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STREFEN INSTANTS 8.75MG GRANULES

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Strefen Instants 8.75mg granules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
One sachet with 850 mg granules contains 8.75 mg of flurbiprofen
Excipient: 4.25 mg of aspartame/sachet
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Granule
White to cream-coloured, free-flowing granule with a characteristic mint odour.

4.1

Therapeutic indications
Strefen Instants are indicated for the short term symptomatic relief of sore
throat.
Strefen Instants are indicated in adults and children over the age 12 years.

4.2

Posology and method of administration
Method of Administration: For oral use only.
Indicated for adults and children over the age of 12 years:
One sachet of granules to be dissolved in the mouth, then swallowed. Strefen
Instants can be taken every 3-6 hours as required, up to a maximum of
5 sachets of granules in a 24 hour period.

The product should not be used for more than 3 days. Undesirable effects may
be minimised by using the lowest effective dose for the shortest duration
necessary to control symptoms (see section 4.4).
There are no specific requirements in relation to food and drink.
Paediatric population
The safety and efficacy of Strefen Instants in children under 12 years has not
been established.
Elderly population
A general dose recommendation cannot be given, since to date clinical
experience is limited. The elderly are at increased risk of the serious
consequences of adverse reactions. If an NSAID is considered necessary, the
lowest effective dose should be used and for the shortest possible duration.
The patient should be monitored regularly for GI bleeding during NSAID
therapy.

4.3

Contraindications
Hypersensitivity to flurbiprofen or any of the excipients in the product.
Patients who have previously shown hypersensitivity reactions (e.g. asthma,
bronchospasm, rhinitis, angiodema or urticaria) in response to aspirin
(acetylsalicylic acid) or other NSAIDs.
Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct
episodes of proven ulceration) and intestinal ulceration.
History of gastrointestinal bleeding or perforation, severe colitis,
haemorrhagic or haematopoietic disorders related to previous NSAIDs
therapy.
Last trimester of pregnancy (See section 4.6)
Severe heart failure, renal failure or hepatic failure (see section 4.4).

4.4

Special warnings and precautions for use
Undesirable effects may be minimised by using the lowest effective dose for the
shortest duration necessary to control symptoms (see section 4.2, and GI and
cardiovascular risks below).
Phenylketonuria

Strefen Instants contains aspartame which is a source of phenylalanine and this
may be harmful for people with phenylketonuria.
Elderly population
The elderly have an increased frequency of adverse reactions to NSAIDs
especially gastrointestinal bleeding and perforation which may be fatal.
Respiratory

Bronchospasm may be precipitated in patients suffering from or with a
previous history of bronchial asthma or allergic disease since NSAIDs have
been reported to precipitate bronchospasm in such patients. Strefen Instants
should be used with caution in these patients.
Other NSAIDs
The use of Strefen Instants with concomitant NSAIDs including cyclo-oxygenase-2
selective inhibitors should be avoided (see section 4.5).
Systemic lupus erythematosus (SLE) 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).
Renal 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 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. Renal function should
be monitored in these patients (see also section 4.3). The habitual
administration of analgesics may lead to persistent kidney damage with the
risk of renal failure, particularly in combination of several analgesic
substances, but this is not usually seen with short term, limited use products
such as Strefen Instants.
Hepatic Impairment
Flurbiprofen is hydrolysed in the liver and impaired hepatic function may
reduce the rate at which the drug is removed from the body. At the short term,
low doses of Strefen Instants this is not believed to be of significant concern.
Cardiovascular and cerebrovascular effects
Appropriate monitoring and advice are required for patients with a history of
hypertension and/or mild to moderate congestive heart failure as fluid
retention and oedema have been reported in association with NSAID therapy.
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). There are insufficient data to exclude such a risk for
flurbiprofen. .

