Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis, juvenile
rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, including spondyloarthritis.
- Painful spinal syndromes.
- Extra-articular rheumatism.
- Painful conditions of inflammation and swelling following trauma and surgical procedures,
e.g. in dental and maxillofacial surgery and in orthopaedics.
- Painful and/or inflammatory conditions in gynaecology, e.g. primary dysmenorrhea, adnexitis.
- Acute gout attack (film-coated tablets).

- As an adjuvant in acute painful inflammatory infections of the ears, nose or throat, e.g.
pharyngotonsillitis, otitis (film-coated tablets).
- In accordance with general medical principles, appropriate therapeutic measures should be
taken for the treatment of underlying diseases. Fever alone is not an indication.

Generally it is advisable to select the dose on an individualised basis. Adverse reactions can be
reduced by administering the lowest effective dose over the shortest possible duration for symptomatic
control (see “4.4 Special Warnings and precautions for use”).
Adults
Film-coated tablets (gastro-resistant)
The initial daily dose of Olfen Lactab film-coated tablets is generally 100-150 mg. For relatively mild
cases and long-term treatment 75-100 mg/d is usually sufficient.
In general, the daily dose is divided into 2-3 single doses.
To avoid nocturnal pain and morning stiffness, administration of one Olfen Rectocap before bedtime
can be combined with ingestion of film-coated tablets during the day (up to a maximum daily dose of
150 mg).
In primary dysmenorrhoea, the daily dose is generally 50-150 mg, individually adjusted; a starting
dose of 50-100 mg should initially be selected and, if required, the dose can be increased over the
course of several menstrual cycles up to a maximum of 150 mg/d.
The gastro-resistant sugar-coated tablets should be taken with some liquid, preferably before meals;
they must not be divided or chewed.
Prolonged-release tablets, prolonged-release capsules
In general, the daily dose of Olfen Depocaps or Olfen Depotabs is 100–150 mg, i.e. one 100 mg
prolonged-release capsule or two 75 mg prolonged-release tablets. For relatively mild cases and longterm
treatment, one 75 mg or 100 mg prolonged-release tablet per day is generally sufficient. If the
symptoms occur most severely during the night or in the morning, Olfen Depocaps or Olfen Depotabs
should preferably be taken in the evening.
The prolonged-release capsules and prolonged-release tablets should be taken unchewed with some
liquid, preferably with meals.
Special dosage instructions
Paediatric population
Depending on the severity of the disease, children aged 1 year and older and adolescents should be
given 0.5-2 mg per kg body weight daily, divided into 2-3 single doses. For the treatment of juvenile
rheumatoid arthritis, the daily dose can be increased to a maximum of 3 mg per kg body weight,
divided into several single doses.
The maximum daily dose of 150 mg should not be exceeded.
Olfen must not be used in children under 1 year of age.
Due to their active substance content, Olfen Lactab 50 mg film-coated tablets are not recommended
for use in children. Olfen Lactab 25 mg film-coated tablets can be used in these patients. Olfen
Depotabs 75 mg prolonged-release tablets and Olfen Depocaps 100 mg prolonged-release capsules are
not suitable for children and adolescents.
Elderly patients (65 years and older)
An initial dose adjustment is not necessary in elderly patients (see “4.4 Special Warnings and
precautions for use”).
Existing cardiovascular disease or significant cardiovascular risk factors 

Treatment with Olfen is generally not recommended in patients with existing cardiovascular disease or
uncontrolled hypertension. If necessary, patients with existing cardiovascular disease, uncontrolled
hypertension or significant risk factors for cardiovascular disease should not be treated with Olfen
until after a careful assessment and if administered for more than 4 weeks they should not receive
doses exceeding 100 mg per day (see “4.4 Special Warnings and precautions for use”).
Patients with renal insufficiency
Olfen is contraindicated in patients with renal insufficiency (see “4.3 Contraindications”).
No specific studies have been conducted in patients with impaired renal function and it is therefore not
possible to make specific dose adjustment recommendations. Caution is required when administering
Olfen to patients with mild to moderate renal function impairment (see “4.4 Special Warnings and
precautions for use”).
Patients with hepatic impairment
Olfen is contraindicated in patients with hepatic insufficiency (see “4.3 Contraindications”).
No specific studies have been conducted in patients with impaired hepatic function and it is therefore
not possible to make specific dose adjustment recommendations. Caution is required when
administering Olfen to patients with mild to moderate hepatic function impairment (see “Warnings
and precautions”).

