Medicine > All about Pegdoxine (Doxorubicin Hydrochloride Pegylated) injection

All about Pegdoxine (Doxorubicin Hydrochloride Pegylated) injection

Name of medicine:- Pegdoxine

Composition:- Doxorubicin Hydrochloride Pegylated

Indication:- Ovarian Cancer, Kaposi’s Sarcoma, and Multiple Myeloma

Description:- Pegdoxine Injection (20 mg/10 ml) is a cancer-fighting drug that belongs to the group of medicines known as Antineoplastic Agents. It is responsible for slowing or stopping the growth of cancerous cells in the body. 

What is Pegdoxine?

Pegdoxine injection is an anticancer drug used to treat various types of cancers including Ovarian Cancer, AIDs related to Kaposi’s Sarcoma, Breast Cancer, and Blood Cancer. It comprises Doxorubicin Hydrochloride Pegylated. It belongs to the class of medicines referred to as Antineoplastic drugs, which are also known as cancer-fighting agents. 

Clinical Relevance

The clinical relevance of the drug tells about its importance and indications. Before administering the injection, it is necessary to know its relevance, safety, and efficacy. Pegdoxine injection is often prescribed for the treatment of the following diseases. 

  • Ovarian Cancer:- Pegdoxine injection is used in the treatment of cancer that begins in the ovaries (the female organs that produce eggs). It is an effective anticancer regimen given as an injection. 

  • Kaposi Sarcoma:- Pegdoxine can be used to treat Kaposi Sarcoma, a type of cancer in which small blood vessels grow below the surface of the skin and inside the mouth. 

  • Blood Cancer:- This injection is also used in the treatment of certain types of Leukemia, Lymphoma, and Myeloma including acute myeloblastic leukemia, acute lymphoblastic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma (NHL), and multiple myeloma. 

  • Breast Cancer:- Pegdoxine injection is a useful regimen for the treatment of Metastatic Breast Cancer. It is administered as an injection.

Clinical Pharmacology

Pharmacodynamics 

Doxorubicin Hydrochloride (Pegdoxine) is an antineoplastic agent in the anthracycline class of drugs. General specifications of medicines in this group include interaction with DNA in different ways such as intercalation (squeezing between the base pairs), DNA strand breakage, and inhibition with the enzyme topoisomerase II. Most of such formulations have been isolated from natural sources and antibiotics. However, they somehow lack the specificity of antimicrobial antibiotics. This is why they produce significant toxicity. The anthracycline agents are among the vital antitumor medicines available. Doxorubicin is broadly used to treat certain solid tumors whereas Daunorubicin and Idarubicin are used to treat a type of Blood Cancer namely leukemia. Doxorubicin may also tend to inhibit polymerase activity. It may affect the regulation of gene expression, and work by producing free radical damage to DNA. the compound also possesses an antitumor effect against a broad spectrum of tumors (grafted or spontaneous). The anthracycline drugs are cell cycle-nonspecific.

Mechanism of Action 

Pegdoxine, comprising Doxorubicin Hydrochloride, has antimitotic and cytotoxic activity through multiple proposed mechanisms of action: the drug forms complexes with DNA through intercalation between base pairs, and it tends to inhibit topoisomerase II activity through stabilizing the DNA-topoisomerase II complex while preventing the religation portion of the ligation-religation reaction that is catalyzed by topoisomerase II.

Pharmacokinetics 

The medication is metabolized in the liver. It is distributed primarily to vascular fluid in intravascular space. Significant levels of doxorubicinol (principal metabolite) do not occur, most probably due to the slow distribution of free doxorubicin to the liver. Halflife is about 55 hours. The compound is excreted primarily in bile. 

Protein Binding 

Doxorubicin along with Doxorubicinol is approximately 74-76% bound to plasma protein. The extent of binding does not depend on plasma concentration. Also, the drug does not cross the blood-brain barrier.

Metabolism 

Doxorubicin is competent to undergo three metabolic routes. However, about half of the dose is excreted from the body unchanged. Two electron reduction yields secondary alcohol, doxorubicinol. This pathway is thought to be the primary metabolic pathway. The one-electron reduction is eased by various oxidoreductases in order to form a doxorubicin-semiquinone radical. Such enzymes include mitochondrial and cystolic NADPH dehydrogenates xanthine oxidase and nitric oxide synthases. Deglycosidation is a minor metabolic pathway that is undergone by only 1-2% of the dose. Enzymes that might be involved with such a pathway include NADPH-cytochrome P450 reductase, xanthine oxidase, and cytosolic NADPH dehydrogenase.

