Dosage & Administration
Recommended dosage: 150 mg orally twice daily. (
The recommended dosage of Zydelig is 150 mg administered orally twice daily with or without food until disease progression or unacceptable toxicity. The optimal and safe dosing regimen for patients who receive treatment longer than several months is unknown.
Swallow tablets whole.
If a planned dose of Zydelig is missed by less than 6 hours, take the missed dose as soon as possible and take the next dose as usual. If a dose of Zydelig is missed by more than 6 hours, skip the missed dose and take the next dose at the usual time.
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Zydelig Prescribing Information
Table 1 presents the dosage modification for specific adverse reactions.
For other severe or life-threatening adverse reactions, withhold Zydelig until resolution. If resuming Zydelig after interruption for other severe or life-threatening toxicities, reduce the dosage to 100 mg orally twice daily. Permanently discontinue Zydelig for recurrence of other severe or life-threatening Zydelig-related toxicity upon rechallenge.
| Abbreviations: ANC: absolute neutrophil count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; ULN, upper limit of normal; CMV, cytomegalovirus; DRESS, drug reaction with eosinophilia and systemic symptoms; PCR: polymerase chain reaction; PJP: Pneumocystis jirovecii pneumonia; SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis | |||
ALT/AST | >3–5 × ULN | >5–20 × ULN | >20 × ULN |
[see Warnings and Precautions (5.1)] | Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. | Withhold Zydelig. Monitor at least weekly until ALT/AST are ≤1 × ULN, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
Bilirubin | >1.5–3 × ULN | >3–10 × ULN | >10 × ULN |
[see Warnings and Precautions (5.1)] | Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. | Withhold Zydelig. Monitor at least weekly until bilirubin is ≤1 × ULN, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
DiarrheaModerate diarrhea: increase of 4–6 stools per day over baseline; severe diarrhea: increase of ≥7 stools per day over baseline. | Moderate diarrhea | Severe diarrhea or hospitalization | Life-threatening diarrhea |
[see Warnings and Precautions (5.2)] | Maintain Zydelig dose. Monitor at least weekly until resolved. | Withhold Zydelig. Monitor at least weekly until resolved, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
Pneumonitis | Any symptomatic pneumonitis | ||
[see Warnings and Precautions (5.3)] | Discontinue Zydelig in patients with any severity of symptomatic pneumonitis. | ||
Infections | Grade 3 or higher sepsis or pneumonia | ||
[see Warnings and Precautions (5.4)] | Interrupt Zydelig until infection has resolved. | ||
Evidence of CMV infection or viremia | |||
| Interrupt Zydelig in patients with evidence of active CMV infection of any grade or viremia (positive PCR or antigen test) until the viremia has resolved. If Zydelig is resumed, monitor patients by PCR or antigen test for CMV reactivation at least monthly. | |||
Evidence of PJP infection | |||
| Interrupt Zydelig in patients with suspected PJP infection of any grade. Permanently discontinue Zydelig if PJP infection is confirmed. | |||
Intestinal Perforation | Evidence of intestinal perforation | ||
[see Warnings and Precautions (5.5)] | Permanently discontinue Zydelig in patients who experience intestinal perforation. | ||
Severe Cutaneous Reactions | Suspected/Confirmed SJS, TEN, DRESS, or other severe or life-threatening (Grade ≥3) cutaneous reactions | ||
[see Warnings and Precautions (5.6)] | Interrupt Zydelig in patients with suspected SJS, TEN, or DRESS until the etiology of the reaction has been determined. Permanently discontinue Zydelig in patients with confirmed SJS, TEN, or DRESS, or other severe or life-threatening (Grade ≥3) cutaneous reactions. | ||
Hypersensitivity Reactions | Evidence of hypersensitivity reactions | ||
[see Warnings and Precautions (5.7)] | Permanently discontinue Zydelig in patients who develop serious hypersensitivity reactions. | ||
Neutropenia | ANC 1.0 to <1.5 Gi/L | ANC 0.5 to <1.0 Gi/L | ANC <0.5 Gi/L |
[see Warnings and Precautions (5.8)] | Maintain Zydelig dose. | Maintain Zydelig dose. Monitor ANC at least weekly. | Interrupt Zydelig. Monitor ANC at least weekly until ANC ≥0.5 Gi/L, then may resume Zydelig at 100 mg BID. |
Thrombocytopenia | Platelets 50 to <75 Gi/L | Platelets 25 to <50 Gi/L | Platelets <25 Gi/L |
[see Adverse Reactions (6.1)] | Maintain Zydelig dose. | Maintain Zydelig dose. Monitor platelet counts at least weekly. | Interrupt Zydelig. Monitor platelet count at least weekly. May resume Zydelig at 100 mg BID when platelets ≥25 Gi/L. |
No dosage modification is recommended for lymphocytosis, which has been observed in some patients taking Zydelig. This observed lymphocytosis is a pharmacodynamic effect and should not be considered progressive disease in the absence of other clinical findings.