 

Hypersensitivity to the active substance or to any of the excipients listed in the composition. History of bronchospasm, urticaria, acute rhinitis, nasal polyps or allergy-like symptoms after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs. Third trimester of pregnancy (see “4.6 Fertility, Pregnancy and lactation”). Active gastric and/or duodenal ulceration, or gastrointestinal haemorrhage or perforation. Inflammatory bowel diseases (such as Crohn's disease, ulcerative colitis). Hepatic insufficiency (Child-Pugh class C) (hepatic cirrhosis and ascites). Renal failure (creatinine clearance < 30 mL/min). Severe cardiac failure (NYHA III-IV). Treatment of postoperative pain after coronary bypass surgery (or use of a heart-lung machine).

General warning about the use of systemic non-steroidal anti-inflammatory drugs
Gastrointestinal ulceration, bleeding or perforation may occur at any time during treatment with nonsteroidal
anti-inflammatory drugs (NSAIDs), whether COX-2 selective or not, even without warning
symptoms or a relevant previous history. To minimise this risk, the lowest effective dose should be
administered for the shortest possible duration.
Placebo-controlled studies have demonstrated that certain selective COX-2 inhibitors increase the risk
of thrombotic cardiovascular and cerebrovascular complications. It is not yet known whether this risk
correlates directly to the COX-1/COX-2 selectivity of the individual NSAIDs. Since no comparable
clinical study data are currently available for diclofenac at maximum dosage during long-term therapy,
the possibility of a similarly high risk cannot be ruled out. Until relevant data are available, diclofenac
should be used in clinically confirmed cases of coronary heart disease, cerebrovascular disease,
peripheral arterial occlusive disease, or in patients with significant risk factors (e.g. hypertension,
hyperlipidaemia, diabetes mellitus, smoking) only after careful consideration of the benefits and risks.
Also because of this risk, the lowest effective dose should be administered for the shortest possible
duration.
The renal effects of NSAIDs entail fluid retention with oedema and/or arterial hypertension.
Diclofenac should therefore be used only with caution in patients with impaired cardiac function and other conditions that predispose them to fluid retention. Caution is also advised in patients taking
diuretics or ACE inhibitors concomitantly, as well as in those with an increased risk of hypovolaemia.
In the elderly, the consequences are generally more serious. If gastrointestinal bleeding or ulceration
occurs in patients on Olfen treatment, administration of the medicinal product should be discontinued.
Skin reactions
Serious, sometimes fatal, skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome and
toxic epidermal necrolysis have very rarely been associated with the use of NSAIDs, including Olfen
(see “4.8 Undesirable effects”). The risk to the patients appears to be greatest at the start of treatment,
and the reaction mostly subsides within the first month of treatment. Olfen should be discontinued at
the first sign of skin rash, mucosal lesions or other signs of hypersensitivity.
As with other NSAIDs, diclofenac can in rare cases result in allergic reactions, including
anaphylactic/anaphylactoid reactions, even without prior exposure to the medicinal product.

Masked signs of infection
The pharmacodynamic properties of Olfen mean that – as with other NSAIDs – the signs and
symptoms of an infection can be masked.
Precautions
General
The concomitant use of Olfen and systemic NSAIDs, such as selective cyclooxygenase-2 inhibitors,
must be avoided since there is a potential for additive undesirable effects (see “4.5 Interactions with
other medicinal products and other forms of interaction”).
For fundamental medical reasons, caution is necessary in elderly patients. In frail elderly patients or
those with a low body weight in particular, it is advisable to administer the lowest effective dose.
Olfen-75 SR Depotabs prolonged-release tablets and Olfen-100 SR Depocaps prolonged-release
capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, severe lactase
deficiency or glucose-galactose malabsorption should not take Olfen-75 SR Depotabs prolongedrelease
tablets and Olfen-100 SR Depocaps prolonged-release capsules.
Respiratory effects (pre-existing asthma)
Reactions to NSAIDs, such as exacerbated asthma (referred to as analgesic intolerance/analgesic
asthma), Quincke's oedema or urticaria, are more common in patients with asthma, seasonal allergic
rhinitis, nasal mucosa swelling (e.g. nasal polyps), chronic obstructive pulmonary disease or chronic
respiratory tract infection (especially if associated with allergic rhinitis-like symptoms) than in other
patients. Therefore, special caution should be exercised in these patients (readiness for an emergency).
This also applies to patients who experience allergic reactions to other substances in the form of skin
rash, pruritus or urticaria, for instance.
Gastrointestinal effect
As with all NSAIDs, including diclofenac, close medical surveillance is imperative and particular
caution required when prescribing Olfen to patients with symptoms indicative of gastrointestinal (GI)
disorders, or to patients with a history of gastric or intestinal ulceration, bleeding or perforation (see
“4.8 Undesirable effects”). The risk of GI bleeding is greater at higher NSAID doses as well as in
patients with a history of ulceration, particularly if additionally complicated by bleeding or
perforation, and in the elderly.
To reduce the risk of GI toxicity in patients with a history of ulceration, particularly if additionally
complicated by bleeding or perforation, and in the elderly, treatment should be initiated and
maintained at the lowest effective dose.
Combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be
considered in these patients, and also in patients requiring concomitant treatment with medicinal
products containing low-dose acetylsalicylic acid (ASA) or other medicinal products likely to increase
the gastrointestinal risk.

Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal
symptoms (especially GI bleeding). Caution is recommended in patients receiving concomitant
medications which could increase the risk of ulceration or bleeding, such as systemic corticosteroids,
anticoagulants, antiplatelet agents or selective serotonin reuptake inhibitors (see “4.5 Interactions with
other medicinal products and other forms of interaction”).
Hepatic effect
Close medical surveillance is necessary when prescribing Olfen Depocaps or Olfen Depotabs to
patients with impaired hepatic function, since their condition may be exacerbated (see “4.8
Undesirable effects”).
As with all NSAIDs, including diclofenac, the levels of one or more liver enzymes may increase
during treatment with Olfen Depocaps or Olfen Depotabs. This has been reported very commonly (in
approx. 15% of patients) in clinical trials of diclofenac, but was rarely accompanied by clinical
symptoms. In the majority of these cases, the increases were marginal. Commonly (in 2.5%), moderate
increases were observed (≥ 3 - <8 times the upper limit of normal) whereas the incidence of marked
increases (≥ 8 times the upper limit of normal) remained at approximately 1%. In the aforementioned
clinical trials, 0.5% of patients had clinically manifest liver damage in addition to elevated liver
enzyme levels. The increases in the enzyme levels were generally reversible after discontinuation of
the medicinal product.
As with other NSAIDs, liver enzyme levels should also be monitored regularly during long-term Olfen
Depocaps or Olfen Depotabs therapy.
Olfen Depocaps or Olfen Depotabs should be discontinued if liver function test results are abnormal or
deteriorate, or if clinical signs or symptoms indicative of developing liver disease, or other
manifestations (e.g. eosinophilia, skin rash) occur.
In addition to liver enzyme elevations, there have been rare cases of severe hepatic reactions, including
jaundice and fulminant hepatitis, liver necrosis and hepatic failure, which were fatal in isolated cases.
Hepatitis can occur without prodromal symptoms. Olfen is to be used with caution in patients with
hepatic porphyria, since it can induce an attack.
Renal effects
Given that prostaglandins play an important role in maintaining renal perfusion, oedema and
hypertension commonly (1%-10%) result from prolonged periods of treatment with high doses of
NSAIDs, including diclofenac. Particular caution is required in patients with impaired cardiac or renal
function; in patients with a history of hypertension; in elderly patients; in patients also taking diuretics
or medications that have a considerable influence on renal function, as well as in patients with
pronounced fluid deficiency in the extracellular space due to any cause, e.g. before or after a major
surgical procedure (see “4.3 Contraindications”). Monitoring of renal function is recommended as a
precautionary measure if Olfen is used in such cases. The patient usually returns to his/her
pretreatment condition on discontinuation of treatment.
Cardiovascular effects
Treatment with NSAIDs, including diclofenac, can be associated with a slight, increased risk of severe
cardiovascular thrombotic events (including myocardial infarction and stroke), especially at high doses
and over prolonged periods.
Treatment with Olfen is generally not recommended in patients with existing cardiovascular disease
(cardiac failure, existing ischaemic heart disease, peripheral arterial occlusive disease) or uncontrolled
hypertension. If necessary, patients with existing cardiovascular disease, uncontrolled hypertension or
significant risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes
mellitus and smoking) should not be treated with Olfen until after a careful assessment and if
treatment is continued for more than 4 weeks they should not receive doses exceeding 100 mg/day.

