Diclofenac Diethylammonium

Registered South African indications:

• Symptomatic relief of localised, traumatic inflammation and pain

Contraindications
South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity of acetylsalicylic acid or non-steroidal anti-inflammatory drug
• Hypersensitivity to isopropyl alcohol or propylene glycol
• Pregnancy
• Breastfeeding
• Porphyria
• Children
• If aspirin and other non-steroidal anti-inflammatory medicine induce symptoms of asthma, rhinitis, angioedema or urticaria

International manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity of acetylsalicylic acid or non-steroidal anti-inflammatory drug
• Those with or without chronic asthma in whom attacks of asthma, angioedema, urticaria or acute rhinitis are precipitated by acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory agents
• Third trimester of pregnancy
• <14 years of age

Cautions

South African manufacturer recommendations

• Renal impairment
• Hepatic impairment
• Elderly
• Higher dosages
• Application of large amounts over large areas of skin and over a prolonged period (See additional prescribing points)
• Skin wounds or open injuries
• Gel not rubbed in completely (See additional prescribing points)
• Excessive exposure to sunlight (See additional prescribing points)
• Significant history of gastrointestinal bleeding (See additional prescribing points)
• Asthma (See additional prescribing points)
• Airtight occlusive dressing (See additional prescribing points)
• Coadministration of systemic non-steroidal anti-inflammatory agents

International manufacturer recommendations

• Pregnancy (First and second trimester)
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Higher dosages
• Application of large amounts over large areas of skin and over a prolonged period (See additional prescribing points)
• Skin wounds or open injuries
• Excessive exposure to sunlight (See additional prescribing points)
• Airtight occlusive dressing (See additional prescribing points)
• Smokers or proximity to naked flames (See additional prescribing points)
• Fabric that has been in contact with this product (See additional prescribing points)
• History of, or active peptic ulceration
• Significant history of gastrointestinal bleeding (See additional prescribing points)
• History of asthma or allergic disease
• Coadministration of systemic non-steroidal anti-inflammatory agents

Forms avail. in SA and covered in this monograph: gel

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Symptomatic relief of localised, traumatic inflammation and pain  

• Topical (gel): Apply 2-4g to the affected area(s), 6-8hrly and rub in gently

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Not to be taken by mouth

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After application, the hands should be washed, unless they are the site being treated

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Duration of treatment will be determined by the initial indication and the relief obtained

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It is recommended that treatment be reviewed after two weeks. Use the lowest effective dose for the shortest possible duration of treatment

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Diclofenac diethylammonium should be applied only to intact skin surfaces, and not to skin wounds or open injuries. It should not be allowed to come into contact with the eyes or mucous membranes

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International manufacturer recommendations

Local symptomatic relief of pain and inflammation
- Trauma of the tendons, ligaments, muscles and joints, e.g. due to sprains, strains and bruises
- Localised forms of soft tissue rheumatism

• Topical (gel): Apply 2-4g to the affected area(s), 6-8hrly and rub in gently; Max: 16g/24hrs

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For cutaneous use only

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After application, the hands should be washed unless they are the site being treated

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A period of at least 4 hours should be left between applications. The dose should not be applied more than 4 times in a 24 hour period

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If symptoms persist after 7 days or get worse at any time, medical advice should be sought

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Not to be used for more than 7 days unless recommended by a doctor

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Diclofenac diethylammonium should be applied only to intact, non-diseased skin and not to skin wounds or open injuries. It should not be allowed to come into contact with the eyes or mucous membranes, and should not be ingested

Paed. forms avail. in SA and covered in this monograph: gel

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

• Not established for use in children

International manufacturer recommendations

Local symptomatic relief of pain and inflammation
- Trauma of the tendons, ligaments, muscles and joints, e.g. due to sprains, strains and bruises
- Localised forms of soft tissue rheumatism

• <14 years: Contraindicated
• ≥14 years: See adult dosage

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If diclofenac diethylammonium is required for more than 7 days for pain relief or if the symptoms worsen the patient/parents of the adolescent is/are advised to consult a doctor

Pregnancy
South African manufacturer recommendations

• Contraindicated
• Safety and efficacy in pregnancy has not been established
• For non-steroidal anti-inflammatory (NSAID) agents, such as diclofenac diethylammonium, with systemic uptake, inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. An increased risk of miscarriage and of cardiac malformation and gastroschisis has been reported after use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy
• Use of NSAIDs during the third trimester of pregnancy may result in premature closure of the foetal ductus arteriosus in utero and possibly in persistent pulmonary hypertension of the newborn
• The onset of labour may be delayed, and its duration increased
• Use of NSAIDs, such as diclofenac diethylammonium, around 20 weeks gestation or later in pregnancy may cause a rare but serious foetal renal dysfunction leading to oligohyramnios and, in some cases, neonatal renal impairment. Complications of prolonged oligohydramnios include limb contractures and delayed lung maturation, which may require invasive procedures such as exchange transfusion or dialysis, in some cases

