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Or, solving by dimensional analysis:
2. How many milliliters of a mixture would provide a patient with a
teaspoonful dose to be taken three times a day for 16 days?
3. How many grams of a drug will be needed to prepare 72 dosage
forms if each is to contain 30 mg?
4. It takes approximately 4 g of ointment to cover an adult patient’s leg.
If a physician prescribes an ointment for a patient with total leg
eczema to be applied twice a day for 1 week, which of the following
product sizes should be dispensed: 15 g, 30 g, or 60 g?
Additional Examples of Calculations of Dose
1. If 0.05 g of a substance is used in preparing 125 tablets, how many
micrograms are represented in each tablet?
Or, solving by dimensional analysis:
2. If a preparation contains 5 g of a drug in 500 mL, how many grams
are contained in each tablespoonful dose?
3. A cough mixture contains 48 mg of hydromorphone hydrochloride in
8 fl. oz. How many milligrams of hydromorphone hydrochloride are
in each 2-teaspoonful dose?
Solving by dimensional analysis:
4. How many milligrams each of hydrocodone bitartrate and
guaifenesin will be contained in each dose of the following
prescription?
5. How many grams of a drug substance are required to make 120 mL of
a solution each teaspoonful of which contains 3 mg of the drug
substance?
Or, solving by dimensional analysis:
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6. A physician ordered 500-mg capsules of tetracycline to be taken twice
a day for 10 days. How many total grams of tetracycline would be
prescribed?
Dosing Options
Low-Dose and High-Dose Therapies
The administration of doses that are much smaller or much larger than the
usual dose of a drug is referred to as low-dose or high-dose therapy,
respectively. This terminology is different in intent from the normal
variation in a standard dose based on a patient’s age, weight, renal
function, or other specific parameter.
The most common example of low-dose therapy is the use of aspirin
in 81-mg amounts (rather than the usual dose of 325 mg) to lower the risk
of heart attack and clot-related stroke. Other examples are low-dose oral
contraceptive use11 and low-dose postmenopausal hormone therapy.
12
High-dose therapy is commonly associated with the
chemotherapeutic treatment of cancer, in which there is an attempt,
through increased dose intensity, to kill tumor cells. Other examples are
the high-dose use of antilipemic statin drugs to reduce death risk of
patients with existing heart disease13 and the high-dose influenza
vaccination of the elderly.
14
Pharmacists must be aware of the use of high-dose therapies while
remaining vigilant in protecting patients against unintended high doses
and consequent drug overdose.
Example Calculations of Low-Dose and HighDose Therapies
1. If a patient is changed from a daily standard-dose postmenopausal
product containing 0.625 mg of conjugated estrogens (CE) to a lowdose formulation containing 0.35 mg CE, how many milligrams less
of CE would the patient take per week?
2. To reduce the inflammation of an optic nerve, a patient is
administered high-dose prednisone, 900 mg/day for 5 days by
intravenous infusion. The usual daily dose of prednisone is 5 to 60
mg/day, depending on the condition being treated. Calculate the
dose that the patient received, as a multiple of the highest usual
daily dose.
Fixed-Dose Combination Products
A variety of prescription and nonprescription products are available
containing two or more therapeutic agents in fixed-dose combinations.
An advantage of combination products is that two or more needed drugs
may be taken in a single dose, which may be more convenient, enhance
compliance, and be less expensive for the patient than taking the same
drugs individually. A disadvantage is the relative inflexibility in dosing
compared with individual drug dosing.
Whether the fixed-dose combination is a liquid (e.g., a syrup) or a
solid (e.g., a tablet) dosage form, when a dose is taken, the component
drugs are taken in a fixed-dose ratio. To provide some options in dosing,
many combinations of prescription drugs are formulated into different
strengths. For example, capsules containing amlodipine and benazepril
HCl (LOTREL), two drugs used in the treatment of hypertension, are
available in strengths of 5 mg/10 mg, 5 mg/20 mg, 10 mg/20 mg, and 10
mg/40 mg. The prescriber can select the desired combination.
Example Calculation Based on Fixed-Dose
Combination Products
Valsartan and hydrochlorothiazide tablets are available separately or in
combination in strengths of 80 mg/12.5 mg, 160 mg/12.5 mg, 160 mg/25
mg, 320 mg/12.5 mg, and 320 mg/25 mg. If a patient was receiving the
lowest-dose combination product and the physician wished to double the
dose of hydrochlorothiazide, what is the option?
The patient was taking a tablet containing 80 mg of valsartan and
12.5 mg of hydrochlorothiazide but now needs 80 mg of valsartan and 25
mg of hydrochlorothiazide. Since this strength is not available in one
tablet, an additional prescription for 12.5 mg of hydrochlorothiazide or
individual prescriptions for 80 mg of valsartan and 25 mg of
hydrochlorothiazide may be written.
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Tablet Splitting and Crushing
A number of tablets are scored, or grooved, to allow breaking into
approximately equal pieces (usually halves). This allows dosage
flexibility, particularly when a patient is started at a half dose and then is
titrated up to a full dosage level. It also enables a patient to take a product
at a strength that is not otherwise available.
