NOZOMIL GRANULES FOR INJECTABLE AQUEOUS SOLUTION (Each gram (g) contains: DIMINAZENE DIACATINATE 445mg

Indications

• Acute pain
• Chronic pain conditions
• Osteoarthritis
• Rheumatoid arthritis
• Musculoskeletal disorders
• Postoperative pain

Dosage

Children: Refer to paediatric dosing guidelines based on age, weight, and specific clinical indication. It is important to consult the relevant paediatric dosing references for accurate dosing information.

Adults: Refer to specific clinical guidelines for dosing recommendations based on the condition being treated. Adjustments may be necessary based on patient response and tolerability.

Mechanism of action

Diacatinate primarily acts as a non-steroidal anti-inflammatory drug (NSAID), inhibiting cyclooxygenase enzymes (COX-1 and COX-2), which are crucial in the conversion of arachidonic acid to prostaglandins. Prostaglandins are mediators of inflammation and pain, and by reducing their synthesis, diacatinate effectively alleviates pain and decreases inflammation.

Pharmacodynamics

The pharmacodynamic effects of diacatinate include analgesia, anti-inflammatory action, and antipyretic effects. The inhibition of COX enzymes leads to reduced levels of prostaglandins, which are responsible for the sensation of pain and the physiological processes associated with inflammation. The onset of action can vary based on formulation and route of administration, with effects generally observed within hours of dosing.

Pharmacokinetics

Diacatinate is absorbed well from the gastrointestinal tract, and its bioavailability can be influenced by food intake. It undergoes hepatic metabolism, primarily via glucuronidation, and is excreted through urine. The drug has a half-life that supports multiple dosing regimens, although specific values may vary based on individual patient factors such as age, liver function, and concomitant medications.

Pregnancy

Due to limited data, diacatinate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when diacatinate is administered to breastfeeding mothers, as its effects on nursing infants are not well studied.

Storage

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

Indications

• Trypanosomiasis (sleeping sickness)
• Nagana in livestock
• Infections caused by Trypanosoma brucei
• Infections caused by Trypanosoma congolense

Dosage

Children: Paediatric dosing of diminazene should be derived from the BNF for Children, taking into account the weight and age of the child. Refer to the BNF for Children for specific dosing recommendations.

Adults: The dosage for adults should be determined based on the specific condition and patient factors. Refer to the BNF for accurate dosing guidelines.

Mechanism of action

Diminazene acts by inhibiting the enzyme dihydrofolate reductase, which is crucial for the synthesis of folate in protozoa. This inhibition disrupts the folate metabolic pathway, leading to a decrease in nucleic acid synthesis and ultimately resulting in the death of the protozoan parasites. Additionally, it may interfere with the mitochondrial function of the parasites, further contributing to its antiparasitic effects.

Pharmacodynamics

The pharmacodynamics of diminazene involve its selective action on trypanosomes, with the drug being less toxic to host cells. It has a high affinity for the target enzyme, allowing for effective suppression of protozoan growth. The drug's therapeutic index is favorable, meaning it can effectively treat infections at doses that are relatively safe for the host.

Pharmacokinetics

Diminazene is well-absorbed following parenteral administration. It is widely distributed throughout the body, with a significant volume of distribution. The drug undergoes hepatic metabolism, and its elimination half-life can vary depending on species and individual health. Excretion is primarily via the urine, with metabolites detected in both urine and feces.

Adverse effects

• Anorexia
• Vomiting
• Diarrhoea
• Lethargy
• Neurological signs (e.g., tremors, ataxia)
• Hypersensitivity reactions

Precautions

• Use with caution in animals with hepatic or renal impairment.
• Monitor for signs of toxicity, especially in cases of overdose.

Pregnancy

Safety during pregnancy has not been established; use only if the benefits outweigh the risks.

Breast-feeding

Safety during breastfeeding has not been established; use with caution.

Storage

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

Formulations

• Injection solution