- Approval Id
- d09eba387d6fd19a
- Drug Name
- STIVARGA TABLET 40MG
- Product Name
- STIVARGA TABLET 40MG
- Approval Number
- SIN14360P
- Approval Date
- 2013-06-07
- Registrant
- BAYER (SOUTH EAST ASIA) PTE LTD
- Licence Holder
- BAYER (SOUTH EAST ASIA) PTE LTD
- Drug Type
- Therapeutic
- Forensic Classification
- PRESCRIPTION ONLY MEDICINES
- Dosage Form
- TABLET, FILM COATED
- Dosage
- <p><strong>4.2 Dosage and method of administration</strong><br>
<strong>4.2.1 Method of administration</strong><br>
For oral use.</p>
<p><strong>4.2.2 Dosage regimen</strong><br>
The recommended dose is 160 mg regorafenib (4 tablets Stivarga each containing 40 mg regorafenib), taken orally once daily for 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks.</p>
<p>Stivarga should be taken at the same time each day. The tablets should be swallowed whole with water after a light meal. If a dose of Stivarga is missed, then it should be taken on the same day as soon as the patient remembers. The patient should not take two doses on the same day to make up for a missed dose.</p>
<p>Treatment should continue until disease progression or unacceptable toxicity occurs (see section ‘Special warnings and precautions for use’ – <em>please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information</em>).</p>
<p><strong>4.2.3 Dose modification</strong><br>
If dose modifications are required, reduce the dose in 40 mg (one tablet) increments; the lowest recommended daily dose of STIVARGA is 80 mg daily.</p>
<p>Interrupt Stivarga for the following:</p>
<ul>
<li>Grade 2 hand-foot skin reaction (HFSR) [palmar-plantar erythrodysesthesia syndrome (PPES)] that is recurrent or does not improve within 7 days despite dose reduction; interrupt therapy for a minimum of 7 days for Grade 3 HFSR</li>
<li>Symptomatic Grade 2 hypertension</li>
<li>Any Grade 3 or 4 adverse reaction</li>
<li>Worsening infection of any grade</li>
</ul>
<p>Reduce the dose of Stivarga to 120 mg:</p>
<ul>
<li>For the first occurrence of Grade 2 HFSR of any duration</li>
<li>After recovery of any Grade 3 or 4 adverse reaction except infection</li>
<li>For Grade 3 aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) elevation; only resume if the potential benefit outweighs the risk of hepatotoxicity</li>
</ul>
<p>Reduce the dose of Stivarga to 80 mg:</p>
<ul>
<li>For re-occurrence of Grade 2 HFSR at the 120 mg dose</li>
<li>After recovery of any Grade 3 or 4 adverse reaction at the 120 mg dose (except hepatotoxicity or infection)</li>
</ul>
<p>Discontinue Stivarga permanently for the following:</p>
<ul>
<li>Failure to tolerate 80 mg dose</li>
<li>Any occurrence of AST or ALT more than 20 times the upper limit of normal (ULN)</li>
<li>Any occurrence of AST or ALT more than 3 times ULN with concurrent bilirubin more than 2 times ULN</li>
<li>Re-occurrence of AST or ALT more than 5 times ULN despite dose reduction to 120 mg</li>
<li>For any Grade 4 adverse reaction; only resume if the potential benefit outweighs the risks</li>
</ul>
<p><strong>4.2.4 Additional information on special populations</strong><br>
<strong>4.2.4.1 Patients with hepatic impairment</strong><br>
Regorafenib is eliminated mainly via the hepatic route.</p>
<p>In clinical studies, no relevant differences in exposure, safety or efficacy were observed between patients with mild hepatic impairment (Child-Pugh A) and normal hepatic function. No dose adjustment is required in patients with mild hepatic impairment. Since only limited data are available for patients with moderate hepatic impairment (Child Pugh B), no dose recommendation can be provided.<br>
Close monitoring of overall safety is recommended in these patients (see also sections ‘Special warnings and precautions for use’ and ‘Pharmacokinetic properties’ – <em>please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information</em>).</p>
<p>Stivarga is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) as Stivarga has not been studied in this population.</p>
<p><strong>4.2.4.2 Patients with renal impairment</strong><br>
Available clinical data indicate similar exposure of regorafenib and its metabolites M-2 and M-5 in patients with mild, moderate or severe renal impairment compared to patients with normal renal function.<br>
No dose adjustment is required in patients with mild, moderate or severe renal impairment. (see also section ‘Pharmacokinetic properties’ – <em>please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information</em>).</p>
<p><strong>4.2.4.3 Pediatric patients</strong><br>
The safety and efficacy of Stivarga in children and adolescents below 18 years of age have not been established.</p>
<p><strong>4.2.4.4 Geriatric patients</strong><br>
In clinical studies, no relevant differences in exposure, safety or efficacy were observed between elderly (aged 65 years and above) and younger patients. No dose adjustment is necessary in elderly patients (see also section ‘Pharmacokinetic properties’ – <em>please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information</em>).</p>
<p><strong>4.2.4.5 Gender</strong><br>
In clinical studies, no relevant differences in exposure, safety or efficacy were observed between male and female patients. No dose adjustment is necessary based on gender (see also section ‘Pharmacokinetic properties’ – <em>please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information</em>).</p>
<p><strong>4.2.4.6 Ethnic differences</strong><br>
In clinical studies, no relevant differences in exposure or efficacy were observed between patients of different ethnic groups. No dose adjustment is necessary based on ethnicity. A higher incidence of hand foot skin reaction (HFSR), severe liver function test abnormalities and hepatic dysfunction was observed in Asian (in particular Japanese) patients treated with Stivarga as compared with Caucasians. The Asian patients treated with Stivarga in clinical studies were primarily from East Asia (~90%).</p>
- Route Of Administration
- ORAL
- Indication Info
- <p><strong>4.1 Indication(s)</strong></p>
<p><strong>Colorectal Cancer</strong><br>
Stivarga is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild type, an anti-EGFR therapy.</p>
<p><strong>Gastrointestinal Stromal Tumors</strong><br>
Stivarga is indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.</p>
<p><strong>Hepatocellular Carcinoma</strong><br>
Stivarga is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.</p>
- Contraindications
- <p><strong>4.3 Contraindications</strong><br>
There is no contraindication to the use of Stivarga.</p>
- Atc Code
- L01XE21
- Atc Item Name
- xl 01 xe 21
- Pharma Manufacturer Name
- BAYER (SOUTH EAST ASIA) PTE LTD