International manufacturer recommendations

• First and second trimester: Caution; not recommended
• Third trimester: Contraindicated
• The systemic concentration of diclofenac is lower after topical administration, compared to oral formulations. With reference to experience from treatment with NSAIDs with systemic uptake, the following is recommended: 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 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 has been shown to result in increased pre-and post-implantation loss and embryo-fetal lethality. In addition, increased 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, diclofenac should not be given unless clearly necessary. If diclofenac is used by a woman attempting to conceive, or during the first and second 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 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, diclofenac is contraindicated during the third trimester of pregnancy

Breastfeeding
South African manufacturer recommendations

• Contraindicated 
• Safety and efficacy in breastfeeding has not been established

International manufacturer recommendations

• Caution 
• Like other NSAIDs, diclofenac passes into breast milk in small amounts. However, at therapeutic doses of this medicine no effects on the breastfeeding child are anticipated. Because of a lack of controlled studies in breastfeeding women, the product should only be used during breastfeeding under advice from a healthcare professional. Under this circumstance, this medicine should not be applied on the breasts of breastfeeding mothers, nor elsewhere on large areas of skin or for a prolonged period of time

Fertility 

• There are no data available on the use of topical formulations of diclofenac, such as diclofenac diethylammonium, and its effect on fertility in humans

Renal Impairment

• Caution; no information available 

Hepatic Impairment

• Caution; no information available

Elderly
South African manufacturer recommendations

• Caution; no information available

International manufacturer recommendations

• No dose adjustment recommended 

Porphyria Information 

• Probably not porphyrinogenic (PNP) 

Drugs in Sport

• Permitted - No warnings

Respiratory Disorders

• Asthma

Skin and Subcutaneous Tissue Disorders

• Rash
• Eczema
• Erythema
• Dermatitis
  - Contact dermatitis
• Pruritus
• Bullous dermatitis
• Photosensitivity reaction
  (See additional prescribing points)
• Pustular rash
• Desquamation
• Skin discolouration

Immune, Blood and Lymphatic System Disorders 

• Hypersensitivity
  - Urticaria
• Angioneurotic oedema

None known
(See additional prescribing points)

• Full blood count
• Blood pressure (baseline and during treatment)
• Liver enzymes (regularly during chronic therapy 4-8 weeks after initiation)
• Blood urea nitrogen (BUN)
• Renal function
  - Serum creatinine
• Potassium

Additional observations

• Urine output
• Occult blood loss

Interactions with other medicines

• Since systemic absorption of diclofenac from a topical application is very low such interactions are very unlikely
• There are no known interactions with diclofenac diethylammonium, consult the oral diclofenac monographs for a list of interactions related to systemic absorption

Higher dosages/large amounts over large areas of skin and over a prolonged period

• The possibility of experiencing systemic adverse events from application of diclofenac diethylammonium gel cannot be excluded if the preparation is used at higher dosages/large amounts over large areas of skin and over a prolonged period

Gel not rubbed in completely

• Mild but transient skin discolouration and staining of clothing may occur if the gel is not rubbed in completely

Asthma

• Diclofenac diethylammonium should be used with caution in asthmatic patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or by other medicines with prostaglandin-synthetase inhibiting activity

Airtight occlusive dressing

• Diclofenac diethylammonium can be used with non-occlusive bandages but should not be used with an airtight occlusive dressing
• Occlusion can lead to an increase in the amount of diclofenac absorbed and may thus cause an increase in side effects

Excessive exposure to sunlight

• Patients should be warned against excessive exposure to sunlight in order to reduce the incidence of photosensitivity

Effect on skin

• If local irritation develops, use of the gel should be discontinued and appropriate therapy should be instituted

Significant history of gastrointestinal bleeding

• Some possibility of gastrointestinal bleeding in those with a significant history of this condition has been reported in isolated cases

Smokers or proximity to naked flames

• Instruct patients not to smoke or go near naked flames- risk of severe burns

Fabric

• Fabric (clothing, bedding, dressings, etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it

Diclofenac is a potent non-steroidal anti-inflammatory drug (NSAID) with effective analgesic, anti-inflammatory, and antipyretic properties. Diclofenac exerts its therapeutic effects primarily through inhibition of prostaglandin synthesis by cyclo-oxygenase 2 (COX-2).

Jel (per 10g) 0.116g

• DicloHexal (Sandoz)

Gel (per 10g) 0,116g

• K-Fenak Gel (Cipla Medpro)

Gel (per 100g) 20mg

• Voltaren Emulgel 12HR  (GSK) originator

Gel (per 100g) 1.16g

• Voltaren Emulgel (GSK) originator

Gel (per 100g) 1.292g

• Panamor Gel (Pharmacare)