TERBANIFINE CREAM

Indications Dermatophytosis
Adult : PO 250 mg once daily. Treatment duration: 2-4 wk (tinea cruris), 4 wk (tinea corporis), 2-6
wk (tinea pedis), 6-12 wk (onychomycosis). Topical As 1% cream/gel/spray: Apply once or bid to
Dosage
affected area(s). Treatment duration: 1-2 wk (tinea corporis, tinea cruris), 1 wk (tinea pedis), 2 wk
(cutaneous candidiasis and pityriasis).
Oral
Dermatophytosis
Adult: 250 mg once daily. Treatment duration: 2-4 wk (tinea cruris), 4 wk (tinea corporis), 2-6 wk
(tinea pedis), 6-12 wk (onychomycosis).
Dosage Details
Topical/Cutaneous
Dermatophytosis
Adult: As 1% cream/gel/spray: Apply once or bid to affected area(s). Treatment duration: 1-2 wk
(tinea corporis, tinea cruris), 1 wk (tinea pedis), 2 wk (cutaneous candidiasis and pityriasis)
Administration May be taken with or without food.
CrCl Dosage
Renal Impairment
<50 Reduce to 50% of usual dosage
Hepatic Impairment
Contraindication Hypersensitivity. Chronic or active hepatic disease. Lactation.
Patient w/ immunosuppression, psoriasis, autoimmune disease (e.g. Lupus erythematosus);
Special Precautions
presence of lesion (topical). Renal impairment (CrCl <50 mL/min). Pregnancy.
Significant: Depression, taste and smell disturbances, wt loss, anxiety. Rarely, SLE; psoriasis
exacerbation; ocular lens and retina changes; blood disorders (e.g. decreased lymphocyte count,
neutropenia, agranulocytosis, pancytopenia).
Nervous: Headache.
GI: Dyspepsia, nausea, vomiting, diarrhoea, abdominal distention/pain, toothache,
pharyngolaryngeal pain, decreased appetite, feeling of fullness.
Resp: Influenza, nasopharygitis, upper resp tract infections, nasal congestion, rhinorrhea.
Adverse Drug Musculoskeletal: Arthralgia, myalgia.
Reaction Ophthalmologic: Vision color changes, color confusion, decreased visual acuity.
Dermatologic: Rash, pruritus, urticaria, skin exfoliation.
Others: Fever, application site reactions (e.g. pain/irritation pigmentation disorder, burning
sensation).
Potentially Fatal: Hepatic failure. Rarely, serious skin and hypersensitivity reaction (e.g. Stevens-
Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis,
bullous dermatitis, drug reaction w/ eosinophilia and systemic symptoms [DRESS] syndrome);
thrombotic microangiopathy (e.g. thrombocytopenic purpura, haemolytic uraemic syndrome).
Pregnancy Status PO/Topical : B
Symptoms: headache, nausea, upper abdominal pain, and dizziness. Management: Symptomatic
Overdosage and supportive treatment. Administer activated charcoal w/in 1-2 hr after ingestion orally or via
nasogastric tube for unconscious patient.
Increased serum concentration w/ cimetidine, CYP450 inhibitors (e.g. fluconazole, amiodarone,
ketoconazole). Decreased serum concentration w/ rifampicin. May increase plasma concentration
Drug Interaction
of TCA(s), β-blockers, SSRIs, antiarrythmics, MAOI(s) type B. May cause menstrual disturbances
(e.g. breakthrough bleeding, irregular cycle) w/ OC. May decrease clearance of despiramine.
Description: Terbinafine is a allylamine derivative that has a wide spectrum of antifungal activity
against pathogens of the skin, hair, and nails. It acts by inhibiting squalene epoxidase, the main
enzyme responsible for fungal sterol synthesis. Thus, resulting to ergosterol deficiency, leading to
membrane disruption and cell death. It is active against dermatophytes, moulds, and certain
dimorphic fungi.
Pharmacokinetics:
Mechanism of Action Absorption: Well absorbed from the GI tract. Minimal absorption through the skin. Bioavailability:
40%. Time to peak plasma concentration: W/in 2 hr (oral).
Distribution: Distributed into the stratum corneum of the skin, nails, sebum, and hair. Enters
breastmilk. Plasma protein binding: >99%.
Metabolism: Rapidly metabolised in the liver by CYP enzymes into inactive metabolites.
Undergoes first-pass metabolism.
Excretion: Mainly via urine (80%, as inactive metabolites); faeces (20%). Terminal elimination

Acer | PHARMACOLOGY LAB 1

 half-life: 200-400 hr (prolonged use). Plasma elimination half-life: 17-36 hr (oral), 14-35 hr
(topical).
MIMS Class Antifungals/Topical Antifungals & Antiparasites
D01BA02 - terbinafine ; Belongs to the class of antifungals for systemic use.
ATC Classification
D01AE15 - terbinafine ; Belongs to the class of other antifungals for topical use.

TRAMADOL
Adult : PO Moderate to severe pain 50-100 mg 4-6 hrly. Extended-release tab: 50-100 mg 1-2
times/day. Max: 400 mg/day. IV/IM Moderate to severe pain 50-100 mg 4-6 hrly. Post-op pain
Dosage
Initial: 100 mg, then 50 mg every 10-20 min if needed, up to 250 mg for the 1st hr. Maintenance:
50-100 mg 4-6 hrly. Max: 600 mg/day.
Oral
Moderate to severe pain
Adult: 50-100 mg 4-6 hrly. Extended-release tab: 50-100 mg once or twice daily. Max: 400
mg/day.
Elderly: >75 yr Increase dosing interval.

Parenteral
Postoperative pain
Dosage Detaills Adult: Initially, 100 mg followed by 50 mg every 10-20 min if necessary, to a total of 250 mg in the
1st hr including initial dose. Thereafter, 50-100 mg 4-6 hrly up to a total daily dose of 600 mg.
Elderly: >75 yr Increase dosing interval.

Parenteral
Moderate to severe pain
Adult: IM/IV: 50-100 mg 4-6 hrly over 2-3 min.
Elderly: >75 yr Increase dosing interval

Pharmacogenomics:
Variations in CYP2D6 polymorphism occur at different frequencies among subpopulations of
different ethnic or racial origin. Some individuals may be ultra-rapid metabolisers. The prevalence
of CYP2D6 ultra-rapid metabolisers varies widely and has been estimated to be 1-10% in Whites
(European, North American), 3-4% in Black (African American), 1-2% in East Asians (Chinese,
Japanese, Korean), and >10% in certain racial/ethnic groups (e.g. Oceanian, Northern African,
Middle Eastern, Ashkenazi Jews, Puerto Rican). Approximately 7-10% Caucasian population has a
deficiency or is completely lacking of functional CYP2D6 activity.