As the cardiovascular risk factors of diclofenac can increase with the dose and duration of
administration, the lowest effective daily dose should be used for the shortest possible duration. The
patient's need for symptomatic relief and the response to the treatment should be reviewed
periodically, particularly if the treatment is continued for more than 4 weeks.
The patient should be alert to signs and symptoms of serious arterial thromboembolic events (e.g.
chest pain, shortness of breath, weakness, slurred speech), which can occur without warning. Patients
should be instructed to consult a doctor immediately in the case of such events.
Haematological effects
Monitoring of the blood count is recommended during long-term treatment with Olfen Depocaps or
Olfen Depotabs, as with other NSAIDs.
Like other NSAIDs, Olfen Depocaps or Olfen Depotabs can also temporarily inhibit platelet
aggregation. Patients with a coagulation disorder should be closely monitored.

 

The following interactions have been observed with Olfen Depocaps or Olfen Depotabs and/or other
pharmaceutical forms of diclofenac.
Reported interactions to be considered
Potent CYP2C9 inhibitors
Caution is recommended when administering diclofenac with potent CYP2C9 inhibitors (e.g.
voriconazole). Significant increases in the peak plasma concentration of diclofenac and a general
increase in the overall exposure to diclofenac following inhibition of diclofenac metabolism can occur.
Lithium
If co-administered, diclofenac can increase the plasma lithium concentration. Monitoring of serum
lithium concentrations is recommended.
Digoxin
If used concomitantly, diclofenac can raise the plasma concentration of digoxin. Monitoring of serum
digoxin concentrations is recommended.
Diuretics and antihypertensive agents
As with other NSAIDs, co-administration of diclofenac with diuretics or antihypertensive agents (e.g.
beta-blockers, angiotensin converting enzyme (ACE) inhibitors) can reduce their antihypertensive
activity. Such a combination should therefore be administered with caution, and patients, the elderly in
particular, should have their blood pressure monitored regularly. Patients should be adequately
hydrated, and attention should be paid to monitoring renal function after initiating concomitant therapy
as well as periodically thereafter, particularly when using diuretics and ACE inhibitors due to the
increased risk of nephrotoxicity (see “4.4 Special Warnings and precautions for use”).
Ciclosporin
Diclofenac, like other NSAIDs, can increase the nephrotoxicity of ciclosporin due to its effects on
renal prostaglandins. Therefore, it should be given at doses lower than those given to patients not
receiving ciclosporin.
Medicinal products known to cause hyperkalaemia
Concomitant treatment with potassium-sparing diuretics, ciclosporin, tacrolimus or trimethoprim can
be associated with elevated plasma potassium levels, which should therefore be checked frequently
(see “4.4 Special Warnings and precautions for use”).

Quinolone antibiotics
There have been isolated reports of convulsions which were possibly attributable to the concomitant
use of quinolones and NSAIDs.
Foreseeable interactions to be considered
Other NSAIDs and corticosteroids
Co-administration of diclofenac with other systemic NSAIDs or corticosteroids can increase the
frequency of adverse gastrointestinal reactions (see “4.4 Special Warnings and precautions for use”).
Anticoagulants and antiplatelet agents
Caution is recommended since concomitant administration could increase the risk of bleeding (see
“4.4 Special Warnings and precautions for use”).
Although clinical trials do not appear to suggest that diclofenac influences the effect of anticoagulants,
there have been isolated reports of an increased risk of bleeding in patients receiving diclofenac and
anticoagulants concomitantly. Such cases therefore need to be monitored closely.
Selective serotonin reuptake inhibitors (SSRIs)
Concomitant administration of systemic NSAIDs, including diclofenac, and SSRIs can increase the
risk of gastrointestinal bleeding (see “4.4 Special Warnings and precautions for use”).
Antidiabetic agents
Clinical trials have demonstrated that diclofenac can be given together with oral antidiabetic agents
without influencing their clinical effect. However, there have been isolated reports of hypoglycaemic
and hyperglycaemic effects following administration of diclofenac, requiring the dosage of the
antidiabetic agents to be adjusted. For this reason, it is advisable to monitor the glycaemia level as a
precautionary measure during combination therapy.
Methotrexate
Caution is advised when administering NSAIDs, including diclofenac, less than 24 hours before or
after treatment with methotrexate, since the blood levels of methotrexate may rise and the toxicity of
methotrexate may be increased.
Phenytoin
If phenytoin is used together with diclofenac, monitoring of the plasma phenytoin concentration is
recommended, as an increase in phenytoin exposure can be expected.

