Dologast-Denk 75/20 mg

Indications

• Pain and inflammation in musculoskeletal disorders
• Rheumatic disease
• Osteoarthritis of the knee
• Postoperative pain
• Control of anterior segment inflammation following ophthalmic surgery

Dosage

Children: For paediatric dosing, please refer to the BNF for Children as specific dosages are not provided in this text.

Adults: For topical application, apply 3–4 times a day to the affected area. For injection, 75 mg may be administered intravenously, then 75 mg after 4–6 hours if required, up to a maximum of 150 mg per day for no more than 2 days.

Mechanism of action

Diclofenac sodium primarily acts as a selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). By blocking these enzymes, diclofenac decreases the production of prostaglandins, which are mediators of inflammation and pain. This mechanism leads to reduced inflammatory responses and alleviation of pain.

Pharmacodynamics

The pharmacological effects of diclofenac include anti-inflammatory, analgesic, and antipyretic properties. The onset of action is typically within a few hours following administration, with peak effects seen within 1 to 2 hours. The duration of analgesia can vary depending on the formulation and dosage used.

Pharmacokinetics

Diclofenac is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver to active metabolites and has a half-life of approximately 1 to 2 hours. The drug is primarily excreted in the urine, with both unchanged drug and metabolites being eliminated. Food can affect the absorption, so it is often recommended to take it on an empty stomach.

Contra-indications

• History of hypersensitivity to diclofenac or other NSAIDs
• Active gastrointestinal ulceration
• History of recurrent gastrointestinal bleeding
• History of cerebrovascular bleeding
• Severe renal impairment
• Severe hepatic impairment
• Dehydration
• Hypovolaemia
• History of asthma precipitated by NSAIDs
• History of gastro-intestinal perforation related to previous NSAID therapy
• History of confirmed or suspected hemorrhagic diathesis

Adverse effects

• Gastrointestinal discomfort
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Headache
• Dizziness
• Rash
• Tinnitus
• Elevated liver enzymes
• Renal impairment
• Fluid retention
• Increased blood pressure

Interactions

• Increased risk of gastrointestinal bleeding when used with other NSAIDs or anticoagulants
• Caution with diuretics due to potential for renal impairment
• May enhance the effects of anticoagulants like warfarin
• Caution with antihypertensive medications due to potential for reduced efficacy

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor renal function in patients with pre-existing renal impairment
• Long-term use may affect female fertility, reversible upon discontinuation
• Use with caution during pregnancy, especially in the third trimester

Pregnancy

Avoid unless the potential benefit outweighs the risk. Avoid during the third trimester due to risks of fetal ductus arteriosus closure and pulmonary hypertension of the newborn.

Breast-feeding

Use with caution; amount in milk is generally too small to be harmful.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Diclofenac sodium 1% gel
• Diclofenac sodium 75 mg injection
• Diclofenac sodium eye drops 0.1% (Voltarol Ophtha)

Indications

• Pain and inflammation in musculoskeletal disorders
• Rheumatic diseases
• Acute gout
• Postoperative pain

Dosage

Children: For children aged 9–13 years (body weight 35 kg and above), up to 2 mg/kg daily in 3 divided doses; maximum 100 mg per day. For children aged 14–17 years, 75–100 mg daily in 2–3 divided doses.

Adults: 75–150 mg daily in 2–3 divided doses.

Mechanism of action

Diclofenac potassium works primarily by inhibiting the cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. This inhibition decreases the synthesis of prostaglandins, which are mediators involved in inflammation, pain, and fever. This action results in reduced inflammation and pain sensation in affected tissues.

Pharmacodynamics

The analgesic effects of diclofenac potassium are evident within a few hours after administration. It shows a dose-dependent response in reducing pain and inflammation, making it effective for managing acute pain and inflammatory conditions. The drug can also have a beneficial effect on reducing fever.

Pharmacokinetics

Diclofenac potassium is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1-2 hours after oral administration. It has a half-life of approximately 1-2 hours, but its anti-inflammatory effects can last longer due to its active metabolites. The drug is extensively metabolized in the liver, and its metabolites are excreted primarily in the urine.

