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1. To be acquainted with the process of drug monitoring.
2. To know the purposes and uses of drug therapy monitoring.
3. To identify the common drugs that requires close drug monitoring.
4. To develop drug therapy monitoring skills.

Drug therapy monitoring has become an essential activity for pharmacists in hospital or even
community pharmacy settings. The reasons for this role include the growing complexity of multiple drug
therapy and the evolution of clinical pharmacy practice. The process of effectively assessing drug therapy
and performing follow-up patient monitoring are often complex in nature and take time and clinical
experience to develop and refine. Today, pharmacists are becoming more involved in providing drug
information and education.

Review each case study given below and answer the questions accompanying each case.

CASE !: A 24-yo female patient is admitted due to uncontrolled seizure despite repeated
injections. The consultant in the acute medical unit prescribes phenytoin loading dose and
maintenance regimen.
(1) List the minimum information required to prescribe a phenytoin loading and
maintenance regimen safely for the patient.
- phenytoin is an anti epileptic drug with a maintenance dose of 100 mg IV (or
orally) 6-8 hrly.
- it should be taken with food
- When administering the drug on nasogastric or other enteral feeds, do not
administer feeds 2 hr before or after a dose.
- Be consistent throughout therapy in relation to feed times.
- Do not switch dosage forms/brands w/o prior consideration.
- May impair ability to drive or operate machinery.
Monitor haematologic, liver function; signs of suicidal ideation and behaviours;
plasma phenytoin concentrations.
- Acute alcohol intake may increase phenytoin serum levels, while chronic use
may decrease serum levels.

(2) Using appropriate references, what can be a suitable loading and maintenance
regimen for a 58-kg patient? What serum concentration should be achieved and
Loading dose of phenytoin is 15-20mg/kg or 870-1160 mg for the patient
Maintenance dose: Maintenance: 100 mg IV 6-8 hrly
Serum concentration : 40-80 (mcmol/L) or 10 - 20 mg/L

(3) How will you monitor serum phenytoin levels following loading and maintenance
dosing? What time during the dose interval should blood samples be taken and how many
days into therapy?
Phenytoin serum levels are monitored using a petient’s blood sample from the
vein through a specific blood test. After a patient has received a loading dose of
intravenous phenytoin, levels can be checked one hour after the dose. This level can aid
in determining maintenance dose or need to reload. After initiation of a maintenance
dose, levels can be taken within three to four days to ensure that the patient’s metabolism
is not remarkably different from the average literature-derived pharmacokinetic

(4) The patient’s phenytoin serum levels after 6 days of therapy at a maintenance dose of
300 mg IV daily is reported as 25 mg/L. Comment on the levels and list possible reasons
why this occurred.
Based on Katzung’s serum concentration reference ranges for some antiseizure
drugs, a phenytoin serum level ranges from 10-20 mg/L which only means the the
patients serum level is too high. Also, based from MIMS the maintenance dose of
intravenous phenytoin is at 100 mg IV (or orally) 6-8 hrly only this only means that the
patient is taking a higher dose than usual. Other possibilities for the occurrence of high
serum level of phenytoin are liver disease, congenital enzyme deficiency or drug
interactions which result in metabolic interference.

(5) After a week, the patient is ready for discharge. Suggest an appropriate oral
maintenance dose for this patient. How often should serum levels be monitored?
The suggested oral maintenance dose would be 200-500 mg/day based on MIMS.
If loading is achieved by oral dosing, phenytoin levels can be checked 24 hours after the
last dose. After initiation of a maintenance dose, levels can be taken within three to four
days to ensure that the patient’s metabolism is not remarkably different from the average
literature-derived pharmacokinetic parameters.

CASE 2: A 36-yo male patient with a history of bipolar disorder controlled with lithium, is
admitted with coarse tremor and loss of coordination. The patient is maintained on slow release
lithium tablets (Priadel)
400 mg twice daily. A serum lithium level is reported as 1.4 mmol/L.
(1) What is the recommended serum concentration range for lithium?
Serum lithium level of 0.4 mmol/L with optimal response achieved at serum levels
between 0.6-0.75 mmol/

(2) What management is given for mild cases of lithium toxicity?

