OTC analgesics & antipyretics

OTC analgesics/antipyretics

OTC drugs available in the USA:- salicylates (aspirin, choline salicylate, Mg

salicylate and Na salicylate)- acetaminophen- ibuprofen- Naproxen Na- Ketprofen

All are similar but Naproxen has slightly a longer duration of action

OTC analgesics/antipyretics

The strength of these products available OTC is less than same products available on prescription

Onset of all of these drugs is ½-1 hr, maximum effect between 2-3 hrs and duration of action is 4-6 hrs.

All will reduce temp by (1.1°- 1.7°C),

Dosage of common OTC drugs

Agent Dosage (maximum)

Analgesic Anti-inflammatory

Acetaminophen

650-1.000 mg q4h (4000 mg)

-

Aspirin 10-15 mg/kg/dose q 4-6 h (4 g/day)

80-100 mg /kg/day q 6-8 hrs

Ibuprofen 200-400 mg q 4-6 hr (1,200 mg/day)

400-800 mg 3-4 td (3,200 mg in 2 wks)

Naproxen Na 220 mg q 8-12 hr (660 mg/day)

275-550 mg 2 t d (1,650 mg/day for 2 wks)

Ketoprofen 12.5-25 mg q 6-8 hr (75 mg/day)

50-75 mg, 3-4 t d (300 mg/day)

Salicylates Active moiety: salicylic acid (irritating)

Choline salicylate: stable in oral solution Mg salicylate + Na salicylate: can be used for patients allergic to aspirinInhibit COX in periphery and CNS

Aspirin Indication: (1) mild to moderate pain of musculoskeletal NOT visceral origin. (2) Fever DOC in RA

Aspirin

Overdose: - with chronic therapy (100 mg/kg per

day for at least 2 days)> mild intoxication- HA, dizziness, N & V, hyperventilation, mental confusion, lassitude….

- Acute intoxication- dose-dependent:<150 mg/kg mild150-300 mg/kg moderate>300 mg/kg severe

Aspirin

Symptoms: lethargy, tinnitus, tachypnea, pulmonary edema, convulsions, coma, haemorrhage and dehydration. First respiratory alkalosis followed by metabolic acidosis (why?)

Hypoglycemia (why?) and fever may be severe in children. Bleeding from GIT or mucosal surface > petechiae at autopsy

Petechiae

Aspirin

Therapeutic Considerations:1. Impaired platelet aggregation- acetyl group (good and bad?!!)

- ASA should be D/C 48 hrs before surgery and shouldn’t be used as analgesic in dental extraction, or surgery etc

- C/I: haemophilia, hypoprthrombinemia, vit K deficiency, Hx of bleeding or PUD

Aspirin

2. Effect on uric acid elimination (dose-dependent)

Avoid all salicylates in all patients with Hx of gout or hyperuricemia (why?)

1-2 g/day plasma level of uric acid2-3 g/day little/ no effect> 5 g/day plasma level of uric acid

(Toxicity)

Aspirin

3. GI irritation & bleeding- two mechanisms of gastric damage (what are

they?)

- Avoid in: elderly, PUD or bleeding, alcoholic liver disease

- Ingesting alcohol + ASA= incidence of GI bleeding

4. Aspirin Allergy- If you experience gastritis or heart burn after

aspirin use NOT

hypersensitivityCommon S.ENOT C/I

for future use

Aspirin Aspirin allergy is uncommon, < 1% of patients within 3 hours of ASA ingestion: urticaria, oedema, difficulty in breathing, rhinitis, bronchospasm or shock Most common in patients with asthma, urticaria or nasal polyps 15% cross-reaction with Tartrazine (colour) Cross reaction with other NSAIDS (rate for acetaminophen 6% and for ibuprofen 97%)

patients allergic to ASA > avoid all NSAIDs > use acetaminophen or nonacetylated salicylates (eg, Na salicylate) instead

Aspirin

5. Pregnancy/ Lactation- Avoid ASA in both- Avoid ASA especially during the 3rd

trimester/pregnancy- Why? > Effect of mother (=3), effect on fetus

(haemorrhage, growth retardation, congenital intoxication, premature closure of ductus arteriosus > still birth)

- Paracetamol is the analgesic of choice in these periods

However,…..

