Teysuno 15 mg/4.35 mg/11.8 mg hard capsules ▼

Each hard capsule contains 15 mg tegafur, 4.35 mg gimeracil and 11.8 mg oteracil (as 14.7 mg of oteracil monopotassium).

Excipient(s)

Each hard capsule contains 70.2 mg lactose monohydrate.

For a full list of excipients, see section 6.1.

Hard capsule (capsule).

The capsule has an opaque white body and opaque brown cap imprinted “TC448” in grey.

 

Teysuno is indicated in adults for the treatment of advanced gastric cancer when given in combination with cisplatin (see section 5.1).

Teysuno should only be prescribed by a qualified physician experienced in treating cancer patients with anti-neoplastic medicinal products.

Posology

The recommended standard dose of Teysuno when administered in combination with cisplatin is 25 mg/m² (expressed as tegafur content) twice daily, morning and evening, for 21 consecutive days followed by 7 days rest (1 treatment cycle). This treatment cycle is repeated every 4 weeks.

The standard and reduced Teysuno and cisplatin doses and calculations according to body surface area (BSA) for doses of Teysuno given in combination with cisplatin are provided in Table 1 and Table 2, respectively. The patient's BSA must be recalculated and the Teysuno dose adjusted accordingly if a patient's weight increases or decreases by ≥10% from the one used for the previous calculation of BSA and the change is clearly not related to fluid retention.

The recommended dose of cisplatin with this regimen is 75 mg/m² by intravenous infusion administered once every 4 weeks. Cisplatin should be discontinued after 6 cycles without withdrawal of Teysuno. If cisplatin is discontinued before 6 cycles, Teysuno treatment alone can be resumed when the criteria for restarting it are met.

Patients treated with Teysuno in combination with cisplatin should be closely monitored and laboratory tests, including haematology, liver function, renal function, and serum electrolytes, should be performed frequently. Treatment should be discontinued if progressive disease or intolerable toxicity is observed.

Refer to the cisplatin summary of product characteristics (SmPC) for pretreatment hyperhydration.

Patients should be provided with outpatient prescriptions for anti-emetic and anti-diarrhoeal medicinal products.

Teysuno doses

Table 1: Standard dose and dose reductions allowed for Teysuno and/or for cisplatin

Medicinal product	Standard dose (mg/m2)		Dose reduction 1 (mg/m2)		Dose reduction 2 (mg/m2)
Teysuno	25a	→	20a	→	15a
and/or
Cisplatin	75	→	60	→	45
a Expressed as tegafur content.

Teysuno dose calculations

Table 2: Standard and reduced dose calculations by body surface area (m²)

Teysuno dose	Each dose in mg (each dosing)a	Total daily dose in mga	Number of capsules for each dose (2 doses/day)
Standard dosea: 25 mg/m2			15 mg capsulea (brown/white)	20 mg capsulea (white)
BSA ≥ 2.30 m2	60	120	0	3
BSA = 2.10 - 2.29 m2	55	110	1	2
BSA = 1.90 - 2.09 m2	50	100	2	1
BSA = 1.70 - 1.89 m2	45	90	3	0
BSA = 1.50 - 1.69 m2	40	80	0	2
BSA = 1.30 - 1.49 m2	35	70	1	1
BSA ≤ 1.29 m2	30	60	2	0
First dose reductiona: to 20 mg/m2
BSA ≥ 2.13 m2	45	90	3	0
BSA = 1.88 - 2.12 m2	40	80	0	2
BSA = 1.63 - 1.87 m2	35	70	1	1
BSA = 1.30 - 1.62 m2	30	60	2	0
BSA ≤ 1.29 m2	20	40	0	1
Second dose reductiona: to 15 mg/m2
BSA ≥ 2.17 m2	35	70	1	1
BSA = 1.67 - 2.16 m2	30	60	2	0
BSA = 1.30 - 1.66 m2	20	40	0	1
BSA ≤ 1.29 m2	15	30	1	0
Calculate BSA to 2 decimal places. a Expressed as tegafur content.

Adjustments during treatment

General

Toxicity due to Teysuno administration should be managed with symptomatic treatment and/or treatment interruption or dose reduction. Patients taking Teysuno should be informed of the risks and instructed to contact their physician immediately if moderate or severe toxicity occurs.

Doses omitted for toxicity are not replaced; and, if a patient vomits after taking a dose, this dose should not be replaced.

Once the Teysuno dose has been reduced, it should not be increased again.

Teysuno dose modification criteria

Dose modifications for toxicity should be made according to Tables 1, 3, 4, and 5. A maximum of two consecutive dose reductions for each medicinal product, as described in Table 1, can be applied in case of toxicity. Each dose reduction results in approximately 20-25% reduction of dose. See Table 2 for the details of the number of Teysuno capsules to be administered for each dose level. For minimum criteria for resumption of Teysuno treatment, see Table 6.

Teysuno dose modifications for toxicity when used in combination with cisplatin can be made in two ways.

• During a 4-week cycle of treatment

Teysuno should only be given on Days 1 to 21 of each cycle, i.e., treatment should not be given on Days 22 to 28 of a cycle. Treatment days missed in a cycle where drug was held due to toxicity should not be replaced.

During a treatment cycle, dose adjustment should be performed for each individual medicinal product that is considered to be causally related to the toxicity, if such a distinction can be made. If both medicinal products are considered to be causing the toxicity or it is not possible to distinguish them, then dose reduction should be performed for both according to the recommended dose reduction schedule.

• At the initiation of subsequent cycles of treatment

If a treatment delay is indicated for either Teysuno or cisplatin, then administration of both medicinal products should be delayed until the requirements for restarting both are met unless one of the medicinal products has been permanently discontinued.