Mild lithium toxicity usually goes away on its own when you stop taking lithium and
drink some extra fluids. However, Depending on the amount you took and how soon
the ingestion of lithium is discovered, treatment may include activated charcoal if
you took other substances as well, or whole bowel irrigation, in which a polyethylene
glycol solution is used to flush large amounts or extended-release lithium from your

(3) List the possible explanations for this patient’s high lithium level and what questions
will you ask the patient?
 The patient has impaired Excretion or he/she is not taking enough fluid or
currently using drugs that reduces glomerular filtration rate that might inflict
chronic toxicity.
 General medical conditions characterized by decreased circulating volume,
including viral infections with fever, gastroenteritis with diarrhea and vomiting,
great heat and sauna and decreased oral intake of water augment renal
reabsorption of sodium and lithium, potentially leading to toxic lithium serum
 Use of interacting drugs; NSAID, ACEI and diuretics causes increased
 Crash diets, change to vegetarian diet (with much lower sodium content)
 Change of Brand use and dosage forms (slow/fast release) have variable
 Due to excessive intake or suicidal intent or accidental ingestion of excessive
amount of lithium tablets result in acute or acute-on-chronic overdose settings
 Have you been taking any anti-inflammatory drugs such as ibuprofen or
mefenamic acid?
 Have you been taking any antihypertensive drugs such as enalapril and captopril
or any diuretics such as furosemide or hydrochlorothiazide?
 Have you been experiencing and physical illness, fever or viral infections or any
GI upset such as vomiting or diarrhea or?
 Did you change your brand?
 How often do you take water?
 Are you experiencing any problems or depression?

(4) The patient admits to borrowing some of his mother’s arthritis tablets for a migraine
that had been bothering him for several days. List several drugs that will interact with
lithium that are also employed for the symptomatic relief of arthritis.

Meperidine (Demerol) interacts with LITHIUM

Lithium increases a chemical in the brain called serotonin. Meperidine (Demerol) can
also increase serotonin in the brain. Taking lithium along with meperidine (Demerol)
might cause too much serotonin in the brain and serious side effects including heart
problems, shivering, and anxiety.

NSAIDs (Nonsteroidal anti-inflammatory drugs) interacts with LITHIUM

NSAIDs are anti-inflammatory medications used for decreasing pain and swelling.
NSAIDs might increase lithium levels in the body. Taking lithium along with NSAIDs
might increase the risk of lithium side effects. Avoid taking lithium supplements and
NSAIDs at the same time.<br><nb>Some NSAIDs include ibuprofen (Advil, Motrin,
Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan,
Naprosyn), piroxicam (Feldene), aspirin, and others.

Tramadol (Ultram) interacts with LITHIUM

Tramadol (Ultram) can affect a chemical in the brain called serotonin. Lithium can also
affect serotonin. Taking lithium along with tramadol (Ultram) might cause too much
serotonin in the brain causing confusion, shivering, stiff muscles and other side effects.
(5) How should this patient be managed once the lithium toxicity has resolved?

Supportive care and monitoring

 Correction of water deficits and ongoing hydration with intravenous

fluid to prevent renal impairment (e.g. normal saline). Monitor urine output, >1 ml/kg/hr is
 Correction of sodium deficits is also important as this too can affect
lithium clearance
 Avoidance and cessation of any drugs that impair lithium clearance


 Lithium level
 Urea, electrolytes (Na) and creatine

CASE 3: A 17-yo obese male patient is admitted in status asthmaticus and the consultant in the
emergency department instructs the administration of aminophylline infusion.
(1) What information would you require before aminophylline infusion can be given to
the patient?
 Before using intravenous aminophylline for an exacerbation of COPD please consider whether
patient may be a suitable for Non Invasive Ventilation. (For example patients with hypercapnic
respiratory failure and a pH
 Allergy or hypersensitivity to aminophylline or theophylline, caffeine or theobromine.
 For obese patients (BMI>30) dose must be calculated using ideal body weight (IBW) to avoid
excessive dosing
 During therapy, he should monitor carefully for signs of toxicity and, where possible, the serum
theophylline levels should also be monitored
 Aminophylline Injection is used in such patients, he should be carefully observed for possible signs
of central stimulation
(2015).Aminophylline hydrate 25mg/ml Solution for injection. Retrieved on Jan 28,2019 from

(2) What dose should be given to a patient who stands 5’6” and weighs 95 kg. Show
appropriate calculations.
Patient 1: Weight = 70kg Patient 45 years old
BMI=33.8 kg/m2

