Rofenac 25mg, 50mg and 100mg suppositories
Adults and Elderly:
Relief of all grades of pain and inflammation in a wide range of conditions,
including:
(i) arthritic conditions: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis,
acute gout,
(ii) acute musculo-skeletal disorders such as periarthritis (for example frozen
shoulder), tendinitis, tenosynovitis, bursitis,
(iii) other painful conditions resulting from trauma, including fracture, low back pain,
sprains, strains, dislocations, orthopedic, dental and other minor surgery.
Rofenac 50mg and 100mg suppositories are not indicated for use in children.
 

Rofenac 12.5mg and 25mg suppositories only
Children (aged 1-12 years): Juvenile chronic arthritis
Children (aged 6 years and above): As monotherapy or as adjunct therapy with
morphine or other opiates (due to its opiate-sparing effect) for the relief of acute postoperative
pain.

Undesirable effects may be minimized by using the lowest effective dose for the
shortest duration necessary to control symptoms (see section 4.4 Special warnings
and precautions for use).
Not to be taken by mouth, as per rectal administration only.
The suppositories should be inserted well into the rectum. It is recommended to insert the
suppositories after passing stools.
Adults:
75-150mg daily, in divided doses (25mg, 50mg and 100mg suppositories only).
The recommended maximum daily dose of Rofenac is 150mg. This may be administered
using a combination of dosage forms, e.g. tablets and suppositories. (25mg and 50mg
suppositories only).
100mg suppositories may also be given as a once daily treatment, usually at night. Where
necessary, therapy may be combined with 25mg or 50mg tablets or suppositories up to the
maximum dose of 150mg per day.
 

Special populations
Elderly:
Although the pharmacokinetics of Rofenac are not impaired to any clinically relevant
extent in elderly patients, nonsteroidal anti-inflammatory drugs should be used with
particular caution in such patients who generally are more prone to adverse reactions.
In particular it is recommended that the lowest effective dosage be used in frail
elderly patients or those with a low body weight (see also Precautions) and the patient
should be monitored for GI bleeding during NSAID therapy.
 

Renal impairment
Diclofenac is contraindicated in patients with severe renal impairment (see section
4.3). No specific studies have been carried out in patients with renal impairment,
therefore, no specific dose adjustment recommendations can be made. Caution is
advised when administering diclofenac to patients with mild to moderate renal
impairment (see section 4.3 and 4.4).
 

Hepatic impairment
Diclofenac is contraindicated in patients with severe hepatic impairment (see section
4.3). No specific studies have been carried out in patients with hepatic impairment,
therefore, no specific dose adjustment recommendations can be made. Caution is
advised when administering diclofenac to patients with mild to moderate hepatic
impairment (see section 4.3 and 4.4).
 

Paediatric population
Children (aged 1-12 years) with juvenile chronic arthritis: 1-3mg/kg per day divided
into 2 or 3 doses (12.5mg and 25mg suppositories only).
Children (aged 6-12 years) with acute post-operative pain: 1-2mg/kg per day in
divided doses.
Treatment of acute post-operative pain should be limited to 4 days treatment (12.5mg
and 25mg suppositories only).

• Hypersensitivity to the active substance or any of the excipients. • Active, gastric or intestinal ulcer, bleeding or perforation. • History of gastrointestinal bleeding or perforation, relating to previous NSAID therapy • Active, or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding). • Last trimester of pregnancy (see section 4.6 Pregnancy and lactation). • Severe hepatic, renal or cardiac failure (see section 4.4 Special warnings and precautions for use). • Like other non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac is also contraindicated in patients in whom attacks of asthma, angioedema, urticaria or acute rhinitis are precipitated by ibuprofen, acetylsalicylic acid or other nonsteroidal antiinflammatory drugs. • Proctitis • Established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease

General
Undesirable effects may be minimized by using the lowest effective dose for the
shortest duration necessary to control symptoms (see section 4.2 Posology and
method of administration and GI and cardiovascular risks below).
The concomitant use of Rofenac with systemic NSAIDs including cyclooxygenase-2
selective inhibitors should be avoided due to the absence of any evidence
demonstrating synergistic benefits and the potential for additive undesirable effects
(see section 4.5 Interactions with other medicaments and other forms of interaction).
Caution is indicated in the elderly on basic medical grounds. In particular, it is
recommended that the lowest effective dose be used in frail elderly patients or those
with a low body weight (see section 4.2 Posology and Method of administration)
As with other nonsteroidal anti-inflammatory drugs including diclofenac , allergic
reactions, including anaphylactic/anaphylactoid reactions, can also occur without
earlier exposure to the drug (see section 4.8 Undesirable effects).
Like other NSAIDs, diclofenac may mask the signs and symptoms of the infection
due to its pharmacodynamic properties.