 

Fertility
Diclofenac can impair female fertility and thus is not recommended in women who wish to conceive.
In women who are having difficulty conceiving or who are undergoing fertility tests, discontinuation
of diclofenac should be considered.
In animals, impairment of male fertility cannot be ruled out based on the corresponding data (see “5.3
Preclinical safety data”). The relevance of these findings to humans is not clear.
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryofoetal
development. Data from epidemiological studies suggest that the risk of miscarriage, as well as cardiac
malformations and gastroschisis, is higher after use of a prostaglandin synthesis inhibitor in early
pregnancy. The risk is believed to increase with the dose and duration of therapy.
In animals, administration of a prostaglandin synthesis inhibitor has been found to increase pre- and
post-implantation loss and embryofoetal lethality. In addition, increased incidences of various malformations, including cardiovascular abnormalities, have been reported in animals given a
prostaglandin synthesis inhibitor during the organogenetic phase (see “5.3 Preclinical safety data”).
Diclofenac should not be given during the first and second trimesters of pregnancy unless absolutely
necessary. If diclofenac is used by a woman attempting to conceive, or during the first or second
trimester of pregnancy, the dose and duration of treatment should be kept to a minimum.
Diclofenac is contraindicated during the third trimester of pregnancy. All prostaglandin synthesis
inhibitors can:
 expose the foetus to the following risks:
 Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and
pulmonary hypertension; see also “Preclinical data”);
 Impaired renal function, which may progress to renal failure with oligohydramniosis;
 expose the mother and child to the following risks:
 Possible prolongation of bleeding time, an inhibitory effect on platelet aggregation
which may occur even at very low doses;
 Inhibition of uterine contractions resulting in delayed or prolonged labour.
Lactation
As with other NSAIDs, small amounts of diclofenac are excreted in human milk. As a precaution,
therefore, diclofenac should not be used in women who are breast-feeding. If treatment is essential, the
baby should be switched to bottle feeding.

Patients who experience visual disturbances, dizziness, vertigo, somnolence or other central nervous
system disorders while taking Olfen Depocaps or Olfen Depotabs should refrain from driving or using
machines

The undesirable effects listed below include those reported with Olfen Depocaps or Olfen Depotabs
and/or other pharmaceutical forms of diclofenac used for short-term or long-term treatment.
Frequency data
Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare
(≥1/10,000 to <1/1,000), very rare (<1/10,000).
Blood and lymphatic system disorders
Very rare: thrombocytopenia, leukopenia, anaemia (including haemolytic and aplastic anaemia),
agranulocytosis.
Immune system disorders
Rare: Hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock).
Very rare: angioedema (including facial oedema).
Psychiatric disorders
Very rare: disorientation, depression, insomnia, nightmares, irritability, psychotic disorder.
Nervous system disorders
Common: headache, light-headedness.
Rare: somnolence.
Very rare: paraesthesia, memory disorders, convulsion, anxiety, tremor, aseptic meningitis, dysgeusia,
cerebrovascular event.
Eye disorders
Very rare: visual disturbance, amblyopia, diplopia.
Ear and labyrinth disorders
Common: vertigo.
Very rare: tinnitus, impaired hearing.
Cardiac disorders
Uncommon*: myocardial infarction, cardiac failure, palpitations, chest pain.
Vascular disorders 

Very rare: hypertension, vasculitis.
Respiratory disorders
Rare: asthma (including dyspnoea).
Very rare: pneumonitis.
Gastrointestinal disorders
Common: nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, bloating, decreased appetite.
Rare: gastritis, gastrointestinal bleeding, haematemesis, diarrhoea haemorrhagic, melaena,
gastrointestinal ulcer (with or without bleeding or perforation).
Very rare: colitis (including haemorrhagic colitis and exacerbation of ulcerative colitis or Crohn’s
disease), constipation, stomatitis, glossitis, oesophageal disorder, intestinal diaphragm disease,
pancreatitis.
Olfen-75 SR Depotabs can produce chronic inflammatory states with pseudo-membranes and
strictures in the lower intestinal tract (small and large intestine).
Hepatobiliary disorders
Common: transaminases increased.
Rare: hepatitis, jaundice, hepatic dysfunction.
Very rare: fulminant hepatitis, hepatic necrosis, hepatic failure.
Skin disorders
Common: skin rash.
Rare: urticaria.
Very rare: bullous dermatitis, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome,
Lyell’s syndrome (acute toxic epidermolysis), exfoliative dermatitis, alopecia, photosensitivity
reaction, purpura, Henoch-Schönlein purpura, pruritus.
Renal and urinary disorders
Common: fluid retention, oedema, hypertension.
Very rare: acute renal insufficiency, haematuria, proteinuria, tubulointerstitial nephritis, nephrotic
syndrome, renal papillary necrosis.
General disorders
Rare: oedema.
* The frequency reflects data from long-term treatment with a high dose (150 mg/day).
Meta-analyses of controlled clinical trials and pharmaco-epidemiological data suggest that the use of
diclofenac, particularly at high doses (150 mg daily) and over prolonged periods, can be associated
with an increased risk of arterial thromboembolic events (e.g. myocardial infarction or stroke) (see
“4.4 Special Warnings and precautions for use”).

