Ibrutinib (Imbruvica) Enhances Survival for Younger Individuals with Diffuse Large B-cell Lymphoma

 

Addition of ibrutinib (Imbruvica) to a standard chemotherapy regimen can enhance survival for some younger individuals with a specific form of diffuse large B-cell lymphoma (DLBCL), as per the reanalysis of data.

The findings, published in the Journal Cancer Cell, come from a new analysis by researchers at the USA’s National Cancer Institute (NCI) of a previously conducted phase-3 clinical trial.

 

Diffuse large B-cell lymphoma is the most common type of lymphoma, accounting for 40 percent of lymphoma cases at the global level. The individuals with the diffuse large B-cell lymphoma are typically treated with R-CHOP, which includes vincristine, cyclophosphamide, doxorubicin, prednisone, and the monoclonal antibody rituximab. But R-CHOP therapy is not useful for everyone with diffuse large B-cell lymphoma.

 

Ibrutinib (Imbruvica) was the first targeted therapy to be assessed for the treatment of diffuse large B-cell lymphoma. It inhibits the function of Bruton tyrosine kinase, a protein that is involved in the growth and survival of B cells. Cancerous cells of the ‘active B cell-like’ (ABC) subtype of diffuse large B-cell lymphoma require this protein in order to survive.

 

A trial named PHOENIX was launched in the year of 2013 to assess the effectiveness of adding ibrutinib to R-CHOP therapy for newly diagnosed patients which do not have the ‘germinal centre B cell–like’ (GCB) type of diffuse large B-cell lymphoma.

 

Outcomes published in 2019 demonstrated that overall, combination of ibrutinib and standard chemotherapy regimen did not help patients with non-germinal centre B cell–like diffuse large B-cell lymphoma in order to live longer.

 

Although, patients aged under 60 years did have improved event-free survival and overall survival, but as this was a secondary endpoint of the trial its significance has remained controversial.

 

Therefore, in this latest study, researchers of the National Cancer Institute as well as their collaborators evaluated the tumour biopsy samples from patients on the trial.

 

They have now concluded that patients aged under 60 years with MCD and N1, specific genetic subtypes of non-germinal centre B cell–like diffuse large B-cell lymphoma, had an exceptional response to the combined therapy or treatment.

All of those patients are alive without disease 3 years following diagnosis.

According to Study co-author Dr Wyndham H. Wilson, senior investigator in the Lymphoid Malignancies Branch, “This new analysis offers a compelling rationale for health specialists to consider addition of ibrutinib (Imbruvica) along with the standard chemotherapy for the initial therapy of younger individuals with non-germinal centre B cell–like diffuse large B-cell lymphoma.”

 

Following the completion of genetic analyses on tumour samples from 773 of the 838 participants and determining their subtypes, researchers found that most of the benefit from ibrutinib (Imbruvica) was in patients with ABC diffuse large B-cell lymphoma.

 

Out of the 4 genetic subtypes of ABC diffuse large B-cell lymphoma, it was found that those patients aged 60 and under with the MCD subtype had 3-year event free and OS rates of 100 percent with ibrutinib (Imbruvica) and R-CHOP. This is compared to 3-year event free survival of 48 percent and 3-year OS of 69.6 percent with R-CHOP alone.

 

Younger individuals with the N1 subtype also had 3-year event-free and OS (overall survival) rates of 100 percent with ibrutinib (Imbruvica) and R-CHOP, in comparison to 3-year event-free and OS of 50 percent with R-CHOP alone.

Individuals with the genetic subtype named BN2 did not benefit from the addition of the ibrutinib (Imbruvica), but this subtype already has an 82 percent OS rate with R-CHOP alone.

Ibrutinib (Imbruvica) was also effective for some other younger individuals with the non-germinal centre B cell–like diffuse large B-cell lymphoma, although the researchers were not able to specify benefits for the A53 subtype.

According to Dr Louis M. Staudt, chief of the Lymphoid Malignancies Branch in the Center for Cancer Research at NCI, “For years we have only had chemotherapy and rituximab to offer these individuals (patients). Now, we expect that the addition of ibrutinib (Imbruvica) to current therapy may provide younger patients a better chance of surviving this aggressive cancer.”

Dosage and Administration of Artesunate

 

Indications & Usage: Artesunate for Injection (Injectable artesunate) is introduced as a first line treatment and recommended by WHO for the initial treatment of severe malaria in adult as well as pediatric patients.

In order to treat severe malaria with injectable artesunate should always be followed by a full or complete treatment course of an apt oral antimalarial regimen.

Limitations of Use: The artesunate an anti-malaria medication does not treat the hypnozoite liver stage forms of Plasmodium and will therefore not prevent the relapses of malaria because of the Plasmodium vivax or Plasmodium ovale. Concomitant therapy with an antimalarial agent such as an 8-aminoquinoline drug is required for treating the severe malaria due to P. vivax or P. ovale.

 

Dosage Forms and Strengths: The injectable artesunate is available as the strength of 110 mg for Injection. It comes as a sterile white or almost white, fine crystalline powder in a clear glass single-dose vial for constitution.

 

Dosage and Administration: The recommended dosage and administration of Artesunate for Injection in adult and pediatric patients is 2.4 mg/kg administered, should be intravenously at 0 hours, 12 hours, and 24 hours, and thereafter, administered once daily until the patient is able to tolerate the oral antimalarial therapy. Administer constituted artesunate injection intravenously as a slow bolus over one minute to two minutes. Do not administer artesunate injection via continuous intravenous infusion. The artesunate injection should be administered with an antimalarial agent that is active against the hypnozoite liver stage forms of Plasmodium, such as an 8-aminoquinoline drug, to patients with the severe malaria due to P. vivax or P. ovale.

 

Preparation of Artesunate for Injection for Intravenous Administration: The Artesunate Injection needs to be constituted with the supplied diluent before administration. A diluent consisting of 12 mL of sterile 0.3 M pH 8.0 sodium phosphate buffer is provided with Artesunate for Injection.

To constitute artesunate injection, withdraw 11mL of this diluent through a needle and syringe and inject into the artesunate vial (when constituted the final concentration of artesunate is 10 mg/mL). Swirl gently (avoid shaking) for up to five to six minutes until the powder is completely dissolved and no visible particles remain.