Gastrointestinal effects:
Gastrointestinal bleeding (haematemesis, melaena) ulceration or perforation which
can be fatal has been reported with all NSAIDs including diclofenac and may occur at
any time during treatment, with or without warning symptoms or a previous history
of serious GI events. They generally have more serious consequences in the elderly.
If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the
drug should be withdrawn.
As with all NSAIDs, including diclofenac close medical surveillance is imperative
and particular caution should be excised when prescribing diclofenac in patients with
symptoms indicative of gastrointestinal disorders, or with a history suggestive of
gastric or intestinal ulceration, bleeding or perforation (see section 4.8 Undesirable
effects). The risk of GI bleeding, ulceration or perforation is higher with increasing
NSAID doses including diclofenac, and in patients with a history of ulcer,
particularly if complicated with haemorrhage or perforation.
The elderly have increased frequency of adverse reactions to NSAIDs especially
gastro intestinal bleeding and perforation which may be fatal (see section 4.2
Posology and method of administration).
To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if
complicated with hemorrhage or perforation, and in the elderly, the treatment should
be initiated and maintained at the lowest effective dose.
Combination therapy with protective agents (e.g. misoprostol or proton pump
inhibitors) should be considered for these patients, and also for patients requiring
concomitant use of medicinal products containing low dose acetylsalicylic acid
(ASA/aspirin or medicinal products likely to increase gastrointestinal risk. (See
section 4.5 Interactions with other medicaments and other forms of interaction).
Patients with a history of GI toxicity, particularly when 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 such as warfarin, selective serotonin-reuptake inhibitors (SSRIs) or
anti-platelet agents such as acetylsalicylic acid (see section 4.5 Interaction with other
medicaments and other forms of interaction).
Close medical surveillance and caution should be exercised in patients with ulcerative
colitis, or with Crohn's disease as these conditions may be exacerbated (see section
4.8 Undesirable effects).

Hepatic effects:
Close medical surveillance is required when prescribing Rofenac to patients with
impairment of hepatic function as their condition may be exacerbated.
As with other NSAIDs, including diclofenac, values of one or more liver enzymes
may increase. During prolonged treatment with Diclofenac, regular monitoring of
hepatic function is indicated as a precautionary measure.
If abnormal liver function tests persist or worsen, clinical signs or symptoms
consistent with liver disease develop or if other manifestations occur (eosinophilia,
rash), Rofenac should be discontinued.
Hepatitis may occur with diclofenac without prodromal symptoms.
Caution is called for when using diclofenac in patients with hepatic porphyria, since it
may trigger an attack.

Renal effects:
As fluid retention and oedema have been reported in association with NSAIDs
therapy, including diclofenac, particular caution is called for in patients with impaired
cardiac or renal function, history of hypertension, the elderly, patients receiving
concomitant treatment with diuretics or medicinal products that can significantly
impact renal function, and those patients with substantial extracellular volume
depletion from any cause, e.g. before or after major surgery (see section 4.3
Contraindications). Monitoring of renal function is recommended as a precautionary
measure when using diclofenac in such cases. Discontinuation therapy is usually
followed by recovery to the pre-treatment state.

Skin 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, including Rofenac (see section 4.8 Undesirable
effects). Patients appear to be at the highest risk of 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. Rofenac should be discontinued at the first appearance of skin
rash, mucosal lesions or any other signs of hypersensitivity.

SLE and mixed connective tissue disease:
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue
disorders there may be an increased risk of aseptic meningitis (see section 4.8
Undesirable effects).

Cardiovascular and cerebrovascular effects:
Patients with significant risk factors for cardiovascular events (e.g. hypertension,
hyperlipidaemia, diabetes mellitus, smoking) should only be treated with diclofenac
after careful consideration. As the cardiovascular risks of diclofenac may increase
with dose and duration of exposure, the shortest duration possible and the lowest
effective daily dose should be used. The patient's need for symptomatic relief and
response to therapy should be re-evaluated periodically.
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
edema have been reported in association with NSAID therapy including diclofenac.
Clinical trial and epidemiological data consistently point towards increased risk of
arterial thrombotic events (for example myocardial infarction or stroke) associated
with the use of diclofenac, particularly at high dose (150mg daily) and in long term
treatment.
Patients with uncontrolled hypertension, congestive heart failure, established
ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease
should only be treated with diclofenac after careful consideration.