Clinical Trials

The clinical relevance and safety of Doxorubicin HCl-containing regimens for the post-operative, adjuvant treatment of Breast Cancer was calculated in a meta-analysis initiated by a Group namely “Early Breast Cancer Trialists Collaborative Group” (EBCTCG). Data from the meta-analysis of trials comparing CMF to no therapy were used to illustrate the historical treatment effect size for CMF regimens. The major safety outcome factors were disease-free survival and overall survival. Out of 3510 women (2157 received doxorubicin HCl-containing regimens and 1353 received CMF treatment) with early breast cancer involving axillary lymph nodes involved in the six trials from the meta-analyses, on average 70% were premenopausal and 30% were postmenopausal. At the moment when the meta-analysis was done, 1745 first recurrences and 1348 deaths had occurred. The analyses showed that the compound retained approximately 75% of the historical CMF adjuvant effect on DFS with a hazard ratio (HR) of 0.91 and on OS with an HR of 0.91.

Drug Category

  • Anthracyclines:- These are the drugs extracted from Streptomyces bacterium. Anthracycline drugs are used in cancer chemotherapy. They work to damage the cell’s genes by interfering with their reproduction. Such medicines are used to treat a number of cancers including cancer in the Breast, Ovaries, and Blood. 

  • Immunosuppressive Agents:- These medications are used in cancer treatment, specifically to prevent organ rejection in transplant patients. Immunosuppressive drugs work to suppress rejection by dampening the autoimmune process. 

  • Topoisomerase Inhibitors:- These are the chemical compounds used to treat various types of cancers. Topoisomerase Inhibitors work by blocking the action of topoisomerases. 

  • Antineoplastic Agents:- Alkylating antineoplastic agents are drugs that are used in the treatment of various types of cancers. These medications are also referred to as chemo or hazardous drugs. They target and kill the cancerous cells over a period of time.

Interactions

Drug-Drug Interactions 

  • Carbamazepine and Phenytoin:- Taking either of these drugs with Pegdoxine may decrease the levels of these drugs in the body. 

  • Cyclosporine:- Administering Cyclosporine with Pegdoxine injection may increase potential AUC for Pegdoxine. This may result in coma and seizures. 

  • Paclitaxel:- Taking Paclitaxel while co-administering Pegdoxine injection may decrease Doxorubicin clearance that might lead to stomatitis. 

  • Phenobarbital:- A sudden increase in Doxorubicin elimination may occur due to the administration of Phenobarbital with Pegdoxine injection. 

  • Progesterone:- There can be a notable increase in doxorubicin-induced thrombocytopenia and neutropenia if Progesterone is administered with Pegdoxine injection.

  • Streptozocin:- Streptozocin when administered with Pegdoxine injection can lead to inhibition of hepatic metabolism of Doxorubicin. 

  • Trastuzumab:- If Trastuzumab is administered with Pegdoxine injection, an increase in cardiotoxicity risk may occur. 

  • Verapamil:-  A notable increase in initial peak Doxorubicin concentration in the heart with the severity of degenerative cardiac tissue changes may occur if Verapamil is administered with Pegdoxine injection. 

Drug-Food Interactions 

  • Grapefruit and pomegranate juice:- These food items inhibit the CYP3A4 metabolism of Doxorubicin. This further can lead to an increase in drug levels. Therefore, to avoid adverse reactions, avoid the consumption of grapefruit and pomegranate juice during the course oF Pegdoxine injection. 

Drug-Herb Interactions

  • Coenzyme Q10 and Glucosamine:- These chemical compounds, when consumed with Pegdoxine injection, may lead to a decrease in chemotherapeutic drug’s efficacy. Therefore, it is important to avoid the consumption of Coenzyme Q10 and Glucosamine during the course of Pegdoxine injection. 

Dosage and Administration

Recommended Dose:- Pegdoxine (Doxorubicin Hydrochloride Pegylated Liposomal) injection should be administered intravenously. Its recommended dose may vary from person to person and disease to disease. The frequency of administration includes a 21-day treatment cycle either in combination with some other drug like Cyclophosphamide or as a monotherapy. 

Dose Modification:- In case of Hepatic impairment or/and Cardiac impairment, dose adjustments may be needed as per the medical condition of the patient. If a patient experiences symptoms of cardiomyopathy, Pegdoxine injection should be discontinued. 