The parenteral drug products need to be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit. It is not advised to administer the Artesunate for Injection in case particulate matter and/or discoloration is observed.

Following constitution, inject the constituted solution intravenously (through an established intravenous line or needle) as a slow bolus over one to two minutes. It is advised to discard the vial and also any unused portion of the medicine product following use.

 

Storage of the Constituted Solution: The constituted solution of Artesunate Injection should be administered within 1.5 hours of constitution with the supplied diluent.

Tocilizumab Side Effects and Precautions

 

Tocilizumab is a prescription medicine named an interleukin-6 (IL-6) receptor antagonist. The

medical uses of tocilizumab are listed as follows:

●       Tocilizumab is used to treat adults with moderately to severely active rheumatoid arthritis (RA) after at least one other medicine called a disease modifying antirheumatic drug (DMARD) has been used and did not work well.

●       Tocilizumab is used to treat adult patients with giant cell arteritis (GCA).

●       Tocilizumab is used to treat patients with active polyarticular juvenile idiopathic arthritis (PJIA) aged 2 years and older.

●       Tocilizumab is used to treat patients with active systemic juvenile idiopathic arthritis (SJIA) aged 2 years and older.

●       Tocilizumab is used for slowing the rate of decline in lung function in adults with systemic sclerosis-associated interstitial lung disease (SSc-ILD) (also named scleroderma-associated ILD).

It is not specified if the drug Tocilizumab is safe and effective in children with PJIA or SJIA aged under two years or in children with conditions other than PJIA or SJIA.

 

Possible Side Effects: The most important side effects of Tocilizumab Injection are:

Serious infections: Tocilizumab is a medication that affects your or your child’s defense system. Tocilizumab can fade the ability of your or your child’s defense system in order to fight infections other than COVID-19. This drug can make you or your child more likely to get infections or worsen any infection that you or your child have, other than COVID-19.

 

Tears (perforation) of the intestines or stomach: Some individuals with Tocilizumab get tears in their intestine or stomach. This occurs most often in those individuals who also administer the NSAIDs (nonsteroidal anti-inflammatory drugs), methotrexate, or corticosteroids.

 

Liver problems (hepatotoxicity): Certain individuals taking treatment with Tocilizumab have experienced severe life-threatening liver problems, which needed a liver transplant or led to death.

 

Changes in certain laboratory test results: Your or your child’s health specialist should  do blood tests before you or your child start receiving Tocilizumab. You or your child should not receive this medicine in case your or your child’s white blood cells or platelet (blood cells that help with blood clotting and halt bleeding) counts are reduced or your or your child’s liver function tests are extremely high.

 

Allergic reactions: Inform your or your child’s health specialist right away in case you or your child have signs and symptoms such as rash, swelling of your lips, tongue, or hives (raised red patches of skin which are often very itchy), or throat. This may indicate that you or your child are having an allergic reaction.

 

Nervous system problems: While rare, Multiple Sclerosis has been diagnosed in those who take Tocilizumab. It is not specified what effect Tocilizumab may have on some nervous system disorders.

 

The most commonly noted side effects of Tocilizumab injection include:

●       headache

●       increased blood pressure (hypertension)

●       injection site reactions

●       upper respiratory tract infections (common cold, sinus infections)

 

Tocilizumab & Pregnancy: Inform your health specialist in case you are planning to become pregnant, are pregnant, plan to breast-feed, or are breast-feeding. You and your health specialist should decide if you will take therapy with Tocilizumab or breast-feed. You should not do both.

Warnings and Precautions of Sorafenib

 

Sorafenib is introduced to treat liver cancer (hepatocellular carcinoma), kidney cancer (advanced renal cell carcinoma), and thyroid cancer (differentiated thyroid carcinoma). The sorafenib a multikinase inhibitor may also be known as a so-called multikinase inhibitor. It acts by slowing down the rate of growth of cancer cells and cutting off the blood supply that keeps cancerous cells growing.

Sorafenib comes in the form of tablets you can take at home. Take sorafenib twice daily. Take the sorafenib tablets with a glass of water at a persistent time each day. The sorafenib tablets should be taken without food or with a low-fat meal. In case you are going to have a high-fat meal, take sorafenib tablets at least one hour prior to or two hours after your meal.

 

WARNINGS AND PRECAUTIONS:

Pregnancy and Lactation: Females should not become pregnant while on sorafenib therapy. Females of childbearing age must be apprised of the potential hazard to the fetus, which includes teratogenicity, and embryotoxicity. Sorafenib therapy should not be used during pregnancy. Also, breastfeeding should be discontinued during Sorafenib therapy.

 

Dermatological Toxicities: Hand-foot skin reaction (palmar-plantar erythrodysaesthesia) and rash represent the most common adverse medicine reactions with Sorafenib. The rash and hand-foot skin reactions (Grade 1 & 2) generally appear during the initial six weeks of therapy with Sorafenib. As noted in one clinical study, the incidence of hand-foot skin reaction may be greater in the Asian group. The management of dermatologic toxicities may include topical therapies for symptomatic relief, temporary treatment interruption or dose modification of Sorafenib, or in severe or persistent cases, permanent discontinuation of Sorafenib.

 

Hypertension: An increased incidence of hypertension was observed in patients treated with Sorafenib. Hypertension was noted mild to moderate at the beginning of the therapy and was amenable in order to manage with the standard antihypertensive therapy. Blood pressure should be monitored regularly and treated, in case needed, in accordance with standard medical practice. In cases of severe or persistent hypertension, or hypertensive crisis despite apt antihypertensive therapy, permanent interruption of sorafenib therapy should be considered.

 

Aneurysms and artery dissections: The VEGF pathway inhibitors used in patients either with or without hypertension can promote the development of aneurysms or artery dissections. Prior to starting Sorafenib therapy, this risk should be precisely considered in all those patients who are with hypertension or a history of aneurysm.

 

Haemorrhage: An increase in the risk of bleeding may occur following the use of Sorafenib. The incidence of serious bleeding events is uncommon. If any bleeding event necessitates medical intervention, it is recommended that permanent discontinuation of therapy with Sorafenib should be considered. Because of the risk of bleeding, bronchial, tracheal, and oesophageal infiltration needs to be treated with localised therapy before administration of Sorafenib in patients with DTC-Differentiated Thyroid Carcinoma.