Symptoms

There is no typical clinical picture that results from diclofenac overdose. Overdose can cause
symptoms such as vomiting, gastrointestinal bleeding, diarrhoea, dizziness, tinnitus or convulsions.
Acute renal failure and liver damage can occur in the event of severe intoxication.
Therapeutic measures
Treatment for acute intoxication from NSAIDs, including diclofenac, essentially comprises supportive
measures and symptomatic treatment. Supportive measures and symptomatic treatment should be
introduced in response to complications such as hypotension, renal failure, convulsions,
gastrointestinal symptoms and respiratory depression.
Specific measures such as forced diuresis, dialysis or haemoperfusion are probably of no help in
eliminating NSAIDs, including diclofenac, due to their high protein-binding capacity and extensive
metabolisation.
Activated charcoal may be considered after ingestion of a potentially toxic overdose, and gastric
decontamination (e.g. vomiting, gastric lavage) after ingestion of a potentially life-threatening
overdose.

 

ATC code: M01AB05
Mechanism of action
Olfen contains the sodium salt of diclofenac, a non-steroidal active substance with pronounced
antirheumatic, anti-inflammatory, analgesic and antipyretic properties.
The inhibition of prostaglandin biosynthesis, demonstrated experimentally, is regarded as significant
in terms of the mechanism of action. Prostaglandins play a considerable role in the development of
inflammation, pain and fever. At concentrations equivalent to those reached in humans, Olfen does not
suppress the in vitro biosynthesis of proteoglycans in cartilage.
Clinical efficacy
In the treatment of rheumatic diseases, the anti-inflammatory and analgesic properties bring about a
marked improvement in symptoms such as pain at rest, pain on movement, morning stiffness, joint
swelling, as well as an increase in functionality. In post-traumatic and postoperative inflammation,
Olfen rapidly ameliorates spontaneous and movement-induced pain, and reduces inflammatory
swelling and wound oedema.
In clinical trials, the pronounced analgesic activity was also observed in moderate and severe nonrheumatic
pain. In primary dysmenorrhoea, it can relieve pain and also reduce the extent of bleeding.

