Dacomitinib is a medication that falls under the category of tyrosine kinase inhibitors (TKIs). It is primarily used for the treatment of a specific type of cancer called non-small cell lung cancer (NSCLC). More specifically, dacomitinib targets and inhibits the activity of certain proteins known as epidermal growth factor receptor (EGFR) tyrosine kinases.

EGFR is a protein that plays a role in cell growth, division, and survival. Mutations in the EGFR gene can lead to the development and progression of certain cancers, including NSCLC. Dacomitinib works by binding to these EGFR proteins and inhibiting their activity. By blocking the signals that drive cancer cell growth and division, dacomitinib can help slow down or even shrink tumors in individuals with EGFR-mutated NSCLC.

Dacomitinib (Vizimpro) is an irreversible EGFR tyrosine kinase inhibitor that is used in the treatment of metastatic non-small cell lung cancer.

Dacomitinib (Vizimpro) Uses:

• Metastatic non-small-cell lung cancer:
  • It is used as the first line of treatment in patients with metastatic non-small cell lung cancer who have the following genetic mutations as detected by an approved test:
    • Epidermal growth factor receptor (EGFR) exon 19 deletion or
    • exon 21 L858R substitution mutations.

Dacomitinib (Vizimpro) Dose in Adults

Note:

• Before starting the treatment, make sure the tumor has specific changes in the EGFR gene, either exon 19 deletions or exon 21 L858R changes.

Dacomitinib (Vizimpro) Dose as the first line of treatment in patients with metastatic non-small cell lung cancer:

For treating a certain type of advanced lung cancer with specific gene changes (EGFR exon 19 deletion or exon 21 L858R mutation), the recommended dose for dacomitinib is:

• Take by mouth: 45 mg once a day.
• Keep taking it: Until the cancer gets worse or if the side effects become too much.

If you forget to take a dose or throw up after taking it:

• Don't take an extra dose to make up for the one you missed.
• Just take the next dose when you're supposed to.

Use in Children:

Not indicated.

Dacomitinib (Vizimpro) Pregnancy Risk Category: N (not assigned)

• Using dacomitinib during pregnancy might harm the baby, based on animal tests and how the drug works.
• Before starting the drug, make sure women who can get pregnant are not already pregnant.
• These women should also use strong birth control while on the drug and continue for at least 17 days after the last dose.

Use of Dacomitinib while breastfeeding

• We don't know if dacomitinib gets into breast milk.
• Because it might harm the baby, the company making the drug says don't breastfeed while taking it and for at least 17 days after the last dose.

Dacomitinib (Vizimpro) Dose in Kidney Disease:

• If your kidney filters (CrCl) between 30 to 89 mL/minute: You can take the regular dose.
• If it's less than 30 mL/minute: The company hasn't given any special dosing instructions because they haven't studied it in this situation.

Dacomitinib (Vizimpro) Dose in Liver disease:

• If you have mild or moderate issues (based on certain blood test numbers): You can take the regular dose.
• If you have severe issues (again, based on specific blood test numbers): The company hasn't given any special dosing instructions because they haven't looked into it in this situation.

Common Side Effects of Dacomitinib (Vizimpro):

• Cardiovascular:
  • Chest Pain
• Central Nervous System:
  • Insomnia
• Dermatologic:
  • Skin Rash
  • Paronychia
  • Xeroderma
  • Alopecia
  • Pruritus
  • Palmar-Plantar Erythrodysesthesia
  • Dermatitis
• Endocrine & Metabolic:
  • Hypoalbuminemia
  • Hyperglycemia
  • Hypocalcemia
  • Hypokalemia
  • Hyponatremia
  • Weight Loss
  • Hypomagnesemia
• Gastrointestinal:
  • Diarrhea
  • Stomatitis
  • Decreased Appetite
  • Nausea
  • Constipation
  • Oral Mucosa Ulcer
• Hematologic & Oncologic:
  • Anemia
  • Lymphocytopenia
• Hepatic:
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Hyperbilirubinemia
• Neuromuscular & Skeletal:
  • Limb Pain
  • Asthenia
  • Musculoskeletal Pain
• Ophthalmic:
  • Conjunctivitis
• Renal:
  • Increased Creatinine Clearance
• Respiratory:
  • Cough
  • Nasal Signs And Symptoms
  • Dyspnea
  • Upper Respiratory Tract Infection

Less Common Side Effects Of Dacomitinib (Vizimpro):

• Central Nervous System:
  • Fatigue
• Dermatologic:
  • Skin Fissure
  • Exfoliation Of Skin
  • Hypertrichosis
• Endocrine & Metabolic:
  • Dehydration
• Gastrointestinal:
  • Vomiting
  • Dysgeusia
• Ophthalmic:
  • Keratitis
• Respiratory:
  • Interstitial Pulmonary Disease

Contraindications to Dacomitinib (Vizimpro):

• In the US: There are no listed reasons to avoid the drug.

