What Is Dacomitinib?
Dacomitinib is a prescription medicine that helps in the treatment of non-small cell lung cancer, which has spread to other regions of the body. It is used as a first-line treatment if the tumor harbors abnormal epidermal growth factor receptor genes. Care must be taken to limit exposure to sunlight when the individual is under treatment with Dacomitinib, as it can cause serious skin problems. Dacomitinib was approved globally to be used as a first-line treatment for non-small cell lung cancer by the US Food and Drug Administration (FDA) on September 27th, 2018.
Available Doses and Dosage Forms:
The drug Dacomitinib is supplied in a package of 30 in a bottle.
Packaging is determined by the dosage.
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15 mg (milligrams) Dosage:
30 tablets in a bottle - Blue film-coated, round biconvex tablets.
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30 mg Dosage:
30 tablets in a bottle - Blue film-coated, round, biconvex tablets.
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45 mg Dosage:
30 tablets in a bottle - Blue film-coated, round, biconvex tablets.
Directions:
The drug Dacomitinib is consumed with or without food at least once a day. 40 mg is the recommended dose.
Warnings:
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Interstitial Lung Disease:
If the diagnosis of interstitial lung disease is confirmed, discontinue the drug Dacomitinib permanently.
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Diarrhea:
The dosage of the drug Dacomitinib is reduced based on the severity of the diarrhea.
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Skin Reactions:
Dacomitinib is withheld, and the dose is reduced based on severity.
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Embryo-Fetal Toxicity:
Fetal harm can be caused by drug administration. For this reason, contraception is advised in females with reproductive potential.
For Patients
What Is Non-small Cell Lung Cancer?
It is a condition in which cancer cells form in the lung tissues. Non-small cell lung cancer is of several types. It is mainly caused by smoking. The condition is characterized by a persistent cough that does not resolve, along with shortness of breath. Wheezing, troubled breathing, hoarseness, and tiredness can also occur.
Staging and diagnosing of non-small cell lung cancer is done by performing certain tests. A biopsy is advised if lung cancer is suspected. The prognosis of the condition is influenced by factors that determine treatment options.
When to Take Dacomitinib?
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Dacomitinib is taken once daily.
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It can be administered with or without food.
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The medication is taken approximately at the same time every day.
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The drug is to be taken at least 6 hours before or 10 hours after if the individual is on antacids or H2 blocker medicine.
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Dacomitinib should not be stopped or discontinued unless and until the physician recommends it.
What Should Be Avoided During Treatment With the Drug Dacomitinib?
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It is better to minimize exposure to sunlight. Exposure to the sun can cause various skin reactions. Moisturizers can be used to eradicate this.
Things to Inform the Doctor Before Taking Dacomitinib
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In the presence of frequent diarrhea and a history of lung or breathing problems, pregnancy planning should be discussed with the physician.
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It is important for a female who has the potential to become pregnant to use effective contraception during treatment for 17 days after the last dose of Dacomitinib.
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It is advised not to breastfeed during the treatment as there is a high risk of passage of the contents to the infant. Hence, individuals planning to breastfeed or breastfeeding should be made aware of their physician.
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Health care providers must be informed of all the medicines, along with herbal or vitamin supplements, as there is a risk of side effects.
What Should Be Done if a Dose Is Missed?
If you miss a dose, do not take an extra one, as it can lead to toxicity.
How to Store the Drug Dacomitinib?
Dacomitinib can be stored at 20 to 25 degrees Celsius. It is kept out of reach of children, as with all other medicines.
Avoid Self-Medication:
The medication can also be used for other purposes. Do not use Dacomitinib for a condition that is not prescribed. It is not right to advise other individuals to take Dacomitinib if they show similar symptoms, as it can harm them.
For Doctors
Indication:
Dacomitinib is indicated for patients with non-small cell lung cancer. It is a first-line treatment. Such disorders with epidermal growth factor receptor exon 19 deletion or substitution mutations can be detected through certain tests.
Dosing:
A dosage of 45 mg is taken orally once daily. This is continued until the level of unacceptable toxicity occurs and is stopped before. Dacomitinib can be taken along with or without food.
Dosing Considerations:
The dose of the drug Dacomitinib is reduced if adverse reactions occur. The dosage is reduced as mentioned below.
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The first dose reduction can be made up to 30 mg.
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The second dose reduction is made up to 15 mg.
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Any grade of lung disease occurring as an adverse reaction should be taken as a warning, and Dacomitinib should be permanently discontinued.
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When an individual develops grade 2 diarrhea, Dacomitinib is withheld until complete recovery or until the diarrhea resolves to grade 1, and the normal dose is resumed thereafter.
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In case of skin adverse reactions, Dacomitinib is discontinued until the symptoms subside, and then the dose is reduced and re-administered.
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The occurrence of any severe adverse reaction is a sign to discontinue the drug Dacomitinib until recovery and then continue with a reduced dose.
Pharmacology
Mechanism of Action:
Dacomitinib is an inhibitor of the kinase activity of certain EGFR mutations. Dose-dependent inhibition of HER2 autophosphorylation and EGFR, along with tumor growth. It also works by exhibiting anti-tumor activity in animals bearing intracranial human tumor xenografts.
Pharmacodynamics:
Cardiac Electrophysiology:
The effect of Dacomitinib on the QT interval is evaluated, and Dacomitinib shows no significant effect on the QT interval at the highest concentration of the drug, which is 45 mg when administered orally.
Exposure-Response Relations:
As exposure to Dacomitinib increases with a recommended dose of 45 mg per day, the occurrence of severe grade-three adverse events can occur.
Pharmacokinetics:
The maximum plasma concentration of the drug Dacomitinib has increased proportionally within the dose range of 2 milligrams to 60 milligrams when administered orally once a day.