Patients with uncontrolled hypertension, congestive heart failure, established
ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular
disease should only be treated with flurbiprofen after careful consideration.
Similar consideration should be made before initiating longer-term treatment
of patients with risk factors for cardiovascular disease (e.g. hypertension,
hyperlipidaemia, diabetes mellitus, smoking).
Effects on the Nervous System
In the event of prolonged use of analgesics or use beyond the regulations cephalea
may occur, which must not be treated with increased doses of the medicinal product.
Impaired female fertility

There is some evidence that drugs which inhibit cyclooxygenase/prostaglandin synthesis may cause impairment of female fertility
by an effect on ovulation. This is reversible on withdrawal of treatment.
It is recommended to discontinue the use of flurbiprofen treatment in women
attempting to conceive, in women who have difficulties conceiving and
women who are undergoing investigation of infertility.
Gastrointestinal
NSAIDs should be given with care to patients with a history of gastrointestinal
disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated
(see section 4.8).
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all
NSAIDs at anytime during treatment, with or without warning symptoms or a
previous history of serious GI events.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID
doses, in patients with a history of ulcer, particularly if complicated with
haemorrhage or perforation (see section 4.3), and in the elderly. These patients
should commence treatment on the lowest dose available. Combination therapy with
protective agents (e.g., misoprostol or proton pump inhibitors) should be considered
for these patients, and also for patients requiring concomitant low dose acetylsalicylic
acid, or other drugs likely to increase gastrointestinal risk (see below and 4.5).
Patients with a history of GI toxicity, particularly when elderly, should report any
unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages
of treatment.
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
acetylsalicylic acid (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving flurbiprofen, the
treatment should be withdrawn.
Haematological effects
Flurbiprofen, like other NSAIDs, may inhibit platelet aggregation and prolong
bleeding time. Strefen Instant should be used with caution in patients with a potential
for abnormal bleeding.

Dermatological

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). Patients
appear to be at highest risk for these reactions early in the course of therapy:
the onset of the reaction occurring in the majority of cases within the first
month of treatment. Strefen Instants should be discontinued at the first
appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Infections
Since in isolated cases an exacerbation of infective inflammations (e.g.
development of necrotising fasciitis) has been described in temporal
association with the use of systemic NSAIDs as a class, the patient is advised
to consult a physician immediately if signs of a bacterial infection occur or
worsen during the Strefen Instants therapy. It should be considered whether
initiation of an anti-infective antibiotic therapy is indicated. In cases of
purulent bacterial pharyngitis/tonsillitis, Strefen Instants should be used with
antibiotic therapy.
If the symptoms get worse or if new symptoms occur the treatment should be
re-evaluated.
If mouth irritation occurs, treatment should be withdrawn.

4.5

Interaction with other medicinal products and other forms of interaction
Flurbiprofen should be avoided in combination with:
Other NSAIDS including cyclooxygenase-2 selective inhibitors
Avoid concomitant use of two or more NSAIDs, unless advised by a doctor, as this
may increase the risk of adverse effects (esp. gastrointestinal adverse events as ulcers
and bleeding), (see section 4.4).
Acetylsalicylic acid (low dose)
As with other products containing NSAIDs, concomitant administration of
flurbiprofen and aspirin is not generally recommended because of the potential for
adverse events. Unless low-dose aspirin (not above 75mg daily) has been advised by
a doctor, as this may increase the risk of adverse reactions (see section 4.4).
Flurbiprofen should be used with caution (not recommended) in combination
with:
Anticoagulants
NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section
4.4).
Anti-platelet Agents

Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Antihypertensive drugs (Diuretics, ACE inhibitors, angiotensin-II-antagonists)
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs may
enhance nephrotoxicity caused by inhibition of cyclooxygenase, especially in patients
with compromised renal function (Patients should be adequately hydrated and
consideration should be given to monitoring of renal function after initiation of
concomitant therapy, and periodically thereafter).
Alcohol
May increase the risk of adverse reactions, especially of bleeding in the
gastrointestinal tract.

Cardiac glycosides
NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside
levels - adequate control and, if necessary, dose adjustment is recommended.
Ciclosporin
Increased risk of nephrotoxicity.
Corticosteroids
May increase the risk of adverse reactions, especially of the gastrointestinal tract (see
section 4.3).
Lithium
May increase serum levels of glycosides – adequate control and, if necessary, dose
adjustment is recommended.
Methotrexate
The administration of NSAIDs within 24 hours before or after administration of
methotrexate may lead to elevated concentrations of methotrexate and an increase in
its toxic effect.
Mifepristone
NSAIDs should not be used for 8 – 12 days after mifepristone administration as
NSAIDs can reduce the effect of mifepristone.
Oral antidiabetics
Alteration of blood glucose levels reported (increased check rate recommended).
Phenytoin
May increase serum levels of phenytoin – adequate control and, if necessary, dose
adjustment is recommended.
Potassium sparing diuretics
Concomitant use may cause hyperkaliaemia (check of serum potassium is
recommended).
Probenecid Sulfinpyrazone
Medicinal products that contain probenecid or sulfinpyrazone may delay the excretion
of flurbiprofen.
Quinolone antibiotics