Some patients use tablet-splitting devices to cut scored or unscored
tablets for economic reasons. For some medications, the price of tablets
of twice the strength required is similar to that of the lower-strength
tablets, and the patient can double his or her supply by tablet splitting.
Unfortunately, this practice often results in unequal portions of tablets
and thus in uneven doses.
15–18
The federal Food and Drug Administration (FDA) has recommended
that consumers consult with their health care professional before splitting
a tablet to discuss the “splitability” of the product.19 (Some products
should not be split or crushed, but must remain intact for proper effects.)
As a part of its drug approval process, the FDA verifies drug products
that have been shown by testing procedures to be capable of being
effectively split.20,
21
Pharmacists can provide guidance to their patients by (a) verifying
tablets that may be safely split; (b) suggesting that the entire dispensed
supply of tablets not be split at one time but only as needed, because split
tablets may be more affected than whole tablets by factors such as heat
and humidity; and (c) suggesting the best device for tablet splitting,
especially for tablets of unique shape and size.
For tablets that can be crushed without destroying desired absorption
characteristics, tablet crushing is a commonly employed practice for
home or institutional patients who are unable to swallow intact solid
dosage forms. In these instances, mortars and pestles or specially
designed tablet crushers may be used (Fig. 7.6). After crushing, the
resulting particles may be suspended in a beverage or mixed with a
foodstuff such as applesauce or yogurt prior to administration.
FIGURE 7.6 An example of a tablet crusher. A tablet is placed
in a paper cup, covered with a second cup, and then placed in
the crusher. When the handles are gently squeezed, the pressure
reduces the tablet to particles that may then be mixed with food
or drink for administration. The device is used in patient care
facilities and wherever a patient may have difficulty
swallowing whole dosage units. (Courtesy of Creative Living
Medical, Brainerd, MN.)
Example Calculation Based on Tablet Splitting
A patient attempted to split in half 20-mg unscored tablets of a drug,
resulting in “half tablets” differing by 1.5 mg in drug content. Assuming
that a whole tablet was uniform in drug content, calculate the amount of
drug in each “half tablet.”
If L = larger “half” and S = smaller “half,”
then L + S = 20 mg and L – S = 1.5 mg
We can add these two equations as shown in the following:
L = 21.5 mg/2 = 10.75 mg
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S = 20 mg − 10.75 mg = 9.25 mg
Proof: 10.75 mg − 9.25 mg = 1.5 mg difference in drug content and
10.75 mg + 9.25 mg = 20 mg total drug content
Special Dosing Regimens
Certain drugs have unique dosing regimens. Among them are
chemotherapeutic agents (discussed in Chapter 8) and oral contraceptives.
In the case of the latter, the prescribed regimen is based on a 28-day
dosing cycle of 21 consecutive days of tablets containing a combination
of estrogen and progestin drugs followed by 7 consecutive days of tablets
containing nondrug material. One tablet is taken daily, preferably at
approximately the same time each day. The tablets generally are colorcoded and packaged in special dispensers to facilitate compliance.
Another example of a drug having a special dosing regimen is
methylprednisolone, as prescribed in dose packs containing 21 tablets of
4 mg each. The tablets are taken in descending dosage over a 6-day
period in the treatment of responsive allergic and inflammatory
conditions such as contact dermatitis. In this regimen, 6 tablets are taken
during the first day with 1 fewer tablet being taken each day thereafter.
Example Calculation Based on Special Dosing
Regimen
The ORTHO TRI-CYCLEN LO 28-day regimen consists of norgestimate
(N), ethinyl estradiol (EE), and nonmedicated tablets as follows:
7 white tablets containing 0.18 mg (N) + 0.025 mg (EE)
7 light blue tablets containing 0.215 mg (N) + 0.025 mg (EE)
7 dark blue tablets containing 0.25 mg (N) + 0.025 mg (EE)
7 green tablets containing 0 mg (N) + 0 mg (EE)
How many milligrams each of norgestimate and ethinyl estradiol are
taken during each 28-day cycle?
1.
2.
3.
4.
5.
PRACTICE PROBLEMS
Doses: Solid Dosage Forms
The ascending dose schedule of ropinirole (REQUIP) in the
treatment of Parkinson’s disease is:
Week 1: 0.25 mg three times a day
Week 2: 0.5 mg three times a day
Week 3: 0.75 mg three times a day
Week 4: 1 mg three times a day
How many 0.25-mg tablets would provide the 4 weeks of
treatment?
The following regimen for oral prednisone is prescribed for a
patient: 50 mg/day × 10 days; 25 mg/day × 10 days; 12.5 mg/day ×
10 days; and 5 mg/day × 10 weeks. How many scored 25-mg
tablets and how many 5-mg tablets should be dispensed to meet the
dosing requirements?
A physician reduces a patient’s once-daily dose of conjugated
estrogen (PREMARIN) from tablets containing 0.625 mg to tablets
containing 0.45 mg. What is the total reduction in conjugated
estrogens taken, in milligrams, during a 30-day month?