 

Warfarin: The infrequent bleeding events or elevations in the International Normalised Ratio (INR) have been observed in certain patients taking warfarin while on Sorafenib therapy. Patients concomitantly with warfarin should be monitored regularly for changes in prothrombin time, INR, and for clinical bleeding episodes.

 

Wound Healing Complications: No formal studies of the effect of concomitantly on wound healing have been conducted. In all those patients who are undergoing any major surgical procedures, temporary interruption of Sorafenib tablets therapy is required just for precautionary reasons. There is limited clinical experience regarding the timing of reinitiation of therapy after major surgical intervention. Thus, the intent to resume Sorafenib therapy after any major surgical intervention should be based on behalf of the clinical judgment of adequate wound healing.

 

Gastrointestinal Perforation: Gastrointestinal perforation has appeared as an uncommon event and has been reported in less than one percent of patients taking treatment with Sorafenib. In certain cases, this was not linked with an apparent intra-abdominal tumour. The sorafenib therapy should be discontinued if gastrointestinal perforation develops.

 

Hepatic Impairment: Experience in Child-Pugh B hepatic impairment is limited. No data is available on patients with Child-Pugh C (severe) hepatic impairment. Since sorafenib medication is mainly eliminated through the hepatic route, exposure could be increased in patients with severe hepatic impairment.

 

Drug-induced Hepatitis: Drug-induced hepatitis has been noted in post-marketing experience. Sorafenib should be interrupted if drug-induced hepatitis is suspected.

Hypocalcaemia: When using Sorafenib in patients with differentiated thyroid carcinoma, precise monitoring of blood calcium level is required. As per clinical trials, hypocalcaemia was observed more frequently and more severely in patients with DTC, especially with a known history of hypoparathyroidism, in comparison to patients with renal cell or hepatocellular carcinoma.

TSH Suppression in Differentiated Thyroid Carcinoma (DTC): In the Differentiated Thyroid Carcinoma clinical trials, increases in TSH levels above 0.5mU/L were noted in patients treated with Sorafenib. When using Sorafenib in differentiated thyroid carcinoma patients, precise monitoring of TSH levels is needed.

Combination of Enasidenib & Azacitidine Significantly Improves Overall Response Rate in AML

 

A new study published in The Lancet Oncology suggests that the combination of enasidenib (Idhifa) and azacitidine are well tolerated and offer improved overall response rate (ORR) in recipients with newly-diagnosed IDH2-mutant acute myeloid leukemia (AML) compared with azacitidine monotherapy.

Enasidenib is specifically a small molecule, oral inhibitor of isocitrate dehydrogenase 2 (IDH2) inhibitor. The current standard of care in acute myeloid leukemia is induction together with myeloablative intensive chemotherapy.

For all those recipients who are not chemo eligible, either due to age or due to poor performance status, lower-intensity strategies are used. These include low doses of chemo and the consideration of targeted agents with FLT3 or IDH2 mutations.

The phase 1/2 findings compared azacitidine monotherapy to the experimental addition of azacitidine and enasidenib. The primary end points are dose-limiting toxicities, AEs, ORR, and pharmacokinetics. Secondary end points basically include event-free survival, complete remission, hematologic improvement rate, OS, duration of response, one-year survival, and time to response.

Phase-1 b assessed the efficacy, along with tolerability, and also clinical activity of the addition. During phase-2, the addition was compared head to head with azacitidine monotherapy.

In terms of safety, 91 percent of patients in the addition group and 81 percent of patients in the monotherapy group experienced adverse events. The common adverse events included thrombocytopenia, vomiting, neutropenia, anemia, and nausea.

Oxaliplatin: Antineoplastic medicine

Oxaliplatin is the medicine sold under the trade name Eloxatin. Oxaliplatin is an antineoplastic drug, which helps treat patients with stage III colon cancer and advanced colorectal cancer. It helps in the treatment of patients suffering from stage III colon cancer and advanced colorectal cancer. It comes in the form of lyophilized powder for solution in injection.

The active ingredient is Oxaliplatin and Lactose monohydrate is the inactive ingredient present in the medicine. The standard strengths of the medicine are 50 mg and 100 mg. According to the professionals, the general dosage of Oxaliplatin 100 mg is to give in combination with the other drug 5-fluorouracil/leucovorin every two weeks. This medicine has numerous side effects: allergic reaction, fatigue, abdominal pain, skin disorder, reaction at the injection site, nausea, diarrhea, vomiting, stomach-related problems, fever, infection, etc. 

One should only administer Oxaliplatin 100 mg injection according to the prescription of the healthcare professionals. Not every patient experiences these side effects of the medicine; if in case of side effects or an overdose of medication, consult the doctor for worsening of signs and symptoms. 

In India, there are numerous certified suppliers of such rare medicines that offer medicines at a lower price than innovators'. Ikris Pharma Network is one such trusted and certified supplier, and Oxaliplatin price is readily available at a reasonable price here. Ikris supplies medicines and medical aids in India and overseas.  

All about comparator drug

Comparator drugs are also known as reference-listed drugs. These drugs have already been approved and have a license. Also, these drugs are already being used in the market to treat patients. Comparing new generic versions with reference-listed drugs shows the biochemical similarity, having the same active ingredient and effect on patients. In its regulatory submissions, a drug company seeks approval to market a generic equivalent and refers to the Reference Listed Drug. 

There is heavy demand for alternatives to generic medicines in the pharmaceutical industry. Heavy demand for alternative generic medicines results in pressure on pharmaceutical companies to frame robust strategies for selecting a Comparator drug and then sourcing and maintaining an uninterrupted supply of that drug to all trial sites in a cost-effective manner. 

The top 10 pharmaceutical companies together spend more than $20 million every year on comparator sourcing. Innovators or drug producers, wholesalers, and local distributors can carry out direct comparator sourcing. 

Participation of Ikris in pharma industry as comparator drug sourcing

Ikris Pharma Network is an internationally acclaimed pharmaceutical wholesaler and service company. It has specialization in sourcing Comparator drug(s)/ innovator samples from worldwide (countries like India, USA, Europe, Canada, Australia, New Zealand, Korea, Japan, and Latin America). Ikris specifically is a one-stop source for all your requirements of innovator samples (single batch/multiple batches of specific quantities) for clinical trials as well as bioequivalence studies.