Ultra-rapid metabolisers:
Carrier of more than two active copies of CYP2D6 (gene duplication noted as *1/*1xN or *1/*2xN).
These individuals convert tramadol into its active metabolite, O-desmethyltramadol (M1), more
Special Treatment rapidly and completely than other people. This rapid conversion results in higher than expected
Group serum M1 levels. Reduce dose by 30% and be alert to adverse drug reactions (e.g. nausea,
vomiting, constipation, respiratory depression, confusion, urinary retention). Analgesics which are
not affected by CYP2D6 polymorphism (e.g. morphine, non-opioid analgesics) may be given as
alternative.

Intermediate metabolisers:
Carrier of one or more reduced or inactive copies of CYP2D6. Monitor for decreased efficacy.
Consider increasing the dose and if the response is still inadequate, either select alternative drug
(not oxycodone or codeine) or be alert to symptoms of insufficient pain relief.

Poor metabolisers:
Carrier of two inactive copies of CYP2D6. Analgesics which are not affected by CYP2D6
polymorphism (e.g. morphine, non-opioid analgesics) may be given as alternative
Oral
CrCl Dosage
<10 Contraindicated
Renal Impairment
10 to <30 Increase dosage interval to 12 hrly
Max : 200 mg/day
Contraindicated (extended release tab)

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 Parenteral
CrCl Dosage
<10 Contraindicated
10 to 30 Increase dosing interval to 12 hrly
Suicidal patients; acute intoxication w/ hypnotics, centrally acting analgesics, opioids, psychotropic
drugs or alcohol; uncontrolled epilepsy, acute or severe bronchial asthma, hypercapnia or
Hepatic Impairment significant resp depression in unmonitored settings or absence of resuscitative equipment. Not
intended for narcotic withdrawal treatment. Severe renal and hepatic impairment. CYP2D6 ultra-
rapid metabolisers. Concomitant use w/ MAOIs or w/in 2 wk after withdrawal of MAOIs.
Suicidal patients; acute intoxication w/ hypnotics, centrally acting analgesics, opioids, psychotropic
drugs or alcohol; uncontrolled epilepsy, acute or severe bronchial asthma, hypercapnia or
Contraindication significant resp depression in unmonitored settings or absence of resuscitative equipment. Not
intended for narcotic withdrawal treatment. Severe renal and hepatic impairment. CYP2D6 ultra-
rapid metabolisers. Concomitant use w/ MAOIs or w/in 2 wk after withdrawal of MAOIs.
Patients who suffer from emotional disturbance or depression, history of epilepsy or risk of
Special Precautions seizure, head injury, increased intracranial pressure. CYP2D6 intermediate and poor metabolisers.
Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Resp depression, seizure, dizziness, headache, somnolence, weakness, CNS stimulation (e.g.
anxiety, euphoria, hallucinations), asthenia, sweating, confusion, coordination disturbance,
paraesthesia, hypoaesthesia, amnesia, cognitive dysfunction, depression, dysphoria, constipation,
Adverse Drug nausea, vomiting, dyspepsia, diarrhoea, abdominal pain, anorexia, flatulence, wt loss,
Reaction gastroenteritis, pruritus, rash, dermatitis, urticaria, bronchospasm, angioedema, anaphylaxis,
allergic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasodilation, orthostatic
hypotension, syncope, tachycardia, flushing, chest pain, palpitations, MI, HTN, peripheral
ischaemia, menopausal symptoms, dysuria, menstrual disorder, micturition difficulty, haematuria.
Pregnancy Status PO : C
Symptoms: Miosis, vomiting, cold and clammy skin, resp depression, lethargy, flaccid skeletal
muscle, coma, seizures, bradycardia, hypotension, cardiac arrest, cardiac collapse. Management:
Overdosage
Supportive treatment w/ maintenance of adequate ventilation. Although naloxone will reverse
some symptoms of overdosage, there is an increased risk of seizures.
Increased risk of convulsions or serotonin syndrome w/ SSRI, serotonin-norepinephrine reuptake
inhibitors (SNRI), TCA and other seizure threshold lowering drugs (e.g. bupropion, mirtazapine,
tetrahydrocannabinol). Decreased serum concentrations w/ carbamazepine. May potentiate the
Drug Interaction
anti-depressant effect of norepinephrine, 5-HT agonists or lithium. Increased INR and ecchymoses
w/ coumarin derivatives (e.g. warfarin).
Potentially Fatal: Increased risk of seizures w/ MAOIs.
Food interaction Enhanced CNS depressant Effect with alcohol
Description: Tramadol inhibits reuptake of norepinephrine, serotonin and enhances serotonin
release. It alters perception and response to pain by binding to mu-opiate receptors in the CNS.
Onset: Approx 1 hr.
Duration: 9 hr.
Pharmacokinetics:
Absorption: Readily absorbed from the GI tract. Bioavailability: Approx 70-75% (oral); 100%
Mechanism of Action
(IM).
Distribution: Widely distributed. Crosses the placenta and enters breast milk.
Metabolism: Extensive hepatic first-pass metabolism. Converted to O-desmethyltramadol (active)
via N- and O-demethylation by CYP3A4 and CYP2D6 isoenzymes and also via glucuronidation or
sulfation.
Excretion: Via urine (as metabolites). Elimination half-life: Approx 6 hr.
MIMS Class Analgesics (Opioid)
ATC Classification N02AX02 - tramadol ; Belongs to the class of other opioids. Used to relieve pain.

CEFUROXIME
Adult : PO Susceptible infections 250 or 500 mg 12 hourly for 7-10 days. Uncomplicated UTI
250 mg 12 hourly for 7-10 days. Resp tract infections 250 - 500 mg 12 hourly for 7-10 days.
Dosage Lyme disease 500 mg bid for 20 days. Uncomplicated gonorrhoea 1 g as a single dose. May be
given w/ oral probenecid 1 g. IM/IV Susceptible infections 0.75 g 8 hrly, may increase up to 1.5 g
6-8 hrly in more severe infections. Pneumonia 1.5 g bid, followed by an oral dose of 0.5 g bid.

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 Acute exacerbations of chronic bronchitis 750 mg bid, followed by an oral dose 500 mg bid.
Prophylaxis of surgical infections 1 or 2 g may be given 0.5 to 2 hours prior to surgery via deep
IM inj or slow IV inj over at least 2-4 minutes. IV Meningitis 3 g 8 hrly. IM Gonorrhoea 1.5 g as a
single dose divided between 2 inj sites. May be given w/ oral probenecid 1 g.
Intramuscular
Gonorrhoea
Adult: As cefuroxime Na: 1.5 g as a single dose divided between 2 inj sites. May be given w/ oral
probenecid 1 g.

