In June 1987, [the U.S.] FDA labeling regulations went into effect requiring a warning about possible allergic-type reactions, including anaphylaxis in the package insert for prescription drugs to which sulfites have been added to the final dosage form. Sulfites are used as preservatives in many injectable drugs, such as antibiotics and local anesthetics. Some inhalants and ophthalmic preparations also contain sulfites, but relatively few oral drugs contain these chemicals. The purpose of the regulation is to protect the estimated 0.2% of the population who suffer allergic reactions from the chemicals. Many of the sulfite-sensitive persons suffer from asthma or other allergic conditions. Previous to the regulations dealing with prescription medication, the FDA issued regulations for the use of sulfites in food. Asthmatics and other patients who may be sulfite-sensitive should be reminded to read the labels of packaged foods and medications to check for the presence of these agents.
The most frequent symptom of a sulfite reaction is difficulty breathing. Other symptoms include diarrhea, nausea and vomiting, abdominal pain and cramps, dizziness, wheezing, hives, itching, local swelling, rash, difficulty swallowing, headache, fainting, change in body temperature, chest pain, change in heart rate, unconsciousness and coma. Symptoms usually occur within minutes of ingesting or taking sulfited foods or drug products.
Sulfiting agents covered by the regulations are potassium bisulfite, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, sodium sulfite and sulfur dioxide.
The labeling of drugs to which sulfites have been added to the final dosage form must contain the following statement in the "Warnings" section of the labeling:
"Contains (name of sulfite), a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than nonasthmatic people."
Sulfite-containing epinephrine for injection for use in allergic emergencies must contain the following statement:
"Epinephrine is the preferred treatment for serious allergic or emergency situations even though this product contains (name of sulfite), a sulfite that may in other products cause allergic-type reactions including anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons. The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulfite(s) in this product should not deter the administration of the drug for treatment of serious allergic or other emergency situations."
The FDA permits the use of sulfites in prescription products, with the proper labeling, because there are no generally suitable substitutes for sulfites to maintain potency in certain medications.
Source: Pharmaceutical Dosage Forms and Drug Delivery Systems, 6th ed. p. 117-118.
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The Bureau of Food and Drugs issued B.O. 67-B s. 1996, dated June 5 1996 "Requiring the Inclusion of Warning Statement for Products Containing Sodium Metabisulfite and other Derivatives of this Sodium Salt." This, however, is currently not available for viewing in the BFAD web site.
Sulfite-Containing Drug Products Available in the Philippines:*
Contains Sodium metabisulfite:
Amikacin Sulfate (Amikacide) 125 mg/mL Injection; 250 mg/mL Injection
Mfr.: SVP Phils., Inc.
Dexamethasone sodium phosphate (Penodex) 4 mg/ml solution for injection
Mfr./Dist.: ROTEXMEDICA/Duopharma
Epinephrine (Hizon Epinephrine) 1 mg/mL Sterile Solution for Injection
Mfr.: Hizon Laboratories, Inc.
Gentamicin Sulfate (Orimed) 40 mg/ml solution for injection
Mfr./Dist.: Oriental Chemical Works, Inc./Medicamenta, Inc.
Gentamicin Sulfate (Topigen) 40 mg/mL Solution for Injection
Mfr./Dist.: Ashford Pharmaceutical Laboratories, Inc./Vendiz Pharmaceuticals, Inc.
Metoclopramide (Plasil) 5 mg/mL ampule
Mfr./Dist.: Gruppo Lepetit SpA/GSK
Metoclopramide (Pharex Metoclopramide) 10 mg/2ml Injection
Mfr./Dist.: Pascual Laboratories, Inc./Pharex Healthcorp
Noradrenaline (Levophed) 1 mg/mL concentrate solution for Injection
Mfr.: Abbott
Paracetamol (Naprex) 150 mg/mL Solution for Injection (IM/IV) (300 mg/2mL)
Mfr.Dist.: SVP Phils., Inc./Pediatrica, Inc.
Contains Sodium Sulfite:
Paracetamol (Aeknil) 150 mg/mL Solution for Injection IM/IV
Mfr./Dist.: Therapeutic Pharmaceuticals/Medicamenta, Inc.
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* This list is incomplete. If you know a sulfite-containing drug product not included in the above list, kindly inform the pinoypharmacist through your comments or through his e-mail address.