We have an internationally established supplying network that helps us procure, store, and provide the products from all the major pharmaceutical manufacturers and authorized distribution channels to and from any locations in the world, specific product sets in a bit huge volumes. We only work with approved sources and validated supply chains.

We have expertise in cold chain shipping and international customs requirements, which helps us ensure that the temperature-sensitive study drugs arrive within the required temperature range at the clinical trial facilities. We use reliable transportation that caters to cold, ambient, and everyday storage and delivery requirements. 

We provide regular updates and advise of product shortages or manufacturer delays allowing you to stay one step ahead and plan your study accordingly. 

We work with the best logistics and courier partners, which enable us to efficiently get your Comparator drug supply to you on or ahead of time.

Our Comparator drug sourcing service included:

• Clinical Trial Services 
• Investigational Medical Products and Comparators
• Rescue medication
• Co-medication
• Analytical samples

Atracurium Besylate- All you need to know about

Atracurium Besylate is also known as Atracurium Besilate. It is used with other medications to provide skeletal muscle relaxation during surgery or mechanical ventilation. Atracurium Besylate is an intermediate duration, non-depolarizing, skeletal muscle relaxant for intravenous administration. It is given via intravenous infusion. The standard strength of Atracurium Besylate is 25 mg. 

Dosage and administration 

Do not administer an Atracurium ampoule before unconsciousness has been induced to avoid distress to the patient. Do not mix Atracurium Besylate in the same syringe, or administer it simultaneously through the same needle, with alkaline solutions, e.g., barbiturate solutions. Administer Atracurium Besylate intravenously. Do not give Atracurium through intramuscular administration because such administration of the medicine may result in tissue irritation. The use of a peripheral nerve stimulator would facilitate Atracurium with other neuromuscular blocking agents, minimizing the possibility of an overdose and assisting in the evaluation of recovery.

The general dosage for adults

A dose of Atracurium infusion of 0.4 to 0.5 mg/kg is the initial recommended dose for most patients. Good conditions for non-emergency intubation can be expected in 2-2.5 minutes in most patients with this dose, with maximum neuromuscular block achieved approximately 3-5 minutes after injecting the medicine. Underbalanced anaesthesia, clinically required neuromuscular block generally lasts 20 to 35.

Atracurium Besylate is intensified by isoflurane or enflurane anaesthesia. The same initial dose of the medicine may use 0.4 to 0.5 mg/kg for intubation before administering these inhalation agents. However, if Atracurium is first administered under the steady-state of isoflurane or enflurane, reduce the initial dose of Atracurium besilate by approximately one third, i.e., to 0.25-0.35 mg/kg. With halothane, which has only a marginal potentiating effect on the medicine, consider the smaller dosage reductions.

Recommended doses of the medicine are 0.08 to 0.10 mg for maintenance of neuromuscular block during prolonged surgeries. Generally, the first maintenance dose required is 20 to 45 minutes after the initial Atracurium infusion, but clinical criteria should determine the need for maintenance doses. 

The general dosage for children

There is no requirement for adjustments of doses of Atracurium Besylate pediatric patients two years of age or older. A dose of 0.3-0.4 mg/kg is recommended as the initial dose for infants under halothane anaesthesia. In infants and children than in adults. Maintenance doses might be required with slightly greater frequency.

Dosage In special cases

An initial dose of the medicine of 0.3 to 0.4 mg/kg is recommended for adults, adolescents, children with significant cardiovascular disease. And adults, adolescents, children with any history (e.g. asthma), suggesting a greater risk of histamine release, give it slowly or in divided doses for 1 minute.

Overdosage

If an overdose happens, the doctor will monitor the patient for symptoms or worsening signs. One can minimize the chances of an overdose by carefully monitoring muscle twitch response to peripheral nerve stimulation. Excessive doses of the medicine can be expected to produce enhanced effects.

Atracurium mechanism of action

The salt Atracurium Besylate is a nondepolarizing skeletal muscle relaxant. Such nondepolarizing agents oppose the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end plate. The antagonism is inhibited, and the neuromuscular block is reversed by acetylcholinesterase inhibitors like neostigmine, pyridostigmine and edrophonium.

Atracurium can be used if muscle twitch response to peripheral nerve stimulation is monitored to assess the degree of relaxation of the muscle. 

The duration of neuromuscular block produced by this medicine is approx one-third to one-half of the block by d-tubocurarine, metocurine, and pancuronium at initially equal doses. As with other nondepolarizing neuromuscular blockers, the onset of paralysis decreases and the duration of maximum effect increases with increasing atracurium doses.   

Precautions

Before Atracurium infusion, ask the patient about any medical history or anaphylactic reactions. Moreover, the healthcare professionals should acknowledge the patient about the after-effects of having Atracurium infusion. 

Although Atracurium is a less potent histamine releaser than d-tubocurarine or metocurine, one must consider the possibility of substantial histamine release in sensitive individuals.

One should take necessary precautions while administering Atracurium to patients in whom substantial histamine release will be especially hazardous, e.g., patients with clinically significant cardiovascular disease. And patients with any history like severe anaphylactoid reactions suggesting a greater risk of histamine release. In such patients, the initial recommended dose is lower (0.3 to 0.4 mg/kg) than other patients. It should be administered slowly or in divided doses over one minute. 

Side effects of Atracurium

The common side effects of Atracurium Besylate are allergic reactions, itching, low blood pressure, skin redness, reactions at the injection site, etc. Medicine's severe side effects are  Severe anaphylactic reactions, paralysis, respiratory arrest, etc.

Price of Atracurium in India

Atracurium price offered by innovators or manufacturers is high as compared to the price offered by suppliers. In India, rare medicines like these are readily available and are cheap. Ikris Pharma Network is one such certified supplier in India delivering medicines and services in India and abroad. 

Treosulfan crystalline powder

Treosulfan is the medication given to people before a bone marrow transplant from a donor known as allogeneic hematopoietic stem cell transplantation. Trecondi is the trade name of Treosulfan. It is given in combination with another drug called fludarabine. It comes in the form of crystalline powder for solution for infusion of 5 gm strength.

Usage of Treosulfan 5 gm

Treosulfan is used before allogeneic hematopoietic stem cell transplantation (alloHSCT). It is used as a 'conditioning' treatment to clear the bone marrow and make space for the transplanted bone marrow cells that can produce healthy blood cells. Healthcare professionals recommend it to adults, children, and old people with severe disorders having allogeneic hematopoietic stem cell transplantation. 