Hematological effects:
During prolonged treatment with diclofenac, as with other NSAIDs, monitoring of
the blood count is recommended.
Rofenac may reversibly inhibit platelet aggregation (see anticoagulants in section 4.5
Interaction with other medicaments and other forms of interactions). Patients with
defects of haemostasis, bleeding diathesis or hematological abnormalities should be
carefully monitored.

Pre-existing asthma:
In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e.
nasal polyps), chronic obstructive pulmonary diseases or chronic infections of the
respiratory tract (especially if linked to allergic rhinitis-like symptoms), reactions on
NSAIDs like asthma exacerbations (so called intolerance to analgesics / analgesics
asthma), Quincke's oedema or urticaria are more frequent than in other patients.
Therefore, special precaution is recommended in such patients (readiness for
emergency). This is applicable as well for patients who are allergic to other
substances, e.g. with skin reactions, pruritus or urticaria.
Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and
other NSAIDs can precipitate bronchospasm if administered to patients suffering
from, or with a previous history of bronchial asthma.

Female fertility:
The use of Rofenac may impair female fertility and is not recommended in women
attempting to conceive. In women who may have difficulties conceiving or who are
undergoing investigation of infertility, withdrawal of Rofenac should be considered
(see section 4.6 Pregnancy and Lactation).

The following interactions include those observed with diclofenac gastro-resistant
tablets and/or other pharmaceutical forms of diclofenac.
Lithium: If used concomitantly, Rofenac may increase plasma concentrations of
lithium. Monitoring of the serum lithium level is recommended.
 

Digoxin: If used concomitantly, Rofenac may raise plasma concentrations of digoxin.
Monitoring of the serum digoxin level is recommended.

Diuretics and antihypertensive agents: Like other NSAIDs, concomitant use of
Rofenac with diuretics and antihypertensive agents (e.g. beta-blockers, angiotensin
converting enzyme (ACE) inhibitors may cause a decrease in their antihypertensive
effect via inhibition of vasodilatory prostaglandin synthesis.
Therefore, the combination should be administered with caution and patients,
especially the elderly, should have their blood pressure periodically monitored.
Patients should be adequately hydrated and consideration should be given to
monitoring of renal function after initiation of concomitant therapy periodically
thereafter, particularly for diuretics and ACE inhibitors due to the increased risk of
nephrotoxicity. Concomitant treatment with potassium-sparing diuretics may be
associated with increased serum potassium levels, which should therefore be
monitored frequently (see section 4.4 Special warnings and precautions for use).

Anticoagulants and anti-platelet agents: Caution is recommended since
concomitant administration could increase the risk of bleeding (see section 4.4
Special warnings and precautions for use). Although clinical investigations do not
appear to indicate that Rofenac has an influence on the effect of anticoagulants, there
are isolated reports of an increased risk of hemorrhage in patients receiving
diclofenac and anticoagulant concomitantly (see section 4.4 Special warnings and
precautions for use). Therefore, to be certain that no change in anticoagulant dosage
is required, close monitoring of such patients is required. As with other nonsteroidal
anti-inflammatory agents, diclofenac in a high dose can reversibly inhibit platelet
aggregation.

Other NSAIDs including cyclooxygenase-2 selective inhibitors and
corticosteroids: Co-administration of diclofenac with other systemic NSAIDs or
corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. Avoid
concomitant use of two or more NSAIDs (see section 4.4 Special warnings and
precautions for use).

Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of
SSRI's may increase the risk of gastrointestinal bleeding (see section 4.4 Special
warnings and precautions for use).

Antidiabetic: Clinical studies have shown that Rofenac can be given together with
oral antidiabetic agents without influencing their clinical effect. However there have
been isolated reports of hypoglycemic and hyperglycemic effects necessitating
changes in the dosage of the antidiabetic agents during treatment with diclofenac. For
this reason, monitoring of the blood glucose level is recommended as a precautionary
measure during concomitant therapy.

