Goodman and Gilman Manual of Pharmacology and Therapeutics

Appendix I
Principles of Prescription Order Writing and Patient Compliance


In writing prescriptions, use English (in the U.S.) or the dominant language of the patient. Latin is no longer the international language of medicine, but a number of commonly used abbreviations derive from obsolete Latin usage and persist in prescription writing. Avoid using them.

Some Latin seems firmly embedded in pharmacy practice. “Rx” is said to be an abbreviation for the Latin word recipere, meaning “take” or “take thus,” as a direction to a pharmacist, preceding the physician’s “recipe” for preparing a medication. The abbreviation “Sig” for the Latin Signatura, is used on the prescription to mark the directions for administration of the medication.


In many states in the U.S., healthcare practitioners other than M.D. and D.O. physicians can write prescriptions. Licensed physician’s assistants (P.A.), nurse practitioners, pharmacists, and clinical psychologists can prescribe medications under various circumstances.


The prescription consists of the superscription, the inscription, the subscription, the signa, and the name and signature of the prescriber, all contained on a single form (Figure AI–1).


Figure AI–1 The prescription. The prescription must be accurately and Legibly prepared to identify the patient, the medication to be dispensed, and the mode of drug administration. Avoid abbreviations and Latin; they lead to dispensing errors. Include the therapeutic purpose in the subscription (e.g., “for control of blood pressure”) to prevent errors in dispensing. For example, the use of Losartan for the treatment of hypertension may require 100 mg/day (1.4 mg/kg/day), whereas for treatment of congestive heart failure, the dose of this AngII receptor antagonist generally should not exceed 50 mg/day. Including the therapeutic purpose of the prescription also can assist patients in organizing and understanding their medications. Including the patient’s weight on the prescription can be useful in avoiding dosing errors, particularly when drugs are administered to children.

The superscription includes the date the prescription order is written; the name, address, weight, and age of the patient; and the Rx (Take). The body of the prescription, or inscription, contains the name and amount or strength of the drug to be dispensed, or the name and strength of each ingredient to be compounded.

The subscription is the instruction to the pharmacist, usually consisting of a short sentence such as: “dispense 30 tablets.” The signa or “Sig” is the instruction for the patient as to how to take the prescription, interpreted and transposed onto the prescription label by the pharmacist. In the U.S., prescriptions should always be written in English. Many physicians continue to use Latin abbreviations; e.g., “1 cap tid pc,” will be interpreted by the pharmacist as “take one capsule three times daily after meals.” However, the use of Latin abbreviations for these directions only mystifies the prescription and is discouraged. The pharmacist should always write the label in English (or, as appropriate, in the language of the patient). The use of such abbreviations or symbols is a confounding practice; many serious dispensing errors can be traced to the use of abbreviations.

Avoid the instruction “take as directed.” Such directions assume an understanding on the part of the patient that may not be realized, and are inadequate for the pharmacist, who must determine the intent of the physician before dispensing the medication. The best directions to the patient will include a reminder of the intended purpose of the medication by including such phrases as “for relief of pain” or “to relieve itching.” The correct route of administration is reinforced by the choice of the first word of the directions. For an oral dosage form, the directions should begin with “take” or “give”; for externally applied products, the word “apply”; for suppositories, “insert”; and for eye, ear, or nose drops, “place” is preferable to “instill.”

Include Patient Information and Dosage Calculations. The patient’s name and address are needed on the prescription order to ensure that the correct medication goes to the proper patient and also for identification and recordkeeping. For medications whose dosage involves a calculation, a patient’s pertinent factors, such as weight, age, or body surface area, also should be listed on the prescription; both the calculated dose and the dosage formula used, such as “240 mg every 8 hours (40 mg/kg/day),” should be included to allow another healthcare professional to double-check the prescribed dosage. Pharmacists always should recalculate dosage equations when filling such prescriptions. Medication orders in hospitals and some clinic settings, such as those for antibiotics or antiseizure medications that are sometimes difficult to adequately dose (e.g., phenytoin), can specify the patient diagnosis and desired drug and request dosing by the clinical pharmacist.

Proper Prescribing Practices Can Help to Prevent Adverse Drug Events. The Institute of Medicine (IOM) estimates that the annual number of medical errors in the U.S. resulting in death is between 44,000 and 98,000. Adverse drug events occur in ~3% of hospitalizations. Good practices (Table AI–1) can minimize these adverse drug events.