Loading dose: 5mg/kg = 5mg x 95kg = 475mg- add to 100ml of infusion fluid and
administer over 20 minutes
Maintenance Dose: 500micrograms/kg/hour = 500micrograms x 95kg per hour =
475000micrograms/hr = 47.5mg per hour Add 500mg aminophylline to 500ml
infusion fluid= 1mg/ml concentration Set rate controlled infusion pump at 47.5ml
infusion per hour
Ideal body weight worked example

Patient RW male, weighs 95kg, height 167.64cm (5ft 6) Males: IBW (kg) = 50 kg + 2.3 kg for each inch
over 5 feet.
 IBW = 50kg + (2.3kg x 10inches) = 63.8kg

Loading dose worked example:

 Dose is 5mg/kg. Based on patient RW with an ideal body weight of 63.8kg:

 5mg x 63.8kg = 319mg

Maintenance dose worked example:

Dose is 500microgram/kg/hr. Based on patient RW with an ideal body weight of 73kg:

500micrograms x 63.8kg = 31.9mg/hr
 Make up 500mg aminophylline in 500millitres of sodium chloride 0.9% (1mg/ml solution) – infuse
at 31.9ml/hour (31.9mg/hr)

(2016).Guideline for Intravenous Aminophylline in adults Retrieved on Jan 28,2019 from

(3) When should blood samples be taken to measure serum theophylline levels and what
is the desired therapeutic range?
 Blood samples be taken to measure serum theophylline levels 24 hours into infusion
 Therapeutic serum concentrations of theophylline are considered to range from 10 to 20 mcg/ml
and levels greater than 20 mcg/ml are often associated with toxic effects
(2018) Labtest online. Theophylline and Caffeine. Retrieved on Jan 28,2019 from
(4) The patient develops severe nausea and vomiting along with tachycardia and a serum
theophylline level is reported as 32 mg/L. List the possible explanations for the high
theophylline level.
This can occur by intentional overdose or unintentionally when metabolism and/or
clearance of theophylline are altered due to certain physiological stressors or
administration of another drug.
Chronic intoxication occurs when excessive doses are administered repeatedly over 24 hrs
or longer or when intercurrent illness or an interacting drug interferes with hepatic
metabolism of theophylline. Nausea and vomiting may occur but is not as common as in
acute overdose.
Theophylline has a low therapeutic index. Theophylline toxicity is most likely to occur
when serum concentrations exceed 20 ug/mL and becomes progressively more severe at
higher serum concentrations. Anorexia, nausea and occasional vomiting commonly occur.
Jonathan J. & Thomas B.(2018). Theophylline Toxicity. Retrieved on Jan 28,2019 from

(4) A family member confirms that the patient regularly takes Slo-Phyllin® and the
aminophylline infusion is stopped. What is the typical half-life of theophylline and
how long would you expect to wait before restarting the infusion?
 Half life of theophylline 8 hours
 steady state is achieved in three days
 Oral theophylline start with the lowest recommended dose. This can be adjusted at 3-7 day
intervals according to clinical response or the development of unwanted effects.
(2012 ).GUY’S, ST THOMAS’ AND LEWISHAM HOSPITALS. Retrieved on Jan 28,2019 from

(5) The patient’s condition stabilizes and the consultant asks you to stop the
aminophylline infusion and convert the patient to oral theophylline. Suggest an
approach to managing the crossover from IV to oral agents and suggest an
appropriate oral regiment.
When changing a patient’s therapy from IV aminophylline to oral therapy with either theophylline or
aminophylline, the bioavailability and the salt equivalence should be considered.

 When converting from IV aminophylline to the oral theophylline dose, the bioavailability and salt
factor must be considered. The salt factor for aminophylline is approximately 0.8 (salt factor = fraction
of labelled dose which is theophylline).
 The total daily dose of IV aminophylline is the same for oral aminophylline (assuming bioavailability is
100% for the oral product).
 If IV aminophylline is changed to oral theophylline, then the total daily dose of IV aminophylline
should be multiplied by 0.8.
 Alternatively, multiply the hourly aminophylline dose by 10, to obtain the theophylline dose to be
given every 12 hours.
When converting from IV to oral therapy, it may not be possible to administer the exact dose
calculated. The nearest practical dose should therefore be used and adjusted according to blood
levels.(2017).How is an intravenous aminophylline dose converted to an oral aminophylline or
theophylline dose?.
version-1.d. Retrieved on Jan 28,2019 from

(6) The patient develops a catheter-associated UTI and microbiology recommends

ciprofloxacin. Evaluate the potential for interaction between ciprofloxacin and
theophylline in this patient and suggest an approach to future management of drug
 Treatment with ciprofloxacin is associated with a significant increase in the risk of theophylline
toxicity. When clinically appropriate, alternate antibiotics should be considered for elderly patients
receiving theophylline.
Antoniou T (2011).Ciprofloxacin-induced theophylline toxicity: a population-based. Retrieved on Jan
28,2019 from .

