drugs are only available as generics. Therapeutic drug monitoring some drugs have a narrow therapeutic. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. Fda has concluded that tacrolimus is a narrow therapeutic index drug based on the following evidence. Narrow therapeutic index drugs are drugs where small differences in dose or blood concentration may lead to serious therapeutic failures andor adverse drug reactions that are life. Use of generic substitution for drugs with narrow therapeutic index and criticaldose drugs therapeutic index provides information about the existing links between the desired and undesired effect. Here now we are providing our readers a comprehensive list of narrow therapeutic range drugs for reference. Tablet splitting of a narrow therapeutic index drug.
List of narrow therapeutic range drugs aminophylline tablets, er tablets. The lower the ti value, the greater the risk of a lethal dose of that drug. Equivalence and interchangeability of narrow therapeutic index drugs in organ transplantation. To test your ability to monitor serum levels for drugs with a narrow therapeutic index to test your ability to interpret serum level results for drugs with a narrow. Narrow therapeutic index drugs evidence search nice. The therapeutic index of a drug is the ratio of the dose that produces toxicity to the dose that produces a clinically desired or effective response in a population of individuals. Name narrow therapeutic index drugs accession number dbcat003972 description. Therapeutic drug monitoring an overview sciencedirect.
Monitoring narrow therapeutic range drugs if the concentration of narrow therapeutic range drugs increase above the therapeutic concentration window, serious toxicities can result. Generic interchange has become routine in pharmacy practice. Small changes in bioavailability of narrow therapeutic index nti drugs can alter clinical outcomes, raising concern over generic nti substitution. Intraindividual variability can also be related to physiologic factors that affect absorption, distribution, metabolism, or excretion of a drug.
For this reason, very recently, usp monograph was updated to reflect potency limits from 90110% to 95105% 23 in order to ensure that the tablets can adequately provide therapeutic concentrations needed for the patients. List of 3a4 substrates with narrow therapeutic index. Bioequivalence and narrow therapeutic index drugs benet. What is therapeutic index and why is it important for drugs. Antiarrhythmic drugs, flecainide, generic drugs, bioequivalence, narrow therapeutic index, safety introductiongeneral considerations on the therapeutic index the therapeutic index ti.
Dec 14, 2007 interindividual variability can be caused by either pharmacokinetic or pharmacodynamic differences, and may play an important role in brand. The pennsylvania generic substitution law states that an nti drug is not substitutable regardless of. Generic substitution of narrow therapeutic index drugs. Defined as those drugs where small differences in dose or blood concentration may lead to dose and blood concentration dependent, serious therapeutic failures or adverse drug reactions. Narrow therapeutic index nti drugs are defined as those drugs where small differences in dose or blood concentration may lead to dose and blood concentration dependent, serious therapeutic failures or adverse drug reactions. Some drugs have a narrow therapeutic index, which means that there is only a small difference between the minimum effective concentrations and the minimum. Beyond chemotherapy, generic drugs are also extensively used in supportive care. G uys w ith l arge d ongles t otally m ake p erfect i nternet c onnections.
Narrow therapeutic index nti drugs are agents for which small changes in systemic concentration can lead to significant changes in. Yu 0 robert lionberger 2 0 office of pharmaceutical quality, center for drug evaluation and research, u. If the ti is small the difference between the two concentrations is very small, the drug must be dosed carefully and the person receiving the drug should be monitored closely for any signs of drug toxicity. Therapeutic drug monitoring is only required for drugs with a narrow therapeutic index.
Bioequivalence of narrow therapeutic index drugs and immunosuppressives dr. Patterns and predictors of generic narrow therapeutic. Results for narrow therapeutic index drugs 1 40 of 765 sorted by relevance date click export csv or ris to download the entire page or use the checkboxes to select a. Even lesssafe are drugs such as digoxin, a cardiac glycoside. Serious events are those that are persistent, irreversible, slowly reversible, or life. Therapeutic window and the closely related concept, therapeutic index, are sometimes taken into account when determining dosing. Other terms also used include drugs with a narrow therapeutic window, narrow therapeutic range, critical dose drugs or narrow therapeutic ratio. Evaluation of the referencescaled approach and variability comparison criterion wenlei jiang 2 fairouz makhlouf 1 donald j. Other states use a negative formulary approach by creating a list of drugs that are not equivalent to a brandname drug. Pdf drugs with narrow therapeutic index as indicators in the risk. Schuirmann 1 xinyuan zhang 2 nan zheng 2 dale conner 2 lawrence x. This draft guidance, when finalized, will represent the.