Absorption
Film-coated tablets
Diclofenac is completely absorbed after passage of the gastro-resistant film-coated tablets through the
stomach. Although absorption takes place rapidly, its onset may be delayed due to the gastro-resistant
coating of the film-coated tablets. Mean peak plasma concentrations of 1.5 μg/mL are achieved, on
average, two hours after administration of a 50 mg film-coated tablet. When a film-coated tablet is
taken with or after a meal, passage through the stomach is slower than when the film-coated tablet is
taken before a meal. However, the amount of absorbed diclofenac remains the same.
Prolonged-release capsules, prolonged-release tablets
Judging by the amount of unchanged diclofenac and its hydroxylated metabolites recovered in the
urine, the same amount of diclofenac is released and absorbed from Olfen Depocaps prolonged-release
capsules and Olfen Depotabs prolonged-release tablets as from Olfen Lactab gastro-resistant filmcoated
tablets. However, the mean systemic availability of diclofenac from Olfen Depocaps or Olfen Depotabs is approximately 82% of that achieved with the same Olfen Lactab dose in the form of gastro-resistant film-coated tablets (possibly due to the release rate-dependent metabolism during the
first pass through the liver). Due to the slower release of the active substance from Olfen Depocaps or
Olfen Depotabs, lower peak plasma concentrations are reached than after administration of gastroresistant
film-coated tablets.
Mean peak plasma concentrations of 0.5 μg/mL and 0.4 μg/mL are achieved, on average, four hours
after administration of a 100 mg or 75 mg prolonged-release capsule/prolonged-release tablet with
modified release. Ingestion with a meal has no appreciable effect on the absorption and systemic
availability of Olfen Depocaps or Olfen Depotabs.
On the other hand, mean plasma concentrations of 13 ng/mL are measured 24 h (16 h) after ingestion
of Olfen-100 SR Depocaps prolonged-release capsules (Olfen-75 SR Depotabs prolonged-release
tablets 75 mg).
When Olfen Depocaps 100 mg prolonged-release capsules are taken once daily or Olfen Depotabs
75 mg prolonged-release tablets twice daily, trough plasma concentrations are about 22 ng/mL and
25 ng/mL, respectively.
The area under the concentration curve (AUC) after oral administration is about half as large as it is
following parenteral administration, since only about half of the active substance undergoes first-pass
hepatic metabolism. The kinetics do not change after repeat administration. Accumulation does not
result when the recommended dosage intervals are maintained. Children reach similar plasma
concentrations as adults after equivalent doses (mg/kg body weight).
Distribution
99.7% of diclofenac is bound to serum proteins, mainly to albumin (99.4%). The apparent volume of
distribution can be calculated and is 0.12-0.17 L/kg, accordingly. Diclofenac penetrates the synovial
fluid. Peak synovial fluid concentrations are measured 2-4 hours after the peak plasma concentrations
have been reached. The apparent elimination half-life in the synovial fluid is 3-6 h. Two hours after
the peak plasma concentrations are reached, the active substance levels in the synovial fluid are
already higher than in the plasma and remain so for up to 12 hours.
A low concentration of diclofenac (100 ng/mL) was detected in the breast milk of one nursing mother.
The estimated amount ingested by an infant consuming breast milk is equivalent to a dose of
0.03 mg/kg/day.
Metabolism
Biotransformation of diclofenac is partly by glucuronidation of the intact molecule, but mainly by
single and multiple hydroxylation and methoxylation. This results in several phenolic metabolites (3’-
hydroxy-, 4’-hydroxy-, 5-hydroxy-, 4’,5-dihydroxy- and 3’-hydroxy-4’-methoxy-diclofenac), which
are then extensively conjugated to glucuronic acid. Two of these phenolic metabolites are
pharmacologically active, albeit significantly less so than diclofenac.
Elimination
Diclofenac is eliminated from the plasma with a systemic clearance of 263 ± 56 mL/min (mean ± SD).
The terminal half-life is 1-2 h. Four of the metabolites, including the two active metabolites, also have
a short half-life of 1-3 h. The virtually inactive metabolite 3’-hydroxy-4’-methoxy-diclofenac has a
much longer half-life.
Approximately 60% of the administered dose is eliminated via the kidneys in the form of metabolites
and less than 1% as unchanged substance. The remainder of the dose is eliminated as metabolites with
the bile in the faeces.
Linearity/Non-linearity
There is a linear relationship between the absorbed and administered amount.

Kinetics in special patient groups
Relevant differences in absorption, metabolism and excretion due to patient age have not been
observed.
In patients with impaired renal function, no accumulation of unchanged active substance can be
inferred from the kinetics of a single dose for the usual dosage regimen. When creatinine clearance is
less than 10 mL/min, the theoretical steady-state plasma level of the metabolites is approximately four
times higher than in healthy people. Nevertheless, the metabolites are ultimately eliminated via the
bile.
In case of impaired hepatic function (chronic hepatitis, compensated hepatic cirrhosis), the kinetics
and metabolism of diclofenac are the same as in patients with a healthy liver.

