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(NAR) VOL. 16 NO. 2 / APRIL - JUNE 2005

[ BFAD BUREAU CIRCULAR NO. 11, S. 2005, June 07, 2005 ]

REVISED LABELING OF SELECTIVE COX-2 INHIBITOR DRUGS AND NSAIDS



For guidance and information of all concerned, BFAD has decided to defer the implementation of PSD Memos 05-2005 and 06-2005.

The Bureau of Food and Drugs is requesting manufacturers to revise the labels (PACKAGE INSERTS) of all marketed selective Cyclooxygenase-2 (COX-2) inhibitor drugs like Celebrex and Arcoxia as well as prescription and over-the-counter (OTC) non-prescription nonsteroidal anti-inflammatory drugs (NSAIDs). Such label changes shall include boxed warnings, highlighting potential for risk of cardiovascular events and the well-described serious potential life-threatening gastrointestinal (GI) bleeding associated with their use. The black box warning shall be placed on the first page of the insert, after posology/dosing statements.

BFAD would like to emphasize in our request to the manufacturers of OTC nonprescription NSAIDs to revise their labeling to provide more specific information about aforementioned risks of individual products and remind patients of limited dose and duration of treatment of these products according to package instructions. Although, aspirin (ASA) is an NSAID, it is exempted from this directive. ASA is a platelet inhibitor. In clinical studies, ASA has been shown to reduce the risk of cardiovascular (CV) events like heart attack and stroke. Likewise, Paracetamol is not included since it is used as antipyretic and analgesic for mild to moderate pain.

With respect to Celebrex and Arcoxia, we advise the manufacturers to implement the following actions:

    1. Include black boxed warning and contraindications about CV and GI risks. Please refer to Bureau Circular No. 8 s. 2005

    2. Inform practitioners to use lowest effective dose for shortest duration consistent with individual patient treatment objectives

    3. Commit to conduct a long-term study and monitoring to assess the safety of Celebrex and Arcoxia

    4. Mandatory Patient Leaflet Information

As to the prescription nonselective NSAIDs, the manufacturers are advised the following product labeling changes

    1. Boxed warning about potential CV events and potentially serious GI adverse events

    2. Contraindications for use in Coronary Artery Bypass Graft (CABG) operations

    3. Instructions to patients to discuss with their doctors the risks and benefits of using NSAIDs and the importance of using the lowest effective dose for the shortest duration possible if treatment for NSAID is required.

For OTC NSAIDs, the available data do not suggest increased risk of serious CV events for short-term and low dosage use of NSAIDs. Such products are to be allowed in the market provided package insert revisions are instituted, which include the following:

    1. More specific information about potential CV and GI risks

    2. Stronger warnings about limiting dose and duration of treatments according to package instructions

    3. Warning about potential skin reactions and to stop treatment once itchiness or rashes occur.

    4. Public information through posters in drugstores.

Posters and leaflets about these products shall be made available in drug outlets.

Illustrative examples are provided in the following annexes.

Adopted: 7 June 2005

(SGD.) PROF. LETICIA BARBARA B. GUTIERREZ, MS
Director

ANNEX A

1. For Selective COX-2 Inhibitors like Celecoxib and Etoricoxib the black box warning should contain:

 

Absolute contraindications:

 
 

Not to be given to those patients who have history of:

 

- Stroke : Cerebrovascular accident, CVA
- Heart attack: Myocardial infarction, MI
- Coronary artery bypass graft: CABG
- Congestive heart failure (CHF) NYHA II - IV

 

2. We advise that above warning be placed right after "Dosage and Administrator", preferably in the first page of the insert.

3. Under CAUTION/WARNING statement:

    a. COX-2 inhibitors are not to be given to patients with allergy to NSAIDS and those with asthma.

    b. Exercise caution when prescribing Selective COX-2 inhibitors in patients with ischemic heart disease and those with risk factors for heart disease; hypertension; hyperlipidemia, diabetes, smoking and patients with peripheral arterial diseases.

    c. Considering association between cardiovascular risk and exposure to COX-2 inhibitors, doctors are advised to use the lowest effective dose for the shortest duration of treatment.

    d. Intake and COX-2 inhibitors should be stopped with appearance of skin rash and signs of hypersensitivity.

    e. If not yet instituted, warning statement should include potential gastrointestinal (gastric and liver) and renal toxicities.

ANNEX B

1. For prescription NSAIDs - same black box warning as COX-2 Inhibitors

 

Absolute contraindications:

 
 

Not to be given to those patients who have history of:

 

- Stroke: cerebrovascular accident, CVA
- Heart attack: Myocardial infarction, MI
- Coronary artery bypass graft: CABG
- Uncontrolled hypertension
- Congestive heart failure (CHF) NYHA II-IV

 

2. We advise that above warning be placed right after "Dosage and Administration", preferably in the first page of the insert.

3. Inclusion of the following warning statement:

    a. Contraindication in patients with history of hypersensitivity to ASA or any other NSAIDs

    b. NSAIDs are contraindicated in patients with previous or active peptic ulceration

    c. Use with caution in patients with cardiac, liver and renal disease. Dose adjustment like using the lowest effective dose and monitoring of renal and liver functions should be instituted.

ANNEX C

POSTER (English and Tagalog) for OTC NSAIDs with suggested contents

A. What is NSAID and examples

B. NSAIDs can have the following side effects:

    1. Bleeding stomach ulcers. Stop taking NSAID (name) if there is burning stomach pain, black bowel movements or bloody coffee-ground vomiting.

    2. Liver impairment the signs of which include nausea, vomiting, tiredness, loss of appetite, jaundice (yellow coloring of skin and eyes), "flu-like symptoms and dark urine. If these happen stop taking NSAID.

    3. Kidney problems. Stop taking this NSAID if there is worsening of kidney problem

    4. Fluid retention in the body and swelling. Fluid retention may occur and potentially serious if there is high blood pressure or heart failure.

    5. Do not take this medicine if you are allergic to aspirin.

 

Consult your doctor if you have:

 
 

- Heart problems
- High blood pressure
- Stomach ulcers or stomach bleeding
- Asthma
- Allergy to aspirin or other NSAID
- Renal problem

 
 

If you are pregnant or trying to be pregnant or are breast feeding - consult your physician or healthcare professional.

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