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ARGOM Appendix 5: Guidelines on OTC applications for specific substances
Note: This guidance document contains references to warning statements that are being included in the current updating of the RASML document. Warning statements marked with an (*) which are included in the updated version of the RASML document will be removed from this guidance document once the updated RASML is implemented.
Claims for the efficacy of allantoin as a wound healing agent will not be accepted, unless evidence is provided to justify these claims.
Alpha hydroxy acids
There is evidence to suggest that the use of topical products containing alpha hydroxy acids (such as glycollic acid, lactic acid, citric acid and other fruit acids) may make users more sensitive to sunlight and especially to the ultraviolet (UV) radiation component of sunlight. UV exposure can damage the skin and at high doses, especially over a long period, can cause skin cancer.
Therefore the labels of products containing alpha hydroxy acids as active ingredients should advise that the product may make the skin more sensitive to sunlight and to take appropriate protection measures against sun exposure. In addition, these products are not recommended for use on children and infants.
The following statements should be included in the labelling of products containing alpha hydroxy acids:
- *This product may make your skin more sensitive to sunlight;
- *Sun exposure should be limited by using a sunscreen and by wearing protective clothing;
- *If you have sensitive skin, test this product on a small area of skin before applying it to a large area;
- *Transient stinging or irritation may occur when using this product. If irritation persists, discontinue use; and
- *Not recommended for use on children or infants.
The labels of lozenges containing a local anaesthetic agent should include a label warning statement such as:
- *Do not take hot food or drink soon after using this product because it may burn your mouth.
Where indicated for use in children, the labels of lozenges containing a local anaesthetic agent should also include a label warning statement such as:
- *Do not give to children under six years of age, unless recommended by a doctor, pharmacist or dental professional.
The labels of all products containing local anaesthetics for dermal use must contain a statement such as:
- *If irritation occurs, stop use immediately and seek medical advice.
In addition, if the product contains:
- cinchocaine for topical use
- concentration of 2% or greater of total local anaesthetic substances (e.g. amethocaine, benzocaine and lignocaine)
the labels must also contain a statement such as:
- *Do not apply to large areas of the body except on the advice of a healthcare practitioner.
Liquid antacids are susceptible to microbiological contamination and deterioration of flavour and fragrance after the container is opened. Experience also indicates that some patients, contrary to the sponsor's advice, drink liquid antacids directly from the bottle. Where liquid antacids do not comply with the criteria as set out in ARGOM Appendix 2 Guidelines on quality aspects of OTC application: Section 10 Microbiological testing, throughout the life of the product in both opened and unopened containers (i.e. on the basis of 'in use' stability data), the label should include a statement advising consumers to discard the contents 3 months after opening the bottle. Consumers will be assisted if a space is provided for the user to write the date of first opening.
The most commonly occurring worms in Australia are threadworms. Other types of worms (e.g. roundworm, hookworm, whipworm and tapeworm) occur less commonly.
The product labels should not encourage the regular use of anthelmintics. In addition, the product labels or a package insert should contain statements such as:
- A common symptom of threadworm infestation is itching around the anus and vagina, which may result in restless sleep and irritability.
- Evidence of infestation should be present before treating for threadworm.
- If a family member has threadworms, then each member of the family should be treated.
- If symptoms persist, see your doctor.
The label indications for products containing mebendazole may include treatment of threadworm and other types of worms (e.g. roundworm, hookworm, whipworm, and tapeworm).
As consumers are unlikely to be able to differentiate between worm types, and the recommended dosage of mebendazole for the treatment of threadworm and other types of worms differs, the labels for products containing mebendazole should only include directions for use in the treatment of threadworm.
The recommended dosage of mebendazole for treatment of threadworms in adults and children aged 2 years and over is 100 mg as a single dose.
If the indications on the product labels include use for other, less commonly occurring types of worms (in addition to use for threadworms), the labels should not include directions for use of mebendazole for the treatment of worms other than threadworms. However, the directions for use on the labels could include a statement such as:
- Roundworm, hookworm and whipworm rarely occur in the general Australian population. If suspected, medical advice should be sought.