Fatal and/or serious hepatotoxicity occurred in 16% of patients treated with Zydelig in combination with rituximab or with unapproved combination therapies. Elevations in ALT or AST greater than 5 times the upper limit of normal have occurred
Avoid concurrent use of Zydelig with other drugs that may cause liver toxicity.
Monitor ALT and AST in all patients every 2 weeks for the first 3 months of treatment, every 4 weeks for the next 3 months, then every 1 to 3 months thereafter. Monitor weekly for liver toxicity if the ALT or AST rises above 3 times the upper limit of normal until resolved. Withhold Zydelig if the ALT or AST is greater than 5 times the upper limit of normal, and continue to monitor AST, ALT and total bilirubin weekly until the abnormality is resolved
Table 1 presents the dosage modification for specific adverse reactions.
For other severe or life-threatening adverse reactions, withhold Zydelig until resolution. If resuming Zydelig after interruption for other severe or life-threatening toxicities, reduce the dosage to 100 mg orally twice daily. Permanently discontinue Zydelig for recurrence of other severe or life-threatening Zydelig-related toxicity upon rechallenge.
| Abbreviations: ANC: absolute neutrophil count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; ULN, upper limit of normal; CMV, cytomegalovirus; DRESS, drug reaction with eosinophilia and systemic symptoms; PCR: polymerase chain reaction; PJP: Pneumocystis jirovecii pneumonia; SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis | |||
ALT/AST | >3–5 × ULN | >5–20 × ULN | >20 × ULN |
[see Warnings and Precautions (5.1)] | Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. | Withhold Zydelig. Monitor at least weekly until ALT/AST are ≤1 × ULN, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
Bilirubin | >1.5–3 × ULN | >3–10 × ULN | >10 × ULN |
[see Warnings and Precautions (5.1)] | Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. | Withhold Zydelig. Monitor at least weekly until bilirubin is ≤1 × ULN, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
DiarrheaModerate diarrhea: increase of 4–6 stools per day over baseline; severe diarrhea: increase of ≥7 stools per day over baseline. | Moderate diarrhea | Severe diarrhea or hospitalization | Life-threatening diarrhea |
[see Warnings and Precautions (5.2)] | Maintain Zydelig dose. Monitor at least weekly until resolved. | Withhold Zydelig. Monitor at least weekly until resolved, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
Pneumonitis | Any symptomatic pneumonitis | ||
[see Warnings and Precautions (5.3)] | Discontinue Zydelig in patients with any severity of symptomatic pneumonitis. | ||
Infections | Grade 3 or higher sepsis or pneumonia | ||
[see Warnings and Precautions (5.4)] | Interrupt Zydelig until infection has resolved. | ||
Evidence of CMV infection or viremia | |||
| Interrupt Zydelig in patients with evidence of active CMV infection of any grade or viremia (positive PCR or antigen test) until the viremia has resolved. If Zydelig is resumed, monitor patients by PCR or antigen test for CMV reactivation at least monthly. | |||
Evidence of PJP infection | |||
| Interrupt Zydelig in patients with suspected PJP infection of any grade. Permanently discontinue Zydelig if PJP infection is confirmed. | |||
Intestinal Perforation | Evidence of intestinal perforation | ||
[see Warnings and Precautions (5.5)] | Permanently discontinue Zydelig in patients who experience intestinal perforation. | ||
Severe Cutaneous Reactions | Suspected/Confirmed SJS, TEN, DRESS, or other severe or life-threatening (Grade ≥3) cutaneous reactions | ||
[see Warnings and Precautions (5.6)] | Interrupt Zydelig in patients with suspected SJS, TEN, or DRESS until the etiology of the reaction has been determined. Permanently discontinue Zydelig in patients with confirmed SJS, TEN, or DRESS, or other severe or life-threatening (Grade ≥3) cutaneous reactions. | ||
Hypersensitivity Reactions | Evidence of hypersensitivity reactions | ||
[see Warnings and Precautions (5.7)] | Permanently discontinue Zydelig in patients who develop serious hypersensitivity reactions. | ||
Neutropenia | ANC 1.0 to <1.5 Gi/L | ANC 0.5 to <1.0 Gi/L | ANC <0.5 Gi/L |
[see Warnings and Precautions (5.8)] | Maintain Zydelig dose. | Maintain Zydelig dose. Monitor ANC at least weekly. | Interrupt Zydelig. Monitor ANC at least weekly until ANC ≥0.5 Gi/L, then may resume Zydelig at 100 mg BID. |
Thrombocytopenia | Platelets 50 to <75 Gi/L | Platelets 25 to <50 Gi/L | Platelets <25 Gi/L |
[see Adverse Reactions (6.1)] | Maintain Zydelig dose. | Maintain Zydelig dose. Monitor platelet counts at least weekly. | Interrupt Zydelig. Monitor platelet count at least weekly. May resume Zydelig at 100 mg BID when platelets ≥25 Gi/L. |
No dosage modification is recommended for lymphocytosis, which has been observed in some patients taking Zydelig. This observed lymphocytosis is a pharmacodynamic effect and should not be considered progressive disease in the absence of other clinical findings.
