ibuprofen

1

Maximum tolerated daily dose of

ibuprofen for a healthy adult

Hawkar Hama Rasheed-----Miran Mustafa Hama Rasheed

Muhamad Akram ---- Muhamad abdul rahman

Department of pharmacy informatics

School of pharmacy

University of Sulaimani

11/9/2013, 3rd stage, Group 4

Question

what is the maximum tolerated daily

dose of ibuprofen for a healthy adult ?

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Introduction

Ibuprofen, a propionic acid derivative, Nonsteroidal

anti-inflammatory drugs have analgesic, antipyretic,

and anti-inflammatory activities. Major mechanism is

believed to be inhibition of cyclooxygenase activity

and prostaglandin synthesis.

Methodology

Primary resouces: Primary acticle;

1- Alimentary Pharmacology & Therapeutics:

A randomized, double-blind trial of 125 patients was

performed. A dose of 2400 mg⁄day of ibuprofen or

an equivalent dose of ibuprofen-PC (ibuprofen-

phosphatidylcholine) was administered for 6 weeks.

GI safety was assessed by endoscopy. Efficacy was

assessed by scores of analgesia and anti inflammatory

activity. Bioavailability of ibuprofen was

pharmacokinetically assessed.

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Result

Ibuprofen-PC and ibuprofen provided similar

bioavailability ⁄therapeutic efficacy.

In the evaluable subjects, a trend for improved GI

safety in the ibuprofen-PC group compared with

ibuprofen that did not reach statistical significance

was observed. However, in patients aged >55 years, a

statistically significant advantage for ibuprofen-PC

treatment vs. ibuprofen in the prevention of NSAID-

induced gut injury was observed with increases in

both mean Lanza scores and the risk of developing

>2 erosions or an ulcer. Ibuprofen-PC was well

tolerated with no major adverse events observed.

( Clinical trial: comparison of ibuprofen phosphatidylcholine and

ibuprofen on the gastrointestinal safety and analgesic efficacy in

osteoarthritic patients ,Aliment Pharmacol Ther 28, 431–442)

2) Primary article: ibuprofen Nonsteroidal anti-

inflammatory drugs (NSAIDs) inhibit both

cyclooxygenase-1 (COX-1) and cyclooxygenase-2

(COX-2) because use for treatment osteoarthritis

(OA) maximum tolerated dose is 2.4g daily.

(Ric Day, MD; Briggs Morrison, MD; Armando Luza, MD; Oswaldo Castaneda,

MD; Alberto Strusberg, MD; Menachem Nahir, MD; Knut Bjorn Helgetveit, MD;

Barbara Kress, RN; Brian Daniels, MD; James Bolognese; Dave Krupa; Beth

Seidenberg, MD; Elliot Ehrich, MD; Arch Intern Med. 2000;160(12):1781-1787 )

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Secondary resources: Abstract;

3) PubMed:Medications containing the drug

ibuprofen relieve pain and reduce inflammation. They

are often used in mild to moderate migraine attacks. In

Germany, pharmacies sell ibuprofen in dosages up to

400 mg per tablet without prescription. To treat

migraine, a healthy adult takes between 200 and 400 mg

at a time. The maximum dose of ibuprofen for

otherwise healthy adults is 1,200 mg per day and

should not be exceeded to ensure safe use (Rabbie R, Derry S, Moore RA, McQuay HJ. Ibuprofen with or

without an antiemetic for acute migraine headaches in adults.

Cochrane Database Syst Rev. 2010)

4) Abstract: Fever was reduced significantly by IV

ibuprofen in burn patients over the initial 24-hour dosing

period and remained reduced throughout the dosing

period. Exposure to the maximum daily recommended

dose of 3200 mg (800 mg every 6 hours) for a total of

120 hours (5 days) was well tolerated. (Promes JT, Safcsak K, Pavliv L, Voss B, Rock A. Source

Department of Surgical Education, Orlando Regional Medical Center,

Orlando, Florida 32806, USA.)

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Tertiary resources: Textbooks;

5) Drug Fact And Comparison: Adults dose –

Do not exceed 3.2 g/day. If GI upset occurs, take

with meals or milk.

Rheumatoid arthritis and osteoarthritis: 1.2 to 3.2

g/day (300 mg 4 times/day or 400, 600, or 800 mg

3 or 4 times/day).

Mild to moderate pain: 400 mg every 4 to 6 hours,

as necessary.

Primary dysmenorrhea: 400 mg every 4 hours, as

necessary.