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Absorption:
The bioavailability is 80 percent after oral administration. The time to reach maximum concentration is approximately 6 hours after a single dose of 45 milligrams. There has been no effect on the pharmacokinetics of Dacomitinib when administered with a high-calorie meal.
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Elimination:
The mean plasma half-life is 70 hours, and the apparent plasma clearance was 36 percent, followed by a single dose of 45 milligrams of Dacomitinib.
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Excretion:
20 percent of Dacomitinib was eliminated in the feces and three percent in the urine following a single 45-milligram oral dose of the drug Dacomitinib.
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Distribution:
The geometric mean volume of distribution of Dacomitinib was 18 percent. The binding of Dacomitinib to human plasma proteins was nearly 98 percent and is not dependent on the concentration of Dacomitinib.
Non-Clinical Toxicity:
Carcinogenesis, Mutagenesis, Impairment of Fertility:
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Carcinogenesis was not studied with the drug Dacomitinib.
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It was found that the drug Dacomitinib was not mutagenic in assays like bacterial reverse mutation and lymphocyte chromosome aberration assay.
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Reversible epithelial atrophy in the cervix occurred when Dacomitinib was administered daily at a dose approximately 0.14 times that of 45 milligrams in female rats. Decreased secretion of the prostate gland resulted from administering 2 mg of Dacomitinib in male rats.
Clinical Studies:
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Effect of Acid-Reducing Agents on Dacomitinib:
Co-administration of multiple doses of a proton pump inhibitor with a single dose of the drug Dacomitinib decreased the Cmax by 51 percent. No major changes were observed when Dacomitinib was administered with a local antacid.
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Effect of Strong CYP2D6 Inhibitors:
The total AUC of Dacomitinib was increased by six percent when Dacomitinib was administered with multiple doses of a strong CYP2D6 inhibitor.
Warnings and Precautions:
Interstitial Lung Disease:
Pneumonitis, or severe and fatal interstitial lung disease, occurred in nearly 0.5 percent of the affected population, of which 0.3 percent were fatal. Symptoms indicating the disease were identified, and the patients were monitored. In clinical conditions with worsening respiratory symptoms, such as cough, dyspnea, and fever, interstitial lung disease is investigated. Once a confirmatory diagnosis is obtained, the drug Dacomitinib should be stopped.
Diarrhea:
Dacomitinib is discontinued until diarrhea severity decreases, and then treatment is resumed at a reduced dosage. Antidiarrheal treatment is initiated with Loperamide or Diphenoxylate hydrochloride.
Dermatologic Adverse Reactions:
Skin rashes and adverse skin reactions occurred during the treatment with the drug Dacomitinib. 78 percent of the affected individuals showed rashes, of which 21 percent were severe. Dacomitinib is withheld until symptoms resolve, and then continued at a reduced dose depending on the clinical condition and the severity of the adverse reaction. Exposure to the sun can increase the severity of the rashes. Moisturizers and measures to prevent or limit sun exposure are initiated along with treatment with Dacomitinib. When a severe rash appears, the treatment and management are initiated with topical steroids and topical antibiotics. Oral antibiotics are indicated for severe adverse dermatologic reactions.
Contraindications:
There is no report of specific contraindications during the treatment with the drug Dacomitinib.
What Are the Drug Interactions of Dacomitinib?
Effect of Other Drugs on Dacomitinib
The concentration of Dacomitinib is reduced when proton pump inhibitors are used concurrently. Hence, a proton pump inhibitor is not indicated in combination with this drug. Instead of proton pump inhibitors, H2 receptor antagonists, or locally acting antacids can be used. Dacomitinib should be administered at least 6 hours before or 10 hours after when used with an H2 receptor antagonist.
Effect of Dacomitinib on CYP2D6 Substrates:
The concentration of Dacomitinib can be increased when Dacomitinib is taken along with CYP2D6 substrates. This can increase the risk of toxicity of Dacomitinib. As the minimal increase in Dacomitinib concentration of CYP2D6 substrate can lead to life-threatening or serious toxicity, it is avoided to be used together for treatment.
Other Specifications
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Pregnancy:
Studies have reported that Dacomitinib can cause harm to the fetus when administered to pregnant women based on the mechanism of action. In animals, studies show that administration of Dacomitinib during pregnancy resulted in post-implantation loss and reduced weight of the fetal body, including post-natal death. Potential risk to the fetus is explained to the pregnant woman, and further advice is given. Two to four percent of the general population has a risk of major birth defects and miscarriages.
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Lactation:
The presence of metabolites or substrates of Dacomitinib in human milk or the effects of Dacomitinib on the infant feeding upon the breast milk of the mother under treatment with this drug has not been reported. It is advised not to breastfeed for at least 17 days after the last dose.
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Females and Male Reproductive Potential:
The female's reproductive potential is verified before starting treatment. The fetus can be harmed due to the administration of this drug, and hence contraception is advised for females of reproductive potential during treatment with this drug.
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Pediatric Use:
The effectiveness and safety of Dacomitinib have not been established in pediatric patients.
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Geriatric Use:
A higher rate of at least 67 percent of individuals above the age of 65 years suffer from adverse reactions, and nearly 10 percent of them experience effects occurring due to drug discontinuation.
Conclusion
Adults with metastatic non-small cell lung cancer who have certain EGFR gene alterations are treated with Dacomitinib, an oral drug. Although this medication is quite effective at slowing down the cancer, a doctor may need to reduce the dosage due to severe side effects such as skin rashes or diarrhea.
This medication is a potent option for those who have the correct genetic match since it blocks the growth of cancer more successfully than previous medications, helping many patients live longer. So it is necessary to consult a cancer specialist before starting this medication.