Table AI–1

Prescribing Practices to Avoid Adverse Drug Events



All prescriptions should be written in ink; this practice is compulsory for schedule II prescriptions under the U.S. Controlled Substances Act (CSA) of 1970. Prescription pad blanks normally are imprinted with a heading that gives the name of the physician and the address and phone number of the practice site (Figure AI–1). When using institutional blanks that do not bear the physician’s information, the physician always should print his or her name and phone number on the face of the prescription to facilitate communication with other healthcare professionals if questions arise. U.S. law requires that prescriptions for controlled substances include the name, address, and Drug Enforcement Administration (DEA) registration number of the physician.

The date of the prescription is an important part of the patient’s medical record, and it can assist the pharmacist in recognizing potential problems. For example, when an opioid is prescribed for pain due to an injury, and the prescription is presented to a pharmacist 2 weeks after issuance, the drug may no longer be indicated. Compliance behavior also can be estimated using the dates when a prescription is filled and refilled. The CSA requires that all orders for controlled substances (Table AI–1) be dated as of, and signed on, the day issued and prohibits filling or refilling orders for substances in schedules III and IV >6 months after their date of issuance. When writing the original prescription, the physician should designate the number of refills allowed. For maintenance medications without abuse potential, it is reasonable to write for a 1-month supply and to mark the prescription form for refills to be dispensed over a period sufficient to supply the patient until the next scheduled visit to the physician. A statement such as “refill prn” (refill as needed) is not appropriate, as it could allow the patient to misuse the medicine or neglect medical appointments. If no refills are desired, “zero” (not “0”) should be written in the refill space to prevent alteration of the prescriber’s intent. Refills for controlled substances are discussed later, in “Refills” under “Controlled Substances.”

Concern about the rising cost of healthcare has favored the dispensing of so-called generic drugs. A drug is called by its generic name (in the U.S., this is the U.S. Adopted Name or USAN) or the manufacturer’s proprietary name, called the trademark, trade name, or brand name. In most U.S. states, pharmacists have the authority to dispense generic drugs rather than brand-name medications. The physician can request that the pharmacist not substitute a generic for a branded medication by indicating this on the prescription (“do not substitute”), although this generally is unnecessary because the U.S. Food and Drug Administration (FDA) requires that generic medications meet the same bioequivalence standards as their brand-name counterparts. In some jurisdictions, prescriptions may not be filled with a generic substitution unless specifically permitted on the prescription. Occasions when substituting generic medications is discouraged are limited to products with specialized release systems and narrow therapeutic indices, or when substantial patient confusion and potential noncompliance may be associated with substitution.


Inappropriate choice of drugs by physicians is a problem in prescribing. Physicians must rely on unbiased sources when seeking drug information that will influence their prescribing habits; use of the original medical literature will ensure instruction of the prescriber’s best judgment. The amount of a drug to be dispensed should be clearly stated and should be only that needed by the patient. Excessive amounts should never be dispensed, because this not only is expensive for the patient but may lead to accumulation of medicines, which can lead to harm to the patient or members of the patient’s family if used inappropriately. Better to require several refills of a prescription than to prescribe and dispense more than necessary at one time.


Prescribers must be aware that patients may visit their doctor to “get” a prescription. Physicians must educate their patients about the importance of viewing medicines as to be used only when really needed and that remaining on a particular medicine when their condition is stable may be preferable to seeking the newest medications available. The Federal Food and Drug Administration Modernization Act of 1997 permits the use of print and television advertising of prescription drugs. The law requires that all drug advertisements contain (among other things) summary information relating to side effects, contraindications, and effectiveness. The benefits of these types of direct-to-consumer (DTC) advertising are controversial. Prescription drug advertising has alerted consumers to the existence of new drugs and the conditions they treat, but it has also increased consumer demand for drugs. This demand has increased the number of prescriptions being dispensed (raising sales revenues) and has contributed to the higher pharmaceutical costs borne by health insurers, government, and consumers. In the face of a growing demand for particular brand-name drugs driven by advertising, physicians and pharmacists must be able to counsel patients effectively and provide them with evidence-based drug information.


In the U.S., the DEA within the Department of Justice is responsible for the enforcement of the federal CSA. The DEA regulates each step of the handling of controlled substances from manufacture to dispensing (21 U.S.C. § 811). The law provides a system that is intended to prevent diversion of controlled substances from legitimate uses. Substances that come under the jurisdiction of the CSA are divided into 5 schedules (Table AI–2); individual states may have additional schedules. Physicians must be authorized to prescribe controlled substances by the jurisdiction in which they are licensed, and they must be registered with the DEA or exempted from registration as defined under the CSA. The number on the certificate of registration must be indicated on all prescription orders for controlled substances. Criminal prosecution and penalties for misuse generally depend on the schedule of a substance and the amount of drug in question.