1. What is meant by drug therapy monitoring? How is this done?
TDM refers to the process of reviewing and identifying the patients’ record also resolving drug
therapy problems such as adverse drugs effects and communicate with prescribers when problems
occur. TDM also refers to measuring and interpreting the blood plasma or serum drug
concentration measurements with the purpose of optimizing a patient’s drug therapy and clinical
outcome while minimizing the risk of drug-induced toxicity involving tailoring of a dose regimen
to an individual patient by maintaining the plasma or blood concentration within a particular
Medication monitoring is optimized by a team approach that includes pharmacists. Following are
the three steps of monitoring:

 Educate patients about their therapy, potential adverse effects, and actions to take if
problems occur. Make patients active partners in their medication management and their
own health decisions.
 Regularly assess patients’ drug therapy. Ensure that patients take their medications as
prescribed, proactively identify and resolve ADEs as they occur, and assess therapeutic
effectiveness. Ensure that appropriate labs are done and assessed.
 Adjust drug therapy as needed based on information from the monitoring process.

2. State the purposes and goals of monitoring patient drug therapy.

 Provides clinicians with the information needed to determine whether the non-drug and
drug intervention achieve the goals of the therapy or whether the interventions need to be
 Provides the data for justifying and documenting why change is necessary;
For example:
 Inadequate response
 Disease progression
 Patient dissatisfaction
 Drug allergy
 Drug interactions
 Undesirable/Potentially dangerous adverse drug reactions
 Provides the clinician with greater insight into the factors determining the patient’s
response to drug therapy
For example
 When a patient fails to respond to a usual therapeutic dose, measurement of plasma
level can help to distinguish a non-compliant patient and a patient who is a true
 To achieve optimal drug therapy wherein 3 objectives should be met:
 To attain desired pharmacological effect of the drug
 To reach the maximal effect in the shortest possible time
 To decrease risk of toxicity
 To monitor drugs with narrow therapeutic index, which are highly protein bound, liable to
interact, and when its metabolite might be toxic
3. What drugs are commonly monitored?
3. What drugs commonly monitored?
Drugs commonly monitored are the following:
Dangerous drugs:
 BUPRENORPHINE - (Norspan Patch)
 CODEINE - (Codipront N Capsule, Codipront N Syrup)
 DIAZEPAM - (Ampule: Anxiol, Diazepam, Lorcam, Trankil, Valium, Zopamid)
 EPHEDRINE SULFATE - (Ephedrine Sulfate Ampule)
 FENTANYL - (Patch: Durogesic, Durogesic D-Trans)
 FENTANYL CITRATE - (Ampule: Fentanyl Citrate, Sublimax, Sublimaze, Trofenyl)
 MIDAZOLAM - (Ampule: Dormicum, Dormizol, Midazolam HCl, Sedoz)
 MORPHINE SULFATE - (Ampule: Morin, Morphine Sulfate; Tablet: Morphine Sulfate, MST
Continus MR, MXL PR, Relimal CR)
 NALBUPHINE HYDROCHLORIDE - (Nubain, Nukain, Nalbuphine HCl)
 OXYCODONE HYDROCHLORIDE - (Oxynorm Capsule, Oxycotin PR Tablet)
 PETHIDINE HYDROCHLORIDE - (Ampule: Deme, Demerol, Pethidine HCl; Vial: Demerol)
 KETAMINE - (Vial: Ketamax, Ketazol, Ketram, Uniket)
 PSEUDOEPHEDRINE SULFATE - (Clarinase Syrup; Clarinase Tablet)
 ALPRAZOLAM - (Tablet: Alprazolam, Altrox, Atrest, Praz, Xanor, Xanor XR)
 BROMAZEPAM - ( Lexotan Tablet)
 CLONAZEPAM - (Tablet: Clonotril, Rivotril)
 DIAZEPAM - (Tablet: Diazepam, Nixtensyn, Solina, Valium)
 ESTAZOLAM- (Esilgan Tablet)
 FLURAZEPAM - (Dalmane Capsule)
 MAZINDOL - (Mazzol Tablet)
 MIDAZOLAM - (Dormicum Tablet)
 NITRAZEPAM - (Mozepam Tablet)
 PHENOBARBITAL SODIUM - (Phenobarbital Tablet)
 PHENTERMINE SODIUM - (Duromine Capsule)
 ZOLPIDEM - (Tablet: Niben, Pidezol, Stilnox, Stilnox MR, Ziohex, Zoldem, Zulnap)

