Vocafen honey and lemon flavour 8.75 mg lozenges – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Vocafen honey and lemon flavour 8.75 mg lozenges

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each lozenge contains 8.75 mg of flurbiprofen

Excipients with known effect

Sucrose: 1,536.51 mg/lozenge

Glucose, liquid: 1,280.43 mg/lozenge

Honey flavour (contains citronellol): 2.4 mg/lozenge

Lemon flavour (contains citral, citronellol, geraniol, limonene and linalool): 9.0 mg/lozenge

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Lozenge

White to pale yellow colored, round, flat bevelled lozenge with honey and lemon flavor, and with a thickness of 7,0 to 8,0 mm and a diameter of 18,0 to 19,0 mm.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Vocafen honey and lemon flavour 8.75 mg lozenges are indicated for the short-term symptomatic relief of sore throat in adults and adolescents over the age of 12 years.

4.2 Posology and method of administration

Posology

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section 4.4).

Adults and adolescents over the age of 12 years

Slowly suck/dissolve one lozenge in the mouth every 3 to 6 hours as needed. Maximum 5 lozenges in every 24-hour period.

This product should be used for a maximum of three days.

Paediatric population

Not indicated for children under 12 years of age.

Elderly population

Due to the limited clinical trials, available, a general dose cannot be recommended. Elderly patients are at higher risk of suffering serious consequences of adverse reactions.

Impaired renal function

In patients with mild to moderate impairment of renal function no dose reduction is required. In patients with severe renal insufficiency flurbiprofen is contraindicated (see section 4.3).

Impaired hepatic function

In patients with mild to moderate impairment of hepatic function no dose reduction is required. In patients with severe hepatic insufficiency (see section 5.2.) flurbiprofen is contraindicated (see section 4.3). Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

Method of administration

For oromucosal administration and short-term use only.

As with all lozenges, Vocafen honey and lemon flavour 8.75 mg lozenges should be moved around inside the mouth to avoid local irritation.

4.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section

  6.1.

• Patients who have previously shown hypersensitivity reactions (e.g. asthma, bronchospasm, rhinitis, angioedema or urticaria) in response to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
• Active or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration) and intestinal ulceration.
• History of gastrointestinal bleeding or perforation, severe colitis, hemorrhage, or hematopoietic disorders related to previous treatment with NSAIDs.
• Last trimester of pregnancy (see section 4.6).
• Severe heart failure, severe renal failure, or severe hepatic failure (see section 4.4)

4.4 Special warnings and precautions for use

Undesirable effects may be minimized by using the lowest effective dose for the shortest possible duration necessary to control symptoms (see GI and cardiovascular risks below).

Elderly population

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal.

Respiratory disorders

Bronchospasm can be triggered in patients suffering from, or with history of bronchial asthma or allergic diseases. Flurbiprofen must be used with caution in these patients.

Other NSAIDs

Concomitant use of flurbiprofen and other NSAIDs, including selective cyclooxygenase -2 inhibitors, should be avoided (see section 4.5).

SLE (Systemic Lupus Erythematosus) and mixed connective tissue disease

Patients with SLE and mixed connective tissue disease may have an increased risk of aseptic meningitis (see section 4.8). However, this effect is not usually seen with short term limited use products such as flurbiprofen lozenges.

Cardiovascular, Renal and Hepatic impairment

NSAIDs have been reported to cause nephrotoxicity in various forms including interstitial nephritis, nephrotic syndrome and renal failure. The administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and precipitate could trigger renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly, However, this effect is not usually seen with short term, limited use products such as flurbiprofen lozenges.

Mild to moderate hepatic dysfunction (see sections 4.3 and 4.8).

Cardiovascular and cerebrovascular effects

Caution (discussion with doctor or pharmacist) is required to starting treatment in patients with history of hypertension and/or heart failure, as fluid retention, hypertension, and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that the administration of some NSAIDs (particularly at high doses and long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example, myocardial infarction or stroke). There is not enough data to exclude this risk for flurbiprofen when administered at a maximum daily dose of 5 lozenges.

Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral artery disease and/or cerebrovascular disease should not be treated with flurbiprofen after careful consideration. The use of flurbiprofen lozenges under the indicated conditions is considered as suitable provided their low dose and short time of use.

Nervous System effects

Analgesic-induced headache: In case of prolonged use of analgesics or used beyond the regulations, headaches may occur, which must not be treated with increased doses of the medicinal product.

Gastrointestinal

NSAIDs should be given with care in patients with history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as these conditions could be exacerbated (see section 4.8).

Gastrointestinal bleeding, ulceration or perforation, which can be fatal has been reported, with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events.

The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing NSAIDs doses, in patients with history of ulcer, particularly if complicated with haemorrahage or perforation (see section 4.3), and in elderly, however this effect is not usually seen with short term limited use products such as Vocafen honey and lemon flavour 8.75 mg lozenges. Patients with a history of gastrointestinal toxicity, particularly elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), to their healthcare professional.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as acetyl salicylic acid (see section 4.5).

In patients taking flurbiprofen, the treatment should be withdrawn if gastrointestinal bleeding or ulceration occurs.

Dermatological effects

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely in association with the use of NSAIDs (see section 4.8). Flurbiprofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

Masking of symptoms of underlying infections

Epidemiological studies suggest that systemic non-steroidal anti-inflammatory drugs (NSAIDs) can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Vocafen honey and lemon flavour is administered while the patient suffers from fever or pain in relation to infection, monitoring of infection is advised.

Infections

The patient should immediately see a doctor if symptoms of bacterial infection occur or get worse during the treatment with flurbiprofen as in isolated cases, exacerbation of infectious inflammations was described (e.g. development of necrotizing fasciitis) in connection with the time when the systemic NSAIDs were used. The need to start antibiotic treatment with an anti-infective agent should be evaluated.

Excipients

This medicinal product contains sucrose and glucose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insuffiency should not take this medicine.

Vocafen honey and lemon flavour contains fragrances with citral, citronellol, geraniol, limonene and linalool which may cause allergic reactions.

4.5 Interaction with other medicinal products and other forms of interaction

Flurbiprofen should be taken with caution in combination with:

So far, studies have not revealed any interaction between flurbiprofen and tolbutamide or antacids.

4.6 Fertility, pregnancy and lactation

Pregnancy

The inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetal development. Epidemiological study results suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformation increased from less than 1% to approximately 1.5%. lt is believed that the risk increases with treatment dose and duration. References on inhibition of prostaglandin synthesis effects in animals are mentioned in section 5.3.

From the 20th week of pregnancy onward, flurbiprofen use may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation. Therefore, during the first and second trimesters of pregnancy, flurbiprofen should not be administered unless strictly necessary. If flurbiprofen is used by women who are trying to conceive, or in the first and second trimesters of pregnancy, the lowest possible dose and the shortest possible treatment should be used. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to flurbiprofen for several days from gestational week 20 onward. flurbiprofen should be discontinued if oligohydramnios or ductus arteriosus constriction are found.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to:

• Cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);

• Renal dysfunction (see above);

  The mother and newborn, at the end of pregnancy, to:

• Possible prolongation of bleeding time, an anti-aggregating effect that may occur even at very low doses.

• Inhibition of uterine contractions resulting in delayed or prolonged labor.

  Consequently, flurbiprofen is contraindicated during the third trimester of pregnancy.

  Breast-feeding

  In limited studies, flurbiprofen appears in the breast milk in very low concentrations and is unlikely to affect breast-fed infant adversely. However, because of possible adverse effects of NSAID on breast-fed infants, flurbiprofen is not recommended for use in nursing mothers.

  Fertility

  There is some evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. However, dizziness, and visual disturbances are possible side effects after taking NSAIDs. If affected, do not drive, or operate machinery. Somnolence is also a possible side effect and could affect driving ability.