Intravenous
Meningitis
Adult: As cefuroxime Na: 3 g 8 hrly.
Child: ≤3 wk 30-100 mg/kg daily by IV inj given as 2 or 3 divided doses; >3 wk <40 kg: 30-100
mg/kg daily by IV inj given as 3 or 4 divided doses; 60 mg/kg daily to most infections.

Oral
Susceptible infections
Adult: As cefuroxime axetil: 250 or 500 mg 12 hourly for 7-10 days.
Child: >3 months weighing <40 kg: 15 mg/kg 12 hourly for 7-10 days. Max: 250 mg 12 hourly.

Oral
Uncomplicated urinary tract infections
Adult: 250 mg 12 hourly for 7-10 days.
Child: >3 mth to 2 yr 10 mg/kg bid. Max 125 mg bid; >2 yr 15 mg/kg bid. Max: 250 mg bid.

Oral
Respiratory tract infections
Adult: 250 - 500 mg 12 hourly for 7-10 days.
Child: >3 months 10 mg/kg 12 hourly. Max: 125 mg 12 houry for 7-10 days

Oral
Uncomplicated gonorrhoea
Dosage Details
Adult: As cefuroxime axetil: 1 g as a single dose. May be given w/ oral probenecid 1 g.

Oral
Lyme disease
Adult: As cefuroxime axetil: 500 mg bid for 20 days.
Child: >3 mth to 2 yr 10 mg/kg bid. Max 125 mg bid; >2 yr 15 mg/kg bid. Max: 250 mg bid.

Parenteral
Prophylaxis of surgical infections
Adult: 1.5 g IV before the procedure followed by 750 mg IM 8 hrly for up to 24-48 hr depending on
the procedure. For total joint replacement: 1.5 g, may be mixed w/ methylmethacrylate cement.

Parenteral
Susceptible infections
Adult: As cefuroxime Na: 0.75 g 8 hrly, by deep IM or slow IV inj over 3-5 min or IV infusion, may
increase up to 1.5 g 6-8 hrly in more severe infections.
Child: ≤3 wk 30-100 mg/kg daily by IV inj given as 2 or 3 divided doses; >3 wk <40 kg: 30-100
mg/kg daily by IV inj given as 3 or 4 divided doses; 60 mg/kg daily to most infections.

Parenteral
Pneumonia
Adult: 1.5 g bid by deep IM or slow IV inj over 3-5 min or IV infusion, followed by an oral dose 0.5
g bid.
Child: ≤3 wk 30-100 mg/kg daily by IV inj given as 2 or 3 divided doses; >3 wk <40 kg: 30-100
mg/kg daily by IV inj given as 3 or 4 divided doses; 60 mg/kg daily to most infections.

Parenteral
Acute exacerbations of chronic bronchitis

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 Adult: 750 mg bid by deep IM or slow IV inj over 3-5 min or IV infusion, followed by an oral dose
500 mg bid.
Child: ≤3 wk 30-100 mg/kg daily by IV inj given as 2 or 3 divided doses; >3 wk <40 kg: 30-100
mg/kg daily by IV inj given as 3 or 4 divided doses; 60 mg/kg daily to most infections.

Patients on haemodialysis should receive an additional 750-mg dose after each dialysis. Patients
on continuous peritoneal dialysis may be given 750 mg bid.
Renal Impairment CrCl Dosage
<10 750 mg once a day
10 to 30 750 mg bid
Oral Susp: Should be taken with food.
Administration
Tab: May be taken with or without food.
Contraindication Hypersensitivity to cefuroxime or to other cephalosporins.
History of hypersensitivity to penicillin, and GI disease (particularly colitis). Renal impairment.
Special Precautions
Pregnancy and lactation.
Rash, fever, pruritus, erythema, urticaria, Stevens-Johnson syndrome, erythema multiforme, toxic
epidermal necrolysis, serum sickness-like reactions, angioedema; mild to moderate hearing loss
(childn); nausea, vomiting, gagging, epigastric burning, GI bleeding and infection, abdominal pain,
flatulence, ptyalism, indigestion, mouth ulcers, swollen tongue, anorexia, thirst, dyspepsia,
stomach cramps, diarrhoea; decreased Hb and haematocrit, thrombocytosis, lymphocytosis,
haemolytic anaemia, increased prothrombin time; transient increase in serum AST (SGOT), ALT
(SGPT), alkaline phosphatase, LDH and bilirubin levels; transient increase in BUN and/or serum
Adverse Drug creatinine concentration, decreased CrCl, bilateral renal cortical necrosis; UTI, kidney pain,
Reaction urethral pain or bleeding, dysuria, vaginitis, vag candidiasis, vulvovaginal pruritus, vag discharge
or irritation; Jarisch-Herxheimer reaction; neck muscle spasm, muscle cramps or stiffness, chest
pain or tightness, shortness of breath, tachycardia, chills, lockjaw-type reaction, viral illness, upper
resp infection, sinusitis, cough, joint swelling, arthralgia; pain at inj site, thrombophlebitis (IV).
Rarely, transient eosinophilia and neutropenia, pancytopenia, leucopenia, thrombocytopenia;
headache, somnolence or sleepiness, dizziness, hyperactivity, irritable behaviour, myoclonic jerks,
seizures, generalised hyperexcitability; jaundice; acute renal failure, interstitial nephritis.
Potentially Fatal: Anaphylaxis, pseudomembranous colitis.
Pregnancy Status IM/IV/Parenteral/PO : B
Symptoms: Encephalopathy, convulsions and coma. Management: Haemodialysis or peritoneal
Overdosage
dialysis may reduce serum levels.
May enhance the nephrotoxic effect of strong-acting diuretics (e.g. furosemide) and
Drug Interaction aminoglycosides. May enhance the effect of oral anticoagulants. May reduce the efficacy of OCs.
Probenecid prolongs the excretion of cefuroxime and elevated peak serum level.
Food interaction May enhance absorption w/ food.
Description: Cefuroxime inhibits bacterial cell wall synthesis by binding to one 1 or more of the
penicillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of
peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis and arresting
cell wall assembly resulting in bacterial cell death.
Pharmacokinetics:
Absorption: Absorbed from the GI tract. Enhanced by the presence of food. Time to peak plasma
Mechanism of Action
concentration: Approx 2-3 hr (oral); 45 min (IM).
Distribution: Widely distributed into the body (including pleural fluid, synovial fluid, aqueous
humour, sputum, bone), CSF even on inflamed meninges. Crosses the placenta and enters breast
milk. Plasma protein binding: Up to 50%.
Excretion: Via urine (66-100% as unchanged drug); bile (small amounts). Plasma half-life: Approx
70 min.
MIMS Class Cephalosporins
S01AA27 - cefuroxime ; Belongs to the class of second-generation cephalosporins. Used in the
treatment of eye infections.
ATC Classification
J01DC02 - cefuroxime ; Belongs to the class of second-generation cephalosporins. Used in the
systemic treatment of infections.