Scheduled Drugs:

Schedule I:  Ethylmorphine  Pentobarbital

 Alprazolam  Nicicidine
 Clonazepam  Nicodicodine Schedule IV:
 Delorazepam  Norcodeine  Acetorphine
 Diazepam  Pholcodine  Acetyl-alpha-
 Phenobarbital  Propiram methylfentanyl
 Secobutabarbital  Alpha-
 Zolpidem Schedule III: methylfentanyl
 Lorazepam  Amobarbital  Alpha-
 Midazolam  Buprenorphine methylthiofentanyl
 Butalbital  Beta-hydroxy-3-
Schedule II:  Cathine methylfentanyl
 Acetyldihydrocodein  Cyclobarbital  Beta-
e  Flunitrazepam hydroxyfentanyl
 Codeine  Glutethimide  Cannabis
 Dextropropoxyphene  Pentazocine  Desomorphine
 Dihyhrocodeine  Etorphine
 Heroin  3-methylfentanyl  Thiofental
 Ketobemidone  3-methylthiofentanyl
Enumerate 15 commonly prescribed drugs and give three specific monitoring parameters for each. Give the therapeutic
serum concentration, if applicable.
Commonly Prescribed Drugs Monitoring Parameters (3) Therapeutic Serum Concentration,
if applicable

1. Vicodin, Norco, Xodol Monitor pain relief, Following a 10 mg oral dose of

(hydrocodone, hydrocodone administered to five
acetaminophen) Monitor respiratory and mental adult male subjects, the mean peak
status, Monitor BP concentration was 23.6 ± 5.2
Monitor signs of misuse, abuse, and ng/mL. Maximum serum levels
addiction; were achieved at 1.3 ± 0.3 hours
and the half-life was determined to
Monitor signs or symptoms of be 3.8 ± 0.3 hours.
hypogonadism or hypoadrenalism
Hydrocodone:Therapeutic range 2
2. Synthroid, Levoxyl, Monitor thyroid function test, In infants with very low (< 5
Unithroid (levothyroxine) clinical signs of hypo- and mcg/dL) or
hyperthyroidism, Monitor heart undetectable serum T4 concentrati
rate ons, the recommended initial
starting dose is 50 mcg/day
Monitor BP of levothyroxine sodium. Levothy
roxine therapy is usually initiated
at full replacement doses, with the
recommended dose per body
weight decreasing with age

3. Delasone, Sterapred Monitor BP, The average daily dose of

(prednisone) prednisone for all patients was 19.4
blood glucose, ± 11.5 mg/day, with doses ranging
electrolytes from 5 to 40 mg/day.

4. Amoxil (amoxicillin) Monitor renal, hepatic, and Orally administered doses of 250-
haematologic functions; signs of mg and 500-mg amoxicillin
anaphylaxis during 1st dose capsules result in average peak
blood levels 1 to 2 hours after
administration in the range of 3.5
mcg/mL to 5.0 mcg/mL and 5.5
mcg/mL to7.5 mcg/mL,

5. Neurontin (gabapentin) Monitor for signs of suicidal The dosage can be increased at 300
ideation and behaviours mg intervals daily up to 900 to
4800 mg per day. The circulating
Monitor WBC
half life is 5 to 7 days. A wide range
Monitor pain relief of serum concentrations, from 2.0
to 20 ug/mL have been associated
with effective seizure control.