4.8 Undesirable effects

Hypersensitivity reactions to NSAIDs have been reported and these may consist of:

• Non-specific allergic reactions and anaphylaxis
• Respiratory tract reactivity such as asthma, asthma worsening, bronchospasm, and dyspnea.

• Several skin reactions, such as itching, urticaria, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiform).

  Oedema, hypertension, and cardiac failure have been reported in association with NSAID treatment.

  Clinical trial and epidemiological data suggest that use of some NSAIDs, (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke), (see section 4.4). There is insufficient data to exclude such a risk for Flurbiprofen 8.75 mg lozenges

  The following list of adverse effects refers to those reported with flurbiprofen at OTC doses, for short-term use:

• (Very common (≥ 1/10, Common (≥ 1/100, < 1/10), Uncommon (≥ 1/1,000, < 1/100),

  Rare (≥ 1/10,000, < 1/1000), Very rare (< 1/10,000), not known (cannot be estimated from available data)).

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

Most patients who have ingested clinically important amounts of NSAIDs will develop no more than nausea, vomiting, epigastric pain, and more rarely diarrhea. Tinnitus, headache and gastrointestinal bleeding are also possible. In more serious poisoning with NSAIDs, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation, blurred vision and disorientation or coma. Occasionally, patients develop convulsions. In serious poisoning with NSAIDs, metabolic acidosis may occur and prothrombin time/INR (International Normalized Ratio) may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur. In asthmatic patients, exacerbation of asthma is possible.

Management

Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until they become stable.

Consider the use of activated charcoal or gastric lavage, and if needed serum electrolyte correction, if less than one hour has elapsed since ingestion or a potentially toxic amount was ingested. Frequent or prolonged convulsions should be treated with intravenous diazepam or lorazepam. Administer bronchodilators for asthma. There is no specific antidote for flurbiprofen.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic Group: Throat preparations, Other throat preparations, ATC Code: R02AX01

Mechanism of action

Flurbiprofen is a propionic acid derivative NSAID which acts through inhibition of prostaglandin synthesis.

Pharmacodynamic effects

In humans, flurbiprofen has potent analgesic, antipyretic and anti-inflammatory properties and the 8.75mg dose dissolved in artificial saliva has been shown to reduce prostaglandin synthesis in cultured human respiratory cells. According to studies using the whole blood assay, flurbiprofen is a mixed COX- 1/COX-2 inhibitor with some selectivity towards COX- 1.

Preclinical studies suggest that both R (-) and S (-) enantiomers of flurbiprofen and related NSAIDs may act on the central nervous system; the suggested mechanism is by inhibition of induced COX-2- at the level of the spinal cord.

Clinical efficacy and safety

A single dose of flurbiprofen 8.75mg delivered locally to the throat in a lozenge has been demonstrated to relieve sore throat, including swollen and inflamed sore throats through a significant reduction (LS Mean Difference) in sore throat pain intensity from 22 minutes (- 5.5mm), reaching a maximum at 70 minutes (-13.7mm) and remaining significant for up to 240 minutes (-3.5mm) including patients with streptococcal and non-streptococcal infections, reduction in difficulty swallowing from 20 minutes (-6.7mm), reaching a maximum at 110 minutes (-13.9mm) and for up to 240 minutes (-3.5mm) and reduction in the feeling of a swollen throat at 60 minutes (-9.9mm), reaching a maximum at 120 minutes (-11.4mm) and for up to 210 minutes (-5.1mm).

Multiple dose efficacy measured using Sum of Pain Intensity Differences (SPID) over 24 hours has demonstrated significant reduction in sore throat pain intensity (-473.7mm*h to - 529.1mm*h), difficulty swallowing (-458.4mm*h to -575.0mm*h) and swollen throat (- 482.4mm*h to -549.9mm*h) with statistically significant greater summed reduction in pain at each hourly interval over 23 hours for all three measures and statistically significantly greater sore throat relief each hour over the 6 hour assessment time. Efficacy of multiple doses after 24 hours and over 3 days has also been demonstrated.

