Overview
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 in the first line of treatment if the tumor has abnormal epidermal growth factor receptor genes. Care has to be taken to limit exposure to sunlight when the individual is under treatment with the drug Dacomitinib, as it can cause serious skin problems. Dacomitinib was approved globally to be used as first line treatment for non-small cell lung cancer by US Food and Drug Administration (FDA).
Available Doses and Dosage Forms:
The drug Dacomitinib is supplied in a package of 30 count in a bottle.
Packaging is done depending on the dosage.
15 mg (milligrams) Dosage: 30 tablets in a bottle - Blue film-coated, round biconvex tablets.
30 mg Dosage: 30 tablets in a bottle - Blue film-coated, round, biconvex tablets.
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. Forty milligrams 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 according to the severity.
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Embryo-Fetal Toxicity: Fetal harm can be caused due to 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 cell formation in lung tissues occurs. Non-small cell lung cancer is of several types. It is majorly caused due to smoking. The condition is presented by a continuous cough that does not subside, 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 affected due to certain factors which determine the treatment options.
Learn More About Dacomitinib
Before Starting
When and Why to Take Dacomitinib?
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Dacomitinib is taken one time every day.
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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 six hours prior or ten 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 the Treatment With the Drug Dacomitinib?
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It is better to minimize sunlight exposure. Exposure to the sun can cause various skin reactions. The use of moisturizers can be done to eradicate this.
Things to Inform the Doctor Before Taking Dacomitinib
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Presence of frequent diarrhea, and a history of lung or breathing problems, pregnancy planning should be informed the physician.
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It is important for a female who is the potential to become pregnant to use effective contraception during treatment for 17 days after the last dose of the drug 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 known to the physician.
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Health care providers must be told of all the medicines along with herbal or vitamin supplements as there are chances of causing side effects.
What Are the Side Effects of Dacomitinib?
They may be serious side effects on using this drug, such as
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Breathing Problems: There can be high-grade inflammation in the lungs which can even lead to death. It can show similar symptoms as that of lung cancer. Any symptoms, mild or severe, relating to respiratory conditions, including cough, fever, and shortness of breath, should be informed to the healthcare provider immediately.
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Diarrhea: It is a common side effect occurring during the treatment with Dacomitinib which can turn out severe. Dehydration and abdominal pain can occur. It is advised to drink more fluids or start treatment with anti-diarrheal medication.
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Skin Reactions: Skin reactions are common and can be severe. Redness of skin, rash, dry skin, itching, acne, and blistering of the skin can occur. Moisturizers should be used every day when under treatment with the drug Dacomitinib. Protective clothing should be worn to cover the skin and limit exposure to sunlight.
What Should Be Done if a Dose Is Missed?
Upon missing a dose, do not take the missed dose, as it can lead to the addition of an extra dose and toxicity.
How to Store the Drug Dacomitinib?
The drug Dacomitinib can be stored at 20 degrees centigrade to 25 degrees centigrade. It is kept out of the reach of children like all other medicines.
Avoid Self-Medication:
The medication can be used for other purposes also. Do not use the drug Dacomitinib for a condition that is not prescribed. It is not right to advise other individuals to take the drug 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 food 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 confers with grade 2 diarrhea, the drug Dacomitinib is withheld until complete recovery or until it recovers to grade 1 and after which the normal dose is resumed.
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In case of adverse reactions of the skin, Dacomitinib is discontinued until the symptoms subside, and then the dose is reduced and 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, is demonstrated by the drug Dacomitinib. It also works by exhibiting anti-tumor activity in animals bearing intracranial human tumor xenografts.
Pharmacodynamics:
Cardiac Electrophysiology: The effect of the drug Dacomitinib on the QT interval is evaluated, and Dacomitinib shows no huge effect on the QT interval at the highest concentration of the drug Dacomitinib 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 two milligrams to 60 milligrams when administered orally once a day.
Absorption:
The bioavailability is 80 percent after oral administration. The time to reach maximum concentration is approximately six hours after a single dose of 45 milligrams. There has been no effect on the pharmacokinetics of the drug Dacomitinib when administered with a high-calorie meal.
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.
Excretion:
20 percent of Dacomitinib was eliminated in the feces and three percent in the urine followed by a single 45-milligram oral dose of the drug Dacomitinib.
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 the drug 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 the drug 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 the drug Dacomitinib in male rats.
Clinical Studies:
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Effect of Acid-Reducing Agents on Dacomitinib: Co-administration of multiple doses of proton pump inhibitor with a single dose of the drug Dacomitinib decreased the Cmax by 51 percent. No major changes were observed when the drug Dacomitinib was administered with a local antacid.
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Effect of Strong CYP2D6 Inhibitors: The total AUC of the drug Dacomitinib was increased by six percent when the drug Dacomitinib is 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 worsened respiratory symptoms, like cough, dyspnea, and fever, interstitial lung disease is investigated. Once a confirmatory diagnosis is obtained, the drug Dacomitinib should be stopped.
Diarrhea:
86 percent of the affected population showed the presence of diarrhea. Among those cases, 0.3 percent were fatal cases. Dacomitinib is discontinued until the severity of diarrhea is decreased, and then the treatment is resumed with a reduced dosage. Antidiarrheal treatment is initiated which includes 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 percentage of them were severe. Dacomitinib is withheld until the symptoms reduce and then Dacomitinib is continued with a reduced dose depending on the clinical condition and severity of the adverse reaction. With exposure to the sun, the severity of the rashes can increase. Moisturizers and measures to prevent or limit exposure to the sun are initiated along with the initiation of treatment with Dacomitinib. When a severe condition of rash appears, the treatment and management is initiated with topical steroids and topical antibiotics. Oral antibiotics are indicated in cases of 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 with the simultaneous use of proton pump inhibitors. Hence use of a proton pump inhibitor is not indicated along with this drug. Instead of proton pump inhibitors, H2 receptor antagonists or locally acting antacids can be used. Dacomitinib should be administered at least six hours before or after ten hours when used along 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:
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 major birth defects risk and miscarriages.
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.
Females and Male Reproductive Potential:
The reproductive potential of the female is verified before starting the treatment.
The fetus can be harmed due to the administration of this drug, and hence contraception is advised for females of reproductive potential during the treatment with this drug.
Pediatric Use:
The effectiveness and safety of Dacomitinib have not been established in pediatric patients.
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 with effects occurring due to drug discontinuations.