Administration and Dosage of Treosulfan 5 g

1. Patients with malignant disease

Treosulfan is given in combination with fludarabine.

The recommended doses and schedule of administration are:

Treosulfan 10 g body surface area (BSA) per day as a two-hour intravenous infusion, given three consecutive days before stem cell infusion. The total treosulfan dose is 30 g.

Administer Fludarabine 30 mg BSA per day for half an hour for intravenous infusion, given five consecutive days before stem cell infusion. The total fludarabine dose is 150 mg. Administer Treosulfan before fludarabine on three consecutive days. 

2. Patients having non-malignant disease. 

Treosulfan can be given in combination with fludarabine with or without Thiotepa Injection. 

The recommended doses and schedule of administration are:

Treosulfan 14 g body surface area (BSA) per day as a two-hour intravenous infusion, given three consecutive days before stem cell infusion. The total treosulfan dose is 42 g.

Fludarabine 30 mg BSA per day as a half an hour intravenous infusion, given five consecutive days before stem cell infusion. The total fludarabine dose is 150 mg

Treosulfan should be administered before fludarabine.

Thiotepa 5 mg twice a day, given as two intravenous infusions over 2–4 hours on the second day before stem cell infusion. 

3. Elderly population

There is no requirement for the dose adjustment in any subset for elderly patients. 

4. Renal and hepatic impairment 

No dose adjustment is required for mild or moderate impairment, but Treosulfan is contraindicated in patients with severe disorders. 

5. Pediatric population

Treosulfan 5 g injection is given in combination with fludarabine with or without thiotepa.

The recommended doses and schedule of administration are:

Treosulfan 10-14 g body surface area per day as a two-hour intravenous infusion, given three consecutive days before stem cell infusion. The total treosulfan dose is 30-42 g. The dose of Treosulfan is administered according to the body surface area of the patient.

Fludarabine 30 mg BSA per day as a half an hour intravenous infusion, given five consecutive days before stem cell infusion. The total fludarabine dose is 150 mg.

• Administer Treosulfan before the dosage of fludarabine.
• Thiotepa (intensified regimen 5 mg twice a day), given as two intravenous infusions over 2– 4 hours on the second day before stem cell infusion.

The safety and efficacy of Treosulfan medicine in children less than 1 month of age have not yet been established.

Precautions before administration

• The shelf-life of an unopened vial of Treosulfan is 5 years.
• Treosulfan is for intravenous infusion for two-hour.
• When handling Treosulfan, one should avoid inhalation, skin contact, or contact with mucous membranes. Keep pregnant women away from cytotoxics.
• Administration of the medicine should be performed using a safe technique to avoid extravasation. 

Side effects 

Treosulfan injection has common side effects such as infections, nausea, stomatitis (inflammation of the lining of the mouth), vomiting, diarrhea, and abdominal pain. Cardiac disorders, gastrointestinal disorders, nervous system disorders, blood and lymphatic system disorders, and many more are severe side effects of the medicine.

Overdose

There is no antidote for overdose of Treosulfan. One should take medicine according to the recommended dosage of the doctor. The principal toxic effect of Treosulfan is profound myeloablation and pancytopenia. Moreover, acidosis, skin toxicity, nausea, vomiting, and gastritis might occur. Healthcare professionals should monitor the patient regularly for worsening symptoms or any such symptoms. 

Cost of Treosulfan

It is seen that the price of medicine made by innovators is more costly than the other suppliers. In India, Treosulfan cost is reasonable the reason is multiple generic brands are available in India. The drug is easily available with the suppliers like Ikris Pharma Network- Pharmaceutical wholesale distributors in India, a trusted brand for delivering such medications in India and abroad at the best possible time.

Fulvestrant Guidance

Fulvestrant helps in treating hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression and HR-positive, HER2-negative advanced breast cancer in combination with palbociclib in women with disease progression after endocrine therapy. Fulvestrant is a selective estrogen receptor degrader (a type of drug which binds to the estrogen receptor). Faslodex is the trade name of Fulvestrant. The strength of the medicine is 250 mg.

Dosage and Administration

Fulvestrant injection is for intramuscular administration. For the proper dosage, the patient should seek a prescription prescribed by the doctor, administer the recommended dose of Fulvestrant 500 mg intramuscularly into the buttocks slowly (1 - 2 minutes per injection) as two 5 ml injections, one in each buttock, on Days 1, 15, 29, and once in a month after that. Fulvestrant 250 mg is also given in combination with other drugs such as palbociclib, abemaciclib, or ribociclib. Administration instructions are as follows: 

1. Remove the glass syringe barrel from the tray and check that it is not damaged.
2. Remove the perforated patient record label from the syringe. 
3. Peel open the safety needle outer packaging. For complete SafetyGlide instructions, refer below to the "Directions for Use of SafetyGlide."
4. Break the white plastic cover seal on the syringe Luer connector to remove the cover with the attached rubber tip cap.
5. Twist to lock the needle to the Luer connector.
6. Remove needle sheath.
7. Remove excess gas from the syringe. 
8. Administer intramuscularly slowly in the buttock. 
9. Immediately activate the needle protection device upon withdrawal from the patient by pushing the lever arm completely forward until the needle tip is fully covered.
10. Visually confirm that the lever arm has fully advanced and the needle tip is covered. If unable to activate, discard immediately into an approved sharps collector. 
11. Repeat steps from 1 to 10 for the second syringe. 

Side Effects  

Fulvestrant 250 mg common side effects are; nausea, injection site reactions, weakness, and elevated transaminases (an indicator of liver dysfunction). Drug's severe side effects are urinary tract infections, hypersensitivity reactions, loss of appetite, headache, blood clots in veins, hot flushes, vomiting, diarrhea, elevated bilirubin, rashes, and intense back pain. 

Precautions

It advises females of reproductive potential of the potential risk to a fetus and uses effective contraception during treatment with inj Fulvestrant and for one year after the last dose. Doctors advise using it with caution in patients with bleeding diathesis, thrombocytopenia, or anticoagulant use. Before taking this medicine, one should go for counseling and run a check-up for medical complications in the future.

Fulvestrant injection price

It is seen that the price of Fulvestrant Injection made by innovators is more costly than the other suppliers. In India, Fulvestrant injection comes at reasonable prices. The drug is readily available with the suppliers like Ikris Pharma Network, a trusted brand for supplying such rare medications in India and abroad ASAP.

Apremilast 30 mg price and availability

Apremilast is advised for patients who have psoriatic arthritis and psoriasis. Apremilast is selling under the trade name of Otezla. Apremilast plays the role of a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and resists the TNF-alpha production from human rheumatoid synovial cells. It has been proven beneficial in some immune system-related inflammatory diseases. 

Apremilast comes in tablet forms for oral administration. Apremilast 30 mg dose after the 5-day titration, recommended is 30 mg twice daily taken orally starting on Day 6. Some of the common side effects of taking Apremilast are nausea, diarrhea, headache, sneezing, sore throat, etc. Some of the severe side effects are unexplained weight loss, depression, allergic reactions, severe diarrhea, severe stomach ache.

There is an observation that Apremilast cost is much lower in India than in any other country it is due to multiple generic versions of apremilast is available in India. Ikris Pharma Network is one of the branded and trusted names in the supply of such rare medicines around the world. Ikris Pharma Network provides effective services in a short time span. Ikris is a WHO-GDP certified International Pharmaceutical wholesaler. For more details you can also contact on TOLL FREE- 1800-889-1064

Note:- Always carry a doctor prescription while buying this medication online or offline.

Medical uses of ATGAM Injection

ATGAM is introduced to manage the allograft rejection in the recipients of renal transplant; when used along with conventional therapy at the moment of rejection this agent increases the frequency of the resolution of the acute rejection episode. 

ATGAM is approved to treat moderate/severe aplastic anemia in recipients unsuitable for the bone marrow transplantation.

The usefulness of atgam injection has not been shown in recipients with aplastic anemia who are suitable candidates for bone marrow transplantation or in recipients with aplastic anemia secondary to neoplastic disease, Fanconi's syndrome, storage disease, myelofibrosis, or in patients known to have been exposed to radiation or myelotoxic agents.

Approval: The ATGAM injection is approved in the US (United States):

• In order to manage moderate/severe aplastic anemia (a blood disorder that damages stem cells).

• In order to prevent the body from rejecting a kidney transplant.

Dosage Form: ATGAM comes in the form of injection. It is intended for intravenous use only with concomitant immunosuppressants. While repeat courses of ATGAM, observe the recipients for signs of allergic reactions. 

The recommended dose of ATG injection for Renal Allograft Recipients is 10 to 15 mg per kg daily administered intravenously for 2 weeks. The supplementary alternate day therapy up to a total of 21 doses can be administered.

The recommended dose for Aplastic Anemia (Moderate to Severe) is 10 to 20 mg per kg daily administered intravenously for 8 to 14 days. The supplementary alternate day therapy up to a total of twenty one doses can be given. Because thrombocytopenia can be related with the use of ATGAM, patients with this therapy for their aplastic anemia may require prophylactic platelet transfusions in order to maintain the count of platelets at the clinically acceptable levels.

Side Effects: Side effects of ATGAM are usually mild and not life threatening. The most commonly reported side effects include chills, fever, nausea, vomiting, diarrhea, dizziness, hives and headache. These side effects due to ATGAM usually go away following treatment.

Cost: The atgam injection price in India may vary depending on the wholesaler or pharmacy and of course the brand you choose. The cost of atgam injection usually depends on the branded to non-branded drugs and certain other factors. 

Medical uses of Octreotide Injection

Octreotide acetate is used for reducing blood levels of growth hormone and IGF-I (somatomedin C) in acromegaly patients who haven't had adequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses.

The octreotide injection is also used for the symptomatic treatment of patients with metastatic carcinoid tumors where this agent is believed to suppress or block the severe diarrhea and flushing episodes associated with the disease.

Octreotide acetate is used in order to treat the profuse watery diarrhea associated with the VIP-secreting tumors. 

Approval: As an octapeptide, the medication octreotide mimics the natural somatostatin pharmacologically, though it is an absolutely potent inhibitor of growth hormone, glucagon, and insulin in comparison to the natural hormone. 

In 1979 Octreotide was initially synthesized by Wilfried Bauer, and binds predominantly to the somatostatin receptors SSTR2 & SSTR5. In 1988 Octreotide was approved for use in the United States.

Dosage Form: Octreotide comes in the form of injection generically and under the brand name Sandostatin. Always use octreotide 100 mcg as per words by a healthcare professional. Depending on the complication being treated, Octreotide is administered by subcutaneous (under the skin) injection or intravenous (into a vein) infusion. In case patients have liver cirrhosis (chronic liver disease), their doctor may need to adjust their maintenance dose. A doctor will explain to a patient how to inject Octreotide injection under the skin, but infusion into a vein must always be performed by a healthcare practitioner.

Side Effects: Side effects of octreotide are usually mild and not life threatening. The commonly reported side effects may include vomiting, headache, hypothyroidism, cardiac conduction changes, diarrhoea, constipation, gallstones, reduction of insulin release, slow heart rate, nausea, injection site reactions, skin reactions and cramps. 

Cost: The octreotide injection price in India may vary depending on the wholesaler or pharmacy and of course the brand you choose. The cost of octreotide 0.05 mg is around Rs. 380 for a supply of vial of 1 injection. 

Medical uses of Artesunate

Artesunate injection is an antimalarial agent introduced as an initial treatment of severe malaria in adult/pediatric patients. Treatment of severe malaria with artesunate 60 mg injection must always be followed by a full treatment course of an apt oral antimalarial regimen.

Artesunate injection basically does not treat the hypnozoite liver stage forms of Plasmodium and is therefore unable to prevent the relapses of malaria because of the Plasmodium vivax or Plasmodium ovale.

The concomitant therapy and an antimalarial medication such as an 8-aminoquinoline are important in treating severe malaria due to P. vivax or P. ovale.

Approval: Artesunate specifically falls under the artemisinin class of medication. In 1977, it was developed by Liu Xu. It is on the WHO's List of Essential Medicines. In May 2020, it was approved for medical use in the United States.

Dosage Form: Artesunate comes in the form of injection generically and under the brand name Falcigo. The standard dose of artesunate injection is 2.4 mg per kg given intravenously at 0 hours, 12 hours, and 24 hours, and thereafter, administered once in a day until the patient is capable of tolerating the oral antimalarial therapy.

Side Effects: Side effects of artesunate are usually mild and not life threatening. The commonly reported side effects may include kidney failure requiring dialysis, jaundice, and hemoglobinuria (the presence of hemoglobin in urine).

Cost: The artesunate 60 mg price in India may vary depending on the wholesaler or pharmacy and of course the brand you choose. The cost of artesunate is around Rs. 224 for a supply of vial of 1 injection. 

Medical uses of Cisplatin Injection

Cisplatin is a well-known chemotherapeutic agent. It is used for treatment of numerous human cancers including lung, bladder, head and neck, ovarian, and testicular cancers. The cisplatin injection is effective against several types of cancers, including lymphomas, carcinomas, germ cell tumors, and sarcomas. Its mode of action has been associated with its ability in order to crosslink with the purine bases on the DNA; interfering with the DNA repair mechanisms, causing the DNA damage, and subsequently inducing the apoptosis in the cancerous cells.

The combination therapies of cisplatin with certain other medications have been highly considered in order to overcome the drug resistance and reduce the toxicity. 

Approval: Cisplatin falls under the platinum based antineoplastic family of drugs, which works in part in order to bind to the DNA and inhibits its replication.

In the year of 1845, this agent was discovered and licensed for medical use in 1978 & 1979.

Dosage Form: Cisplatin comes in the form of injection generically and under the brand name Platinol. The recommended dose of cisplatin for injection should be administered intravenously. 

The recommended dose of cisplatin for advanced testicular cancer is 20 mg/m2 daily for 5 days per cycle. 

The recommended dose of cisplatin for advanced ovarian cancer: 75 mg/m2 to 100 mg/m2 per cycle once every 3-4 weeks. 

The recommended dose for advanced bladder cancer is cisplatin 50 mg/m2 to 70 mg/m2 intravenously per cycle once every 3-4 weeks. 

Side Effects: Side effects of cisplatin are usually not life threatening. The commonly reported side effects include nephrotoxicity, myelosuppression, peripheral neuropathy, nausea, vomiting, and ototoxicity. 

Cost: The cisplatin price in India may vary depending on the wholesaler/pharmacy and of course the brand you choose. The cost of cisplatin starts from around 278 INR to 590 INR for a supply of a single vial of injection. 

Lenalidomide History

Lenalidomide, which is sold under the name of revlimid, is used for the treatment of MM (Multiple Myeloma) and myelodysplastic syndromes (is a group of cancers in which immature blood cells in the bone marrow do not mature, so do not become healthy blood cells).

Before knowing history, one needs to know that thalidomide, a pioneer to lenalidomide, was not developed for the treatment of multiple myeloma. It is said that the history of lenalidomide is one of the most interesting stories in medical science. In the late 50s when thalidomide developed it was known as sleeping pills because people feel sleepy after taking that. And when it was developed no one knew about the exact mechanism of medication.

In the early 60s when pregnant women inhaled thalidomide for morning sickness it was observed that they gave birth to babies with malformations. After that, it was felt that the drug is for some other mechanism too.

In 1971, the concept discovered called anti-angiogenesis which involves blocking the formation of new blood vessels important for a tumor to survive. Then only this showed progress by preventing the growth of new blood vessels. Then when thalidomide and then lenalidomide came into the spotlight.

Approval history

On December 27, 2005, lenalidomide was first approved by the US Food and Drug Administration for the treatment of multiple myeloma who received at least one prior therapy.

Dosage and usage 

After knowing about the history of lenalidomide, it is important to know about the drugs how and when to consume them. First of all, it is recommended to consult the doctor, and is not advisable to consume any drug dose without the doctor's prescription.

The lenalidomide is in a form of a capsule and strength of 2.5mg, 5mg, 10mg, 15mg, 20mg, and 25mg. Lenalidomide is suggested to be taken daily once orally at the same time. Lenalidomide should be swallowed fully with water and not break, crush or split.

Usage of medication in Multiple Myeloma (MM) as starting dose is 25mg once daily from Day 1 to day 21 repeated 28 days cycle.

Later we all see this part called pricing. Lenalidomide price in India is different and depends on different trade such as 

• Lenalid cost approximately Rs. 4386 – Rs. 9297
• Lenmid cost approximately Rs795 –Rs 2797
• Lenid cost approximately Rs 1500 – Rs 2900

Carfilzomib along with immunomodulatory drugs, and dexamethasone for Relapsed/Refractory Multiple Myeloma

The triplet carfilzomib, immunomodulatory drugs, and dexamethasone has shown effective outcomes for the treatment of relapsed/refractory (R/R) multiple myeloma.

Apart from this, for numerous authorities, this combination has a little bit of a high cost. On behalf of new data, this triplet (carfilzomib, thalidomide, and dexamethasone) could be a safe as well as a cost-effective alternative.

The carried out study enrolled patients with relapsed/refractory MM who had between 1 to 3 prior lines of treatment. Total 83 of the patients had a median age of about 66 years. Patients were taken 12 cycles, each lasting one month, of this triplet.

The main result that is measured at the end of a study in order to see if a given treatment worked was PFS (Progression-Free Survival). Secondary endpoints were ORR (Overall Response Rate), OS (Overall Survival), SE (side effects), and QoL (Quality of Life).

The median progression-free survival was noted as 20 months. The progression free survival rate at 6.5 months was noted as 76.2%. Median OS has not been achieved in the carried out study. The combination achieved an overall response rate of 86.4%.

Maximum side effects noted in the study population were grade 2 or lower. The most commonly reported side effects were peripheral neuropathy, with 16% of patients reporting, followed by upper respiratory tract infections in 12% of patients. Those most recent data indicates that 41% of patients have completed 18 cycles of treatment.

An interview was held in between Targeted Oncology and Hang Quach, MD, a consultant clinical and laboratory haematologist at St. Vincent’s Hospital, in which Hang Quach discussed the phase-II Australasian Leukaemia and Lymphoma Group multiple myeloma 018/ Asian Myeloma Network 002 study and how it can be responsible for impacting the treatment of relapsed/refractory MM in the future.