Table AI–2

Controlled Substance Schedules


State agencies may impose additional regulations, such as requiring that prescriptions for controlled substances be printed on triplicate or state-issued prescription pads or restricting the use of a particular class of drugs for specific indications. Some U.S. states, such as California, have placed marijuana, classified by the FDA as a schedule I substance, in a special category by decriminalizing its possession and sale for medical use. Under California’s medical marijuana laws, patients and caregivers are exempt from prosecution by the state of California, contrary federal law notwithstanding. This legal difference of opinion between state and federal regulation is the source of considerable controversy. Generally, the most stringent law takes precedence, whether it is federal, state, or local.

PRESCRIPTION ORDERS FOR CONTROLLED SUBSTANCES. To be valid, a prescription for a controlled substance must be issued for a legitimate medical purpose by an individual practitioner acting in the usual course of his or her professional practice. An order that does not meet these criteria, is not considered a legitimate prescription within the meaning of the law, and thus does not protect either the physician who issued it or the pharmacist who dispensed it. Most states prohibit physicians from prescribing controlled substances for themselves; it is prudent to comply with this guideline even if it is not mandated by law.

EXECUTION OF THE ORDER. Prescriptions for controlled substances should be dated and signed on the day of their issuance and must bear the full name and address of the patient and the printed name, address, and DEA number of the practitioner and should be signed the way one would sign a legal document. Preprinted orders are not allowed in most states, and pre-signed blanks are prohibited by federal law. When oral orders are not permitted (schedule II), the prescription must be written with ink or typewritten. The order may be prepared by a member of the physician’s staff, but the prescriber is responsible for the signature and any errors that the order may contain.

ORAL ORDERS. Prescriptions for schedule III, IV, and V medications may be telephoned to a pharmacy by a physician in the same manner as a prescription for a noncontrolled substance, although it is in the physician’s best interest to keep his or her DEA number as private as possible (see “Preventing Diversion”). Schedule II prescriptions may be telephoned to a pharmacy only in emergency situations, i.e.:

• Immediate administration is necessary.

• No appropriate alternative treatment is available.

• It is not reasonably possible for the physician to provide a written prescription prior to the dispensing.

For an emergency prescription, the quantity must be limited to the amount adequate to treat the patient during the emergency period, and the physician must have a written prescription delivered to the pharmacy for that emergency within 72 h. If mailed, the prescription must be postmarked within 72 h. The pharmacist must notify the DEA if this prescription is not received.

REFILLS. No prescription order for a schedule II drug may be refilled under any circumstance. For schedule III and IV drugs, refills may be issued either orally or in writing, not to exceed 5 refills or 6 months after the issue date, whichever comes first. Beyond this time, a new prescription must be ordered. For schedule V drugs, there are no restrictions on the number of refills allowed, but if no refills are noted at the time of issuance, a new prescription must be made for additional drug to be dispensed.

PREVENTING DIVERSION. Prescription blanks often are stolen and used to sustain abuse of controlled substances. To prevent this type of diversion, prescription pads should be protected in the same manner as one would protect a personal checkbook. A prescription blank should never be pre-signed for a staff member to fill in at a later time. Also, a minimum number of pads should be stocked, and they should be kept in a locked, secure location. If a pad or prescription is missing, it should be reported immediately to local authorities and pharmacies. Ideally, the physician’s full DEA number should not be pre-printed on the prescription pad, because most prescriptions will not be for controlled substances and will not require the registration number, and anyone in possession of a valid DEA number may find it easier to commit prescription fraud. Some physicians may intentionally omit part or all of their DEA number on a prescription and instead write “pharmacist call to verify” or “call for registration number.” This practice works only when the pharmacist may independently verify the authenticity of the prescription, and patients must fill the prescription during the prescriber’s office hours. Pharmacists can ascertain the authenticity of a physician’s DEA number using an algorithm.

Another method employed by the drug seeker is to alter the face of a valid prescription to increase the number of units or refills. By spelling out the number of units and refills authorized instead of giving numerals, the prescriber essentially removes this option for diversion. Controlled substances should not be prescribed excessively or for prolonged periods, as the continuance of a patient’s addiction is not a legitimate medical purpose.