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CLINDAMYCIN TOPICAL
Adult : PO Serious anaerobic infections 150-300 mg 6 hrly, up to 450 mg in severe infections.
Max: 1.8 g/day. IM/IV Severe anaerobic infections 0.6-2.7 g/day in 2-4 divided doses, increased
Dosage to 4.8 g/day in life-threatening infections. Infuse IV admin over 10-60 min and at a rate of ≤30
mg/min. Topical/Cutaneous Acne As 1% preparation: Apply a thin layer onto affected area bid.
Vag Bacterial vaginosis As pessary or 2% cream: 100 mg at bedtime for 3-7 days.
Oral
Severe anaerobic infections
Adult: 150-300 mg 6 hrly, up to 450 mg in severe infections. Max: 1.8 g/day.
Child: 3-6 mg/kg 6 hrly. <10 kg: ≥37.5 mg 8 hrly.

Parenteral
Severe anaerobic infections
Adult: 0.6-2.7 g daily in 2-4 divided doses, increased to 4.8 g daily in life-threatening infections.
Infuse IV admin over 10-60 min and at a rate of ≤30 mg/min. Single dose of IM inj should not
exceed 600 mg nor is admin of above 1.2 g in a single 1 hr infusion.
Dosage Details Child: >1 mth 15-25 mg/kg daily in 3 or 4 divided doses; in severe infections, increase to 40 mg/kg
daily and a min dose of 300 mg daily should be given regardless of body wt.

Topical/Cutaneous
Acne
Adult: As 1% preparation: Apply a thin layer onto affected area bid.

Vaginal
Bacterial vaginosis
Adult: As pessary or 2% cream: 100 mg at bedtime for 3-7 days.

Granules: Should be taken with food.

Administration Cap: May be taken with or without food. Swallow whole w/ a full glass of water & in an upright
position.
Contraindication Hypersensitivity to clindamycin or lincomycin.
Patient w/ history of GI disease particularly colitis, atopic individuals. Not intended for the
Special Precautions
treatment of CNS infections. Severe renal and/or hepatic impairment. Pregnancy and lactation
Nausea, vomiting, abdominal pain or cramps, taste disturbances, oesophagitis, oesophageal
ulceration, rashes, urticaria, erythema multiforme, Stevens-Johnson syndrome, drug rash w/
eosinophilia and systemic symptoms (DRESS), exfoliative and vesiculobullous dermatitis,
Adverse Drug leucopenia, agranulocytosis, eosinophilia, thrombocytopenia, polyarthritis, renal dysfunction (e.g.
Reaction azotemia, oliguria, proteinuria), local irritation, skin dryness, contact dermatitis, cervicitis,
vaginitis, vag candidiasis, vulvovaginal irritation, sterile abscess and thrombophlebitis.
Potentially Fatal: Clostridium difficile-associated diarrhoea (CDAD) or pseudomembranous colitis,
toxic epidermal necrolysis (TEN).
Pregnancy Status IM/IV/Parenteral/PO/Topical/Vag: B
May enhance the action of neuromuscular blocking agents (e.g. atracurium). May antagonise the
effects of parasympathomimetics. May competitively inhibit the effects of macrolides, ketolides,
Drug Interaction
streptogramins, linezolid and chloramphenicol. Increased coagulation tests (prothrombin
time/INR) and/or bleeding w/ vit K antagonists (e.g. warfarin, acenocoumarol, fluindione).
Description: Clindamycin inhibits protein synthesis by reversibly binding to the 50S ribosomal
subunit, thus blocking the transpeptidation or translocation reactions of susceptible organisms
resulting to stunted cell growth.
Pharmacokinetics:
Absorption: Rapidly absorbed from the GI tract (approx 90%); skin (approx 4-5%); and
systemically as an intravaginal preparation (approx 5%). Food may reduce rate of absorption.
Mechanism of Action Time to peak plasma concentration: W/in 60 min (oral); 1-3 hr (IM).
Distribution: Widely distributed in body fluids and tissues, including bone. Crosses the placenta
and enters breast milk. Volume of distribution: Approx 2 L/kg. Plasma protein binding: >90%.
Metabolism: Undergoes hepatic metabolism to the active N-demethyl and sulfoxide metabolites
and some inactive metabolites.
Excretion: Via urine as active drug or metabolites (approx 10%); faeces (approx 4%); and the
remainder as inactive metabolites. Plasma half-life: 2-3 hr.
MIMS Class Topical Antibiotics / Other Antibiotics