Animal data indicate that NSAIDs can increase the risk of convulsions associated
with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an
increased risk of developing convulsions.
Selective serotonin reuptake inhibitors (SSRI’s)
Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Tacrolimus
Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine
Increased risk of haematological toxicity when NSAIDs are given with zidovudine.
There is evidence of an increased risk of haemarthroses and haematoma in HIV (+)
haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

No studies so far have revealed any interactions between flurbiprofen and
tolbutamide or antacids.

4.6

Pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the
embryo/foetal development. Data from epidemiological studies suggest an increased
risk of miscarriage and of cardiac malformation and gastroschisis after use of a
prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for
cardiovascular malformation was increased from less than 1%, up to approximately
1.5%. The risk is believed to increase with dose and duration of therapy. In animals,
administration of a prostaglandin synthesis inhibitor had been shown to result in
increased pre- and post-implantation loss and embryo-foetal lethality. In addition,
increase incidences of various malformations, including cardiovascular, have been
reported in animals given a prostaglandin synthesis inhibitor during the organogenetic
period. During the first and second trimester of pregnancy, flurbiprofen should not be
given unless clearly necessary. If flurbiprofen is used by a women attempting to
conceive, or during the first and second trimester of pregnancy, the dose should be
kept as low as possible and duration of treatment as short as possible,
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may
expose the foetus to:
• Cardiopulmonary toxicity (with premature closure of the ductus arteriosus
and pulmonary hypertension)
• Renal dysfunction, which may progress to renal failure with olgiohydroamniosis;
The mother and the neonate, at the end of pregnancy, to:
• Possible prolongation of bleeding time, an anti-aggregation effect which may
occur even at very low doses.
• Inhibitions of uterine contractions resulting in delayed or prolonged labour.
Consequently, flurbiprofen is contraindicated during the third trimester of pregnancy.

Breastfeeding
In limited studies, flurbiprofen appears in the breast milk in very low concentration.
However, because of possible adverse effects of NSAIDs on breast-fed infants,
Strefen Instants are not recommended for use in nursing mothers.
Female 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.
Dizziness and visual disturbances are possible undesirable effects after taking
NSAIDS. If affected, patients should not drive or operate machinery.

4.8

Undesirable effects
a) Summary of safety profile
Low dose Flurbiprofen indicated for the short term treatment of sore throats exhibits
primarily gastrointestinal adverse events. These are non-serious and transient in
nature. Other non-serious, transient events noted during clinical assessment are
typical of the patient group likely to be seeking alleviation of sore throat and similar
symptoms associated with colds and influenza-type illness.
Common undesirable effects include a burning sensation or discomfort in the mouth,
alteration of taste, headache and diarrhoea. All of these effects are transient and nonserious in nature.

b)

Summary of adverse reactions
The following list of adverse effects relates to clinical assessment with
flurbiprofen 8.75mg at OTC doses for short-term use.
(Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to
<1/100), Rare (≥1/10000 to <1/1000), Very rare (<1/10000), not known
(cannot be estimated from the available data))
Blood and lymphatic system disorders
Uncommon: Lymphadenopathy
Rare: Anaemia
Very Rare: Haematopoietic disorders
Cardiac disorders
Rare: Palpitations
Ear and labyrinth disorders