Methotrexate: Diclofenac can inhibit the tubular renal clearance of methotrexate
hereby increasing methotrexate levels. Caution is recommended when NSAIDs,
including diclofenac, are administered less than 24 hours before treatment with
methotrexate, since blood concentrations of methotrexate may rise and the toxicity of
this substance be increase. Cases of serious toxicity have been reported when
methotrexate and NSAIDs including diclofenac are given within 24 hours of each
other. This interaction is mediated through accumulation of methotrexate resulting
from impairment of renal excretion in the presence of the NSAID.

Ciclosporin: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of
ciclosporin due to the effect on renal prostaglandins. Therefore, it should be given at
doses lower than those that would be used in patients not receiving ciclosporin.

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with
tacrolimus. This might be mediated through renal antiprostagladin effects of both
NSAID and calcineurin inhibitor.

Quinolone antibacterials: Convulsions may occur due to an interaction between
quinolones and NSAIDs. This may occur in patients with or without a previous
history of epilepsy or convulsions. Therefore, caution should be exercised when
considering the use of a quinolone in patients who are already receiving an NSAID.

Phenytoin: When using phenytoin concomitantly with diclofenac, monitoring of
phenytoin plasma concentrations is recommended due to an expected increase in
exposure to phenytoin.

Colestipol and cholestyramine: These agents can induce a delay or decrease in
absorption of diclofenac. Therefore, it is recommended to administer diclofenac at
least one hour before or 4 to 6 hours after administration of
colestipol/cholestyramine.

Cardiac glycosides: Concomitant use of cardiac glycosides and NSAIDs in patients
may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone
administration as NSAIDs can reduce the effect of mifepristone.

Potent CYP2C9 inhibitors: Caution is recommended when co-prescribing
diclofenac with potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole),
which could result in a significant increase in peak plasma concentrations and
exposure to diclofenac due to inhibition of diclofenac metabolism.

Pregnancy
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the
embryo/fetal development. Data from epidemiological studies suggest an increased
risk of miscarriage and or 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 in believed to increase with dose and duration of therapy. In animals,
administration of a prostaglandin synthesis inhibitor has shown to result in increased
pre-and post-implantation loss and embryo-foetal lethality.
In addition, increased incidences of various malformations, including cardiovascular,
have been reported in animals given a prostaglandin synthesis inhibitor during
organogenetic period. If Rofenac is used by a woman attempting to conceive, or
during the 1st trimester of pregnancy, the dose should be kept as low and duration of
treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may
expose the fetus to:
- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and
pulmonary hypertension)
- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis
The mother and the neonate, at the end of the pregnancy, to:
- possible prolongation of bleeding time, an anti-aggregating effect which may occur
even at very low doses
- inhibition of uterine contractions resulting in delayed or prolonged labour
Consequently, Rofenac is contraindicated during the third trimester of pregnancy.
With reference to experience from treatment with NSAIDs with systemic uptake, the
following is recommended:
Consequently, Rofenac is contraindicated during the third trimester of pregnancy (see
section 4.3)

Lactation
Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore
Diclofenac should not be administered during breast feeding in order to avoid
undesirable effects in the infant.

Female fertility
As with other NSAIDs, the use of diclofenac may impair female fertility and is not
recommended in women attempting to conceive. In women who may have difficulties
conceiving or who are undergoing investigation of infertility, withdrawal of
diclofenac should be considered. See also section 4.4 Special warnings and
precautions for use, regarding female fertility.

Patients who experience visual disturbances, dizziness, vertigo, somnolence, central
nervous system disturbances, drowsiness or fatigue while taking NSAIDs should
refrain from driving or operating machinery.

Adverse reactions are ranked under the heading of frequency, the most frequent first, using the following convention: 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.

The following undesirable effects include those reported with other short-term or long-term use.