Sponsors may include dosage instructions for treatment of worms other than threadworms in a product information document. The recommended dosage of mebendazole for treatment of worms other than threadworms in adults and children aged 2 years and over is 100 mg twice a day for three days. Where this information is included in the Product Information (PI) and a Consumer Medicine Information (CMI) document and/or package insert is supplied, the CMI and/or package insert should include a statement such as:
- Medical advice should be sought before use of the product for worms other than threadworms.
Prophylactic use of topical antifungal agents, including application to shoes or clothing, should be justified.
Because fungal infections may recur if treatment is stopped as soon as symptoms disappear, product labels should state that the product should be applied for 14 days after symptoms disappear. This is not required on the labels of topical products containing terbinafine, or for other products where the sponsor can justify its omission.
In some circumstances, such as communal showers and tropical climates, more frequent use of a topical antifungal agent may be appropriate, but the directions for use should set out the relevant circumstances.
Topical oral mucosal application - miconazole
Some azole antifungal agents (miconazole and fluconazole, in particular) may increase international normalised ratio (INR, a measure of blood clotting) levels in patients who are taking warfarin or other anticoagulants [due to inhibition of Cytochrome P450 2C9 (CYP2C9), which metabolises (S)-warfarin)].
The PI for OTC topical products for oral mucosal application containing miconazole should state that miconazole has been shown to increase INR levels in patients taking warfarin, as inhibition of CYP2C9 by miconazole reduces the metabolism of warfarin. Therefore, these patients may be at risk of increased bleeding or bruising. Consistent information should be included in the CMI for these products.
The labels or package inserts of OTC topical products for oral mucosal application containing miconazole should include a statement advising people who are taking warfarin or other anticoagulants to ask their doctor or pharmacist before using the product, because bleeding or bruising may occur.
Use for vaginal candidiasis
Unless otherwise justified, the labels or package inserts of topical antifungal agents for vaginal use should include advice that the use of condoms or diaphragms for contraception is not recommended during treatment (as some excipients in many vaginal cream or pessary formulations may damage the integrity of the condom or diaphragm).
The PI for OTC vaginal products containing miconazole and OTC oral fluconazole products for vaginal thrush should state that the active ingredient (miconazole or fluconazole) has been shown to increase INR levels in patients taking warfarin, as inhibition of CYP2C9 by the active ingredient (miconazole or fluconazole) reduces the metabolism of warfarin. Therefore, these patients may be at risk of increased bleeding or bruising. Consistent information should be included in the CMI for these products.
The labels or package inserts of OTC vaginal products containing miconazole and OTC oral fluconazole products for vaginal thrush should include a statement advising people who are taking warfarin or other anticoagulants to ask their doctor or pharmacist before using the product, because bleeding or bruising may occur.
No data are available on whether this interaction may also occur with OTC vaginal products containing butoconazole. In the absence of data indicating that this interaction will not occur following vaginal administration of butoconazole, the PI should include advice such as the following (under the subheading, 'Interactions with other medicines', or similar):
- Studies have not been conducted to evaluate the potential for interactions between butoconazole and coumarin anticoagulants, such as warfarin. However, some azole antifungal agents, such as miconazole and fluconazole, have been shown to increase INR levels in patients taking warfarin, due to inhibition of CYP2C9 and reduced metabolism of warfarin. Therefore, caution is advised in patients taking coumarin anticoagulants, as butoconazole may increase INR, and these patients may be at risk of increased bleeding or bruising.
The CMI for OTC vaginal products containing butoconazole should include a statement that people who are taking warfarin or other anticoagulants should ask a doctor or pharmacist before using the product, because bleeding or bruising may occur. Advice that no interactions have been reported with the product could also be included in the CMI. The product labels or package insert should also include this information.
Use in respiratory tract infections
Clinical data must be provided to justify claims for the use of antihistamines for lower respiratory tract conditions (including infections and asthma).
Use as hypnotics
Antihistamines (H1 receptor antagonists), especially ethanolamines (e.g. doxylamine, diphenhydramine) and phenothiazines (e.g. promethazine), have hypnotic properties. In general, sleep disorders should be medically assessed, as they may be symptomatic of more serious conditions such as depressive illness. The use of non-medically prescribed hypnotics is therefore not encouraged, and OTC products will not be registered for long-term use in insomnia.