Drugs with a low therapeutic index have a narrow margin of safety. A closer look at generic interchangeability in narrow. The proposed bioequivalence limits for narrow therapeutic index drugs of 90. There are low therapeutic index drugs and high therapeutic drugs, represented by ti values of less than 1 to greater than 100. Narrow therapeutic index nti drugs are agents for which small changes in systemic concentration can lead to significant changes in pharmacodynamic response. Jan 23, 2020 these products, including synthroid, are considered narrow therapeutic index drugs. Drug list by therapeutic category cardiovascular drugs 01.
In general, the narrower this margin, the more likely the drug is to produce unwanted side effects. Your doctor will determine the best dose based on your weight and adjust it as needed. In clinical practice, the ti is the range of doses at which a medication appeared to be effective in clinical trials for a median of participants without. The fda defines narrow therapeutic range ntr drug products as containing certain drug substances subject to therapeutic drug concentration or pharmacodynamic monitoring, andor where product labeling indicates a narrow therapeutic range designation. Therapeutic index, margin of safety that exists between the dose of a drug that produces the desired effect and the dose that produces unwanted side effects. Pdf drugs with narrow therapeutic index as indicators in. This is a sample list of nti drugs published by the fda in 1988.
The larger the therapeutic index ti, the safer the drug is. With a narrow therapeutic index drug, if your dose doesnt stay even, you could experience side effects or your underactive thyroid might get worse. Bioequivalence of narrow therapeutic index drugs and. In earlier article we have discussed in details about what is therapeutic index and what is meant by narrow therapeutic index drug. Some drugs are classified as narrow therapeutic index drugs ntis that have such narrow dosing requirements it makes substitution potentially unsafe. Immunosuppressive drugs very soon after the introduction of cyclosporin immunosuppression in transplant recipients in the early 1980s, it became evident that standard dosing regimens were unsafe because of the drug s narrow therapeutic index and variable pharmacokinetics. Drugs having wider therapeutic index are safer in comparison to those having low therapeutic index because minor modification in the dose of such drugs aspirin, acetaminophen will not produce toxic effects. Legal definition of nti in the code of federal register section 320. Interaction with cyp2d6 substrates with a narrow therapeutic index.
Lisinoprilhydrochlorothiazide prinzide, zestoretic 3. The proposed study design and data analysis should provide greater assurance of therapeutic equivalence of narrow therapeutic index drug products. May 20, 2020 a ratio that compares the blood concentration at which a drug becomes toxic and the concentration at which the drug is effective. Pharmacometric approach to define narrow therapeutic.
Generic versions of narrow therapeutic index drugs. Quality and bioequivalence standards for narrow therapeutic index. The need for different bioequivalent standards for drugs with a narrow therapeutic index is recognized by regulatory agencies. Novel bioequivalence approach for narrow therapeutic index. Christoph baumgartel, md, msc, senior scientific expert, riskcoordinationpoint to head of agency, ages austrian medicines and medical devices agency and austrian federal office for safety in health care, traisengasse. Bioequivalence among generic and innovator drug products does not always ensure therapeutic equivalence, especially with regard to nti drugs. Management of narrow therapeutic index drugs springerlink. The aaps journal a bioequivalence approach for generic narrow therapeutic index drugs. There is less than a 2fold difference in median lethal dose ld50 and median effective dose ed50 values, or b. A ratio that compares the blood concentration at which a drug becomes toxic and the concentration at which the drug is effective. Novel bioequivalence approach for narrow therapeutic index drugs. Narrow therapeutic index nti drugs are defined as those drugs where small differences in dose or blood concentration may lead to dose and blood concentration.
Drugs with narrow therapeutic index as indicators in the risk management of hospitalised patients. The international association of therapeutic drug monitoring and clinical toxicology adopted the following definition for drug monitoring. This was only sample list of drugs published by the fda in 1988. Drugs with a high therapeutic index have a wide margin of safety and less danger of producing toxic effects. Therapeutic drug monitoring tdm becomes essential to determine the dose at which a drug will be safe and effective, especially with those with a narrow therapeutic index.
