NINTEDANIB 150 EUROLAB

Indications

• Allergic rhinitis
• Urticaria
• Conjunctival allergic reactions
• Allergic skin conditions

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on age and weight.

Adults: Refer to the specific product guidance or clinical guidelines as dosing can vary based on the formulation and indication.

Mechanism of action

Esilate exerts its pharmacological effects primarily through the selective antagonism of H1 histamine receptors. By inhibiting the action of histamine, a compound released during allergic reactions, esilate reduces symptoms such as itching, sneezing, and increased mucus production. This mechanism helps to restore normal respiratory and skin function in allergic conditions.

Pharmacodynamics

Esilate demonstrates a high affinity for H1 receptors, which allows it to effectively prevent the binding of histamine. This leads to a reduction in the physiological effects associated with histamine release, including vasodilation, increased vascular permeability, and stimulation of sensory nerves that cause itching. The drug's action is both rapid and sustained, providing relief from allergic symptoms over an extended period.

Pharmacokinetics

Esilate is well-absorbed after oral administration, with peak plasma concentrations typically occurring within a few hours. It has a bioavailability that allows for once-daily dosing in most cases. The drug is metabolized in the liver, with hepatic enzymes playing a significant role in its breakdown, and is excreted primarily in urine. The elimination half-life of esilate is generally favorable for once-daily dosing, allowing for consistent therapeutic levels in the body.

Contra-indications

• Hypersensitivity to esilate or any component of the formulation
• Severe renal impairment
• Active gastrointestinal bleeding

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Dizziness
• Fatigue
• Hypotension

Interactions

• May enhance the effects of anticoagulants, increasing the risk of bleeding
• Potential interaction with antihypertensives, leading to additive hypotensive effects
• Caution should be exercised when used with other medications that affect renal function

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of gastrointestinal bleeding
• Consider potential drug interactions when prescribing

Pregnancy

Esilate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines and literature for specific recommendations.

Breast-feeding

Caution is advised when administering esilate to breastfeeding mothers, as it is unknown if it is excreted in human breast milk.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Oral solution

Indications

• Idiopathic pulmonary fibrosis
• Endometrial cancer
• Other targeted therapy responsive malignancies

Dosage

Children: Refer to the BNF for Children for paediatric dosing information.

Adults: Refer to the BNF for specific adult dosing guidelines.

Mechanism of action

Nintedanib functions by inhibiting several receptor tyrosine kinases, including vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), and platelet-derived growth factor receptors (PDGFR). This inhibition disrupts the signaling pathways involved in cell proliferation, survival, angiogenesis, and fibrosis, ultimately leading to reduced tumor growth and progression.

Pharmacodynamics

The pharmacodynamic effects of nintedanib include its ability to decrease the proliferation of cancer cells and inhibit angiogenesis. By blocking key growth factor receptors, nintedanib impairs the signaling pathways that contribute to tumor growth and the development of fibrosis, particularly in lung tissue associated with idiopathic pulmonary fibrosis.

Pharmacokinetics

Nintedanib has a bioavailability of approximately 4.5% when taken orally. It undergoes extensive metabolism primarily via the cytochrome P450 enzyme CYP3A4, resulting in multiple metabolites. The mean elimination half-life of nintedanib is about 10 hours, allowing for once-daily dosing. The drug's clearance is influenced by hepatic function, and it is primarily excreted in the feces.

Contra-indications

• Hypersensitivity to nintedanib or any of its excipients
• Severe liver impairment

Adverse effects

• Alopecia
• Anaemia
• Diarrhoea
• Dizziness
• Dry eye
• Dyspnoea
• Electrolyte imbalance
• Eosinophilia
• Fatigue
• Gastrointestinal discomfort
• Headaches
• Hypertension
• Nausea
• Oedema
• Pain
• Palpitations
• Peripheral neuropathy
• QT interval prolongation
• Thrombocytopenia
• Vomiting
• Weight loss

Interactions

• Carbamazepine (decreases exposure)
• Voriconazole (increases exposure)
• Verapamil (increases exposure)
• Ciclosporin (increases exposure)
• Cobicistat (increases exposure)
• Ivacaftor (increases exposure)
• Lapatinib (increases exposure)
• Macrolides (increases exposure)
• Neratinib (increases exposure)
• Calcium channel blockers (increases exposure)

Precautions

• Monitor liver function during treatment
• Monitor for signs and symptoms of cardiovascular events
• Risk of hepatitis B reactivation in carriers
• Consider the risk of thromboembolic events

Pregnancy

Avoid use unless potential benefit justifies potential risk to the fetus; effective contraception is recommended during treatment and for up to two weeks after stopping.

Breast-feeding

It is not known whether nintedanib is excreted in human milk; caution is advised.

Storage

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

Formulations

• Nintedanib 150 mg capsules
• Nintedanib 200 mg capsules