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:

• It is important to confirm tumor epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations before treatment initiation.

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

Patients must be EGFR exon 19 deletion- or exon 21 L858R substitution mutation-positive:

• 45 mg orally once a day.
• The treatment is continued until disease progression or unacceptable toxicity.

• Missed doses:

  • In case, a dose is missed or vomited, avoid giving an extra dose to make up for the missed dose.
  • Follow the schedule and give the next dose as scheduled.

Use in Children:

Not indicated.

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

• Although it has not been tested in pregnant women, the drug's mechanism of action could prove to be harmful to the foetus.
• Assess your pregnancy status before starting treatment.
• Effective contraception must be used during treatment and for at least 17 days following the last dose.

Use of Dacomitinib while breastfeeding

• It is unknown if the drug will be excreted into breastmilk.
• The manufacturer suggests that breastfeeding be stopped during treatment, and at least for 17 days after the last dose.

Dacomitinib (Vizimpro) Dose in Kidney Disease:

• CrCl 30 to 89 mL/minute:

  • Adjustment in the dose is not necessary.

• CrCl <30 mL/minute:

  • The drug has not been studied in patients with a CrCl of less than 30 ml/minute.
  • The manufacturer has not provided any dosage recommendations.

Dacomitinib (Vizimpro) Dose in Liver disease:

• Mild hepatic impairment (total bilirubin ≤ ULN with AST > ULN or total bilirubin >1 to 1.5 times ULN with any AST) or
• Moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment:
  • Adjustment in the dose is not necessary.
• Severe (total bilirubin >3 to 10 times ULN and any AST) impairment:
  • The drug has not been studied in patients with severe hepatic impairment.
  • The manufacturer has not provided any dosage recommendations.

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):

There are no contraindications for its use, according to the manufacturer. Canadian labeling

• Hypersensitivity to any drug component or drug ingredient

Warnings and precautions

• Dermatologic toxicities:

  • Drug-induced skin reactions, such as drug rashes or exfoliative skin eruptions, can occur. 
  • These skin reactions can be life-threatening and may even cause death (Grade 3 or 4).
  • Drug-induced rashes can be common and may affect more than 75% of patients.
  • Sun exposure can cause skin reactions that may become more severe. When starting treatment, patients should be warned to avoid sun exposure and use sunscreens and moisturizers.
  • If the patient is suffering from persistent skin toxicity, or dermatologic toxicity of grade 3, 4, or 5, treatment must be stopped immediately. 
  • Once the severity of skin toxicity has decreased to grade 1, treatment may be resumed. Treatment may be repeated at a lower or the same dose depending on severity.
  • For grade 1 skin-related toxicities, topical steroids and antibiotics may be recommended. Patients with grade 2 or higher toxicities may need oral or parenteral therapy.
  • Dry skin and nail disorders are less common skin-related problems.

• Gastrointestinal toxicities:

  • Diarrhea can be common during therapy. During therapy, diarrhea was common in most patients.
  • It can be life-threatening or severe (Grade 3 or 4).
  • Patients with gastrointestinal toxicities of grade 2 or greater must have their treatment stopped immediately. 
  • Depending on severity and degree of GI toxicity, treatment may be resumed at the same dose or reduced.
  • It is important to immediately begin antidiarrheal treatment, as well as the replacement of fluids or electrolytes.
  • Antidiarrheal treatments may include loperamide, diphenoxylate and/or atropine.
  • Patients can also experience stomatitis or mucositis.

• Toxicity in the lungs:

  • It is not unusual for patients to experience pulmonary toxicity. Patients with severe and fatal ILD or pneumonitis have been known to develop interstitial lung disease.
  • Watch out for signs and symptoms that could indicate ILD or pneumonitis in patients.
  • Patients with persistent or worsening symptoms of the respiratory system should stop receiving treatment until they resolve their pulmonary symptoms.
  • Patients with confirmed ILD must stop receiving treatment.

 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 treatment begins, confirm epidermal growth factors receptor exon 19 deletion status or exon 21 substitution mutation status.
• Before treatment begins, a pregnant test is done on females to determine their reproductive potential.
• You should be aware of signs and symptoms that could indicate drug-induced toxicity.
• These include pulmonary toxicity, which can manifest as dyspnea and cough, interstitial lung disease, and pneumonitis.
• GI toxicity manifests as diarrhea and mucositis. Dermatologic toxicity manifests as a rash and skin exfoliation.
• Monitor compliance with treatment.

How to administer Dacomitinib (Vizimpro)?

• It is administered orally with or without food at the same time each day.
• Avoid the concomitant use of PPIs (proton pump inhibitors).
• If an H-2 blocker or an antacid is used, dacomitinib should be administered at least 6 hours before or 10 hours after the H-2 blocker or antacid.

Mechanism of action of Dacomitinib (Vizimpro):

Dacomitinib (epidermal Growth Factor Receptor) tyrosine kinase inhibit is irreversible. It is capable of fighting the following cell mutations:

• • EGFR/HER1
  • HER2, HER4,
  • EGFR-activating mutations: exon 19 deletion or exon21 L858R substitution mutation
  • In vitro, it has also got activity against DDR1, EPHA6, LCK, DDR2, and MNK1.

Protein binding:

• ~98%

Metabolism:

• It is metabolized in the liver primarily via oxidation and glutathione conjugation;
• CYP2D6 is involved in the formation of O-desmethyl dacomitinib (active), and CYP3A4 contributes to the formation of minor oxidative metabolites

Bioavailability:

• 80%

Half-life elimination:

• 70 hours

Time to peak:

• ~6 hours (range: 2 to 24 hours)

Excretion:

• Feces: 79% (20% as parent drug);
• Urine: 3% (<1% as parent drug)

International Brand Names of Dacomitinib:

• Vizimpro

Dacomitinib Brand Names in Pakistan:

• No Brands Available in Pakistan.