OTC use (minor aches and pains, dysmenorrhea,

fever reduction): 200 mg every 4 to 6 hours while

symptoms persist. If pain or fever do not respond

to 200 mg, 400 mg may be used. Do not exceed 1.2

g in 24 hours. Do not take for pain for longer than

10 days or for fever for longer than 3 days

unless directed. (Drug Fact And Comparison 2007 Edition)

6) Renal drug hand book:

Initially: 1.2–1.8 g daily in 3–4 divided doses, after

food. Maximum 2.4 g daily dose for pain

(The Renal Drug Handbook ,Third Edition,Edited by Caroline Ashley

and Aileen Currie, UK Renal Pharmacy Group)

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7) American Society of Healthsystem Pharmacists

(AHFS Drug): Adults dose

Inflammatory Diseases:

Osteoarthritis or Rheumatoid Arthritis

Oral: 1.2-3.2 g daily, given as 300 mg 4 times daily,

or 400, 600, or 800 mg 3 or 4 times daily.

Pain:

Oral: For mild to moderate pain, 400 mg every 4-6

hours as needed.

For self-medication of minor aches and pain, 200 mg

every 4-6 hours; may increase dosage to 400 mg

every 4-6 hours if needed.

For self-medication of migraine pain, 400 mg once in

a 24-hour period.

IV:

Individuals ≥17 years of age: 400-800 mg every 6

hours as needed.

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Dysmenorrhea:

Oral: 400 mg every 4 hours as necessary; initiate at

earliest onset of pain.

For self-medication, 200 mg every 4-6 hours; may

increase to 400 mg every 4-6 hours if necessary.

Fever:

Oral: For self-medication, 200 mg every 4-6 hours;

may increase to 400 mg every 4-6 hours if needed.

IV:

Individuals ≥17 years of age: 400 mg initially; then

400 mg every 4-6 hours or 100-200 mg every 4

hours.

(AHFS Drug information book 2008)

8) Drug Information Handbook: Inflammatory

disease: Oral: 400-800 mg/dose 3-4 times/day

(maximum: 3.2 g/day)

Analgesia/pain/fever/dysmenorrhea: Oral: 200-400

mg/dose every 4-6 hours (maximum daily dose: 1.2

g, unless directed by physician; under physician

supervision daily doses 2.4 g may be used)

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OTC labeling (analgesic, antipyretic): Oral: 200 mg

every 4-6 hours as needed (maximum: 1200 mg/24

hours); treatment for >10 days is not recommended

unless directed by healthcare provider.

(Drug Information Handbook, 17th Edition)

9) Martindale: The usual oral dose for painful

conditions is 1.2 to 1.8 g daily in divided doses

although maintenance doses of 600 mg to 1.2 g daily

may be effective in some patients. If necessary the

dose may be increased; in the UK the maximum

recommended dose is 2.4 g daily whereas in the USA

it is 3.2 g daily. Modified-release preparations of

ibuprofen are available for once- or twice-daily

dosing, although actual dosages vary with different

preparations. Patients with rheumatoid arthritis

generally require higher doses of ibuprofen than

those with osteoarthritis. The recommended dose for

fever reduction is 200 to 400 mg every 4 to 6 hours to

a maximum of 1.2 g daily.

[Martindale: The Complete Drug Reference, (2009) 36th ed.]

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10) BNF : . ADULT, initially 300–400 mg 3– 4

times daily; increased if necessary to max. 2.4 g

Daily for Analgesia/pain/fever/dysmenorrhea .

[BNF:British National Formulary (2011) 61th ed.]

11) National drug formulay Ethiopia:

Antirheumatic: Oral: 1.2 to 3.2gms a day in three or

four divided doses. After a satisfactory response has

been obtained, the dosage should be reduced to the

lowest maintenance dose that provides continuing

control of symptoms. Note - Higher doses are

generally required in rheumatoid arthritis than in

osteoarthritis.

(Drug Administration and Control Authority of Ethiopia September

2007)

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Tertiary Resources: Databases;

12) Medscape: Adult dose

Pain

300-800 mg PO q6hr

Fever

100-200 mg PO q4-6hr PRN

Inflammatory Disease

400-800 mg/dose PO q6-8hr

Dysmenorrhea

400-600 mg PO q6-8hr or 800 mg PO q8hr; not to

exceed 2,400 mg/day

Osteoarthritis

300 mg, 400 mg, 600 mg, or 800 mg PO q6-8hr; not

to exceed 3.2 g/day Monitor for GI risks

Rheumatoid Arthritis

300 mg, 400 mg, 600 mg, or 800 mg PO q6-8hr; not

to exceed 3.2 g/dayMonitor for GI risks

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Tertiary Resources : Review article;

13) Review Articles:Low doses of ibuprofen

(200 mg, and sometimes 400 mg) are available over

the counter (OTC) in most countries. Ibuprofen has a

dose-dependent duration of action of approximately

4–8 hours, which is longer than suggested by its short

half-life. The recommended dose varies with body

mass and indication. Generally, the oral dose is 200–

400 mg (5–10 mg/kg in children) every 4–6 hours,

adding up to a usual daily dose of 800–1,200 mg.