Updates: NSAIDS and Pregnancy

September 6, 2011 — Use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy is linked to twice the risk for miscarriage, according to the results of a nested case-control study reported online September 6 in the Canadian Medical Association Journal.

Of the 4705 patients with spontaneous abortion, 352 (7.5%) had NSAID exposure, as did 1213 (2.6%) of 47,050 control participants. The use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk for spontaneous abortion, after adjustment for potential confounders. There was no apparent dose-response effect.

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Aspirin Unlabelled/Investigational Use:Low doses have been used in the prevention of pre-eclampsia, recurrent spontaneous abortions, pematurity, fetal growth retardation (including complications associated with autoimmune disorders such as lupus) 60-80 mg/day during gestational weeks 13-26 (patient selection criteria not established)

Aspirin

6. Reye’s Syndrome- Acute potentially fatal illness (50%) occurs

almost exclusively in children < 15 years of age

- Produces fatty liver + encephalopathy- Occurs usually within 1-7 days of viral

infections with influenza or chickenpox.- Ch.Ch: persistent vomiting, CNS damage,

signs of hepatic injury & stupor > convulsions > coma

- Nonacetylated NSAIDs > not associated with Reye’s

International Aspirin/Reye’s Syndrome Warning statements

UK: March 2002, the CSM recommended a revised warning statement:“Do not give aspirin to children under 12 years unless medically indicated, and avoid in children aged up to and including 15 years if feverish”.

USA: “Children and teenagers who have or are recovering from chicken pox, flu symptoms or flu should NOT use this product. If nausea, vomiting, or fever occur, consult a doctor because these symptoms could be an early sign of Reye’s Syndrome, a rare but serious

illness.” final rule issued on 17 April 2003, on all oral and rectal OTC drug products containing aspirin, and on OTC drug products containing non-aspirin salicylates

Australia, April 2004

NSAIDs- D#D interactions

Analgesic Drug Potential Interaction

Management/Prevention measures

Aspirin Valproic acid

valproic acid level > toxicity

Avoid concurrent use, use Naproxen

Salicylates sulfonylureas

hypoglycemic effect

Avoid concurrect use, monitor glucose level whn changing salicylate level

NSAIDs (several)

Anti-hypertensive agents

anti-HTN effect, hyperkalemia with K-sparing D or ACE-I

Monitor BP, K level and cardiac function

NSAIDs- D#D interactions

Analgesic Drug Potential Interaction

Management/Prevention measures

Salicylates Uricosoric agents

uricosoric effect, uric acid

Avoid concurrent use, avoid all NSAID in patients with gout, hyperurecemia

NSAIDs Alcohol GI bleeding risk Minimise alcohol intake while using NSAIDs

NSAIDs Warfarin risk of bleeding Avoid concurrent use

NSAIDs- D#D interactionsAnalgesic

Drug Potential Interaction

Management/Prevention measures

NSAIDs (several)

Methotrexate (MTX)

MTX clearance> MTX toxicity> pancytopenia

Avoid NSAIDs with high dose MTX therapy, monitor with concurrent use.