Uncommon: Ear pain
Rare: Ear congestion, Deafness, Ear discomfort, Vertigo
Eye disorders
Rare: Conjunctivitis, Eye irritation, Photophobia, Lacrimation increased,
Occular hyperaemia, Vision blurred
Gastrointestinal disorders
Common: Abdominal pain (general, upper or lower), Diarrhoea, Mouth
ulceration, Nausea, Oral discomfort, Oral pain, Parasthesia oral,
Uncommon: Abdominal discomfort, Abdominal distension, Constipation, Dry
mouth, Dyspepsia, Dysphagia, Glossodynia, Hypoaesthesia oral, Oral
dysaethesia, Stomatitis, Tongue ulceration, Vomiting
Rare: Flatulence, Gastroesophageal reflux, Gingival bleeding, Gingival pain,
Gingival ulceration, Malaena, Oral pruritis, Swollen tongue, Tongue coated,
Tongue dry
Very Rare: Hepatitis and cholestatic icterus (jaundice)
General disorders and administration site conditions
Common: Influenza-like illness
Uncommon: Chest discomfort, Fatigue, Malaise, Pain, Pyrexia
Rare: Asthenia, Chest pain, Oedema peripheral, Thirst, Chills, Feeling hot,
Sensation of a foreign body, Swelling, Ulcer
Immune system disorders
Rare: Seasonal allergy
Infections and infestations
Common: Upper respiratory tract infection
Uncommon: Ear infection, Eye infection, Gingival infection, Influenza,
Laryngitis, Lower respiratory tract infection, Nasopharyngitis, Oral herpes,
Pharyngitis, Rhinitis, Sinusitis, Tonsillitis, Viral infection
Rare: Bronchitis, Peritonsilar abcess, Urinary tract infection, Vulvovaginal
candidiasis
Investigations
Rare: Blood glucose increased, Body temperature increased
Metabolism and nutrition disorders
Rare: Dehydration.
Musculoskeletal and connective tissue disorders
Uncommon: Arthralgia, Back pain
Rare: Joint swelling, Neck pain, Muscle spasms, Pain in extremity,
Nervous system disorders
Common: Dizziness, Dysgeusia, Headache, Parasthesia,
Uncommon: Aphonia, Burning sensation, Migraine, Somnolence
Rare: Hypoaesthesia, Lethergy, Ageusia,

Psychiatric disorders
Uncommon: Insomnia,
Rare: Confusional state, Sleep disorder, Abnormal dreams
Renal and urinary disorders
Rare: Pollakiuria, Urinary abnormality, Chromaturia, Interstitial nephritis,
Nephritis syndrome
Reproductive system and breast disorders
Rare: Menorrhagia
Respiratory, thoracic and mediastinal disorders
Common: Cough, Oropharyngeal pain, Throat irritation, Wheezing
Uncommon: Asthma, Dry throat, Dysphonia, Dysponoea, Epistaxis, Increased
upper airway secretion, Nasal congestion, Nasal discomfort, Pharyngeal
erythema, Pharangeal hypoaesthesia, Productive cough, Rales, Rhinalgia,
Rhinorrhoea, Sneezing,
Rare: Bronchospasm, Haemoptysis, Oropharangeal blistering, Pharangeal
oedema, Sinus congestion, Aggravation of asthma
Skin and subcutaneous tissue disorders
Uncommon:Hyperhidrosis, Pruritus, Rash, Rash pruritic,
Rare: Acne, Dry skin, Eczema, Psoriasis, Skin nodule, Swelling face
Very Rare: Stevens-Johnson syndrome, Lyell syndrome
Vascular disorders
Rare: Hot flush
Adverse reactions reported with flurbiprofen, tablet form (i.e. at a higher
dose and/or in the treatment of chronic conditions, under long-term
treatment, not indicated for the Strefen Instants).
(Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to
<1/100), Rare (≥1/10000 to <1/1000), Very rare (<1/10000), not known
(cannot be estimated from the available data))
Cardiac disorders
Very rare: 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).
Blood and lymphatic system disorders
Rare: haematological reactions (including anaemia, prolonged bleeding time)
Very rare: thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia
and haemolytic anaemia).

Respiratory, thoracis and mediastinal disorders
Rare: bronchospasm, dyspnoea
Gastrointestinal disorders
Rare: GI bleeding, ulceration and perforation and ulcerative stomatitis
Renal and urinary disorders
Rare: renal dysfunction (including interstitial nephritis, nephritic syndrome
and renal failure)
Skin and subcutaneous tissue disorders
Very rare: skin reactions (including Stevens Johnson syndrome and Lyell’s
syndrome)
General disorders and administration site conditions

Rare: Fever
Immune System disorders
Very rare: anaphylactic shock
Hepatobiliary disorders
Very rare: hepatic disorders (including hepatitis and cholestatic jaundice)

Adverse events associated with use of NSAIDs in general
(Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to
<1/100), Rare (≥1/10000 to <1/1000), Very rare (<1/10000), not known
(cannot be estimated from the available data))
Cardiac disorders
Oedema, hypertension and cardiac failure have been reported in association
with NSAID treatment.
Clinical trial and epidemiological data suggest that use of NSAIDs (particularly at
high doses 2400 mg daily) 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).