Dose modifications for Teysuno for adverse reactions in general except for haematologic and renal toxicities

Table 3: Teysuno dose reduction schedule for treatment-related toxicities in general, except for haematologic and renal toxicities

Toxicity grades a	Teysuno dose changes within a 21-day treatment cycle	Teysuno dose adjustment for next dose / next cycle
Grade 1
Any occurrence	Maintain treatment at same dose level	None
Grade 2b,c
Any occurrence	Suspend treatment until Grade 0 or 1	None
Grade 3 or Higherc
First occurrence	Suspend treatment until Grade 0 or 1	Reduce by 1 dose level from previous level
Second occurrence	Suspend treatment until Grade 0 or 1	Reduce by 1 dose level from previous level
Third occurrence	Discontinue treatment	Discontinue treatment
a According to the Common Terminology Criteria for Adverse Events (CTCAE) of the Cancer Therapy eva luation Program, US National Cancer Institute, version 3.0. b For Grade 2 nausea and/or vomiting, the anti-emetic therapy should be optimized prior to a suspension of Teysuno. c At the discretion of the treating physician, patients may continue with treatment without reduction or interruption for adverse reactions (irrespective of grade) considered unlikely to become serious or life-threatening (e.g., alopecia, changes in sexual function, and dry skin).

Dose modifications for renal toxicities

Creatinine clearance (CrCl) must be determined for every cycle before the start of treatment on Day 1.

Table 4: Teysuno and cisplatin dose modification according to creatinine clearance values at the start of a cycle of treatment

Creatinine clearance	Teysuno dose modification at the start of the cycle of treatment	Cisplatin dose modification at the start of the cycle of treatment
≥50 ml/min	No dose modification	No dose modification
30 to 49 ml/min	Start treatment at one reduced dose level	Start cisplatin treatment at a 50% dose reduction from the previous cycle
<30 ml/mina	Suspend treatment until resumption criterion (≥30 ml/min) is met and then start treatment at one reduced dose level	Suspend cisplatin treatment until resumption criterion (≥30 ml/min) is met and then start treatment at a 50% dose reduction from the previous cycle
a Treatment for patients with CrCl <30 ml/min is not recommended unless the benefits of Teysuno treatment clearly outweigh the risks. Refer to paragraph Dose modifications for special populations / Renal impairment for guidance.

Dose modifications for haematologic toxicities

Table 5: Haematologic toxicities for which Teysuno treatment should be suspended

Units	Neutrophils	Platelets	Haemoglobin	Teysuno dose modification
IU	<0.5 x 109/l	<25 x 109/l	4.0 mmol/l	Suspend treatment until resumption criterion is met (see Table 6) and then resume dosing at one reduced dose level.

Resumption criteria for Teysuno treatment

Table 6: Minimum criteria to resume Teysuno treatment following its suspension due to a toxicity

Non-haematologic	Haematologic
Baseline or Grade 1	Platelet count ≥100 x 109/l
Calculated creatinine clearance ≥30 ml/mina	Neutrophils ≥1.5 x 109/l
	Haemoglobin ≥6.2 mmol/l
CrCl must be calculated at the beginning of every cycle before the start of treatment with Teysuno on Day 1.
a Treatment for patients with CrCl <30 ml/min is not recommended unless the benefits of Teysuno treatment clearly outweigh the risks. Refer to paragraph Dose modifications for special populations / Renal impairment for guidance.

Dose modifications for special populations

Renal impairment

• Mild renal impairment (CrCl 51 to 80 ml/min)

No adjustment of the standard dose is recommended in patients with mild renal impairment (see section 5.2).

• Moderate renal impairment (CrCl 30 to 50 ml/min)

The recommended standard dose in patients with moderate renal impairment is 20 mg/m² twice daily (expressed as tegafur content) (see sections 4.8 and 5.2).

• Severe renal impairment (CrCl below 30 ml/min)

Although roughly similar daily exposure to 5-FU would be expected in patients with severe renal impairment at a dose of 20 mg/m² once daily compared to 30 mg/m² twice daily in patients with normal renal function (see section 5.2), administration of Teysuno is not recommended due to possibly higher incidence of adverse events of the blood and lymphatic system disorders unless the benefits clearly outweigh the risks (see sections 4.4 and 4.8).

No data is available regarding Teysuno administration in patients with end stage renal disease requiring dialysis (see section 4.3).

Elderly

No adjustment of the standard dose is recommended in patients >70 years old (see section 4.8).

Hepatic impairment

No adjustment of the standard dose is recommended for patients with hepatic impairment (see section 5.2).

Ethnicity

No adjustment of the standard dose is recommended for patients of Asian ethnicity (see section 5.2).

Paediatric population

The safety and efficacy of Teysuno in children and adolescents under 18 years old have not been established. No data are available. Therefore, Teysuno should not be administered to children or adolescents under 18 years of age.

Method of administration

Capsules should be taken by mouth with water at least 1 hour before or 1 hour after a meal (see section 5.2).

• Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil) or to any of the excipients (see sections 4.4 and 6.1).

• History of severe and unexpected reactions to fluoropyrimidine therapy.

• Known dihydropyrimidine dehydrogenase (DPD) deficiency.

• Pregnancy and breastfeeding.

• Severe bone marrow suppression (severe leukopaenia, neutropaenia, or thrombocytopaenia; see section 4.2, Table 5).

• End stage renal disease patients requiring dialysis.

• Co-administration of other fluoropyrimidines with Teysuno.

• Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.

• Contraindications for cisplatin; refer to the cisplatin SmPC.