Votrient 400mg

Drug profile of Votrient 400mg

Votrient 400mg tablets are including a functioning component like Pazopanib Hydrochloride; recommend as hydrochloride salt of Pazopanib which a little molecule isexpelcontrolling movement against tyrosine kinase with opposed to malignancy impact.

Votrient 400mg is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Indications of Votrient 400mg

Votrient 400mg tablets are majorly indicated in the conditions such as;

• Metastatic renal cell carcinoma
• Advanced soft tissue sarcoma

Mechanism of Votrient 400mg

Pazopanib is belongs to tyrosine kinase inhibitor (TKI). Tyrosine kinases are proteins that act as chemical enzymes in cells. There are several different tyrosine kinases and they trigger cancer cells to grow.

Pazopanib stops a number of these proteins and is called a multi tyrosine kinase inhibitor (multi TKI). It blocks cancer cells forming blood vessels which they requireto grow. This is called anti-angiogenesis treatment.

Absorption

Votrient 400mg tablets after administration, reaches maximum plasma concentration time between 2 to 4 hours.

While compared the administration of whole tablets, with crushed powder of tablet causes increased bioavailability and absorption of Pazopanib frequently.

The effect of food with Pazopanib causes elevation in systemic exposure of Pazopanib; Votrient 400mg tablets should be administered at least 1 hour earlier or 2 hours after the food intake.

Distribution

The human plasma protein binding capacity of Pazopanib is very high nearly it reaches as 99%.

Metabolism

The metabolism of Pazopanib is undergoes with the help of CYP3A4 with lesser contribution of CYP1A2 & CYP2C8.

Excretion

The terminal half-life period of Pazopanib is 30.9 hours.

The primary elimination of Pazopanib is occurs via feces; lesser in urine.

Dosage regimens and administration

The daily recommended dose of Votrient tablets are 800mg should be taken orally as a single dose.

The dose of Votrient should not be exceeded to 800mg

Votrient tablet contains 400mg of Pazopanib hydrochloride.

Dose alteration:

In renal cell cancer; the starting dose is 400mg and followed by decreasing or increasing the dose of 200mg depends upon the tolerability of the patients.

In soft tissue sarcoma, the dose should be reduced or elevates as 200mg based onpatient’s tolerability.

In liver impairment:

There is no dosage adjustment should be recommended for mild condition.

In moderated impaired patients, other than Votrient tablet should be considered; the dose of Votrient should be decreased to 200mg daily.

Votrient treatment should be discontinued in case of severe hepatic impairment condition.

Concurrent use of CYP3A4 inhibitors:

This combinational therapy causes elevation of Pazopanib concentration and leads to adverse.

 To avoid this problem, this concomitant use should not be allowed.

If this combination of Pazopanib with CYP3A4 inhibitors is necessary for the patients, the dose of Pazopanib should be reduced to 400mg and monitor the adverse effects frequently.

Concurrent use of CYP3A4 inducers:

This usage may reduce the concentration of Pazopanib, to overcome the problem avoid this concomitant use.

In case of patient is necessary for using strong CYP3A4 inducers, stop the Votrient 400mg therapy

The administration of Votrient tablets should be recommended as without food.

It should be taken as 1 hour earlier or 2 hours after food intake.

Over dosage

Votrient 400mg over dosage should not have any antidote, if it may occur patients should be provided with supportive measures and monitor the signs and symptoms.

Hemodialys is should not be suggested, because Pazopanib is largely bounds to human plasma protein and it founds difficult to remove by hemodialysis.

Votrient 400mg caused side effects

The major adverse effects

Increased blood pressure

Infections

Increased toxicities

Thrombotic microangiopathy

Liver toxicity

Prolongation of QT intervals

Cardiac dysfunction

Hemorrhage

Venous & arterial thromboembolic

GI perforations

Interstitial lung disease

Reversible posterior leukoencephalopathy syndrome

The common side effects

In renal cell

Diarrhea

Hypertension

Hair color altered

Nausea

Anorexia

Vomiting

Fatigue

Asthenia

Abdominal pain

Headache

Lab abnormalities:

Leucopenia

Neutropenia

Thrombocytopenia

Lymphocytopenia

Elevation of AST & ALT

Hyperglycemia

Elevation of bilirubin

Depletion of phosphorus

Depletion of sodium, magnesium

Lab abnormalities:

Depletion of sodium

Elevation of total bilirubin, potassium

Lipase level increase

Pneumothorax

Bradycardia

Retinal detachment

Pancreatitis

Polycythemia

Leucopenia

Neutropenia

Thrombocytopenia

Lymphocytopenia

Elevation of AST & ALT

Hyperglycemia

Depletion of albumin

Elevation of alkaline phosphatase

Drug- drug interaction

Votrient 400mg absorption should be affected by gastric regulators; co administration of this combination should be avoided. It should be administered with dosing intervals for avoid the problem like depletion of exposure of Pazopanib.

Votrient 400mg tablet concomitant use of CYP3A4 inhibitors causes elevating the concentration of Pazopanib. In this condition the dose of Votrient 400mg should be reduced to 400mg, in case of increased adverse effects, discontinue the therapy.

Interaction of Votrient 400mg tablet with the drugs metabolized by CYP3A4, CYP2D6 or CYP2C8 should not be allowed, this combination may causeinhibition of metabolism of these products and leads to severe effect.

Interaction of Votrient 400mg tablets with simvastatin leads to elevate the levels of ALT, to avoid this problem discontinue the therapy.

Contraindications

No suspected contraindications occur

Hypersensitivity reactions may occur due to patients may contraindicate to the component of Votrient 400mg tablet.

Contraindicated to pregnancy and lactation

Precaution

Hepatic toxicity

Examine by taking hepatic function test periodically

Stop the therapy

Avoid concomitant use of simvastatin

Avoid the combination with the drugs may causes hepatic function abnormalities

QT extension

Monitor ECG of patient regularly

Provide with alternative medicines

Stop the therapy in severe condition

Cardiac dysfunction

Interrupt or discontinue the therapy, while cardiac dysfunctions like ischemic condition, myocardial infarction etc.

Hemorrhagic

Stop the treatment

Embryo fetal toxicity

Can cause fetal harm when administered to a pregnant woman; advise females of reproductive potential of the potential hazard to fetus and to use specific contraception during therapy and for at least 2 weeks after last dose.

Arterial thromboembolic events

GI perforation

Gastrointestinal perforation or fistula resulted; fatal break events have reported; use with caution in patients at risk for gastrointestinal perforation or fistula.

Interstitial lung disease

Reversible posterior leukoencephalopathy syndrome

Hypertension

Wound healing

Hypothyroidism

Proteinuria

Infection

Increased toxicity

For all these above-mentioned conditions, discontinue the treatment.

Pregnancy and lactation

Pregnancy category: D

Votrient 400mg should not be advised to pregnancy and lactating women

Votrient 400mg may cause fetal damage

Storage and handling

Votrient 400mg tablet container should be stored at 20^oC & 25^oC.

Protect the container from moisture, heat & light.

Missed dose

Do not administered the missed dose of Votrient 400mg tablet; if it is less than 12 hours for the next dose