Table 1

Blood and lymphatic system disorders
Very rare	Thrombocytopenia, leucopoenia, anemia (including hemolytic and aplastic anaemia), agranulocytosis.
Immune system disorders
Rare Very rare	Hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock). Angioneurotic edema (including face edema).
Psychiatric disorders
Very rare	Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder.
Nervous system disorders
Common Rare Very rare Unknown	Headache, dizziness. Somnolence, tiredness. Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident. Confusion, hallucinations, disturbances of sensation, malaise.
Eye disorders
Very rare Unknown	Visual disturbance, vision blurred, diplopia. Optic neuritis.
Ear and labyrinth disorders
Common Very rare	Vertigo. Tinnitus, hearing impaired.
Cardiac disorders
Very rare	Palpitations, chest pain, cardiac failure, myocardial infarction.
Vascular disorders
Very rare	Hypertension, hypotension, vasculitis.
Respiratory, thoracic and mediastinal disorders
Rare Very rare	Asthma (including dyspnoea). Pneumonitis.
Gastrointestinal disorders
Common Rare Very rare	Nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia. Gastritis, gastrointestinal hemorrhage, haematemesis, diarrhea hemorrhagic, melaena, gastrointestinal ulcer with or without bleeding or perforation (sometimes fatal particularly in the elderly). Colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis.
Hepatobiliary disorders
Common Rare Very rare	Transaminases increased. Hepatitis, jaundice, liver disorder. Fulminant hepatitis, hepatic necrosis, hepatic failure.
Skin and subcutaneous tissue disorders
Common Rare Very rare	Rash. Urticaria. Bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), dermatitis exfoliative, loss of hair, photosensitivity reaction, purpura, allergic purpura, pruritus.
Renal and urinary disorders
Very rare	Acute renal failure, haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.
General disorders and administration site conditions
Rare	Edema
Reproductive system and breast disorders
Very rare	Impotence.

Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high doses (150mg 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 Special warnings and special precautions for use).

Adverse reactions are ranked under the heading of frequency, the most frequent first, using the following convention: 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.

Very rare (<1/10,000)	Rare ( ≥1/10,000, <1/1,000)	Uncommon ( ≥1/1,000, <1/100)	Common (≥ 1/100, <1/10)	Organ system
		Eye pain, lacrimation disorder	Conjunctivitis	Eye Disorders
Gastrointestinal hemorrhage		Abdominal pain, diarrhea, nausea		Gastrointestinal Disorders
			Application site reactions (including inflammation, irritation, pain and tingling or blistering at the treatment site)	General Disorders and Administration Site Conditions
Topical application of large amounts may result in systemic effects including all types of hypersensitivity (including urticaria, angioneurotic oedema)				Immune System Disorders
Rash pustular				Infections and Infestations
			Hyperesthesia, Nervous System hypertonia, localised paraesthesia	Nervous System
Renal failure				Renal and Urinary System Disorders
Asthma				Respiratory, Thoracic and Mediastinal Disorders
Photosensitivity reaction	Dermatitis bullous	Alopecia, face oedema, maculopapular rash, seborrhoea	Dermatitis (including contact dermatitis), eczema, dry skin, erythema, edema, pruritus, rash, scaly rash, skin hypertrophy, skin ulcer, vesiculobullous rash	Skin and Subcutaneous Tissue Disorders
		Hemorrhage		Vascular Disorders

 

Temporary hair discoloration at the application site has been reported. This is usually
reversed on stopping treatment.

To report any side effect(s):  The National Pharmacovigilance and Drug Safety Centre (NPC) o Fax: +966-11-205-7662 o Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340. o Toll free phone: 8002490000 o E-mail: npc.drug@sfda.gov.sa o Website: www.sfda.gov.sa/npc

 

 

Symptoms
There is no typical clinical picture resulting from diclofenac over dosage. Over
dosage can cause symptoms such as headache, nausea, vomiting, epigastric pain,
gastrointestinal bleeding, diarrhea, dizziness, disorientation, excitation, coma,
drowsiness, tinnitus, fainting or convulsions. In the case of significant poisoning
acute renal failure and liver damage are possible.
 

Therapeutic measures
Patients should be treated symptomatically as required. Within one hour of ingestion
of a potentially toxic amount, activated charcoal should be considered. Alternatively,
in adults gastric lavage should be considered within one hour of ingestion of
potentially toxic amounts. Frequent or prolonged convulsions should be treated with
intravenous diazepam. Other measures may be indicated by the patients clinical
condition.

Pharmacotherapeutic group
Nonsteroidal anti-inflammatory drugs (NSAIDs).