In the case of products containing antihistamines with hypnotic properties that are indicated for short-term use in occasional insomnia:
- the pack size should be limited to not more than 10 doses;
- the CMI, package insert or label should include the following principles of good sleep hygiene:
- go to bed and arise at the same time daily
- engage in relaxing activities before bedtime
- exercise regularly but not in the late evening
- avoid eating meals or large snacks just before bedtime
- eliminate daytime naps
- avoid caffeine-containing drinks after midday
- avoid alcohol or the use of nicotine late in the evening
- minimise external disruption (e.g. light and noise)
- if you are unable to sleep, do not become anxious; leave the bedroom and participate in relaxing activities such as reading or listening to music until you are tired.
In addition, the labels of these products should include the following statements:
- *Not recommended for use by pregnant or lactating women.
- *This product should be taken on medical or pharmacist advice.
- *This product is for temporary use.
- *This preparation is to aid sleep. Drowsiness may continue the following day. If affected do not drive or operate machinery. Avoid alcohol.
The requirements relating to the pack size and principles of good sleep hygiene need not be applied to antihistamine products with indications for short-term use for sedation that are primarily intended for paediatric use.
Antimicrobial sore throat treatments
Aspartame is a sweetening agent based on the essential amino acid phenylalanine which is normally metabolised to tyrosine. The enzyme required for this metabolism is lacking in people with phenylketonuria. Aspartame is included in the First Schedule of the Therapeutic Goods Order No. 69 (TGO 69) General requirements for labels for medicines.
Medicines containing aspartame or phenylalanine should include the following warning statement:
- *Phenylketonurics are warned that this product contains aspartame (phenylalanine).
Sponsors may use indications consistent with any or all of the representative indications set out below, as appropriate to a particular product, without the need to supply supporting efficacy data:
- For the temporary relief of pain (and discomfort) and/or inflammation associated with:
- migraine headache
- rheumatic pain
- tension headache
- menstruation/period pain
- sinus pain
- dental procedures
- sore throat
- tennis elbow
- muscular aches and pains
- colds and flu
- Reduces fever and/or the discomfort associated with fever.
Sponsors may propose other indications but should contact the TGA for advice on whether data will be required to support the safety and efficacy of the product for those indications.
Combination OTC analgesic products that contain aspirin and codeine may include claims of 'strong' or 'powerful' pain relief (or similar). These claims will not be accepted for products that contain aspirin as the only analgesic agent, or aspirin in combination with another analgesic agent, unless the claims are justified on the basis of clinical efficacy data.
As fever is a normal and generally beneficial response to infection, no elaboration to the words "reduces fever" will be accepted except in the context of limits to the duration of treatment, relief of discomfort associated with fever or examples of conditions where fever may occur.
For aspirin products that are indicated for reduction of the risk of heart attack and stroke in patients with known cardiovascular or cerebrovascular disease and inhibition of platelet aggregation, the ARTG indications should be consistent with the following:
- For the treatment of patients with known cardiovascular or cerebrovascular disease, as an antiplatelet agent for prophylaxis against acute myocardial infarction, unstable angina, transient ischaemic attack and cerebrovascular accident (stroke).
Where there is a PI document, the 'Indications' section should be consistent with ARTG indications.
An exemption is required under Section 42DK of the Therapeutic Goods Act 1989 (the Act) for the use of claims relating to the cardiovascular or cerebrovascular system or use as an antiplatelet agent on product labelling.
Adult dosage recommendations (adults and children over 12 years):
- 300 mg to 1000 mg every four hours as necessary. Dosage should not exceed 4 g (expressed on the label as the number of units, e.g. tablets) in 24 hours. Products containing aspirin should not be taken for more than 10 days (except on medical advice).
The labels of products containing aspirin should not include dosage instructions for children aged 12 years and under.
Dosage instructions consistent with 75 - 325 mg aspirin once daily will not require clinical data or further justification.
The product labelling should clearly state that aspirin should only be used as an antiplatelet agent on the advice of a doctor.
