Medicine > All about Sunicine (Sunitinib Malate) tablet

All about Sunicine (Sunitinib Malate) tablet

Name of Medicine: Sunicine 

Composition: Sunitinib Malate

Chemical Formula: C26H33FN4O7

Description: Sunicine capsule is a prescription drug indicated to treat gastrointestinal stromal tumors (a form of tumor that grows in the stomach, intestine (bowel), or esophagus tumors (the tube that connects the throat with the stomach). 

Sunicine is an effective formulation of Sunitinib Malate, a form of multi-targeted receptor tyrosine kinase. It is available in the form of capsules indicated for oral use. Its strength is 50mg. Sunicine works by blocking an enzyme to slow or stop the growth or multiplication and spread of cancer cells in the body. 

Clinical Relevance 

The clinical relevance of Sunicine tells about its importance in the healthcare segment. Sunicine, comprising Sunitinib Malate, is prescribed for the treatment of gastrointestinal stromal tumors (a form of tumor that grows in the stomach, intestine (bowel), or esophagus tumors (the tube that connects the throat with the stomach) with evidence of disease progression and/or advanced renal cell carcinoma and/or pancreatic neuroendocrine tumors. 

Clinical Pharmacology 

Mechanism of Action

Sunitinib is a small molecule responsible for the inhibition of a number of RTKs, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was studied for its inhibitory activity against more than 80 kinases and was identified as an inhibitor of platelet-derived growth factor receptors, vascular endothelial growth factor receptors, stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony-stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). The inhibition of Sunitinib of the activity of such RTKs has been shown in biochemical and cellular assays, and inhibition of function has been represented in cell proliferation assays. The primary metabolite tends to exhibit similar potency in comparison with Sunitinib in biochemical and cellular assays.

Absorption 

Cmax (maximum plasma concentrations) of the compound are generally seen in an interval of 6 to 12 hours (Tmax) after its administration. Food has shown no effect on the bioavailability of Sunitinib Malate. Sunicine can be taken either with or without food. The pharmacokinetics of this drug were similar in healthy volunteers and the solid tumor patient populations tested, including patients suffering from gastrointestinal stromal tumor and RCC.

Metabolism 

Primarily this compound is metabolized by the cytochrome P450 enzyme, CYP3A4, to initiate the production of its primary active metabolite, which is then metabolized by CYP3A4.

Route of Elimination

Primarily this compound is metabolized by the cytochrome P450 enzyme, CYP3A4, to initiate the production of its primary active metabolite, which is then metabolized by CYP3A4. Elimination is primarily executed through feces. In a human mass balance study of Sunitinib Malate, 61% of the overall dose was excreted in feces and 16% of the administered dose was excreted via kidneys.

Clinical Trials 

The active ingredient of Sunicine is a potent inhibitor of multiple tyrosine kinase receptors. The Tmax of this compound is reached within approximately 6 to 12 hours, and food may not affect the bioavailability. Sunitinib Malate is primarily metabolized by cytochrome P450 (CYP) 3A4 to an active metabolite, SU12662, which is then metabolized by CYP3A4 to an inactive moiety. The parent compound along with active metabolite has relatively similar biochemical activity and potency and tends to reach similar concentrations of plasma. Sunitinib Malate has tl/2 of 40 to 60 hours and SU12662 has a tl/2 of 80 to 110 hours. After about 10 to 14 days of Sunitinib therapy, steady-state concentrations of both active entities are expected to reach. In a Phase III trial aiming to compare sunitinib with interferon-alfa, Sunitinib Malate was associated with an average progression-free survival of about 11 months, compared with 5 months with IFN-CZ (P < 0.001). A randomized, double-blind, placebo-controlled trial evaluating sunitinib as second-line therapy for GIST discovered a median time to progression of 28.9 weeks in the Sunitinib arm, compared with 7 weeks in the placebo arm. In Phase II trials, Sunitinib also had anti-tumor activity in patients suffering from Breast Cancer, Neuroendocrine Tumors, and Non-Small Cell Lung Cancer. Further calculation and study concerning these tumors, and in patients suffering from a type of Blood Cancer namely Acute Myelogenous Leukemia, may cause expanded indications. The approved recommended dose of Sunitinib is 50 mg/d PO for 4 weeks, followed by a 2-weeks off; where this predefined pattern is repeated till tumor progression or the occurrence of intolerable adverse events. 