For those patients taking antibiotics for streptococcal infection, there was statistically significant greater relief of sore throat pain intensity for flurbiprofen 8.75 mg from 7 hours and onwards after antibiotics were taken. The analgesic effect of flurbiprofen 8.75 mg was not reduced by the administration of antibiotics to treat patients with streptococcal sore throat.

At 2 hours post first dose, flurbiprofen 8.75mg lozenges provided significant resolution of some of the associated symptoms of sore throat present at baseline including coughing (50% vs 4%), loss of appetite (84% vs 57%) and feverishness (68% vs 29%). The lozenge format dissolves in the mouth over 5 - 12 minutes and provides a measurable soothing and coating effect at 2 minutes.

Paediatric Population

No specific studies in children have been undertaken. Efficacy and safety studies on flurbiprofen 8.75mg lozenges have included adolescents aged 12 – 17 years, although small sample size means that no statistical conclusions can be drawn.

5.2 Pharmacokinetic properties

Absorption

Lozenges dissolve over 5 – 12 minutes and the flurbiprofen is readily absorbed, with detection in the blood at 5 minutes and plasma concentrations peaking at 40 – 60 minutes after administration but remaining at a mean low level of 2.65 μg/mL. Absorption of flurbiprofen can occur from the buccal cavity by passive diffusion. Rate of absorption is dependent on pharmaceutical form with peak concentrations achieved more rapidly than, but of similar magnitude to, those achieved after an equivalent swallowed dose.

Distribution

Flurbiprofen is rapidly distributed throughout the body and is extensively bound to plasma proteins.

Biotransformation

Flurbiprofen is mainly metabolized by CYP2C9 by hydroxylation.

Elimination

Flurbiprofen is mainly excreted via the kidneys. It has an elimination half-life of 3 to 6 hours. Flurbiprofen is excreted in very small amounts in human milk (less than 0.08 μg/ml). Approximately 20-25% of a flurbiprofen oral dose is excreted unchanged.

Special population

No difference in pharmacokinetic parameters between elderly and young adult volunteers has been reported following oral administration of flurbiprofen tablets.

5.3 Preclinical safety data

Acute and chronic toxicity:

Toxicology studies were performed after a single and repeated administration in several animal species for up to 2 years. Gastrointestinal damages were observed with flurbiprofen in smaller oral doses (10, 20 or 40 mg/kg). The number of lesions increased with increasing dose. The chronic oral administration of flurbiprofen to rats (oral doses from 0.5 up to 8.0 mg/kg) led to gastric ulcerations and/or erosions, that were seen in both 3-month and 2-year studies. Relatively few intestinal lesions were noted.

Mutagenic and carcinogenic potential:

Carcinogenicity and mutagenicity studies revealed no evidence of carcinogenic or mutagenic potential.

Reproductive toxicology:

In animals, the administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidence of several malformations, including cardiovascular, have been reported in animals that received a prostaglandin inhibitor during the organogenesis period.

In rats exposed to doses of 0.4 mg/kg/day and above, during pregnancy, an increased incidence of stillborn pregnancy has been observed. However, the relevance of this fact to humans is doubtful and not reflected in human experience with flurbiprofen so far.

Published data have shown that flurbiprofen may pose a risk for the aquatic compartment, especially for fish.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose

Glucose liquid

Macrogol 400

Levomenthol

Honey flavour (contains citronellol)

Lemon flavour (contains citral, citronellol, geraniol, limonene, and linalool)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC - PVDC Aluminum blisters in a printed cardboard box.

Pack size: 16 lozenges

6.6 Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

This medicinal product may pose a risk to the environment (see section 5.3).

7 MARKETING AUTHORISATION HOLDER

Mapaex Consumer Healthcare (Ireland) Private Limited

IDA Business Park, Green Road, Newbridge

KILDARE

W12 X902

Ireland

8 MARKETING AUTHORISATION NUMBER(S)

PL 57980/0001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

12/06/2025

10 DATE OF REVISION OF THE TEXT

12/06/2025