Products containing aspirin together with one or more other active ingredients, which are similar to existing registered products, will usually not require efficacy or safety data, provided they comply with the guideline on fixed dose combination products (see ARGOM Appendix 1 - Guidelines on efficacy and safety aspects of OTC application: Section 9 Fixed dose combination products). Where new combinations are proposed (i.e. combinations and/or strengths that are not included in the ARTG for supply in Australia), the safety and efficacy of the combination will need to be justified.
Oily products intended for use in the bath may cause the bath to become slippery or, when used in a baby's bath, may cause the baby to become slippery. Products of this type should contain a label warning statement such as:
- Caution: Use of this product may cause the body and bathroom surfaces to become slippery. Particular care should be exercised when handling a baby.
See 'Anaesthetics, dermal'
Labels of unscheduled products containing benzoyl peroxide should include the following statements:
- *Keep from eyes, lips, mouth and sensitive areas of the neck.
- *If excessive swelling, irritation, redness or peeling occurs, discontinue use.
- *If these persist, consult a physician.
- *Avoid excessive exposure to sunlight and other sources of ultra violet light.
Efficacy and safety data will not be required for:
- topical 'leave-on' products (e.g. topical creams or ointments) containing 2.5% to 10% benzoyl peroxide that are intended for treatment of acne; or
- topical wash products containing 2.5% to 10% benzoyl peroxide that are intended for treatment of mild to moderate acne, with directions for use advising contact times of at least 30 seconds.
Efficacy and safety data will be required for:
- indications or strengths other than those noted above; and/or
- topical wash products with contact times shorter than 30 seconds.
Bowel cleansing oral preparations - sodium salts
Severe dehydration and electrolyte disturbances may occur in 'at risk' patient groups (such as elderly people, and patients with impaired renal function, diabetes or heart conditions) following ingestion of oral products containing sodium phosphate or sodium picosulfate and intended for bowel cleansing purposes (e.g. prior to colonoscopy or other procedures).
The PI, CMI and/or other package insert, and labels of these products should include 'boxed warnings' consistent with the following:
- Product Information: WARNING: Life threatening dehydration and/or electrolyte disturbances may occur in 'at risk' groups - see Contraindications and Precautions
- CMI and/or package insert: WARNING: Life threatening dehydration and/or electrolyte disturbances may occur in some people. Read the section with the heading 'Before you take [this product]'
- Labels: WARNING: Life threatening dehydration and/or electrolyte disturbances may occur in some people. Read the enclosed leaflet before you take this product.
The PI should advise that these products should not be used in patients with clinically significant renal impairment, and that the products should be used with caution in patients with impaired kidney function, diabetes, heart conditions or pre-existing electrolyte disturbances, patients taking other medicines that may affect electrolyte levels, and elderly or debilitated patients. Advice that adequate hydration is very important for safe and effective use of the product, and that medications such as diuretic may exacerbate volume depletion associated with bowel cleansing, should also be included in the product information.
The CMI, package insert and/or labels should advise elderly people, and people with impaired kidney function, diabetes or heart conditions, to discuss use of the product with their doctor prior to use. Patients should also be advised to discuss any other medicines they are taking with their doctor prior to the taking of the product.
Nephrocalcinosis and renal impairment may occur following use of oral sodium phosphate products in 'at risk' or inappropriate patient groups. The PI, CMI and/or other package insert of oral sodium phosphate products indicated for bowel cleansing should include warnings advising healthcare professionals and consumers that nephrocalcinosis and renal impairment may occur following use of these products.
Bronchitis, use of term
Bronchitis is an inflammation of the mucous membranes of the bronchi. The condition is serious and complications can be severe. Products which provide symptomatic relief should not include the word "bronchitis" as part of the product's name, and should not include the word "bronchitis" on the labels, other than in the context of a statement such as:
- For the relief of cough of bronchitis. If the cough persists, seek medical advice.
Burn treatment products
The label of these products should indicate that immediate treatment should consist of the rapid application of cold water or cold packs for at least 20 minutes and that the product should only be applied later. Ice should not be applied directly to the burnt area.
Directions for use should indicate clearly that the product is for the first-aid treatment of minor burns only and that medical advice should be sought for the treatment of more serious burns.