Blood and lymphatic system disorders
Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia,
pancytopenia, agranulocytosis). First signs are: fever, sore throat, superficial
mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and
bruising.
Nervous System disorders
Uncommon: Headache
Very rare: Aseptic meningitis – single cases have been reported very rarely.
Respiratory, thoracis and mediastinal disorders
Exacerbation of asthma and bronchospasm.

Gastrointestinal disorders
The most commonly-observed adverse events are gastrointestinal in nature.
Uncommon: abdominal pain, nausea, dyspepsia.
Rare: diarrhoea, flatulence, constipation and vomiting.
Very rare: peptic ulcer, perforation or gastrointestinal haemorrhage, melaena,
haematemesis, sometimes fatal, particularly in the elderly. Ulcerative
stomatitis, gastritis. Exacerbation of colitis and Crohn’s disease (see section
4.4).
Renal and Urinary disorders
Very rare: Acute renal failure, papillary necrosis, especially in long-term use,
associated with increased serum urea and oedema.
Skin and subcutaneous tissue disorders
Uncommon: Various skin rashes.
Very rare: Severe forms of skin reactions such as bullous reactions, including
Stevens-Johnson Syndrome, erythema multiforme and toxic epidermal
necrolysis can occur.
Immune System disorders
Uncommon: Hypersensitivity reactions with urticaria and pruritus.
Very rare: severe hypersensitivity reactions. Symptoms could be facial,
tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension,
(anaphylaxis, angioedema or severe shock).
In patients with existing auto-immune disorders (such as systemic lupus
erythematosus, mixed connective tissue disease) during treatment with
ibuprofen, single cases of symptoms of aseptic meningitis, such as stiff neck,
headache, nausea, vomiting, fever or disorientation have been observed (see
section 4.4).
Hepatobiliary disorders
Very rare: liver disorders.

c) Description of selected adverse events.
Consumers of low-dose flurbiprofen indicated for the treatment of sore throat may
experience sensations described variously as burning, tingling or prickling in the
mouth. The sense of taste may also be affected. These phenomenon are non-serious
and transient in nature.
Headaches may also be experienced which are also transient and non-serious.
Some individuals may suffer minor, temporary gastrointestinal discomfort.
Flurbiprofen belongs to the pharmacological class of drugs known as non-steroidal
anti-inflammatory drugs (NSAIDs). Hypersensitivity reactions to NSAIDs have
occasionally been reported and these may consist of:

(a) Non-specific allergic reactions and anaphylaxis
(b) Respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm,
dyspnoea
(c) Various skin reactions, e.g. pruritus, urticaria, angioedema and more rarely
exfoliative and bullous dermatoses (including epidermal necrolysis and erythema
multiforme).

4.9

Overdose
Symptoms
Most patients who have ingested clinically important amounts of NSAIDs will
develop no more than nausea, vomiting, epigastric pain, or more rarely diarrhoea.
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 the prothrombin time/INR may be prolonged,
probably due to interference with the actions of circulating clotting factors. Acute
renal failure and liver damage may occur. Exacerbation of asthma is possible in
asthmatics.

Management
Management should be symptomatic and supportive and include the maintenance of a
clear airway and monitoring of cardiac and vital signs until stable. Consider oral
administration of activated charcoal or gastric lavage and if necessary correction of
serum electrolytes if the patient presents within one hour of ingestion of a potentially
toxic amount. If frequent or prolonged, convulsions should be treated with
intravenous diazepam or lorazepam. Give bronchodilators for asthma. There is no
specific antidote to flurbiprofen.

5.1

Pharmacodynamic properties
Pharmacotherapeutic Group: Other throat preparations, throat preparations.
ATC Code: R02 AX01
Flurbiprofen is a propionic acid derivative NSAID which acts through
inhibition of prostaglandins synthesis. In humans flurbiprofen has potent
analgesic, antipyretic and anti-inflammatory properties. According to studies
using the whole blood assay, flurbiprofen is a mixed COX-1/COX-2 inhibitor
with some selectivity towards COX-1.
Pre-clinical studies suggest that the R (-) enantiomer 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.
Strefen Instants have been demonstrated to relieve sore throat through a
reduction in severity of throat soreness from 1 minute (-0.95; SD=1.45) and

