T he term chemotherapy applies to the treatment o disease with chemical drugs or che- mother apeutic agents. Chemotherapy is primarily associated with the treatment o cancer patients and is considered the mainstay o such treatment in that it is e ective in widespread
8 • c al ula on of Do : Pa n Param r 143 or metastatic cancer, whereas treatments such as surgery and radiation therapy are limited to speci c body sites. Chemotherapeutic agents most o ten are administered orally, by intra- venous injection, or by continuous intravenous in usion.
Although a single anticancer drug may be used in a patient’s treatment plan, com- bination chemotherapy perhaps is more usual. By using combinations o drugs having di erent mechanisms o action against the target cancer cells, the e ectiveness o treat- ment may be enhanced, lower doses used, and side e ects reduced. T he combination chemotherapy plans o ten include two-agent regimens, three-agent regimens, and four- agent regimens.7–11
Cancer chemotherapy is unique in the ollowing ways:
• It may involve single or multiple drugs o well-established drug therapy regimens or protocols, or it may involve the use o investigational drugs as a part o a clinical trial.
• Combinations o drugs may be given by the same or di erent routes o administra- tion, most o ten oral and/or intravenous.
• T he drugs may be administered concomitantly or alternately on the same or di er- ent days during a prescribed treatment cycle (e.g., 28 days). T he days o treatment generally ollow a prescribed ormat o written instructions, with D or “day,” ol- lowed by the day(s) o treatment during a cycle, with a dash (−) meaning “to” and a comma (,) meaning “and.” T hus, D 1–4 means “days 1 to 4,” and D1,4 means “days 1 and 4.”9
• T he drugs used in combination chemotherapy o ten t into a standard drug/dosage regimen identi ed by abbreviations or acronyms. For example, a treatment or blad- der cancer re erred to as MVAC consists o methotrexate + vinblastine + doxorubicin (or actinomycin) + cisplatin; a treatment or colorectal cancer called FU /LU con- sists o f uorouracil + leucovorin; a treatment or lung cancer called PC consists o paclitaxel + carboplatin; and one or ovarian cancer called CH AD consists o cyclo- phosphamide + hexamethylmelamine + Adriamycin + diamminedichloroplatinum (cisplatin).
CASE IN POINT 8 .4 A ho p al pharma on ul d on h appropr a do of lop na r/r ona r (KALe t RA) oral olu on n h r a m n of an Hiv-1 nf on n a 12-mon h-old p d a r pa n . t h oral olu on on a n , n a h m ll l r, 80 mg of lop na r and 20 mg of r ona r, xpr d a “KALe t RA 80/20.” A ord ng o h pharma y’ pro o ol, h p d a r do for pa n gr a r han 6 mon h of ag , no r ng o h r on om an h rapy, may al ula d a d on h r b s A or ody w gh a follow :
• 2 30/57.5 mg/m2, adm n r d w da ly
• 1 2/3 mg/kg for pa n <15 kg, adm n r d w da ly
• 10/2.5 mg/kg for pa n >15 kg adm n r d w da ly t h pa n m a ur 28 n h n l ng h and w gh 22 l . (a) c al ula h ngl do , n mg, u ng h b s A qua on.
( ) t ran la h al ula d ngl do from (a) n o orr pond ng m ll l r of h oral olu on.
( ) c al ula h da ly do , n mg, a d on h pa n ’ w gh .
(d) t ran la h da ly do from ( ) n o orr pond ng m ll l r of oral olu on.
144 Pharma euti al c al ulations
• In addition to the use o abbreviations or the drug therapy regimens, the drugs them- selves are commonly abbreviated in medication orders, such as MT X or “metho- trexate,” D OX or “doxorubicin,” VLB or “vinblastine,” and CD DP or “cisplatin.”
Tables o standard chemotherapy treatments, dosing regimens, and abbreviations o the drugs and treatment regimens may be ound in the indicated re erences.7–11
• For systemic action, chemotherapeutic agents are usually dosed based either on body weight or on body sur ace area. O ten, the drug doses stated in standard regimens must be reduced, based on a particular patient’s diminished kidney or liver unction and, thus, his or her ability to metabolize and eliminate the drug(s) rom the body.
• For certain patients, high-dose chemotherapy is undertaken in an e ort to kill tumor cells.