Ibuprofen, high dose of salicylates

Phynetoin Displacement from plasma proteins > phynetoin toxicity

Monitor unbound phynetoin level, adjust dose

NSAIDs (several)

Digoxin renal clearance Monitor digoxin level, adjust doses

NSAIDs (several)

Aminoglycosides

renal clearance Monitor antibiotics level, adjust doses

Comparison of aspirin and non-acytelated salicylates

Less effect on platelet aggregation Less GI erosions and bleeding Fewer renal complications cross-reactivity in aspirin intolerant patients Less anti-inflammatory effect

Acetaminophen

An effective analgesic and antipyretic (works centrally), no anti-inflammatory (not used clinically for this purpose)

Used for mild to moderate pain of non-visceral origin Paediatric dose= 10-15 mg/kg q 4-6 hrsAdult dose: 325-650 mg q 4-6 hrs or 1000 mg 3-4 times daily (do not exceed 4g/day) Rectal bioavailability=50-60% (compare with ASA)

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Acetaminophen- Overdose

Hepatotoxicity after ingestion of a single dose of 10-15 g (150-250 mg/kg) - 20-25 g fatal first 2 days: abdominal pain, N & V, drowsiness, confusion 2-4 days: clinical manifestaions of hepatotoxicty: ALT & AST, bilirubin in plasma, prothrombin time

Acetaminophen- Therapeutic Consideration

~ is hepatotoxic if > 4 g/day especially for people at risk

Avoid alcohol and fasting while using acetaminophen

No significant D#D interactions with acetaminophen

The appropriate dosing for acetaminophen is 10 to 15 mg/kg per dose given every 4 to 6 hours orally, which produces an antipyretic effect within 30 to 60 minutes in approximately 80% of children. The appropriate dosing for ibuprofen is 10 mg/kg per dose.

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Ibuprofen- Therapeutic Considerations

ibuprofen >> aspirin or other salicylates or acetaminophen for the relief of dysmenorrhoea

Ibuprofen Dose: for those > 12 years old, 200-400 mg q 4-6 hrs not to exceed 1,200 mg per dayCan be given as young as 6 months old

Overdose: asymptomatic (43%) or minimal symptoms (abd pain, N&V, lethargy, dizziness..)

Ibuprofen- Therapeutic Considerations

Less gastric bleeding and ulceration than ASA (S.E: dyspepsia, heartburn, Nausea, anorexia, epigastric pain)

Ibuprofen effect on platelet aggregation, unlike that of ASA, is reversible within 24 hours. Caution: avoid using alcohol or warfarin+ ibuprofen prolongation of prothrombin time

Ibuprofen- Therapeutic Considerations

Patients with Hx of impaired renal function, CHF or diseases that compromise the renal haemodynamics should not self-medicate with ibuprofen (why?) because ibuprofen reduces the renal blood flow and GFR by inhibiting the synthesis of renal prostaglandins BUN and serum creatinine

C/I: in aspirin intolerant patients (cross reaction 97%).No data about passage in milk, thus better to avoid.

D#D: Table 7, similar to other NSAIDs- Note: Phynetoin and Li+

Naproxen-Na

Analgesic, anti-inflammatory and antipyretic For minor pain Not recommended for those < 12 yr old (only under medical supervision) Dose: 220-440 mg q 8-12 hrs (if 12-65 years old)

Very similar to ibuprofen in OD and D#D compatible with breast-feeding

Ketoprofen Very similar to Naproxen and ibuprofen except that label advise to avoid in nursing mothers.Not recommended for patients < 16 year old Dose: > 16 years 12.5 mg q 4-6 hours (maximum 75 mg/day), may take a second dose after 1 hour if needed.

1 tablet of ketoprofen (12.5mg) is equivalent to 1 tablet (200 mg) of ibuprofen.

March 3, 2011 — Treatment of febrile children should focus on improving the child's comfort rather than bringing the temperature down to normal levels or preventing the onset of fever, according to a new clinical report issued by the American Academy of Pediatrics (AAP).

According to the study authors, there is "no evidence that reducing fever reduces morbidity or mortality from a febrile illness" or that it decreases the recurrence of febrile seizures.

The article outlines strategies to counsel caregivers about treating febrile illness, stating that acetaminophen and ibuprofen, "when used in appropriate doses, are generally regarded as safe and effective agents in most clinical situations."

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