1,200 mg is considered the maximum daily dose for

over-the-counter use, though under medical direction,

the maximum amount of ibuprofen for adults is 800

milligrams per dose or 3200 mg per day (4 maximum

doses).

(News Medical:www.news-medical.net)

Consumer health information

14) FDA: Ibuprofen has been available as

aprescription drug for the treatment of osteoarthritis

and rheumatoid arthritisat a dose of 1,200 to 3,200

milligrams(mg) per (/) day

(FDA: www.fda.gov/cder)

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15) Drug info: Ibuprofen Dosing for Adult

Usual Adult Dose for Dysmenorrhea: 200 to 400 mg

orally every 4 to 6 hours as needed.

Usual Adult Dose for Osteoarthritis:

Maintenance dose: May be increased to a maximum

daily dose of 3200 mg based on patient response and

tolerance.

Usual Adult Dose for Rheumatoid Arthritis:.

Maintenance dose: May be increased to a maximum

daily dose of 3200 mg based on patient response and

tolerance.

Usual Adult Ibuprofen Dose for Pain:

Oral: Mild to moderate pain:

200 to 400 mg orally every 4 to 6 hours as needed.

Doses greater than 400 mg have not been proven to

provide greater efficacy.

IV: (Patients should be well hydrated before IV

ibuprofen administration):

Pain: 400 to 800 mg intravenously over 30 minutes

every 6 hours as needed.

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Usual Adult Dose for Fever:

Oral: 200 to 400 mg orally every 4 to 6 hours as

needed.

IV: (Patients should be well hydrated before IV

ibuprofen administration):

Fever: Maintenance: 400 mg every 4 to 6 hours or

100 to 200 mg every 4 hours as needed.

(drug info:www.drug.com)

16) Mayo Clinic: For mild to moderate pain:

Adults 400 mg every four hours, 2400 mg per day

For osteoarthritis and rheumatoid arthritis:

Adults 1200 milligrams (mg) up to 3200 mg per day.

(mayo clinic:www.mayo clinic.com)

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Answer the question

Ibuprofen use as analgesic, antipyretic, and anti-

inflammatory for adult ,according to maximum

daily dose :

*osteoarthritis

[300-800 mg PO tid-qid]

Max: 3200 mg/day; Info: use lowest effective dose,

shortest effective tx duration; give water and food

if GI upset occurs

*rheumatoid arthritis

[300-800 mg PO tid-qid]

Max: 3200 mg/day; Info: use lowest effective dose,

shortest effective tx duration; give w/ food if GI

upset occurs

*dysmenorrhea

[400 mg PO q4-6h]

Max: 2400 mg/day; Info: use lowest effective dose,

shortest effective tx duration; give w/ food if GI

upset occurs

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*pain, mild-moderate

[400 mg PO q4-6h]

Max: 2400 mg/day; Info: use lowest effective dose,

shortest effective tx duration; give w/ food if GI

upset occurs

*fever

[200-400 mg PO q4-6h]

Max: 1200 mg/day; Info: use lowest effective dose,

shortest effective tx duration; give w/ food if GI

upset occurs

*for anti-inflammatory uses

[600 mg PO qid x7-14 days]

Max: 2400 mg/day; Alt: 800 mg PO tid; Info: use

lowest effective dose, shortest effective tx duration;

give w/ food if GI upset occurs

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Stop Ibuprofen use or continue?

Stop use and ask a doctor if

1-an allergic reaction occurs. Seek medical help

right away.

2-pain gets worse or lasts more than 10 days

3-fever gets worse or lasts more than 3 days

4-stomach pain gets worse or lasts occurs with

the use of this product

5-redness or swelling is present in the painful

area is red or swollen

6-any new or unexpected symptoms appear

occur

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Alternative

1- Acetaminophen (Paracetamol) is used for the

relief of pains and reducing fever .The common

adult dose is 500 mg to 1000 mg. The

recommended maximum daily dose, for adults,

is 4000 mg.

2- Naproxen is commonly used for the reduction of

pain, fever, inflammation. The maximum daily

dose is 1000 mg .

3- ibuprofen-PC (ibuprofen-phosphatidylcholine)

have analgesia and anti inflammatory activity, the

maximum daily dose is 2400 mg⁄day .

4-Dexibuprofen is the S(+)-enantiomer of

ibuprofen and is used similarly in the management

of mild to moderate pain , inflammation and It may

be used as an antipyretic to reduce fever.The usual

adult dose is 600 to 900 mg daily by mouth in up to

3 divided doses, adjusted according to response, to

a usual maximum of 1.2 g daily