To help prevent errors in chemotherapy, pharmacists must correctly interpret medica- tion orders or the chemotherapeutic agents prescribed, ollow the individualized dosing regimens, calculate the doses o each medication prescribed, and dispense the appropriate dosage orms and quantities/strengths required.12
Example Calculations of Chemotherapy Dosage Regimens
(1) Regimen: VC11
Cycle: 28 days; repeat or 2–8 cycles
Vinorelbine, 25 mg/m2, IV, D 1,8,15,22 Cisplatin, 100 mg/m2, IV, D 1
For each o vinorelbine and cisplatin, calculate the total intravenous dose per cycle or a patient measuring 5 eet 11 inches in height and weighing 175 lb.
From the nomogram or determining BSA, (a) f nd the patient’s BSA and (b) calculate the quantity o each drug in the regimen.
(a) BSA = 2.00 m2
(b) Vinorelbine: 25 mg × 2.00 (BSA) × 4 (days o treatment) = 200 mg Cisplatin: 100 mg × 2.00 (BSA) × 1 = 200 mg
(2) Regimen: CM F11 Cycle: 28 days
Cyclophosphamide, 100 mg/m2/day PO, D 1–14 Methotrexate, 40 mg/m2, IV, D 2,8
Fluorouracil, 600 mg/m2, IV, D 1,8
Calculate the total cycle dose or cyclophosphamide, methotrexate, and f uorouracil or a patient having a BSA o 1.5 m2.
Cyclophosphamide: 100 mg × 1.5 (BSA) × 14 (days) = 2100 mg = 2.1 g
Methotrexate: 40 mg × 1.5 × 2 = 120 mg
Fluorouracil: 600 mg × 1.5 × 2 = 1800 mg = 1.8 g
(3) Using Table 8.7 as a re erence, calculate the quantities o doxorubicin and cyclophospha- mide administered per treatment cycle to a woman measuring 5 eet 4 inches in height and weighing 142 lb during the “AC” protocol or breast cancer.
BSA ( rom Table 8.2) = 1.70 m2
1.70 m2 × 60 mg/m2 doxorubicin = 102 mg doxorubicin
1.70 m2 × 600 mg/m2 cyclophosphamide = 1020 mg cyclophosphamide
(4) A variation o the “AC” protocol, re erred to as “AC → T,” ollows 4 cycles o the AC protocol with paclitaxel (TAXOL), 175 mg/m2 by intravenous in usion every 14 to 21 days
8 • c al ula on of Doses: Pa en Parame ers 145
for 4 cycles.11 Calculate the total quantity of paclitaxel, in milligrams, that the patient in the previous problem would receive during this treatment plan.
BSA m
m mg m paclitaxel mg per cycle cy
=
× = ×
1 70
1 70 175 297 5 4
2
2 2
.
. / . ( ) ( ccles)
=1190 mg paclitaxel
(5) If an injection is available containing paclitaxel, 6 mg/mL, calculate the volume required per cycle to treat the patient in the previous problem.
297.5 mg ÷ 6 mg/mL = 49.6 mL paclitaxel injection
CASE IN POINT 8.513 in rea ng a 54-year-old female pa en , an on olog s sele s he drug emozolom de, an an umor agen used n he rea men of refra ory as ro y- oma (bra n umor). t he drug s used as par of a 28-day reg men, dur ng wh h he f rs 5 days of rea men n lude emozolom de a a on e-da ly dose of 150 mg/m2/day.
t he pa en ’s med al har nd a es ha she measures 5 fee n he gh and we ghs 1 17 lb. t he phys an asks he pharma s o de erm ne he proper omb na on of ava lable apsules o use n dos ng he pa en . t he drug s ava lable n apsules
on a n ng 5, 20, 100, and 2 50 mg of emozolom de. Wha omb na on of apsules would prov de he da ly dose of h s drug?
Tab e 8 .7 • ExAmPl ES OF DOSAGE REGImENS IN CANCER Ch EmOTh ERAPya
T pe of
Cancerb Abbreviation Drug/Dose Route
Da (s) of Ad inistration per Treat ent C c ec
Bladder MVAC methotrexate, 30 mg/m2
vinblastine, 3 mg/m2
doxorubicin (Adriamycin),30 mg/m2 cisplatin, 70 mg/m2
IV IV IV IV
days 1, 15, and 22 days 2, 15, and 22 day 2
day 2
Breast AC doxorubicin (Adriamycin), 60 mg/m2
cyclophosphamide, 600 mg/m2
IV IV
day 1 day 1 Esophagus DCF docetaxel, 75 mg/m2
cisplatin, 75 mg/m2
5-fluorouracil, 750 mg/m2/day
IV IV IV
day 1 day 1 days 1–5
Lung CAE cyclophosphamide, 1000 mg/m2
doxorubicin, 45 mg/m2 etoposide, 100 mg/m2
IV IV IV
day 1 day 1 days 1–3
Stomach ELF etoposide, 120 mg/m2
leucovorin, 150 mg/m2 5-fluorouracil, 500 mg/m2
IV IV IV
days 1–3 days 1–3 days 1–3
aTable from references.8–11
bTypes of cancer are stated broadly and not differentiated by subclassifications.
cThe frequency and number of treatment cycles vary according to the specific protocols employed.