Contra-indications

• Active gastrointestinal bleeding
• Active gastrointestinal ulceration
• History of recurrent gastrointestinal haemorrhage
• Cerebrovascular disorders
• History of hypersensitivity to aspirin or any other NSAID
• Severe cardiac impairment
• Severe hepatic impairment
• Severe renal impairment
• History of allergic disorders

Adverse effects

• Diarrhoea
• Gastrointestinal disturbances
• Headache
• Insomnia
• Malaise
• Acute gout pain
• Palpitations
• Skin reactions
• Vertigo
• Angioedema
• Decreased appetite
• Dyspepsia
• Hypertension
• Nephritis
• Neutropenia
• Photosensitivity
• Severe cutaneous adverse reactions
• Syncope
• Tachycardia
• Thrombocytopenia
• Tinnitus
• Blurred vision

Interactions

• Increased risk of gastrointestinal bleeding with other NSAIDs
• Caution with anticoagulants due to potential increased bleeding risk
• Caution with antihypertensives as NSAIDs may reduce their efficacy
• Caution with diuretics due to potential renal impairment

Precautions

• Caution in patients with dehydration
• Caution in elderly patients due to increased risk of serious side effects
• Caution in patients with a history of cardiovascular disease
• Use with caution in patients with renal impairment
• Monitor for signs of gastrointestinal bleeding

Pregnancy

Avoid unless the potential benefit outweighs the risk. Avoid during the third trimester due to risk of fetal ductus arteriosus closure and possible persistent pulmonary hypertension in the newborn.

Breast-feeding

Use with caution during breastfeeding; no specific information available.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Oral tablets
• Oral suspension

Indications

• Gastric ulcer
• Duodenal ulcer
• Gastro-oesophageal reflux disease (GERD)
• Severe oesophagitis
• Helicobacter pylori eradication (in combination therapy)
• Prevention of NSAID-associated gastric and duodenal ulcers
• Zollinger-Ellison syndrome

Dosage

Adults: The usual dose for adults is 20 mg once daily for 4 weeks for duodenal ulcer and GERD. For gastric ulcer, the dose may be 20 mg to 40 mg once daily

Mechanism of action

Omeprazole works by specifically binding to the proton pump (H+/K+ ATPase) in the gastric parietal cells, leading to irreversible inhibition of acid secretion. This binding prevents the exchange of hydrogen ions for potassium ions, effectively reducing the production of gastric acid and promoting healing of acid-related conditions.

Pharmacodynamics

The pharmacodynamic effects of omeprazole manifest as a significant decrease in gastric acidity, which improves symptoms related to excessive acid secretion. The onset of action typically occurs within an hour of administration, with maximum effect seen within 2 to 4 days of continuous use. The duration of action allows for once-daily dosing in most indications.

Pharmacokinetics

Omeprazole is rapidly absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 0.5 to 3.5 hours after oral administration. It is extensively metabolized in the liver via the cytochrome P450 system, primarily CYP2C19 and CYP3A4, leading to the formation of inactive metabolites. The elimination half-life is approximately 0.5 to 1 hour, but the effects on gastric acid secretion last much longer due to the irreversible nature of proton pump inhibition. Omeprazole is excreted mainly in the urine as metabolites, with less than 1% of the drug excreted unchanged.

Contra-indications

• Hypersensitivity to omeprazole or any component of the formulation
• Use with caution in patients with severe liver impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Headache
• Abdominal pain
• Flatulence
• Constipation
• Dizziness
• Fatigue
• Rash
• Muscle weakness
• Gastrointestinal candidiasis
• Aggression
• Agitation
• Bronchospasm
• Encephalopathy

Interactions

• Cenobamate may increase exposure to omeprazole
• Fedratinib may increase exposure to omeprazole
• Apalutamide may decrease exposure to omeprazole
• Cilostazol may increase exposure to omeprazole

Precautions

• Monitor patients for gastrointestinal symptoms
• Use caution in patients with a history of liver disease
• Consider potential for vitamin B12 deficiency with long-term use
• Monitor for signs of Clostridium difficile infection in the colon

Pregnancy

Not known to be harmful during pregnancy, but should be used only if clearly needed.

Breast-feeding

Excreted in breast milk, caution is advised when administered to nursing mothers.

Storage

Store below 25 degrees Celsius. Protect from moisture. Keep out of reach of children.

Formulations

• Orodispersible tablets
• Gastro-resistant capsules
• Intravenous injection
• Oral suspension

Indications

• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Acute pain
• Dysmenorrhea
• Postoperative pain
• Inflammatory conditions

Dosage

Children: For children, the dosage must be determined based on weight and the specific indication. It is essential to refer

Adults: The usual oral dose for adults is 50 mg taken two to three times daily, with a maximum daily dose of 150 mg. In specific cases, doses may vary based on the condition being treated and the patient's response.