Drugs with a narrow therapeutic index the therapeutic window of a certain drug reflects the concentration range that provides efficacy without unacceptable toxicity. Pharmacometric approach to define narrow therapeutic index. Pennsylvania generic substitution law this information is only to provide guidance on the generic substitution law and narrow therapeutic index nti drugs. Dec 11, 2014 drugs having wider therapeutic index are safer in comparison to those having low therapeutic index because minor modification in the dose of such drugs aspirin, acetaminophen will not produce toxic effects. Quality and bioequivalence standards for narrow therapeutic. Narrow therapeutic index drugs are defined as those drugs where small. Ld50, or median lethal dose, is the dose of drug that causes death in 50% of experimental animals, and ed50, or median effective dose, is the dose that produces a specified effect response in 50% of the population under study. This may result in potentially subtherapeutic or toxic effects, particularly in patients with advanced age, comorbid illness, or those receiving multiple medications. List of narrow therapeutic range drugs in earlier article we have discussed in details about what is therapeutic index and what is meant by narrow therapeutic index drug.
Also, monitoring might be required when the patient is affected by a medical condition that has an adverse effect on the clearance of. Therapeutic index abughazaleh major reference works. The inhibitory effect of a single dose of varubi on cyp2d6 lasts at least 7 days and may last longer. Serious events are those which are persistent, irreversible, slowly reversible, or lifethreatening, possibly resulting. Therapeutic drug monitoring some drugs have a narrow therapeutic index, which means that there is only a small difference between the minimum effective concentrations and the minimum toxic concentrations in the blood. Please still refer to official definition or contact specific drug manufacturer for accurate determination if a drug has a narrow therapeutic index or range. Bioequivalence for narrow therapeutic index drugs springerlink. Drugs with narrow therapeutic index as indicators in the risk. Drug dosage needs to be adjusted according to plasma drug levels because of the small safety range between the effective dose and the lethal dose.
Drugs that have a low therapeutic index need to be used extremely carefully and more often than not, need concentration levels monitored when used. Concerns about this act of faith have been expressed for many years, particularly in the wake of the generic scandals that occurred in 19891990, and especially relative to the drugs with a narrow therapeutic range. The therapeutic index ti is the range of doses at which a medication is effective without unacceptable adverse events. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. For examples nsaids have wider therapeutic index and warfarin has narrow therapeutic index as it has therapeutic index less than two.
Over 75% of filled prescriptions are done so with a generic formulation, which has resulted in significant savings in healthcare costs. Levothyroxine qualifies as an nti drug under this statute which means that pharmacists need to get the documented consent of the prescriber and the patient before switching manufacturers on refills. The therapeutic window refers to the drug dose needed, where there is a pressing need to maintain exposure within a range that is effective and yet avoids undue aes. We surveyed pharmacists to identify their perceptions of generic nti drugs, their frequency of performing generic nti substitution, and predictors of this behavior. The committee must consist of an equal number of members 228 from each board. Aug 26, 2010 levothyroxine is a narrow therapeutic index drug with clinical efficacy dependent even on slight variation in its dose. Jun 18, 2009 the fda defines narrow therapeutic range ntr drug products as containing certain drug substances subject to therapeutic drug concentration or pharmacodynamic monitoring, andor where product labeling indicates a narrow therapeutic range designation.
In everyday practice, children with acute lymphoblastic leukaemia or patients with earlystage breast cancer are treated and cured with generics. To initiate a search enter one or more keywords to search for using the search engine. Therapeutic drug monitoring an overview sciencedirect topics. Bioequivalence approach for narrow therapeutic index drugs, refer to guidance on warfarin sodium. Published studies from 2002 through february 2007 were identified through a medline search of englishlanguage articles, using the mesh terms, drugs, generic, and therapeutic equivalency. Pharmacists should be aware that the narrow therapeutic index drug concept is found in the states product selection law, g. Narrow therapeutic index nti drugs are those drugs where small differences in dose or blood concentration may lead to serious therapeutic failures andor adverse drug reactions that are lifethreatening or result in persistent or significant disability or incapacity. A bioequivalence approach for generic narrow therapeutic. Therefore, the concerns expressed in the paper of y tony yang and. Therefore a relatively small number of drugs approximately 5060 drugs require routine monitoring. Original research drugs with narrow therapeutic index as.
1524 510 164 68 1070 650 132 1243 809 467 651 1109 842 1366 1115 444 288 473 327 502 164 491 362 1465 1205 1484 204 1109 1275 1104 647 73