146 Pharma euti al c al ulations
PRACTICE PROBl EmS Calculations Based on Body Weight
1. T he dose of a drug is 500 mcg/kg of body weight. H ow many milligrams should be given to a child weighing 55 lb?
2. T he dose of gentamicin for premature and full-term neonates is 2.5 mg/kg administered every 12 hours. W hat would be the daily dose for a newborn weigh- ing 5.6 lb?
3. T he dose of gentamicin for patients with impaired renal function is adjusted to ensure therapeutically optimal dosage. If the normal daily dose of the drug for adults is 3 mg/kg/day, administered in three divided doses, what would be the single (8-hour) dose for a patient weighing 165 lb and scheduled to receive only 40% of the usual dose, based on renal impairment?
4. A patient weighing 120 lb was administered 2.1 g of a drug supposed to be dosed at 30 mg/kg. Was the dose administered correct, or was it an overdose, or was it an underdose?
5. In a clinical trial of ciprofloxacin (CIPRO), pediatric patients were initiated on 6 to 10 mg/kg intravenously every 8 hours and converted to oral therapy, 10 to 20 mg/kg, every 12 hours. Calculate the ranges of the total daily amounts of ciprofloxacin that would have been administered intravenously and orally to a 40-lb child.
6. Erythromycin ethylsuccinate 400 mg/5 mL Disp. 100 mL
Sig. tsp. q.i.d. until all medication is taken.
If the dose of erythromycin ethylsuccinate is given as 40 mg/kg/day
(a) W hat would be the proper dose of the medication in the signa, if the prescrip- tion is for a 44-lb child?
(b) H ow many days will the prescribed medication last?
7. If the pediatric dosage of chlorothiazide (DIU RIL) is 10 to 20 mg/kg of body weight per day in a single dose or two divided doses, not to exceed 375 mg/day, calculate the daily dosage range of an oral suspension containing 250 mg chloro- thiazide per 5 mL that should be administered to a 48-lb child.
8. Cyclosporine is an immunosuppressive agent administered before and after organ transplantation at a single dose of 15 mg/kg. H ow many milliliters of a 50-mL bottle containing 100 mg of cyclosporine per milliliter would be administered to a 140-lb kidney transplant patient?
9. T he adult dose of a liquid medication is 0.1 mL/kg of body weight. H ow many teaspoonfuls should be administered to a person weighing 220 lb?
10. A hospitalist prescribed dimenhydrinate to treat a 48-lb child. T he labeled dose of the drug is 1.125 mg/kg. T he available oral solution contains dimenhydrinate, 12.5 mg/5 mL. Prior to administering the solution, the floor nurse decides to check her calculated dose of 9.8 mL with the hospital pharmacist. Were her cal- culations correct?
11. Fluconazole tabs 100 mg Disp. tabs
Sig: tab ii stat, then 3 mg/kg b.i.d. × 7 days thereafter.
Calculate the number of tablets to dispense to a patient weighing 147 lb.
12. A physician desires a dose of 10 mcg/kg of digoxin for an 8-lb newborn child.
H ow many milliliters of an injection containing 0.25 mg of digoxin per milliliter should be given?
8 • c al ulation of Doses: Patient Parameters 147 13. Intravenous digitalizing doses of digoxin in children are 80% of oral digitalizing
doses. Calculate the intravenous dose for a 5-year-old child weighing 40 lb if the oral dose is determined to be 10 mcg/kg.
14. An intratracheal suspension for breathing enhancement in premature infants is dosed at 2.5 mL/kg of birth weight. H ow many milliliters of the suspension should be administered to a neonate weighing 3 lb?
15. A 142-lb patient was receiving filgrastim (N EUPOGEN ) in doses of 10 mcg/kg/day when, as a result of successful blood tests, the dose was lowered to 6 mcg/kg/day.
Using an injection containing 0.3 mg filgrastim per 0.5 mL, calculate the previous and new dose to be administered.
(a) 17.7 mL and 64.6 mL (b) 5.23 mL and 3.14 mL (c) 1.08 mL and 0.65 mL (d) 3.87 mL and 2.3 mL
16. A 25-lb child is to receive 4 mg of phenytoin per kilogram of body weight daily as an anticonvulsant. H ow many milliliters of pediatric phenytoin suspension containing 30 mg per 5 mL should the child receive?