Therapeutic range is 2.0 - 20.0


6. Prinivil, Zestril (lisinopril) Monitor vital signs, serum In general if the

electrolytes and creatinine levels desired therapeutic effect cannot
frequently. Correct volume and/or be achieved in a period of 2 to 4
salt depletion prior to treatment. weeks on a certain dose level, the
Monitor renal function during the dose can be further increased. The
1st few wk of treatment and maximum dose used in long-term,
periodically thereafter controlled clinical trials was
80mg/day. Symptomatic
hypotension may occur following
of therapy with lisinopril.

7. Lipitor (atorvastatin) Monitor creatine kinase (CK) LIPITOR is 10 or 20 mg once daily.

periodically and LFT. Discontinue if Patients who require a large
there is significant or persistent reduction in LDL-C (more than
increase in CK levels, serum 45%) may be started at 40 mg
aminotransferase levels or evidence once daily. The dosage range of
of myopathy LIPITOR is 10to 80mg once daily.

Monitor renal functions

8. Glucophage (metformin) Monitor renal function regularly. The values ranged from 0.129 to 90
Haematologic parameters (e.g. Hb, mg/L, and the lowest and highest
hematocrit, erythrocyte indices) boundaries were 0 and 1800 mg/L.
should be evaluated prior to Only four original research studies
initiation of therapy and at least determined a "therapeutic
annually during treatment concentration".

Monitor red blood cell indices generally less than 1 mcg/mL

9. Zofran (ondansetron) ECG monitoring of patients w/ Subsequent doses (0.15 mg/kg up

electrolytes abnormalities e.g. to a maximum of 16 mg per dose)
hypomagnesaemia or are administered 4 and 8 hours
hypokalaemia, CHF or after the first dose of ZOFRAN. The
bradyarrhythmias and on drug should be infused
medication that can prolong QT intravenously over 15 minutes.
about 30 ng/mL are attained
Monitor CHF, or bradyarrhythmias approximately 1.5 hours after an 8
mg dose.
Monitor potassium, magnesium.
Monitor for signs of serotonin
syndrome; monitor for decreased
bowel activity

10. Motrin (ibuprofen) Monitor CBC, occult blood loss, K Ibuprofen was adjusted to
levels, LFTs and renal function; maintain a serum concentration of
signs and symptoms of ophthalmic- 50—100 mcg/ml. Most patients
related reactions required a dose of 20—30 mg/kg
PO twice daily. The maximum daily
dose administered was 3200

A typical therapeuticibuprofen
level is 3 mg/dL

11. Norvasc (amlodipine Monitor BP and heart rate Adults: The usual initial
besylate) antihypertensive oral dose
Monitor cardiac function of NORVASC is 5 mg once daily
with a maximum dose of 10 mg
once daily. Small, fragile, or elderly
individuals, or patients with hepatic
insufficiency may be started on 2.5
mg once daily and this dose may be
used when adding NORVASC to
other antihypertensive therapy.

8 ng/ml

12. Prilosec (omeprazole) Susceptibility testing is Plasma omeprazole concentrations

recommended in patients who are usually in a range of 0.2–
fail H. pylori-eradication regimen; 1.2 mg/l in persons receiving the
magnesium levels (prior to drug therapeutically by the oral
initiation of therapy and route and 1–6 mg/l in victims of
periodically thereafter). acute overdose.

Monitor Mg concentrations prior

to initiation and periodically

13. Zithromax (Azithromycin) Liver function tests, The serum protein binding
of azithromycin is variable in
CBC w/ differential the concentration range
Monitor renal functions approximating human exposure,
decreasing from 51% at 0.02 μg/mL
to 7% at 2 μg/mL. Biliary excretion
of azithromycin, predominantly as
unchanged drug, is a major route of

14. Zocor (simvastatin) Monitor creatine kinase (CK) In contrast, the

periodically and LFT. Discontinue if mean concentration of statins in
there is significant or persistent human serum (at therapeuticdose
increase in CK levels, serum s) is only 1–15 nmol L−1 (Table 1).
aminotransferase levels or evidence In addition, the protein binding
of myopathy of statins in human blood is high,
95–99%, and it is only the free
Monitor renal functions fraction (0.01–0.5 nmol L−1) that is
pharmacologically active

15. COZAAR Monitor BP, electrolytes and renal Patients were randomized to
(losartan potassium) function receive once daily COZAAR 50
mg or atenolol 50 mg. If goal
blood pressure (<140/90 mmHg)
was not reached,
hydrochlorothiazide (12.5 mg) was
added first and, if needed, the dose
of COZAAR or atenolol was then
increased to 100 mg once daily.