The most commonly observed clinical adverse events attributable to Sunitinib include: 

  • Diarrhea 

  • Mucositis/Stomatitis 

  • Hypertension 

  • Rash 

  • Skin discoloration 

  • Altered taste

The commonly experienced laboratory abnormalities include: 

  • Gastrointestinal toxicity

  • Renal toxicity 

  • Hematologic toxicity

Out of grade 3/4 toxicities experienced with Sunitinib (which are uncommon, with a percentage of <10%), those that are clinically vital include:

  • Hypertension

  • Diarrhea

  • Fatigue

  • Hand-foot syndrome

Interactions 

Drug-Drug Interactions

No separate dedicated drug-drug interaction studies have been initiated for investigating Sunicine. However, the clinical studies of Sunitinib Malate give a brief of its drug interactions with the following:

  • CYP3A4 Inhibitors: When a  CYP3A4 inhibitor (Ketoconazole) is administered with Sunicine (Sunitinib Malate) capsules, the plasma concentrations of Sunitinib may increase. Therefore, it is recommended to select a concomitant drug with no or minimal potential for enzyme inhibition. If a strong CYP3A4 inhibitor can not be avoided with Sunicine, dose adjustments (reduction) should be done in the strength of Sunicine. 

  • CYP3A4 Inducers: Administration of a CYP3A4 Inducer (Rifampin) while co-administering Sunicine capsules may lead to a decrease in plasma concentration of Sunitinib Malate. If a strong CYP3A4 Inducer can not be avoided with Sunicine, dose adjustments (increase) should be done in the strength of Sunicine. 

Drug-Food Interactions

No separate dedicated drug-food interaction studies have been initiated for investigating Sunicine. However, the clinical studies of Sunitinib Malate give a brief of its food interactions with the following:

  • Grapefruit Products: Grapefruit and related products may lead to reduced CYP3A4 metabolism of Sunitinib Malate. Avoid its consumption. 

  • St. John's Wort: This herb tends to induce CYP3A4 metabolism that can further decrease the serum concentration of Sunitinib. 

Drug Category 

  • Antineoplastic Agents: Antineoplastic medications are agents that are used for the treatment of certain types of cancers. Such medicines are also known as chemo or hazardous drugs. They work to target and kill the cancerous cells in the body over a period of time.

  • Angiogenesis Inhibitors: These medicaments tend to stop the division and multiplication of new blood vessels that are needed by the tumors to grow in the body. Such agents are considered to be powerful cancer-fighting agents. 

  • Tyrosine Kinase Inhibitors: These are the pharmaceutical drugs that inhibit tyrosine kinase. Tyrosine Kinase Inhibitors tend to activate a number of proteins by signal transduction cascades in the body. This is done by initiating the addition of the phosphate group to the protein. 

Dosage and Administration 

Recommended Dosage: The recommended dose of Sunicine (Sunitinib Malate) for patients suffering from gastrointestinal stromal tumor after evidence of disease progression and/or advanced renal cell carcinoma is one capsule (50mg) administered orally once daily following a schedule of 4 weeks on Sunicine therapy and 2 weeks off. It can be taken with or without food. 

The recommended dose of Sunicine (Sunitinib Malate) for patients suffering from pancreatic neuroendocrine tumors is 37.5 mg administered orally once daily continuously without any day off. It can be taken with or without food.

Overdosage: There is no specific formulation of an antidote for the treatment of patients in case of an overdose of Sunicine. The elimination of unabsorbed medicine can be done by emesis or gastric lavage. To treat patients of overdose, usually, general supportive measures should be adopted. 

 

Dose Adjustments: When a  CYP3A4 inhibitor (Ketoconazole) is administered with Sunicine (Sunitinib Malate) capsules, the plasma concentrations of Sunitinib may increase. Therefore, it is recommended to select a concomitant drug with no or minimal potential for enzyme inhibition. If a strong CYP3A4 inhibitor can not be avoided with Sunicine, dose adjustments (reduction) should be done in the strength of Sunicine. 

Administration of a CYP3A4 Inducer (Rifampin) while co-administering Sunicine capsules may lead to a decrease in plasma concentration of Sunitinib Malate. If a strong CYP3A4 Inducer can not be avoided with Sunicine, dose adjustments (increase) should be done in the strength of Sunicine.