Overdosage:- If symptoms of overdose such as mucositis, leucopenia, or/and thrombocytopenia occur, it is important to call the nearest emergency medical center or your healthcare provider. Know about the symptoms beforehand from your doctor and do not avoid any of them. Seek immediate support from a qualified healthcare professional. 

Adverse Reactions

After the administration of Pegdoxine injection, an individual might face certain adverse effects. These are due to the body’s response to the drug. In most cases, side effects go on their own after a certain period of time. However, if side effects last longer than a certain period of time, it becomes important to consult a healthcare professional in order to discuss the ways to manage them.

Injection site reactions are very common after the administration of an injection. This includes reactions such as dry skin, skin rash, skin discoloration, alopecia (loss of hair), skin disorder, erythematous streaking along vein proximal to the injection site, and

severe cellulitis (bacterial skin infection).

Some patients may experience severe effects on the central nervous system including headache, anxiety, asthenia, paresthesia, malaise, dizziness, somnolence, and emotional lability. These reactions may be accompanied by fever and chills. 

Several ENT (Eyes, Nose, and Throat) side effects may be faced by individuals including rhinitis (runny or stuffy nose and sneezing), pharyngitis (sore throat), conjunctivitis (inflammation of the outer membrane of the eyeball), and retinitis (inflammation of the retina).  

Certain cardiovascular reactions may occur after administering the injection. Some of the possible effects are chest pain, cardiotoxicity, peripheral edema, hypotension, and tachycardia. These effects are more common in patients who are already suffering from heart disease. 

Patients may experience certain gastrointestinal disorders such as nausea, vomiting, diarrhea, constipation, stomatitis (inflammation of the mucous membrane), dyspepsia (indigestion), oral candidiasis (mouth thrush), mouth ulceration, glossitis (inflammation of the tongue), stomach ache, esophagitis (inflammation of the esophagus), dysphagia (difficulty in swallowing), taste perversion, and enlarged abdomen. 

A genitourinary disorder like albuminuria which is a sign of kidney disease may occur in some patients after the administration of the Pegdoxine injection. This includes reactions like shortness of breath, more frequent urination, loss of appetite, muscle cramping at night, and swelling in the face or legs. 

A number of hematologic reactions may be experienced by a patient including bone marrow depression, increased prothrombin time, and hemolysis (rupture of red blood cells). Respiratory diseases such as dyspnea (shortness of breath), increased cough, and pneumonia may occur for a few or more days. 

Hepatic and metabolic disturbances like hyperbilirubinemia (discoloration of eyes and skin), hypocalcemia (low level of calcium in the blood), dehydration, and hyperglycemia (high levels of blood sugar) might be experienced by the patient. 

Packaging and Storage 

Pegdoxine injection is packed in a 10 ml single-use vial in the strength of 2mg/ml. Handle the vial with utmost care as it is a cytotoxic agent. Store Pegdoxine injection between 2°to 8°C. Do not freeze it. Keep it away from the reach of pets and children. Protect the injection from direct heat, light, and moisture. Do not use an expired solution. Check the labels for the same carefully. Also, make sure to know the ways to dispose of the used vials or expired solutions from your pharmacist. 

Warnings and Precautions

During the Administration

  • Pegdoxine injection should be administered at an initial rate of 1 mg/minute to avoid infusion reactions. 

  • Dose modification should be considered in the case of patients who are suffering from heart disease, hepatic impairment, or any other related disorder.

  • This injection is administered intravenously by a nurse or qualified healthcare professional. Do not self-administer. 

Special Population

  • Pregnant women:- During pregnancy, Pegdoxine injection may cause fetal harm to the fetus. Its administration during pregnancy should be avoided. 

  • Nursing women:- During breastfeeding, Pegdoxine injection may cause fetal harm to the newborn baby. Its administration during pregnancy should be avoided.

  • Hypersensitive patients:- In hypersensitive patients or in patients who have an allergy to Doxorubicin, the administration of Pegdoxine injection should be avoided. If severe allergies are observed after the administration of the injection, Pegdoxine’s administration should be discontinued. 

  • Cardiac impairment:- In the case of Cardiac impairment, dose adjustments may be needed as per the medical condition of the patient.

  • Hepatic impairment:- In the case of Hepatic impairment, dose alteration may be needed as per the medical condition of the patient.