17. T he loading dose of digoxin in premature infants with a birth weight of less than 1.5 kg is 8 mcg/kg administered in three unequally divided doses (½, ¼, ¼) at 8-hour intervals. W hat would be the initial dose for an infant weighing 1.2 kg?
18. T he pediatric dose of cefadroxil is 30 mg/kg/day. If a child was given a daily dose of 2 teaspoonfuls of a pediatric suspension containing 125 mg of cefadroxil per 5 mL, what was the weight, in pounds, of the child?
19. H ow many milliliters of an injection containing 1 mg of drug per milliliter of injection should be administered to a 6-month-old child weighing 16 lb to achieve a dose of 0.01 mg/kg?
20. Prior to hip replacement surgery, a patient receives an injection of an anticoagu- lant drug at a dose of 30 mg. Following the patient’s surgery, the drug is injected at 1 mg/kg. For a 140-lb patient, calculate the total of the pre- and postsurgical doses.
21. Using Table 8.2 and a daily dose of 2 mg/kg, how many 20-mg capsules would a 176-lb patient be instructed to take per dose if the daily dose is to be taken in divided doses, q.i.d.?
22. For a 22-lb pediatric patient, the dose of cefdinir (O MN ICEF) was determined to be 7 mg/kg. W hat quantity of an oral suspension containing 125 mg of cefdinir in each 5 mL should be administered?
(a) 2.8 mL (b) 5.6 mL (c) 8.9 mL (d) 13.6 mL
23. H ow many capsules, each containing 250 mg of clarithromycin, are needed to provide 50 mg/kg/day for 10 days for a person weighing 176 lb?
24. If the pediatric dose of dactinomycin is 15 mcg/kg/day for 5 days, how many micrograms should be administered to a 40-lb child over the course of treatment?
25. If the administration of gentamicin at a dose of 1.75 mg/kg is determined to result in peak blood serum levels of 4 mcg/mL, calculate the dose, in milligrams, for a 120-lb patient that may be expected to result in a blood serum gentamicin level of 4.5 mcg/mL.
148 Pharma euti al c al ulations
26. A medication order calls for tobramycin sulfate, 1 mg/kg of body weight, to be administered by IM injection to a patient weighing 220 lb. Tobramycin sulfate is available in a vial containing 80 mg per 2 mL. H ow many milliliters of the injec- tion should the patient receive?
27. T he usual pediatric dose of acyclovir is 20 mg/kg administered by infusion and repeated every 8 hours. W hat would be the single dose, in milligrams, for a child weighing 33 lb?
28. If the recommended dose of tobramycin for a premature infant is 4 mg/kg/day, divided into two equal doses administered every 12 hours, how many milligrams of the drug should be given every 12 hours to a 2.2-lb infant?
29. If a 3-year-old child weighing 35 lb accidentally ingested twenty 81-mg aspirin tablets, how much aspirin did the child ingest on a milligram per kilogram basis?
30. T he recommended pediatric dose of epinephrine for allergic emergencies is 0.01 mg/kg. If a physician, utilizing this dose, administered 0.15 mg, what was the weight of the patient in pounds?
31. T he initial maintenance dose of vancomycin for infants less than 1 week old is 15 mg/kg every 18 hours.
(a) W hat would be the dose, in milligrams, for an infant weighing 2500 g?
(b) H ow many milliliters of an injection containing 500 mg per 25 mL should be administered to obtain this dose?
32. T he loading dose of indomethacin in neonates is 0.2 mg/kg of body weight by intravenous infusion.
(a) W hat would be the dose for a neonate weighing 6 lb 4 oz?
(b) H ow many milliliters of an injection containing 1 mg of indomethacin per 0.5 mL should be administered to obtain this dose?
33. 13 Jimmy Jones Age: 8 years W t: 88 lb
Metronidazole suspension 7.5 mg/kg/day
M.ft. dose = 5 mL
Sig: 5 mL b.i.d. × 10 days
(a) H ow many milligrams of metronidazole will the patient receive per dose?
(b) H ow many milliliters of the prescription should be prepared and dispensed?
(c) If metronidazole is available in 250-mg tablets, how many tablets will be needed to fill the prescription?
34. 13 Betty Smith Age: 4 years Weight: 52.8 lb
Erythromycin ethylsuccinate (EES) 200 mg/5 mL Disp. 300 mL
Sig: mL q.i.d. until gone
(a) If the dose of EES is 50 mg/kg/day, how many milliliters would provide each dose?
(b) H ow many days would the prescription last the patient?