Adverse Reactions 

Administration of Sunicine (Sunitinib Malate) capsules may lead to certain adverse reactions that may or may not be managed at home through supportive care and over-the-counter prescription drugs. It is absolutely necessary to know the risks and benefits of consuming Sunicine capsules before starting the course of this medicine. The following is a brief of side effects that occur more commonly. 

Gastrointestinal effects may occur in some patients including vomiting, chest pain, diarrhea, dyspepsia (indigestion), constipation, nausea, abdominal pain (pain in the belly), and heartburn, incontinence (involuntary leakage of urine).

Skin or Dermatological Disorders may be experienced by some patients such as photosensitivity reaction, nail disorder, urticaria (itchy welts that result from a skin reaction), dermatitis, pigmentation disorder (a condition in which skin loses its pigment cells), dry skin, acne, and hyperhidrosis. Consult a medical practitioner right away for immediate medical attention. 

Sunicine (Sunitinib Malate) capsules may cause adverse effects on the central nervous system that might show some reactions like dizziness and headache. Such effects are accompanied by severe drowsiness resulting in high fever and weakness.

A number of neurological side effects may occur including depression, altered taste, mood changes, increased thirst and/or urination, tremors (shaking), irregular heartbeat, unexpected weight gain, and lack of interest. 

Cardiovascular adverse reactions may occur during the course of Sunicine capsules. Some of these effects are chest pain, cardiotoxicity, peripheral edema, hypotension, and tachycardia. Such reactions occur more commonly in patients who are already suffering from known heart disorders. 

Warnings and Precautions 

General Warnings

  • As a fixed combination, Sunitinib 50mg capsules should not be given simultaneously with other medicines that contain any of the same active ingredients.

  • Sunitinib 50mg capsules should not be administered simultaneously with some CYP3A4 Inhibitors such as Ketoconazole. 

  • Sunitinib 50mg capsules should not be administered simultaneously with CYP3A4 Inducers such as Rifampin.

  • Sunitinib 50mg capsules should not be administered to the patients who are allergic to Sunitinib Malate. 

Special Population

  • Pregnancy: When given to a pregnant woman, the Sunicine capsule has the potential to damage the fetus. Patients who are pregnant or planning to become pregnant should not take this medication. Women possessing child-bearing potential are advised to start using proper contraceptive measures 28 days before consuming these capsules. 

  • Breastfeeding: Sunitinib 50mg capsules is not believed to be excreted in human milk. Since the majority of other medications are excreted in human milk, steps must be taken to prevent adverse reactions. As a result, breastfeeding should be stopped while on Sunitinib care.

  • Pediatric and Geriatric Use: The safety and efficacy of Sunitinib 50mg capsules have not been established in pediatric patients. Also, no overall differences in the safety and efficacy of this drug were observed in patients over 65 years of age in comparison with other adult patients. 

  • Hepatic Impairment: No initial dose adjustments are recommended in patients suffering from hepatic impairment. However, further dose modifications may be needed as per the tolerance and reactions during the course of this medication. 

  • Renal Impairment: No initial dose adjustments are recommended in patients suffering from renal impairment. However, further dose modifications may be needed as per the tolerance and reactions during the course of this medication.

  • Patients administering CYP3A4 Inhibitors: When a CYP3A4 inhibitor (Ketoconazole) is administered with Sunicine (Sunitinib Malate) capsules, the plasma concentrations of Sunitinib may increase. Therefore, it is recommended to select a concomitant drug with no or minimal potential for enzyme inhibition. If a strong CYP3A4 inhibitor can not be avoided with Sunicine, dose adjustments (reduction) should be done in the strength of Sunicine. 

  • Patients administering CYP3A4 Inducers: Administration of a CYP3A4 Inducer (Rifampin) while co-administering Sunicine capsules may lead to a decrease in plasma concentration of Sunitinib Malate. If a strong CYP3A4 Inducer can not be avoided with Sunicine, dose adjustments (increase) should be done in the strength of Sunicine.

Packaging and Storage

Sunicine (Sunitinib Malate) is available in the form of capsules indicated for oral use in a high-density polyethylene bottle containing 28 capsules. Store the capsules at 59°F to 86°F (15°C to 30°C). Keep Sunicine capsules away from the reach of pets and children. Do not place the bottle/capsules under direct light and heat. Protect them from moisture. Know the ways to dispose of the used and expired packs of Sunicine from a pharmacist. Women who are pregnant should not handle Sunicine capsules without protection (gloves).