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MEFENAMIC ACID
Adult : PO Mild to moderate pain; Postoperative pain; Pain and inflammation associated
Dosage with musculoskeletal and joint disorders; Rheumatoid arthritis; Osteoarthritis; Dental
pain; Headache; Primary dysmenorrhoea; Menorrhagia 500 mg tid.
Oral
Dental pain, Headache, Menorrhagia, Mild to moderate pain, Osteoarthritis, Pain and
inflammation associated with musculoskeletal and joint disorders, Postoperative pain,
Dosage Details Primary dysmenorrhoea, Rheumatoid arthritis
Adult: 500 mg tid.
Child: ≥14 years Same as adult dose.
Elderly: Initiate at a lower dose and shortest possible duration.
Renal Impairment Severe: Contraindicated
Hepatic Impairment Severe: Contraindicated
Hypersensitivity. Patients with active or history of recurrent peptic ulcer/haemorrhage, history of
gastrointestinal bleeding or perforation (related to previous NSAID therapy), inflammatory bowel
disease, severe heart failure, history of asthma, bronchospasm, rhinitis, angioedema, urticaria, or
Contraindication
allergic-type reactions after taking aspirin or other NSAIDs. Treatment of peri-operative pain in
the setting of CABG surgery. Renal (CrCl <30 mL/min) and severe hepatic impairment. Pregnancy
(3rd trimester).
Administration Should be taken with food
Patient with risk factors for CV events (e.g. hypertension, hyperlipidaemia, diabetes mellitus,
Special Precautions smoking), mild to moderate heart failure, hypovolaemia, dehydration. Debilitated patient. Renal
and hepatic impairment. Elderly. Pregnancy (1st-2nd trimester) and lactation.
Significant: Anaphylactoid reactions, fluid retention, anaemia, hyperkalaemia.
Blood and lymphatic system disorders: Eosinophilia, leukopenia, thrombocytopenia, purpura,
agranulocytosis.
Cardiac disorders: Dyspnoea.
Ear and labyrinth disorders: Tinnitus.
Gastrointestinal disorders: Diarrhoea, nausea, vomiting, abdominal pain, flatulence, constipation,
dyspepsia, heartburn, gastritis.
Hepatobiliary disorders: Hepatitis, jaundice.
Investigations: Increased liver enzymes.
Adverse Drug
Nervous system disorders: Aseptic meningitis, headache.
Reaction
Psychiatric disorders: Nervousness, insomnia, confusion, depression.
Renal and urinary disorders: Dysuria, cystitis.
Reproductive system and breast disorders: Haematuria.
Respiratory, thoracic and mediastinal disorders: Asthma.
Skin and subcutaneous tissue disorders: Pruritus, urticaria, rash, erythema multiforme.
Vascular disorders: Hypertension.
Potentially Fatal: CV thrombotic events including MI and stroke, gastrointestinal inflammation,
bleeding, ulceration, perforation. Rarely, exfoliative dermatitis, toxic epidermal necrolysis,
Stevens-Johnson syndrome, fulminant hepatitis, liver necrosis, hepatic failure.
Pregnancy Status PO: C, D (Avoid during 3rd trimester or near delivery.)
Symptoms: Lethargy, drowsiness, headache, nausea, vomiting, epigastric pain, gastrointestinal
bleeding. Rarely, diarrhoea, disorientation, excitation, tinnitus, fainting, hypertension, acute renal
Overdosage
failure, respiratory depression, and coma. Management: Symptomatic and supportive treatment.
Administer activated charcoal or consider emesis within 4 hours of ingestion of large overdoses.
May increase the risk of bleeding with other NSAIDs or salicylates (e.g. aspirin), anticoagulants
(e.g. warfarin), corticosteroids, SSRI. Increased the risk of nephrotoxicity of ciclosporin or
tacrolimus. May decrease efficacy of antihypertensive agents (e.g. ACE inhibitors, angiotensin II
Drug Interaction
antagonists, ß-blockers). Decreased natriuretic effect of diuretics (e.g. furosemide,
hydrochlorothiazide). Increased plasma levels and reduced renal clearance of lithium. Increased
serum concentration of digoxin and methotrexate.
Description: Mefenamic acid, an anthranilic acid derivative, is an NSAID. It reversibly inhibits
cyclooxygenase-1 and -2 (COX-1 and -2), thus resulting in reduced rate of prostaglandin synthesis.
It exhibits analgesic, anti-inflammatory and antipyretic properties.
Mechanism of Action Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration:
2-4 hours.
Distribution: Present in breast milk. Volume of distribution: 1.06 L/kg. Plasma protein binding:

Acer | PHARMACOLOGY LAB 7

 >90% to albumin.
Metabolism: Metabolised in the liver by CYP2C9 isoenzyme to 3-hydroxymethyl mefenamic acid,
which may then be oxidised to 3-carboxymefenamic acid.
Excretion: Via urine (approx 52%; 6% as glucuronides, 25% as 3-hydroxymefenamic acid, 21% as
3-carboxymefenamic acid), faeces (up to 20%, mainly as unconjugated 3-carboxymefenamic acid).
Elimination half-life: Approx 2 hours
MIMS Class Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
M01AG01 - mefenamic acid ; Belongs to the class of non-steroidal antiinflammatory and
ATC Classification
antirheumatic products, fenamates.

FERROUS SULFATE
Indication Iron-deficiency Anemia
Dosage Adult : PO As elemental Fe: Treatment: 100-200 mg/day. Prevention: 60 mg/day.
Oral
Iron-deficiency anaemia
Dosage Details
Adult: As elemental Fe: Treatment: 100-200 mg daily. Prevention: 60 mg daily.
Child: As elemental Fe: Treatment: 3-6 mg/kg daily in 3 divided doses.
Should be taken on an empty stomach. Best taken on an empty stomach. May be taken w/ meals to
Administration
reduce GI discomfort.
Haemochromatosis, haemosiderosis and other Fe overload syndromes, haemolytic anemia, active
Contraindication peptic ulcer, regional enteritis and ulcerative colitis. Patients receiving repeated blood
transfusions or concomitant parenteral Fe therapy.
Patient w/ haemoglobinopathy, Fe-storage/absorption diseases, history of peptic ulcer; post-
Special Precautions
gastrectomy patients. Pregnancy and lactation.
GI: Epigastric pain, GI discomfort, nausea, vomiting, constipation or diarrhoea, faecal impaction,
Adverse Drug dark stools, anorexia, reversible dental staining.
Reaction Genitourinary: Urine discoloration.
Dermatologic: Allergic reactions.
Pregnancy Status
Symptoms: Early signs (1st phase, up to 6 hr after ingestion) include GI toxicity (predominantly
vomiting and diarrhoea), hypotension, tachycardia, metabolic changes (e.g. acidosis,
hyperglycaemia) and CNS depression ranging from lethargy to coma. Temporary remission or
clinical stabilisation may occur during the 2nd phase (6-24 hr after ingestion). GI toxicity may
recur w/ shock, metabolic acidosis, convulsions, coma, hepatic necrosis and jaundice, oliguria or
renal failure, hypoglycaemia, coagulation disorders and pulmonary oedema in the 3rd phase. A 4th
Overdosage phase (several wk after ingestion) may follow and is characterised by GI obstruction and possibly,
late hepatic damage. Management: Gastric lavage followed by instillation of desferrioxamine 5 g in
the stomach. Supportive and symptomatic treatment w/ IV desferrioxamine may be given in
severe cases. Gastric lavage w/ bicarbonate 5% and saline cathartics; eggs and milk w/ bismuth
carbonate 5 g hrly as demulcents. Chelating agents (e.g. disodium Ca edetate) may also be
considered. For severe poisoning in infants, administer IM desferrioxamine 90 mg/kg followed by
15 mg/kg/hr IV until the serum Fe is w/in the plasma binding capacity.
Reduced absorption w/ antacids, Zn, Ca, phosphorus, trientine, and cholestyramine. Enhanced
absorption w/ ascorbic acid. May reduce the bioavailability of methyldopa. May reduce the
Drug Interaction
absorption of penicillamine, fluoroquinolones, and levodopa. Concurrent admin w/ tetracyclines
may impair absorption of both agents. Enhanced nephrotoxic effect w/ dimercaprol.
Food interaction Decreased absorption w/ food esp cereals, dietary fibre, eggs, milk, coffee, tea.
Description: Ferrous sulfate facilitates O2 transport via Hb. It is used as iron source as it replaces
Fe found in Hb, myoglobin and other enzymes.
Onset: Haematologic response: Approx 3-10 days.
Mechanism of Action Pharmacokinetics:
Absorption: Absorbed in the duodenum and upper jejunum.
Distribution: Plasma protein binding: Bound to transferrin.
Excretion: Via urine, sweat, sloughing of the intestinal mucosa and menses.
MIMS Class Vitamins & Minerals (Pre & Post Natal) / Antianemics
B03AA07 - ferrous sulfate ; Belongs to the class of oral iron bivalent preparations. Used in the
ATC Classification
treatment of anemia.