The U.S. Pharmacopeial Convention, Inc. is a nongovernmental organization that disseminates authoritative standards and information on medicines and other healthcare technologies. This organization is home to the U.S. Pharmacopeia (USP), which, together with the FDA, the pharmaceutical industry, and health professions, establishes authoritative drug standards. These standards are enforceable by the FDA and the governments of other countries and are recognized worldwide. Drug monographs are published in the USP/National Formulary (USP-NF), the official drug standards compendia that organize drugs into categories based on pharmacological actions and therapeutic uses. The USP also provides chemical reference standards to carry out the tests specified in the USP-NF. For example, a drug to be manufactured and labeled in units must comply with the USP standard for units of that compound. Such standards are essential for agents possessing biological activity, such as insulin.

The USP also is home to the USP Dictionary of U.S. Adopted Names (USAN) and International Drug Names. This compendium is recognized throughout the healthcare industry as the authoritative dictionary of drugs. Entries include 1 or more of the following: U.S. Adopted Names, official drug names for the National Formulary (NF), previously used official names, International Nonproprietary Names, British Approved Names, Japanese Accepted Names, trade names, and other synonyms. In addition to names, the records in this file contain other substance information such as Chemical Abstract Service (CAS), registry number (RN), molecular formula, molecular weight, pharmacological and/or therapeutic category, drug sponsor, reference information, and structure diagram, if available. The USP maintains an electronic website that can be accessed for useful drug naming, classification, and standards information (

In the U.S., drug products also are coded under the National Drug Code (NDC). In the U.S., the NDC serves as a universal product identifier for drugs used in humans. The current edition of the National Drug Code Directory is limited to prescription drugs and a few selected over-the-counter products. Each drug product listed under the Federal Food, Drug, and Cosmetic Act is assigned a unique 10-digit, 3-segment number. This number, known as the NDC number, identifies the labeler/vendor, product, and package size. The labeler/vendor code is assigned by the FDA. The second segment, the product code, identifies a specific strength, dosage form, and formulation for a particular drug company. The third segment, the package code, identifies package sizes. Both the product and package codes are assigned by the manufacturer. In addition to classification of drugs by therapeutic category, drugs also are grouped by control schedule. Drug schedules in the U.S. are listed in Table AI–2 and are discussed above under “Controlled Substances.”

The FDA also categorizes drugs that may be used in pregnant women. These categories are similar to those used in other countries and provide guidance based on available science. The categories range from A to X, in increasing order of concern:

Pregnancy Category A: Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters). Because of the obvious nature of the risk associated with the use of medications during gestation, the FDA requires a body of high-quality data on a drug before it can be considered for Pregnancy Category A.

Pregnancy 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, OR animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.

Pregnancy 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 use of the drug in pregnant women despite potential risks.

Pregnancy 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 use of the drug in pregnant women despite potential risks.

Pregnancy Category X: 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.

Physicians should realize that the pregnancy categories by themselves provide little guidance for the physician treating pregnant women. For example, angiotensin-converting enzyme (ACE) inhibitors such as captopril cause developmental toxicity (Category X) only after the first trimester. Physicians’ primary responsibility remains treating the pregnant patient. However, the risks of withholding treatment to the mother because of possible risks to the fetus have to be considered as well.

Drugs also are grouped by their potential for misuse under British and U.N. legal classifications as class A, B, or C. The classes are linked to maximum legal penalties in a descending order of severity, from A to C.


Compliance is the extent to which the patient follows a regimen prescribed by a healthcare professional. The patient is the final and most important determinant of how successful a therapeutic regimen will be and should be engaged as an active participant who has a vested interest in its success. Whatever term is used—compliance, adherence, therapeutic alliance, or concordance—physicians must promote a collaborative interaction between doctor and patient in which each brings an expertise that helps to determine the course of therapy. The patient’s quality-of-life beliefs may differ from the clinician’s therapeutic goals, and the patient will have the last word every time when there is an unresolved conflict.

Hundreds of variables that may influence compliance behavior have been identified. A few of the most frequently cited are discussed here, along with some suggestions for improving compliance, although none provides 100% compliance (Table AI–3).

Table AI–3

Suggestions for Improving Patient Compliance


Noncompliance may be manifest in drug therapy as intentional or accidental errors in dosage or schedule, overuse, underuse, early termination of therapy, or not having a prescription filled; therapeutic failures can result. Noncompliance always should be considered in evaluating potential causes of inconsistent or nonexistent response to therapy. The reported incidence of patient noncompliance usually is in the range of 30-60%; the rate for long-term regimens is c50%.


