APRITANT IV

Indications

• Magnetic resonance imaging (MRI)
• Computed tomography (CT) scans
• Angiography

Dosage

Children: Refer to the BNF for Children for paediatric dosing recommendations based on age and weight.

Adults: Refer to specific guidelines and protocols for adult dosing based on the imaging procedure being performed.

Mechanism of action

Dimeglumine works by increasing the contrast of images obtained during diagnostic imaging procedures. It does this by providing a higher concentration of iodine in the bloodstream, which absorbs X-rays more effectively than surrounding tissues. The iodine in dimeglumine enhances the contrast of tissues and vascular structures, enabling clearer imaging of organs and blood vessels.

Pharmacodynamics

The pharmacodynamics of dimeglumine is characterized by its ability to improve the contrast in imaging modalities. The compound is rapidly distributed in the vascular system, leading to enhanced visualization of blood vessels and organs. Its non-ionic nature reduces the likelihood of adverse reactions commonly associated with ionic contrast agents, such as allergic reactions and nephrotoxicity.

Pharmacokinetics

Dimeglumine is administered intravenously and is distributed throughout the vascular system. It is eliminated primarily via the kidneys. The pharmacokinetics involve rapid distribution and clearance, with peak plasma concentrations occurring shortly after administration. The compound has a short half-life, which allows for quick imaging procedures and minimizes prolonged exposure to contrast agents.

Contra-indications

• Hypersensitivity to dimeglumine or any of its components
• Severe renal impairment
• Dehydration
• Hyperthyroidism

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Headache
• Allergic reactions including rash and itching
• Nephrotoxicity in patients with pre-existing renal conditions

Interactions

• Increased risk of nephrotoxicity when used with other nephrotoxic agents
• May interfere with thyroid function tests

Precautions

• Monitor renal function before and after administration, especially in patients with existing renal impairment
• Use caution in patients with a history of asthma or allergic reactions
• Ensure adequate hydration before administration

Pregnancy

The safety of dimeglumine 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 dimeglumine is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Injection solution for intravenous use

Indications

• Prevention of nausea and vomiting associated with moderately emetogenic chemotherapy
• Prevention of nausea and vomiting associated with highly emetogenic chemotherapy

Dosage

Adults: For adults, the initial dose is 125 mg taken orally 1 hour before chemotherapy, followed by 80 mg once daily for 2 days. When administered intravenously, the dose is 150 mg infused over 20-30 minutes

Mechanism of action

Fosaprepitant is converted to its active form, aprepitant, which acts as a selective antagonist of neurokinin-1 (NK1) receptors. This action inhibits the emetic signals transmitted through these receptors, thereby reducing the likelihood of vomiting. Aprepitant has been shown to enhance the antiemetic effects of 5-HT3 receptor antagonists and corticosteroids, effectively managing both acute and delayed nausea and vomiting induced by chemotherapy.

Pharmacodynamics

As a prodrug, fosaprepitant is converted to aprepitant, which selectively binds to NK1 receptors in the brain. This binding inhibits the action of substance P, a neuropeptide involved in the vomiting reflex. Aprepitant has a high affinity for NK1 receptors and does not significantly interact with serotonin or dopamine receptors, making it a unique addition to antiemetic therapy for chemotherapy-induced nausea and vomiting.

Pharmacokinetics

Fosaprepitant is well absorbed following oral administration and is converted to aprepitant in the liver. Its bioavailability is approximately 60%, with peak plasma concentrations occurring within 4 hours after oral dosing. The half-life of aprepitant is approximately 9 to 13 hours, allowing for once-daily dosing after the initial dose. It is primarily metabolized by CYP3A4 and has potential drug interactions with other medications metabolized by this enzyme.

Contra-indications

• Acute porphyrias

Adverse effects

• Appetite decreased
• Asthenia
• Constipation
• Gastrointestinal discomfort
• Headache
• Anemia
• Anxiety
• Burping
• Dizziness
• Muscle weakness
• Oedema
• Chest discomfort
• Cognitive disorder
• Skin reactions
• Thrombophlebitis
• Urinary disorders
• Photosensitivity reaction
• Weight decreased

Interactions

• Mitotane - Severe (decreases exposure)
• Benzodiazepines - Unknown (increases exposure)
• Alprazolam - Unknown (increases exposure)
• Midazolam - Unknown (increases exposure)
• Bosutinib - Unknown (increases exposure)
• Ceritinib - Unknown (increases exposure)
• Cobicistat - Unknown (increases exposure)
• Guanfacine - Unknown (increases concentration)
• Ibrutinib - Unknown (increases exposure)
• Idelalisib - Unknown (increases exposure)

Pregnancy

Caution is advised; limited data on safety in pregnancy.

Breast-feeding

Caution is advised; it is not known if it is excreted in human milk.

Storage

Store below 30 degrees Celsius, protect from light.

Formulations

• Intravenous infusion 150 mg
• Oral solution 125 mg
• Oral capsules 80 mg
• Oral capsules 125 mg

Mechanism of action

Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT₃-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis. In summary, the active form of fosaprepitant is as an NK1 antagonist which is because it blocks signals given off by NK1 receptors. This therefore decreases the likelihood of vomiting in patients experiencing.

Pharmacodynamics

Fosaprepitant is a prodrug of Aprepitant. Once biologically activated, the drug acts as a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT₃), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).