Acer | PHARMACOLOGY LAB 8

CELECOXIB
Adult : PO Osteoarthritis 200 mg/day as a single dose or in 2 divided doses, may increase up to
200 mg bid. Ankylosing spondylitis 200 mg/day as a single dose or in 2 divided doses, may
Dosage increase to max dose of 400 mg/day after 6 weeks. Rheumatoid arthritis 100-200 mg bid.
Primary dysmenorrhoea; Acute pain Initial: 400 mg followed by additional dose of 200 mg if
necessary on day 1. Subsequently, 200 mg bid as needed.
Oral
Osteoarthritis
Adult: 200 mg daily as a single dose or in 2 divided doses, may increase up to 200 mg bid as
needed. Max: 400 mg daily.
Elderly: <50 kg: Use the lowest recommended dose.

Oral
Acute pain, Primary dysmenorrhoea
Adult: Initially, 400 mg followed by additional dose of 200 mg if necessary on day 1. Subsequently,
200 mg bid as needed.
Elderly: Acute pain: <50 kg: Use the lowest recommended dose.

Oral
Dosage Details Ankylosing spondylitis
Adult: 200 mg daily as a single dose or in 2 divided doses, may increase to max dose of 400 mg
daily after 6 weeks if necessary.
Elderly: <50 kg: Use the lowest recommended dose.

Oral
Rheumatoid arthritis
Adult: 100 or 200 mg bid. Max: 400 mg daily.
Elderly: <50 kg: Use the lowest recommended dose.

Oral
Juvenile idiopathic arthritis
Child: ≥2 years 10-25 kg: 50 mg bid; >25 kg: 100 mg bid.

Pharmacogenomics:
Celecoxib is metabolised by CYP2C9 enzyme into hydroxycelecoxib. Genetic polymorphism of
CYP2C9 may have direct impact on the pharmacokinetics of celecoxib and variability in drug
responses. CYP2C9 genotyping test may be considered prior to initiation of therapy in order to
select the dose of celecoxib and to avoid possible side effects.
Special Treatment
Group
CYP2C9 poor metabolisers (carriers of allele *3/*3)
Patient may have reduced metabolism of celecoxib and may have higher risk of adverse effects,
particularly gastrointestinal bleeding. Reduce initial dose by 50% of the lowest recommended
dose in adults and alternative treatments may be considered in children with juvenile idiopathic
arthritis. Shortest possible duration of treatment is recommended.
Renal Impairment Severe: Contraindicated.
Moderate (Child-Pugh class B): Reduce dose by 50%. Severe (Child-Pugh class C or ≥10 score):
Hepatic Impairment
Contraindicated.
Hypersensitivity (including urticaria, asthma, angioneurotic edema) to celecoxib and other
NSAIDs, aspirin or sulfonamides. Active peptic ulceration or gastrointestinal bleeding,
inflammatory bowel disease, CHF (NYHA II-IV), established ischaemic heart disease,
Contraindication
cerebrovascular disease or peripheral arterial disease. Treatment of postoperative pain in the
setting of CABG surgery. Severe renal (CrCl <30 mL/min) and hepatic (Child-Pugh class C or ≥10
score) impairment. Pregnancy (3rd trimester) and lactation.
Patient with history of gastrointestinal complications (e.g. ulceration and bleeding), hypertension,
diabetes mellitus, hyperlipidaemia, recent MI, and other CV disease risk factors (e.g. smoking,
alcoholism); pre-existing asthma (without known aspirin sensitivity), pre-existing oedema,
Special Precautions
hypovolaemia. Dehydrated patient. May mask underlying fever and other signs of inflammation.
CYP2C9 poor metabolisers. Moderate hepatic impairment. Children and elderly. Pregnancy (1st-
2nd trimester).

Acer | PHARMACOLOGY LAB 9

 Significant: Fluid retention, oedema, hypertension, renal papillary necrosis (prolonged use).
Blood and lymphatic system disorders: Anaemia.
Cardiac disorders: Angina pectoris.
Gastrointestinal disorders: Nausea, abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting,
dysphagia, GERD, irritable bowel syndrome.
General disorders and administration site conditions: Influenza-like symptoms.
Injury, poisoning and procedural complications: Accidental injury.
Investigations: Increased blood creatinine, weight increased, elevated ALT or AST.
Musculoskeletal and connective tissue disorders: Arthralgia.
Nervous system disorders: Headache, hypertonia.
Adverse Drug
Psychiatric disorders: Insomnia.
Reaction
Renal and urinary disorders: Nephrolithiasis, UTI.
Reproductive system and breast disorders: Benign prostatic hyperplasia.
Respiratory, thoracic and mediastinal disorders: Sinusitis, upper respiratory tract infection,
pharyngitis, dyspnea, rhinitis, cough.
Skin and subcutaneous tissue disorders: Rash, pruritus.
Potentially Fatal: Gastrointestinal perforation, ulceration, or bleeding; CV thrombotic events
including MI and stroke, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal
necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalised
exanthematous pustulosis, anaphylaxis, severe hepatic reactions (e.g. fulminant hepatitis, hepatic
necrosis, hepatic failure).
Pregnancy Status PO: C (prior to 30 weeks gestation), D (starting at 30 weeks gestation)
Increased risk of gastrointestinal ulceration or bleeding with anticoagulants (e.g. warfarin,
apixaban), antiplatelet agents (e.g. aspirin), SSRIs, corticosteroids (e.g. glucocorticoids), other
NSAIDs. May reduce the antihypertensive effect of ACE inhibitors, angiotensin II receptor
antagonists, diuretics, β-blockers and other antihypertensive agents. May increase the nephrotoxic
Drug Interaction effect of ciclosporin and tacrolimus. Increases the serum concentration of lithium, digoxin and
methotrexate. Increased plasma concentration with CYP2C9 inhibitors (e.g. fluconazole).
Decreased plasma concentrations with CYP2C9 inducers (e.g. rifampicin, carbamazepine,
barbiturates). May increase serum concentration and toxicity of CYP2D6 substrates (e.g.
aripiprazole, perhexiline, atomoxetine).
Description: Celecoxib, an NSAID, is a selective cyclooxygenase-2 (COX-2) inhibitor primarily
responsible for inhibition of prostaglandin synthesis. It exhibits anti-inflammatory, analgesic and
antipyretic activities.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. High fat meal may delay absorption
time. Time to peak plasma concentration: Approx 2-3 hours.
Mechanism of Action
Distribution: Extensively distributed in tissues and present in breastmilk. Volume of distribution:
Approx 400 L. Plasma protein binding: Approx 97%, mainly to albumin.
Metabolism: Metabolised in the liver by CYP2C9 to form inactive metabolites such as a primary
alcohol, corresponding carboxylic acid and its glucuronide conjugate.
Excretion: Via urine (27% as metabolites, <3% as unchanged drug), faeces (approx 57% as
metabolites, <3% as unchanged drug). Elimination half-life: Approx 11 hours.
MIMS Class Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
M01AH01 - celecoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic
ATC Classification
products, coxibs.

Acer | PHARMACOLOGY LAB 10

ETORICOXIB
Adult : PO Osteoarthritis 30 mg once daily, may increase to 60 mg once daily as necessary.
Ankylosing spondylitis; Rheumatoid arthritis 60 mg once daily, may increase to 90 mg once
Dosage daily as necessary. Once patient is clinically stable, may reduce dose to 60 mg once daily. Acute
gouty arthritis 120 mg once daily. Max duration: 8 days. Pain and inflammation associated
with dental surgery 90 mg once daily. Max duration: 3 days.
Oral
Ankylosing spondylitis, Rheumatoid arthritis
Adult: 60 mg once daily, may increase to 90 mg once daily as necessary. Once patient is clinically
stable, may reduce dose to 60 mg once daily.

Oral
Osteoarthritis
Adult: 30 mg once daily, may increase to 60 mg once daily as necessary.
Dosage Details
Oral
Acute gouty arthritis
Adult: 120 mg once daily. Max duration: 8 days.

Oral
Pain and inflammation associated with dental surgery
Adult: 90 mg once daily. Max duration: 3 days.
CrCl Dosage
Renal Impairment
<30 Contraindicated
Mild (Child-Pugh score 5-6): Max: 60 mg once daily. Moderate (Child-Pugh score 7-9): Max: 30 mg
Hepatic Impairment
once daily. Severe (Child-Pugh score ≥10): Contraindicated.
Hypersensitivity. Patient with active peptic ulceration or gastrointestinal bleeding, inflammatory
bowel disease, congestive heart failure (NYHA II-IV), uncontrolled hypertension or with
persistently high blood pressure (>140/90 mmHg), ischaemic heart disease, peripheral arterial
Contraindication disease, cerebrovascular disease, history of bronchospasm, acute rhinitis, nasal polyps,
angioneurotic oedema, urticaria or allergic-type reactions after taking aspirin, NSAIDs including
COX-2 inhibitors. Children and adolescent <16 years. Renal (CrCl <30 mL/min) and severe hepatic
(Child-Pugh ≥10) impairment. Pregnancy.
Patient with history of gastrointestinal disease (e.g. ulceration, gastrointestinal bleeding), with risk
factors for cardiovascular events (e.g. hyperlipidaemia, hypertension, diabetes mellitus, smoking),
Special Precautions
uncompensated heart failure, cirrhosis, history of cardiac failure, left ventricular dysfunction, pre-
existing oedema, dehydration. Mild to moderate hepatic impairment. Elderly. Lactation.
Significant: Fluid retention, oedema, hypertension, increased ALT or AST, hypersensitivity
reactions including anaphylaxis and angioedema.
Cardiac disorders: Palpitations, arrhythmia.
Gastrointestinal disorders: Abdominal pain, constipation, flatulence, gastritis, heartburn, diarrhoea,
dyspepsia, nausea, vomiting, oesophagitis, oral ulcer.
Adverse Drug
General disorders and admin site conditions: Asthenia, flu-like disease.
Reaction
Infections and infestations: Alveolar osteitis.
Nervous system disorders: Headache.
Respiratory, thoracic and mediastinal disorders: Bronchospasm.
Potentially Fatal: Gastrointestinal perforations, ulcers or bleedings, exfoliative dermatitis,
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
Symptoms: Gastrointestinal events, cardiorenal events. Management: Supportive treatment e.g.
Overdosage
removal of unabsorbed drug from the gastrointestinal tract and clinical monitoring.
Increased INR with anticoagulants (e.g. warfarin). May decrease effect of diuretics and
antihypertensive agents. Concomitant use with ACE inhibitor or angiotensin II antagonist may
further deteriorate renal function. May increase rate of gastrointestinal ulceration with
Drug Interaction
concomitant low dose acetylsalicylic acid. Increased plasma concentrations of ethinylestradiol,
lithium, methotrexate, and other drugs metabolised by human sulfotransferases (e.g. oral
salbutamol, minoxidil). Decreased plasma concentrations with rifampicin.
Description: Etoricoxib, an NSAID, is a selective cyclo-oxygenase-2 (COX-2) inhibitor. Its anti-
inflammatory and analgesic action is exhibited by inhibition of prostaglandin synthesis via
Mechanism of Action
inhibition of COX-2.
Pharmacokinetics:

Acer | PHARMACOLOGY LAB 11

 Absorption: Well absorbed from the gastrointestinal tract, food delays rate of absorption.
Absolute bioavailability: Approx 100%. Time to peak plasma concentrations: Approx 1 hour
(without food), 2 hours (with food).
Distribution: Volume of distribution: 120 L. Plasma protein binding: Approx 92%.
Metabolism: Extensively metabolised via CYP3A4 isoenzyme to form 6’-hydroxymethyl derivative
of etoricoxib, then oxidised to 6’-carboxylic acid derivative (major metabolite).
Excretion: Mainly via urine (70%), 20% in faeces, <2% as unchanged drug. Elimination half-life:
Approx 22 hours.
MIMS Class Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
M01AH05 - etoricoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic
ATC Classification
products, coxibs.

FUSIDIC ACID
dult : PO Cutaneous staphylococcal infections 250 mg twice daily. Staphylococcal infections
500 mg 8 hrly, may double in severe cases. IV Severe staphylococcal infections >50 kg: 500 mg 3
Dosage
times/day; <50 kg: 6-7 mg/kg 3 times/day. Topical Skin infections As 2% oint/cream/gel: Apply
3-4 times/day.
Intravenous
Susceptible infections
Adult: >50 kg: 500 mg tid; may increase to 1 g tid in fulminating infections. <50 kg: 6-7 mg/kg tid.
To be given by slow IV infusion over at least 2 hr; should be given via a large vein with good blood
flow.
Child: 20 mg/kg daily in 3 divided doses. To be given by slow IV infusion over at least 2 hr; should
be given via a large vein with good blood flow.