Non-clinical data from studies of safety pharmacology, acute toxicity and repeated dose toxicity as
well as from genotoxicity, mutagenicity and carcinogenicity studies with diclofenac reveal no special
hazard for humans at the intended therapeutic dosages.
The increased incidence of lymphoma (thymus) in mice, and the increased incidence of subcutaneous
fibromas, fibroadenomas (mammary gland) or C-cell adenomas (thyroid) in rats, were all within the
historical control range of the laboratory for the tested animal strain and were classified as
coincidental.
All the toxicity studies performed on rats reported hypertrophy of the mesenteric lymph nodes or
lymphadenitis with reactive hyperplasia. These changes were accompanied by neutrophilia, which was
also observed in the studies on monkeys. These reactions are suspected to be secondary to the ulcers
noted in the gastrointestinal tract. In a 2-year study with diclofenac in rats, a dose-dependent increase
in thrombotic vascular occlusions in the heart was reported.
Additional studies suggested that fertility was influenced (reduced testosterone levels and decreased
epididymal and testicular weights combined with histopathological changes) in rats given repeated
oral doses of diclofenac (> 1 mg/kg body weight). Similar effects were also observed in the
F1 generation after doses of ≥1.25 mg/kg in a 2nd generation study. In dogs, a daily subcutaneous
dose of 2 mg/kg diclofenac sodium resulted in an increased sperm count. Other studies report that the
percentage of mating female rats was reduced following repeated diclofenac doses of ≥0.5 mg/kg.
Hence, an influence on both male and female fertility cannot be ruled out.
Diclofenac crosses the placental barrier in rodents. The administration of NSAIDs (including
diclofenac) inhibited ovulation in rabbits, implantation and placentation in rats, and premature closure
of the ductus arteriosus in pregnant rats. In rats, maternal toxic doses of diclofenac were linked to
dystocia, prolonged gestation, decreased foetal survival and delayed intrauterine growth. The minimal
effects of diclofenac on reproduction parameters and birth, as well as on closure of the ductus
arteriosus in utero, represent the pharmacological activity of this class of prostaglandin synthesis
inhibitors (see “4.3 Contraindications” and “4.6 Fertility, Pregnancy and lactation”).
Teratogenicity (cleft palate) was noted at the maternal toxic dose of 4 mg/kg in a study of mice. No
teratogenic effects were reported in rats and rabbits treated with doses up to the maternal toxic level.
Delayed ossification and reduced foetal weight in one study of rabbits were the only changes observed
in these tests.
At maternal toxic doses, perinatal and postnatal development of the progeny was adversely affected
(for fertility see above, as well as birth weight and delayed postnatal growth).

Olfen ‑ 25 / 50 Lactab
Tablet core:
Sodium starch glycolate
Microcrystalline cellulose
Sodium stearyl fumarate 

Colloidal anhydrous silica
Talc
Hypromellose
Coating (gastro-resistant):
Methacrylic acid/ethyl acrylate copolymer 1:1
Triethyl citrate
Talc
Coating (colour):
Hypromellose
Titanium dioxide E171
Talc
Quinoline yellow E104
Iron oxide yellow E172
Macrogol 6000
Olfen ‑ 75 SR Depotabs
Tablet core:
Lactose monohydrate
Cellulose microcrystalline
Hypromellose
Talc
Magnesium stearate
Coating:
Hypromellose
Titanium dioxide E171
Iron oxide red E172
Macrogol 6000
Olfen ‑ 100 SR Depocaps
Capsule contents:
Lactose monohydrate
Microcrystalline cellulose
Carboxymethylcellulose sodium
Glycerin trimyristate
Titanium dioxide E171
Ammonio methacrylate copolymer dispersion (Type B)
Triethyl citrate
Silica colloidal hydrated.
Capsule shell:
Gelatin
Titanium dioxide E171
Iron oxide black E172
Iron oxide red E172
Erythrosine E127
Printing ink:
Shellac Glaze-47.5 % (22 % esterified)
Iron oxide black E172

Not applicable.

Olfen ‑ 25/50 Lactab - 60 Months Olfen ‑ 75 SR Depotabs – 60 Months Olfen ‑ 100 SR Depocaps – 36 Months

Store in the original package.
Keep out of the sight and reach of children.
Do not store above 30° C.
Do not use Olfen after the expiry date which is stated on the blister and carton after “EXP”. The expiry date
refers to the last day of that month.

Olfen ‑ 25 Lactab
Packs: 10 and 30 tablets; hospital packs.
The tablets are packed in PVC/PVDC - Aluminium blisters.
Not all pack sizes may be marketed.
Olfen ‑ 50 Lactab
Packs: 10 and 20 tablets; hospital packs.
The tablets are packed in PVC/PVDC - Aluminium blisters.
Not all pack sizes may be marketed.
Olfen ‑ 75 SR Depotabs
Packs: 10 and 30 tablets; hospital packs.
The tablets are packed in PVC/PVDC - Aluminium blisters.
Not all pack sizes may be marketed.
Olfen ‑ 100 SR Depocaps
Packs: 10 and 20 capsules; hospital packs.
The capsules are packed into PVC/PE/PVDC-Aluminium blisters.
Not all pack sizes may be marketed.

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away
medicines you no longer use. These measures will help protect the environment.