• In Canada: Don't take it if you're allergic to dacomitinib or anything else in the pill.

Warnings and precautions

Dermatologic toxicities:

• Rash and skin problems can happen with dacomitinib.
• Rash is common, affecting many patients.
• Sunlight can make these skin problems worse, so use sunscreen and avoid too much sun.
• Start using moisturizers when you start taking dacomitinib.
• If you have bad rash (grade 2 or worse), stop taking dacomitinib until it gets better (grade 1 or less). You might restart at the same dose or lower dose.
• For mild rash (grade 1), use creams. For worse rash (grade 2 or more), use oral antibiotics.
• Dry skin and nail issues are also common with this drug.

Gastrointestinal toxicities:

• Severe and even deadly diarrhea can happen with dacomitinib.
• Most patients experience diarrhea, with some having very bad cases.
• If you have moderate to severe diarrhea (grade 2 or worse), stop taking dacomitinib. Restart at the same or lower dose when the diarrhea improves to mild or none (grade 1 or less).
• If you get diarrhea, start taking diarrhea medicine right away, like loperamide.
• Mouth sores (mucositis/stomatitis) can also occur with this drug.

Toxicity in the lungs:

• A lung problem called Interstitial Lung Disease (ILD), which can be severe or even deadly, has been seen with dacomitinib.
• Watch out for symptoms like trouble breathing, cough, and fever.
• If someone has worsening breathing symptoms, stop taking dacomitinib and quickly check if it's ILD.
• If it's confirmed to be ILD, don't take dacomitinib again.

Dacomitinib: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Before Starting Treatment:

• Check for specific gene changes: exon 19 deletion or exon 21 L858R changes.
• For women who can get pregnant, do a pregnancy test.

While on Treatment:

• Watch out for lung issues like trouble breathing, cough, and fever.
• Keep an eye on diarrhea and skin problems.
• Make sure the patient is taking the medication as prescribed.

How to administer Dacomitinib (Vizimpro)?

• Take it at the same time every day, with or without food.
• Don't take dacomitinib with medicines called proton pump inhibitors.
• If using an H2 blocker or antacid, take dacomitinib 6 hours before or 10 hours after that medicine.

Mechanism of action of Dacomitinib (Vizimpro):

• Dacomitinib is a drug that permanently blocks certain cell receptors (EGFR/HER1, HER2, HER4) and specific changes in them (like exon 19 deletion or exon 21 L858R change).
• This mainly helps stop some cancer cells from growing.
• It also affects a few other targets in the lab, like DDR1, EPHA6, and some others.

Distribution:

• Volume of distribution: 1,889 liters (a measure of how the drug spreads in the body)

Protein Binding:

• Binds to proteins in the blood: About 98% of the drug attaches to proteins.

Metabolism:

• Processed by the liver: Primarily broken down in the liver through chemical changes like oxidation and joining with glutathione.
• Specific enzymes involved: CYP2D6 helps create O-desmethyl dacomitinib (which is active), and CYP3A4 helps form minor products through oxidation.

Bioavailability:

• Amount that gets into bloodstream: Around 80% of the drug taken gets into the bloodstream.

Half-life:

• Time it takes to reduce by half: The drug takes about 70 hours to decrease in the body by half.

Time to Peak:

• When it's highest in the blood: It usually takes around 6 hours after taking the drug to reach its highest level in the blood. This can vary between 2 to 24 hours.

Excretion:

• Leaving the body: Most of the drug leaves through the feces (79%), with only a small amount (3%) in the urine. Only a fraction of this is the original drug; the rest is transformed.

International Brand Names of Dacomitinib:

• Vizimpro

Dacomitinib Brand Names in Pakistan:

Not available.