Patient satisfaction with the physician has a significant impact on compliance behavior. Patients are more likely to follow instructions and recommendations when their expectations for the patient–provider relationship and for their treatment are met. These expectations include not only clinical but also interpersonal competence; thus, cultivating good interpersonal and communication skills is essential.

When deciding on a course of therapy, it can be useful to discuss a patient’s habits and daily routine as well as the therapeutic options with the patient. This information may suggest cues for remembrance. A lack of information about a patient’s lifestyle can lead to situations such as prescribing a medication to be taken with meals 3 times daily for a patient who only eats twice a day or a medication to be taken each morning for a patient who works a night shift and sleeps during the day. Rarely is there only 1 treatment option for a given problem, and it may be better to prescribe an adequate regimen that the patient will follow instead of an ideal regimen that the patient will not. Attempts should be made to resolve collaboratively any conflicts that may hinder compliance.


Patients are more likely to be compliant when they perceive that they are susceptible to the disease, that the disease may have serious negative impact, that the therapy will be effective, and that the benefits outweigh the costs, and when they believe in their own efficacy to execute the therapy. The actual severity of and susceptibility to an illness is not necessarily an issue; rather, the patient’s perception of severity affects compliance. Patients’ beliefs can lead them to deliberately alter their therapy, whether for convenience, for personal experiments, because of a desire to remove themselves from the sick role, as a means to exercise a feeling of control over their situation, or for other reasons. This reinforces the need for excellent communication and a good patient–provider relationship to facilitate the provision of additional or corrective education when the beliefs would suggest poor compliance as an outcome.

Pharmacists have a legal and professional responsibility to offer medication counseling and can educate and support patients by discussing prescribed medications and their use. Because they often see the patient more frequently than does the physician, pharmacists who take the time to inquire about a patient’s therapy can help identify compliance and other problems, educate the patient, and notify the physician as appropriate. Indeed, data from the Asheville Project indicate that a pharmacist-based medication management program provides significant advantages with respect to compliance, health outcomes, and cost.

Elderly patients often face a number of barriers to compliance related to their age: increased forgetfulness and confusion; altered drug disposition and higher sensitivity to some drug effects; decreased social and financial support; decreased dexterity, mobility, or sensory abilities; and the use of a greater number of concurrent medicines (both prescription and over-the-counter) whose attendant toxicities and interactions may cause decreased mental alertness or intolerable side effects. There are drugs known to be inappropriate to prescribe to elderly patients and some that may adversely affect compliance. Despite these obstacles, evidence does not show that elderly patients in general are significantly less compliant than any other age group. Physicians must be careful in choosing medications for the elderly. Pharmacists must pay particular attention to thorough and compassionate counseling for elderly patients and should assist patients in finding practical solutions when problems, such as polypharmacy, are noted.


Increased complexity and duration of therapy are perhaps the best-documented barriers to compliance. The patient for whom multiple drugs are prescribed for a given disease or who has multiple illnesses that require drug therapy will be at higher risk for noncompliance, as will the patient whose disease is chronic. The frequency of dosing of individual medications also can affect compliance behavior. Simplification, whenever possible and appropriate, is desirable.

The effects of the medication can make adherence less likely, as in the case of patients whose medicines cause confusion or other altered mental states. Unpleasant side effects from the medicine may influence compliance in some patients but are not necessarily predictive, especially if patient beliefs or other positive factors tend to reinforce adherence to the regimen. A side effect that is intolerable to one patient may be of minor concern to another. The cost of medicine can be a heavy burden for patients with limited economic resources, and healthcare providers should be sensitive to this fact. Mobile phones and tablets running drug formulary/therapeutic applications can provide the costs of medications, as can physicians who are familiar with the patient’s insurance plan. Mobile phone systems that provide reminders and collect patient response information are being introduced and may become more popular as patients and providers become increasingly tech savvy.


The era of e-prescribing has begun. Computerized prescription ordering eliminates some of the subjective features of prescribing. Thus, if the proper information is entered correctly in the electronic system, medication errors due to illegible handwriting, incorrect dose, incorrect medication for medical condition, and drug interactions can be reduced, because each prescription can be linked to high-quality drug databases that check that the information on the prescription is appropriate for the patient (e.g., age, weight, gender, condition, laboratory values, disease being treated, concurrent medications) and that known warnings and potential problems are brought to the attention of the physician, pharmacist, and patient. Such systems must not be used as a substitute for personal attention to the individual patient by healthcare workers but, rather, as an adjunct measure that ensures safe, high-quality, efficient care.