Description

Daconib 45 tablet: Each film coated tablet contains Dacomitinib Monohydrate INN equivalent to Dacomitinib 45 mg.

 

Product Features

Product Name	:	Daconib
Generic Name	:	Dacomitinib
Formulation	:	Tablet
Available Pack Size	:	30’s Pot
Available Strength	:	45 mg
Registrations	:	Export Only

 

Dacomitinib Mechanism of Action

Dacomitinib works by inhibiting the activity of certain proteins known as kinases within the human EGFR (Epidermal Growth Factor Receptor) family. These kinases include EGFR/HER1, HER2, and HER4. Additionally, it targets specific mutations found in EGFR, such as exon 19 deletion or exon 21 L858R substitution.

In laboratory studies, Daconib has shown to also inhibit the activity of other proteins like DDR1, EPHA6, LCK, DDR2, and MNK1 at concentrations relevant to its clinical use.

By blocking these kinases and mutations, Daconib effectively interferes with the signaling pathways involved in cell growth and proliferation, particularly those related to cancer development. This interference leads to a slowdown or halt in the growth of tumor cells, both in laboratory settings and in animal models with human tumor xenografts. Therefore, Daconib demonstrates its effectiveness by hindering the growth and progression of cancer cells driven by the EGFR family and related pathways.

 

Drug Interactions

Dacomitinib and Proton Pump Inhibitors (PPIs): Concomitant use of Dacomitinib with PPIs can decrease concentrations, potentially reducing its effectiveness. It is advised to avoid using PPIs with Dacomitinib.

Dacomitinib and CYP2D6 Substrates: When taken together, Dacomitinib can increase the concentration of drugs that are substrates of CYP2D6. This elevation in concentration may raise the risk of toxicities associated with those drugs. Therefore, it’s recommended to avoid concomitant use of Dacomitinib with CYP2D6 substrates, particularly when even slight increases in their concentration could lead to severe or life-threatening reactions.

 

Use in Specific Populations

Pregnancy: Dacomitinib may cause harm to the fetus when administered to pregnant women. However, there are no available data on its use during pregnancy.

Lactation: There is no information on whether Dacomitinib or its metabolites are present in human milk or their effects on breastfed infants or milk production. Due to potential serious adverse reactions in breastfed infants, women should avoid breastfeeding during treatment and for at least 17 days after the last dose.

Contraception: Women of reproductive potential should use effective contraception during treatment and for at least 17 days after the final dose to prevent potential fetal harm.

Pediatric Use: The safety and effectiveness of Dacomitinib have not been established in pediatric populations.

Geriatric Use: In clinical studies, patients aged 65 and older showed a higher incidence of Grade 3 and 4 adverse reactions, more frequent dose interruptions, and more frequent discontinuations due to adverse reactions compared to younger patients.

Renal Impairment: No dose adjustment is needed for patients with mild or moderate renal impairment. However, the recommended dose has not been established for patients with severe renal impairment.

Hepatic Impairment: No dose adjustment is necessary for patients with mild or moderate hepatic impairment. The recommended dose has not been determined for patients with severe hepatic impairment.

 

Warnings and Precautions

Interstitial Lung Disease (ILD): Severe and fatal ILD/pneumonitis have occurred in patients taking this medication, affecting 0.5% of patients treated with it. 0.3% of these cases resulted in death. Patients should be monitored for symptoms like difficulty breathing, coughing, and fever which may indicate ILD. Treatment should be stopped immediately if ILD is confirmed.

Diarrhea: Severe and fatal diarrhea have been reported in patients using this medication. Diarrhea affected 86% of patients, with 11% experiencing Grade 3 or 4 diarrhea. Treatment should be withheld for Grade 2 or higher diarrhea until it improves, and then resumed at the same or lower dose. Anti-diarrheal treatment should be initiated promptly.

Dermatologic Adverse Reactions: Rash and exfoliative skin reactions are common in patients taking this medication, with 78% experiencing rash and 7% experiencing exfoliative skin reactions. 21% of patients experienced Grade 3 or 4 rash. Treatment should be withheld for persistent Grade 2 or higher dermatologic reactions until improvement. Then resumed at the same or lower dose. Measures should be taken to limit sun exposure and moisturizers should be used. Treatment with topical antibiotics and steroids may be necessary.

Embryo-Fetal Toxicity: Based on animal studies, this medication can harm unborn babies when taken by pregnant women. It has been associated with an increased risk of post-implantation loss and reduced fetal body weight in animal studies. Women of reproductive potential should use effective contraception during treatment and for at least 17 days after the final dose.

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