over 6 hours (-2.25; SD=1.76), sore throat pain relief with significance from 1
minutes (2.58; SD=1.37) and over 6 hours (3.26; SD=1.52), relief from
difficulty swallowing with significance from 5 minutes (-13.63; SD=16.15)
and over 6 hours (-23.50; SD=15.96) and reduction in sore throat pain
intensity from 5 minutes (-13.81; SD=15.96) and over 6 hours (-22.62;
SD=18.63). Multiple dose efficacy has also been observed. Patients also
recorded a significant improvement in wellbeing at 3 hours and after 3 days
treatment.
The mint flavoured granule format dissolves quickly in the mouth and contains
polymers for adherence and retention.
Paediatric Population
No specific studies in children have been undertaken, although efficacy and
safety studies on Strefen 8.75mg lozenges have included children 12 – 17
years, although small sample size means that no statistical conclusions can be
drawn.

5.2

Pharmacokinetic properties
Absorption
Strefen Instants dissolve rapidly and the flurbiprofen is readily absorbed, with plasma
concentrations peaking at 60 - 70 minutes. 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, but more
slowly than an equivalent lozenge dose.
Distribution
Flurbiprofen is rapidly distributed throughout the body and is extensively bound to
plasma proteins.
Metabolism / Excretion
Flurbiprofen is mainly metabolised by hydroxylation and 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 0.05ug/ml). Approximately 20-25% of a
flurbiprofen oral dose is excreted unchanged.
Special Groups
No difference in pharmacokinetic parameters between elderly and young adult
volunteers has been reported following oral administration of flurbiprofen tablets. No
pharmacokinetic data have been generated in children below 12 years of age
following administration of Flurbiprofen 8.75 mg however administration of both
flurbiprofen syrup and suppository formulations indicate no significant differences in
pharmacokinetic parameters compared with adults.

5.3

Preclinical safety data
Flurbiprofen displays dose dependent effects typical of NSAIDS, including
gastrointestinal effects such as ulceration, bleeding and perforation in rats,
delayed onset and duration of parturition in pregnant rats, especially when
exposure occurs late in pregnancy.
Genotoxicity
In-vitro and in-vivo studies to assess the genotoxicity potential of flurbiprofen
demonstrate that the drug is unlikely to pose a risk of genotoxicity among
humans. The chemical structure of flurbiprofen does not contain structural
alerts for genotoxicity and NSAIDS are not considered to be mutagenic.
Systemic Toxicity
The principle toxic reaction to flurbiprofen is gastrointestinal erosion and
ulceration in all species studies, with death at high doses due to ulceration and
associated peritonitis. Renal papillary necrosis, liver toxicity and anaemia have
been documented in several species.
Carcinogenicity
Carcinogenicity studies in mice and rats revealed no evidence of treatment
related carcinogenicity.
Reproductive and Developmental toxicology
Fertility, reproductive performance and foetal development have been studied
in rats and mice. Dose-dependent effects on dams (female rats) and offspring
observed in these studies included prolonged pregnancy and labour, increased
numbers of stillbirths, gastrointestinal ulceration and reduction in number of
pups born to rats. Transfer of flurbiprofen to foetus and transfer from mother’s
milk to the neonate have been observed, but no evidence of teratogenic effects
has been seen.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Xylitol
Mannitol
Carbomer
Sodium hydrogen carbonate

Cool Mix for Mint Flavour
Peppermint Flavour
Aspartame
Citric Acid anhydrous
Silicon Dioxide
Sodium Chloride

6.2

Incompatibilities
Not applicable

6.3

Shelf life
24 months

6.4

Special precautions for storage
Do not store above 25°C

6.5

Nature and contents of container
Each sachet is composed of:
12 micron Polyester (PET) 12 micron Polyethylene (PE)/9 micron Aluminium/37
gsm Polyethylene (PE)
Or
12 micron Polyester (PET)12 micron Polyethylene (PE)/12 micron Aluminium/37
gsm Polyethylene (PE)
Pack sizes contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 sachets. Not all
pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements

7

MARKETING AUTHORISATION HOLDER
Reckitt Benckiser Healthcare (UK) Limited
103 – 105 Bath Road
Slough
SL1 3UH

8

MARKETING AUTHORISATION NUMBER(S)
PL 00063/0563

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
10/07/2012

10

DATE OF REVISION OF THE TEXT
14/06/2013

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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