Mechanism of action
Rofenac is a nonsteroidal agent with marked analgesic/anti- inflammatory properties.
It is an inhibitor of prostaglandin synthetase, (cyclo-oxygenase).
Diclofenac sodium in vitro does not suppress proteoglycan biosynthesis in cartilage at
concentrations equivalent to the concentrations reached in human beings.
12.5mg/25mg Suppositories only
There is a limited clinical trial experience of the use of diclofenac in JRA/JIA paediatric
patients. In a randomised, double-blind, 2-week, parallel group study in children aged 3-
15 years with JRA/JIA, the efficacy and safety of daily 2-3 mg/kg BW diclofenac was
compared with acetylsalicylic acid (ASS, 50-100 mg/kg BW/d) and placebo – 15 patients
in each group. In the global evaluation, 11 of 15 diclofenac patients, 6 of 12 aspirin and 4
of 15 placebo patients showed improvement with the difference being statistically
significant (p <0.05). The number of tender joints decreased with diclofenac and ASS but
increased with placebo. In a second randomised, double-blind, 6 week, parallel group
study in children aged 4-15 years with JRA/JIA, the efficacy of diclofenac (daily dose 2-
3 mg/kg BW, n=22) was comparable with that of indomethacin (daily dose 2-3 mg/kg
BW, (n=23).

There is limited kinetic data from 6 children aged 6-16 years with juvenile chronic
arthritis who received a once daily dose of diclofenac for 2 weeks. When corrected
for a body weight of 75kg, kinetic parameters were similar to those in adults. (12.5mg
and 25mg suppositories only)

Absorption
Absorption is rapid; although the rate of absorption is slower than from enteric-coated
tablets administered orally. After the administration of 50mg suppositories, peak
plasma concentrations are attained on average within 1 hour, but maximum
concentrations per dose unit are about two thirds of those reached after administration
of enteric-coated tablets (1.95 ± 0.8μg/ml (1.9μg/ml ≡ 5.9μmol/l)).

Bioavailability
As with oral preparations the AUC is approximately a half of the value obtained from
a parenteral dose.
Pharmacokinetic behaviour does not change on repeated administration.
Accumulation does not occur, provided the recommended dosage intervals are
observed.
The plasma concentrations attained in children given equivalent doses (mg/kg, b.w.)
are similar to those obtained in adults. (12.5mg and 25mg suppositories only)

Distribution
The active substance is 99.7% protein bound, mainly to albumin (99.4%).
Diclofenac enters the synovial fluid, where maximum concentrations are measured 2-
4 hours after the peak plasma values have been attained. The apparent half-life for
elimination from the synovial fluid is 3-6 hours. Two hours after reaching the peak
plasma values, concentrations of the active substance are already higher in the
synovial fluid than they are in the plasma and remain higher for up to 12 hours.
Diclofenac was detected in a low concentration (100 ng/mL) in breast milk in one
nursing mother. The estimated amount ingested by an infant consuming breast milk is
equivalent to a 0.03 mg/kg/day dose (see section 4.6 Pregnancy and lactation).
 

Metabolism
Biotransformation of diclofenac takes place partly by glucuronidation of the intact
molecule, but mainly by single and multiple hydroxylation and methoxylation,
resulting in several phenolic metabolites , most of which are converted to glucuronide
conjugates. Two phenolic metabolites are biologically active, but to a much lesser
extent than diclofenac.

Elimination
The total systemic clearance of diclofenac in plasma is 263 ± 56 mL/min (mean value
± SD). The terminal half-life in plasma is 1-2 hours. Four of the metabolites,
including the two active ones, also have short plasma half-lives of 1-3 hours.
About 60% of the administered dose is excreted in the urine in the form of the
glucuronide conjugate of the intact molecule and as metabolites, most of which are
also converted to glucuronide conjugates. Less than 1% is excreted as unchanged
substance. The rest of the dose is eliminated as metabolites through the bile in the
faeces.

Characteristics in patients
No relevant age-dependent differences in the drug's absorption, metabolism, or
excretion have been observed, other than the finding that in five elderly patients, a 15
minute iv infusion resulted in 50% higher plasma concentrations than expected with
young healthy subjects.
Patients with renal impairment: In patients suffering from renal impairment, no
accumulation of the unchanged active substance can be inferred from the single-dose
kinetics when applying the usual dosage schedule. At a creatinine clearance of less
than 10 mL/min, the calculated steady-state plasma levels of the hydroxy metabolites
are about 4 times higher than in normal subjects. However, the metabolites are
ultimately cleared through the bile.

Patients with hepatic disease: In patients with chronic hepatitis or nondecompensated
cirrhosis, the kinetics and metabolism of diclofenac are the same as in
patients without liver disease.

None stated.

For Rofenac suppository:

 

Excipients

Witepsol H-15

Witepsol w-35

 

 

Not Applicable

2 years

Store below 30°C

Rofenac suppositories:
10/pack (12.5mg and 25mg)
5/pack (100mg)
White Opaque Thermoformed PVC

No Special Disposal