Mechanism of action

Diclofenac inhibits cyclooxygenase-1 and -2 (COX-1 and COX-2), enzymes responsible for the conversion of arachidonic acid to prostaglandins. This inhibition reduces the levels of prostaglandins G2, leading to decreased inflammation, pain, and fever. Prostaglandin E2 (PGE2), a primary mediator of nociception, is suppressed, which lowers pain sensitivity and peripheral sensitization via G-protein coupled receptors.

Pharmacodynamics

Diclofenac reduces inflammation and nociceptive pain while also exhibiting antipyretic effects. Its action can increase the risk of gastrointestinal ulceration due to the inhibition of protective mucus secretion in the stomach, which is a common side effect of NSAIDs.

Pharmacokinetics

Diclofenac is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a high volume of distribution and is extensively metabolized in the liver, primarily by cytochrome P450 enzymes. The elimination half-life is approximately 1 to 2 hours, with metabolites excreted in urine. Its pharmacokinetics can be influenced by factors such as age, liver function, and concurrent medications.

Contra-indications

• Untreated local infection

Adverse effects

• Gastrointestinal ulceration
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Dizziness
• Rash

Interactions

• Ciclosporin: Unknown (increases concentration)
• Iron chelators: Unknown (increases exposure)
• Deferiprone: Unknown (increases exposure)

Precautions

• Use with caution in patients with a history of gastrointestinal disease
• Monitor renal function in long-term use
• Consider cardiovascular risks in patients with pre-existing conditions

Pregnancy

Manufacturer advises to avoid unless essential.

Breast-feeding

Manufacturer advises to avoid unless essential.

Storage

Store below 25°C. Protect from light and moisture.

Formulations

• Diclofenac 50 mg oral tablet
• Diclofenac 100 mg extended-release oral tablet
• Diclofenac 75 mg injection
• Diclofenac 1% gel

Indications

• Hormone replacement therapy
• Pain management
• Chronic disease management
• Certain psychiatric conditions
• Hormonal imbalance

Dosage

Children: Refer to specific product information and guidelines, as dosing will vary based on the active ingredient and clinical indication.

Adults: Refer to specific product information and guidelines, as dosing will vary based on the active ingredient and clinical indication.

Mechanism of action

Pellets can contain various active pharmaceutical ingredients that may act through different mechanisms. For example, hormone pellets release hormones such as testosterone or estrogen into the bloodstream, where they bind to specific receptors to exert their physiological effects. The controlled release mechanism allows for a gradual increase in hormone levels, mimicking the body's natural secretion patterns.

Pharmacodynamics

The pharmacodynamic effects of pellets depend on the active ingredients contained within them. For hormone pellets, the effects can include modulation of reproductive processes, alleviation of menopausal symptoms, or enhancement of muscle mass and strength in the case of testosterone. The controlled release mechanism helps maintain therapeutic levels of the drug in the plasma, which can lead to more stable and effective treatment outcomes.

Pharmacokinetics

The pharmacokinetics of pellets vary based on the specific drug formulation. Generally, after administration, pellets dissolve or disintegrate, allowing the active ingredient to be absorbed into the bloodstream. The rate of absorption and the time to peak plasma concentration will depend on the pellet's composition, the solubility of the drug, and the physiological conditions of the gastrointestinal tract or the application site. The half-life of the drug will also influence the dosing schedule and the duration of action.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Mechanism of action

Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G₂ which is the precursor to other PGs. These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac. PGE₂ is the primary PG involved in modulation of nociception. It mediates peripheral sensitization through a variety of effects. PGE₂ activates the G_q-coupled EP₁ receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE₂ also activates the EP₄ receptor, coupled to G_s, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE₂ act via EP₃ to increase sensitivity to bradykinin and via EP₂ to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP₂ receptor which couples to G_s. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI₂ is known to play a role via its G_s-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain. PGI₂ and PGE₂ contribute to acute inflammation via their IP and EP₂ receptors. Similarly to β adrenergic receptors these are G_s-coupled and mediate vasodilation through the AC/PKA pathway. PGE₂ also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury. PGD₂ plays a role in the activation of endothelial cell release of cytokines through its DP₁ receptor. PGI₂ and PGE₂ modulate T-helper cell activation and differentiation through IP, EP₂, and EP₄ receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation. PGE₂ can cross the blood-brain barrier and act on excitatory G_q EP₃ receptors on thermoregulatory neurons in the hypothalamus. This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE₂ thereby reducing the activity of these neurons. Diclofenac has pharmacologic actions similar to those of other prototypical NSAIAs. The drug exhibits anti-inflammatory, analgesic, and antipyretic activity. The exact mechanisms have not been c

Pharmacodynamics

Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever. It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach.