Avastin

Avastin is an anti-neoplastic medication which is containing Bevacizumab as an active substance, which is involved in the treatment of various cancers. It is a monoclonal antibody, which target a tumor cell protein known as vascular endothelial growth factor (VEGF). This VEGF is responsible for cancer to form their blood vessels, so they can easily acquire food and oxygen from blood for survival. The treatment involved by interceding with development of blood supply, so it is termed as anti-angiogenesis therapy.

Bevacizumab

Avastin

100mg/4ml

Roche






Indication of Avastin

The most important prescribing information of Avastin is;

Metastatic colorectal cancer:
In this condition, Avastin should be used in combination with intravenous 5-FU based chemotherapy. This is considered as first or second line therapy. Avastin is concurrently used with fluoropyrimidine Irinotecan or fluoropyrimidine oxaliplatin based therapy should be used as second line treatment in advanced colon rectal cancer for the patients who are advanced with first line therapy of Avastin. Avastin is not a supporting therapy for colon cancer.

Non-squamous non-small cell lung cancer:
Avastin is used as first line therapy for this condition by combining with carboplatin & paclitaxel.

Recurrent Glioblastoma:
Avastin is majorly used in this condition

Advanced renal cell cancer:
In this condition, Avastin should be combined with interferon alfa medicine.

Advanced cervical cancer:
For treating this condition, Avastin should be concurrently used with paclitaxel & cisplatin or paclitaxel & topotecan.

Epithelial ovarian, fallopian tube or primary peritoneal cancer:
Avastin should be combined with carboplatin & paclitaxel, followed by Avastin as a single therapy. In platinum resistance epithelial ovarian, fallopian or peritoneal cancer, Avastin should be combined with paclitaxel, pegylated liposomal doxorubicin or topotecan. In platinum sensitive recurrent epithelial ovarian, fallopian tube or peritoneal cancer, Avastin should be combined with carboplatin & paclitaxel or carboplatin & gemcitabine.

Mechanism of action of Avastin

Bevacizumab is majorly binds to the protein like vascular endothelial growth factor and prevent the interaction of protein to its receptors. The communication of protein with its receptors causes cell production by forming new blood vessels which comes under the process of angiogenesis. Bevacizumab is involved in inhibition of new blood vessel formation leads to death of cancer cells due to loss of oxygen and food.



Pharmacokinetic

The pharmacokinetic of Avastin is to be linear; the concluded time to reach more than 90% of steady state concentration is 84 days. The median trough concentration of Bevacizumab is 80.3mcg/ml on day 84.

Volume of distribution of Bevacizumab is 2.9L

The drug has been experienced with opsonization for elimination. This may occur through reticuloendothelial system at time of binding to endothelial cells.

The terminal half-life period of Bevacizumab is nearly 20 days. Creatinine clearance value is 0.23 (33)L/day





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Brand Avastin
Ingredients Bevacizumab
Strength 100mg/4ml
Manufactured Roche
Rating

Dosage regimens and administration of Avastin

The most important administration factors are, Avastin should not be used until at least 28 days following surgery and lesion is completely healed.

Advanced colon rectal cancer
Avastin combined with 5-FU The dose of Avastin is; The dose of 5mg/kg of Avastin should be taken for every 2 weeks administered through intravenously in combination with bolus IFL. 10mg/kg of Avastin should be taken for every 2 weeks administered intravenously by combining with FOLFOX4. The dose of Avastin is 5mg/kg should be administered intravenously as every 2 weeks or 7.5mg/kg should be given IV for every 3 weeks by combining with fluoropyrimidine Irinotecan or fluoropyrimidine oxaliplatin based chemotherapy regimens.

Non-squamous non-small cell lung cancer
The suggested dose of Avastin is 15mg/kg should be administered through IV for every 2 weeks by combining with carboplatin & paclitaxel.

Recurrent Glioblastoma
The usual suggested dose of Avastin is 10mg/kg should be administered IV for every 2 weeks

Advanced renal cell cancer
The usual suggested dose of Avastin is 10mg/kg should be given intravenously for every 2 weeks by combining with interferon alfa.

Advanced cervical cancer
The advised dose of Avastin in this condition is 15mg/kg of drug should be given intravenously for every 3 weeks by combining with paclitaxel & cisplatin or by combining with paclitaxel & topotecan.

Epithelial ovarian, fallopian tube, or peritoneal cancer
Therapy of stage III or IV: The usual dose of Avastin is 15mg/kg IV for every 3 weeks by combining with carboplatin & paclitaxel for period of 6 cycles, continued by Avastin 15mg/kg for every 3 weeks as a single regimen, for total duration of treatment is 22 cycles.

Therapy of frequent disease

Platinum resistance condition
The prescribed dose of Avastin is 15mg/kg given IV for every 3 weeks by combining with topotecan (every 3 weeks).

Platinum sensitive
The prescribed dose of Avastin is 15mg/kg should be given as IV for every 3 weeks, by combining with carboplatin & paclitaxel for period of 6 to 8 cycles, continued by Avastin 15mg/kg for every 3 weeks as a single regimen. The prescribed dose of Avastin is 15mg/kg IV for every 3 weeks by combining with carboplatin & gemcitabine for period of 6 to 10 cycles, continue with Avastin 15mg/kg as a single regimen.

Administration
Avastin should be administered through intravenous infusion over the period of 90 minutes as first infusion and consecutive infusions may follow over 60 minutes. 100mg of Avastin containing 4ml solution which is diluted in 100ml of 0.9% sodium chloride solution. Avastin should not be diluted in dextrose solution. Avastin should be administered as intravenous site. It should be administered with or without food.

Over dosage

There is no chance of getting over dosage in Avastin receiving patients, because Avastin is a cytotoxic drug which is administered only under the supervision of medical oncologist. Avastin should be used cautiously.

Common side effects

Diarrhea, Nausea, Stomatitis, Fatigue, Arthralgia, Muscle weakness, Pain, Dysarthria, Headache, Dyspnea, Epistaxis, Nasal mucosal disorders, Hypertension, Neutropenia, Mucosal inflammation, Peripheral sensory neuropathy, Palmar plantar erythrodysaesthesia, Contusion, Back pain, Insomnia

The most common adverse effects in Avastin treatment

GI perforations & fistulae, Surgery and wound healing complications, Hemorrhage, Arterial thromboembolic events, Venous thromboembolic events, Hypertension, Posterior reversible encephalopathy syndrome, Renal damage & Proteinuria, Infusion reactions, Ovarian failure, Congestive heart failure

Precautions

Some warning signs should be taken into consideration: Gastrointestinal perforation, surgery & wound lesions complexity or hemorrhages are the major adverse effect occurs during the treatment with Avastin injection.

In GI perforation:
Treatment should be discontinued and providing supportive measures

In wound or surgery complications:
Avastin treatment should be interrupt during the surgery until the wound should be completely healed. Nearly 28 days after & before the surgery, therapy should be withheld.

Hemorrhage:
Severe hemorrhages like GI bleeding, hemoptysis, Hematemesis, CNS hemorrhage, Epistaxis & vaginal bleeding are occurring during the Avastin treatment. Discontinue the treatment.

Arterial thromboembolic events:
Discontinue the therapy with Avastin in patients who are suffered with severe ATE.

Venous thromboembolic events:
Incidence of toxicity should be detected; in case of severe condition therapy should be stopped.

Hypertension:
Increased blood pressure in patients who are receiving Avastin therapy, should be monitor frequently with blood pressure and provided with alternative medication for correct the pressure. In hypertension crisis or encephalopathy should be discontinue the treatment.

Posterior reversible encephalopathy syndrome:
Symptoms should be cleared with providing supportive measures after discontinuing the Avastin therapy and PRES should be monitored by undergoing MRI. In severe condition, patients should be discontinuing with Avastin treatment.

In renal injury & Proteinuria:
Toxicity grade should be resolved by monitoring the renal function and Proteinuria.

Infusion reactions:
In severe infusion reactions, patients should not take Avastin treatment.

Embryo fetal damage:
Avastin is contraindicated to pregnancy condition, produce fetal harm.

Ovarian failure:
Avastin receiving patients may have a chance of getting ovarian failure.

Congestive heart failure:
In anthracycline based chemotherapy, Avastin treatment should not be used. Avastin treatment should be discontinuing while CHF occurs.

Drug- drug interaction

Avastin combined with paclitaxel & carboplatin causes reducing exposure of paclitaxel after completion of 4 cycles of therapy. When patients receiving paclitaxel & carboplatin as alone, causes elevation of paclitaxel exposure at day 63.



No specific contraindications occur. Hypersensitivity reactions may present in patients who are contraindicate to component of Avastin. Avastin is contraindicated to pregnant & lactating women.

Pregnancy category: C Avastin should be contraindicated to pregnancy condition; breast feeding is also not suggested. Avastin produces some embryo fetal damage which may leads to cause fetal harm. The potency of Bevacizumab should not be evaluated in pediatric patients. There is an increased chance of getting arterial thromboembolic events in > or equal to 65 years of age.

Avastin vial should be stored in 2°C to 8°C. Protect the container from moisture, heat & light. Discard the unused portion immediately. The diluted solution of Avastin should be stored at 2 to 8°C for up to 8 hours. There are no compatibilities occurs between Avastin& polyvinylchloride or polyolefin bags has been detected

If patients are missed to take cycles of Avastin , must consult with medical oncologist and follow the instructions. Do not miss the cycle of Avastin.

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