Ophthalmic
Conjunctivitis
Adult: As 1% eye drops: Instill 1 drop into the affected eye every 12 hr for 7 days.
Child: ≥2 yr: As 1% eye drops: Instill 1 drop into the affected eye every 12 hr for 7 days.

Oral
Dosage Details
Susceptible infections
Adult: 500 mg tid. May increase to 1 g tid in severe infections.
Child: <1 year 6mg/kg; 1-5 years 250 mg; 5-12 years 500 mg; >12 years Same as adult dose. Doses
to be taken tid.

Topical/Cutaneous
Skin infections
Adult: As a 2% ointment/cream/gel: Apply onto affected area 3-4 times daily until there is
improvement. If gauze dressing is used, then frequency of application may be reduced to 1-2 times
daily.
Child: As a 2% ointment/cream/gel: Apply onto affected area 3-4 times daily until there is
improvement. If gauze dressing is used, then frequency of application may be reduced to 1-2 times
daily.

Administration Should be taken with food.

Contraindication Hypersensitivity
Special Precautions Hepatic disease, monitor liver function. Neonates: pregnancy, lactation
Adverse Drug Jaundice and liver dysfunction (reversible); GI disturbances. IV: Venospasm, thrombophloebitis
Reaction and haemolysis; hypocalcaemia. SC/IM: Tissue necrosis. Topical: Rashes and irritation
Pregnancy Status
Overdosage
Drug Interaction Synergistic action with antistaphylococcal penicillin. Antagonism with ciprofloxacin.
Food interaction Delays absorption for oral preparations.
Description: Fusidic acid disrupts translocation of peptide subunits and elongating the peptide
chain of susceptible bacteria, thus inhibiting protein synthesis.
Pharmacokinetics:
Mechanism of Action
Absorption: Well-absorbed from the GI tract (oral); mean plasma concentrations of 30 mcg/ml
after 2-4 hr (500-mg dose). More rapid absorption in children than in adults.
Distribution: Widely distributed into tissues and body fluids including bone, pus and synovial

Acer | PHARMACOLOGY LAB 12

 fluid; crosses the placenta and enters breast milk. Protein-binding: 95%.
Metabolism: Hepatic; converted to multiple metabolites.
Excretion: Bile (mainly as metabolites), faeces (2% as unchanged drug), urine; 5-6 hr (elimination
half-life).
MIMS Class Topical Antibiotics/Other Antibiotics

ROSUVASTATIN
Adult : PO Hyperlipidaemias; Prophylaxis of CV events in high-risk patients Initial: 5 or 10
Dosage
mg/day, may increase at 4-wk intervals to 20 mg/day if needed. Max: 40 mg/day.
Oral
Hyperlipidaemias, Prophylaxis of cardiovascular events in high-risk patients
Adult: Initially, 5 or 10 mg once daily, may increase dose at 4-wkly intervals to 20 mg daily if
Dosage Detaills necessary. Max: 40 mg once daily.
Child: Heterozygous familial hypercholesterolaemia: ≥10 yr Initially, 5 mg once daily, may be
adjusted at intervals of at least 4 wk. Max: 20 mg once daily.

Asian patients: Initial: 5 mg once daily. 40 mg dose is contraindicated.

Pharmacogenomics:

The SLCO1B1 gene, which encodes the transporter protein OATP1B1 and the efflux transporter
ABCG2, both play a role in the disposition of rosuvastatin and mediate the hepatic uptake of statins.
Genetic polymorphism in SLCO1B1 can affect the plasma concentrations of rosuvastatin.

SLCO1B1 with CC genotype:

Patient may have higher plasma concentrations of rosuvastatin but no change in LDL-cholesterol
level has been noted.
Special Treatment
Group
SLCO1B1 with TT genotype:
Patient may have lower plasma concentrations of rosuvastatin but no change in LDL-cholesterol
level has been noted.

ABCG2 with GG genotype:

Patient may have lower plasma concentrations of rosuvastatin and may have reduced response to
treatment, determined by lower reduction in LDL-cholesterol.

ABCG2 with TT genotype:

Patient may have higher plasma concentrations of rosuvastatin and may have better response to
treatment, determined by higher reduction in LDL-cholesterol.
CrCl Dosage
Renal Impairment <30 Contraindicated
30-60 Initially, 5 mg once daily to max 20 mg once daily
Administration May be taken with or without food
Active liver disease or unexplained persistent elevated serum transaminases. Severe renal
Contraindication
impairment. Concomitant use w/ ciclosporin and gemfibrozil. Pregnancy and lactation.
Patients with SLCO1B1 and ABCG2 polymorphism; predisposing factors for myopathy (e.g.
Special Precautions
untreated hypothyroidism, renal impairment), history of chronic liver disease and alcoholism.
Headache, dizziness, constipation, nausea, vomiting, abdominal pain, myalgia, chest pain,
peripheral oedema, depression, insomnia, rash, paraesthesia, asthenia, abnormal LFT, elevated
Adverse Drug
serum transaminase levels.
Reaction
Potentially Fatal: Severe rhabdomyolysis w/ acute renal failure. Hepatitis, pancreatitis. Rare:
Stevens-Johnson syndrome, anaphylaxis, toxic epidermal necrolysis.
Pregnancy Status PO:X
May increase serum levels of warfarin and oral contraceptives. May increase serum levels w/
itraconazole, HIV protease inhibitors. May decrease serum levels w/ erythromycin and antacids.
Drug Interaction
May increase risk of myopathy w/ fenofibrate, niacin.
Potentially Fatal: Increased risk of rhabdomyolysis w/ gemfibrozil and ciclosporin
Description: Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-
Mechanism of Action limiting enzyme in cholesterol synthesis. It increases the number of hepatic LDL receptors on the
cell surface, enhancing uptake and catabolism of LDL. It also decreases apolipoprotein B,

Acer | PHARMACOLOGY LAB 13

 triglycerides and increases HDL.
Pharmacokinetics:
Absorption: Incompletely absorbed from the GI tract. Time to peak plasma concentration: Approx
5 hr. Absolute bioavailability: Approx 20%.
Distribution: Volume of distribution: 134 L. Plasma protein binding: Approx 90%.
Metabolism: Limited metabolism via CYP2C9 isoenzyme.
Excretion: Via faeces (approx 90%); urine (approx 5% as unchanged drug). Elimination half-life:
Approx 19 hr.
MIMS Class Dyslipidemic agents
C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the
ATC Classification
treatment of hyperlipidemia.

COMPILATION OF
DRUGS (PHARMA LAB)
SECTION B1 AND B2

Acer | PHARMACOLOGY LAB 14