Reference:

https://www.targetedonc.com/view/expert-reviews-results-of-carfilzomib-combination-in-r-r-multiple-myeloma

Zoledronic Acid: A Bisphosphonate Therapy

Zoledronic acid injection, also addressed as zoledronate, specifically is a drug prescribed for the treatment of bone diseases including high blood calcium due to cancer, bone breakdown due to cancer, osteoporosis, and Paget’s disease of bone. 

Mechanism of Action: Zoledronic acid falls under a class of substances named Bisphosphonates. It binds specifically to bone and it does not stay in your blood. The zoledronic acid injection helps in order to slow down the bone resorption (caused by osteoclasts) which enables the bone-forming cells (osteoblasts) time in order to rebuild the normal bone.

Dosage & Administration: The zoledronic acid injection is administered as an infusion into a vein for 15 minutes by your healthcare practitioner. 

Your healthcare practitioner will recommend you to consume at least 2 glasses of water (500 mL or 2 cups) prior to and following the treatment.

In order to prevent Osteoporosis, 5 mg should be given as a single dose.

In order to prevent Paget’s disease, 5 mg should be given as a single dose.

The zoledronic injection may work for over 1 year, and your healthcare professionals will inform you in case you need to be treated again. 

It is crucial to take calcium as well as vitamin D supplements as directed by your healthcare practitioner in order to reduce the probability of having reduced blood calcium levels, to prevent the loss of bone and to help rebuild the bone.

Possible Side Effects: Like all drugs, zoledronic acid injection may also be responsible for causing some unwanted adverse reactions in addition to its beneficial effects.

The most common zoledronic acid side effects include:

• Fever
• Fatigue
• Chills
• Headache
• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Back pain
• Pain in extremity
• Influenza-like illness
• Weakness
• Pain
• Shortness of breath
• Dizziness
• Excessive sweating
• Tiredness
• Disturbed digestion
• Decreased appetite
• Non-cardiac chest pain
• Malaise (unwell feeling)
• Bone, joint or muscle pain or stiffness

Other side effects: There's possibility that some other side effects due to zoledronic acid infusion may also occur, which are listed as follows:

• Numbness
• Tingling sensations
• Allergic reactions
• Urinary tract infection
• Constipation
• High blood cholesterol levels
• Pain in jaw
• Pain in neck
• Joint sprain
• Post-traumatic pain
• Cough
• Seasonal allergy
• Vaginal dryness
• Congestion of the nose
• Pharyngolaryngeal pain 
• Increased or irregular heartbeat
• Rheumatoid arthritis/arthritis (inflammation of the joints)

Warning & Precautions:

• Administration of zoledronic acid injection is not recommended for patients aged under 18 years.
• Prior to taking zoledronate infusion talk to your doctor if you're unable to take daily calcium/vitamin D supplements. 
• Ensure that you have talked about zoledronic acid injection treatment with your healthcare practitioner. 
• In case you're taking treatment with another intravenous form of zoledronic acid 4mg, you're not allowed to be treated with the zoledronic acid injection.
• In case you're being treated with this injection, treatment should be avoided with other bisphosphonates (such as risedronate, alendronate, clodronate, etidronate, pamidronate and ibandronate) at the same time.
• Use of zoledronate is not recommended in case you are pregnant or plan to become pregnant or are breast-feeding.
• Talk to your healthcare practitioner in case you've any pain in your hip, groin, or thigh. This injection may be responsible for causing the unusual fractures in the thigh bone.
• Inform your doctor if you've a sudden headache, numbness in your limbs, confusion, trouble talking, vision problems, and trouble walking.
• Tell your healthcare team if you have kidney problems. Cases of worsening of kidney function, including kidney failure may happen when you take the zoledronic acid 4mg injection.

Drug Interactions: You need to inform your healthcare team in case you're taking or have recently taken any other drugs, including any kind of drug you have bought without a prescription. It is specifically crucial for your healthcare team to know if you are taking :

• any drugs known to be harmful to your kidneys (such as Non-Steroidal Anti-inflammatory Drugs).
• water pill (diuretics)
• aminoglycoside antibiotics (a type of drug used to treat severe infections).

Drug Overdose: In case you have received or taken too much zoledronic acid dose, contact your healthcare practitioner, hospital emergency department as soon as you can, even if there are no signs and symptoms.

Storage Guidelines: Store these injections at the room-temperature between 15°C-30°C. Original packaging should be kept unchanged as well as sealed until a healthcare practitioner administers the inj zoledronic acid. Don't forget to keep the injection and all drugs safely away from the children.

Cost: The zoledronic acid price may vary from branded (innovator) to non-branded (generic) drugs. The price for a bottle of Aclasta 5mg/100ml Infusion (Trade Name) is around 20492 INR. 

Frequently Asked Questions:

From which class of drug Zoledronic acid belongs? 

Zoledronic acid specifically belongs to a class of drugs named bisphosphonates that helps in order to prevent the abnormal breakdown of bones.

What is Zoledronic acid? What is it used for?

Zoledronic acid is used in order to prevent and treat osteoporosis and fractures in patients with metastatic cancer (a cancer which spreads to newer areas of the body). This drug can also be used in order to treat hypercalcemia (elevated blood calcium levels).

How should Zoledronic acid be given? 

Zoledronic acid is given by injection into a vein.

How does Zoledronic acid act? 

Zoledronic acid acs in order to block the activity of osteoclast cells and thus reduces the bone breakdown. 

How long should I take Zoledronic acid?

This medication should be taken in the dose as well as duration recommended by healthcare professionals. Zoledronic takes around 6-month in order to show its maximum benefits on bones. Although, in certain cases, the healthcare practitioner may suggest this medication for a longer period of time. The appropriate duration will depend on the condition you're currently being treated for.

What are the commonly reported side effects of Zoledronic acid? 

Commonly reported side effects of Zoledronic acid include joint pain, high blood pressure, fever, diarrhea, and feeling tired.

What are the severe side effects of Zoledronic acid? 

Severe side effects of Zoledronic acid may include low blood calcium, osteonecrosis of the jaw and kidney problems. 

What if Zoledronic acid is used during pregnancy? 

Use of zoledronic acid during pregnancy may be responsible for harm to the baby.

NOTE: The information provided about zoledronic acid injection in this article is only for informational purposes and is not served as a substitute for the medical treatment, consultation, diagnosis, of a qualified healthcare practitioner.