A fixed-dose combination product contains amlodipine besylate
and atorvastatin calcium (CADUET) for the treatment of both
hypertension and hypercholesterolemia. If a physician starts a
patient on a 5-mg/10-mg dose for 14 days and then raises the dose
to 10 mg/20 mg, how many milligrams of each drug will the patient
take during the first 30 days?
A patient cuts 100-mg scored tablets to take his 50-mg prescribed
daily dose. A prescription for thirty 100-mg tablets costs $45, and a
prescription for thirty 50-mg tablets costs $40. The patient asked
the pharmacist to weigh an uncut tablet on an electronic balance
into two “halves.” The uncut tablet was found to weigh 240 mg,
and the cut “halves” weighed 125 mg and 115 mg, respectively. (a)
How much money did the patient save on a monthly basis by
dosing with half tablets? (b) What was the percentage error in the
weight of the cut tablets compared with “exact halves”?
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6.
7.
8.
9.
The recommended dose of memantine HCl (NAMENDA) is:
Week 1, 5 mg/day
Week 2, 10 mg/day (5 mg b.i.d.)
Week 3, 15 mg/day (10 mg a.m., 5 mg p.m.)
Week 4, 20 mg/day (10 mg b.i.d.)
How many 5-mg tablets must be dispensed for a 4-week supply of
the medication?
Prior to a colonoscopy, a patient is instructed to take OSMOPREP
tablets, each of which contains 1.102 g sodium phosphate
monobasic monohydrate and 0.398 g sodium phosphate dibasic
anhydrous. The dose is:
The evening before the procedure: 4 tablets with 8 ounces of clear
liquids every 15 minutes for 5 cycles
Starting 3 hours before the procedure: 4 tablets with 8 ounces of clear
liquids every 15 minutes for 3 cycles
How many tablets, how much liquid, and how much total sodium
phosphates are taken?
a. 8 tablets, 16 ounces liquid, 2 g sodium phosphates
b. 16 tablets, 1000 mL liquid, 32 g sodium phosphates
c. 32 tablets, 1 quart liquid, 40 g sodium phosphates
d. 32 tablets, 0.5 gallon liquid, 48 g sodium phosphates
Varenicline tartrate (CHANTIX), for smoking cessation, is
available in two strengths, 0.5-mg and 1-mg tablets. The dose is:
Days 1 to 3: 0.5 mg once daily
Days 4 to 7: 0.5 mg twice daily (AM and PM)
Days 8 to end of treatment: 1 mg twice daily (AM and PM)
The treatment period is 12 weeks. How many 0.5-mg tablets and 1-mg
tablets should be dispensed?
a. 7 0.5-mg tablets and 11 1-mg tablets
b. 8 0.5-mg tablets and 84 1-mg tablets
c. 10 0.5-mg tablets and 84 1-mg tablets
d. 11 0.5-mg tablets and 154 1-mg tablets
Doses: Drops
A ciprofloxacin otic solution contains 0.5 mg of ciprofloxacin in a
0.25-mL single-use package. Based on 20 drops/mL, (a) how many
11.
12.
13.
14.
15.
16.
17.
drops would be administered to provide a 0.25-mL dose and (b)
how many micrograms of ciprofloxacin would be in each drop?
a. If acetaminophen oral drops contain 1.5 g of acetaminophen
per 15-mL container, how many milligrams are there in each
prescribed dose?
b. If the dropper is calibrated to deliver 22 drops/mL, how many
drops should be administered per dose?
RESTASIS ophthalmic emulsion contains 0.05% w/v cyclosporine.
If a dose of one drop measures 28 μL, how many micrograms of
cyclosporine are present?
The oral dose of a drug is 2.5 mg. If a solution contains 0.5% w/v
of the drug in a dropper bottle that delivers 12 drops/mL, how
many drops would supply the dose?
22
Infants’ MYLICON antigas drops contain 2 g of simethicone in a
30-mL container. (a) How many milligrams of simethicone are
contained in each 0.3-mL dose? And if 12 doses per day are not to
be exceeded, calculate the corresponding 12-dose (b) volume and
(c) simethicone content.
Doses: Oral Liquids
Guaifenesin solution contains 9.46 g of guaifenesin in each 473-
mL bottle of liquid. How many milligrams of guaifenesin would
there be in 2.5 mL delivered by oral dispenser?
If a liquid medicine is to be taken three times daily, and if 180 mL
are to be taken in 4 days, how many tablespoonfuls should be
prescribed for each dose?
A pediatric patient is prescribed 40 mg of prednisolone per day in
two divided doses. How many divided doses are available in 6
fl.oz. of oral solution containing prednisolone 20 mg/5 mL
dispensed to this patient?
The dose of posaconazole in the treatment of oropharyngeal
candidiasis is 100 mg twice a day on the first day and then 100 mg
once a day for the next 13 days. Posaconazole oral suspension
(posaconazole, 40 mg/mL) is available in 4-fluidounce bottles.
How many bottles should be dispensed to meet the dosing
requirements?
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