Severe diarrhea or colitis (Grade 3 or higher) occurred in 20% of patients treated with Zydelig in combination with rituximab or with unapproved combination therapies
Table 1 presents the dosage modification for specific adverse reactions.
For other severe or life-threatening adverse reactions, withhold Zydelig until resolution. If resuming Zydelig after interruption for other severe or life-threatening toxicities, reduce the dosage to 100 mg orally twice daily. Permanently discontinue Zydelig for recurrence of other severe or life-threatening Zydelig-related toxicity upon rechallenge.
| Abbreviations: ANC: absolute neutrophil count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; ULN, upper limit of normal; CMV, cytomegalovirus; DRESS, drug reaction with eosinophilia and systemic symptoms; PCR: polymerase chain reaction; PJP: Pneumocystis jirovecii pneumonia; SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis | |||
ALT/AST | >3–5 × ULN | >5–20 × ULN | >20 × ULN |
[see Warnings and Precautions (5.1)] | Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. | Withhold Zydelig. Monitor at least weekly until ALT/AST are ≤1 × ULN, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
Bilirubin | >1.5–3 × ULN | >3–10 × ULN | >10 × ULN |
[see Warnings and Precautions (5.1)] | Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. | Withhold Zydelig. Monitor at least weekly until bilirubin is ≤1 × ULN, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
DiarrheaModerate diarrhea: increase of 4–6 stools per day over baseline; severe diarrhea: increase of ≥7 stools per day over baseline. | Moderate diarrhea | Severe diarrhea or hospitalization | Life-threatening diarrhea |
[see Warnings and Precautions (5.2)] | Maintain Zydelig dose. Monitor at least weekly until resolved. | Withhold Zydelig. Monitor at least weekly until resolved, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
Pneumonitis | Any symptomatic pneumonitis | ||
[see Warnings and Precautions (5.3)] | Discontinue Zydelig in patients with any severity of symptomatic pneumonitis. | ||
Infections | Grade 3 or higher sepsis or pneumonia | ||
[see Warnings and Precautions (5.4)] | Interrupt Zydelig until infection has resolved. | ||
Evidence of CMV infection or viremia | |||
| Interrupt Zydelig in patients with evidence of active CMV infection of any grade or viremia (positive PCR or antigen test) until the viremia has resolved. If Zydelig is resumed, monitor patients by PCR or antigen test for CMV reactivation at least monthly. | |||
Evidence of PJP infection | |||
| Interrupt Zydelig in patients with suspected PJP infection of any grade. Permanently discontinue Zydelig if PJP infection is confirmed. | |||
Intestinal Perforation | Evidence of intestinal perforation | ||
[see Warnings and Precautions (5.5)] | Permanently discontinue Zydelig in patients who experience intestinal perforation. | ||
Severe Cutaneous Reactions | Suspected/Confirmed SJS, TEN, DRESS, or other severe or life-threatening (Grade ≥3) cutaneous reactions | ||
[see Warnings and Precautions (5.6)] | Interrupt Zydelig in patients with suspected SJS, TEN, or DRESS until the etiology of the reaction has been determined. Permanently discontinue Zydelig in patients with confirmed SJS, TEN, or DRESS, or other severe or life-threatening (Grade ≥3) cutaneous reactions. | ||
Hypersensitivity Reactions | Evidence of hypersensitivity reactions | ||
[see Warnings and Precautions (5.7)] | Permanently discontinue Zydelig in patients who develop serious hypersensitivity reactions. | ||
Neutropenia | ANC 1.0 to <1.5 Gi/L | ANC 0.5 to <1.0 Gi/L | ANC <0.5 Gi/L |
[see Warnings and Precautions (5.8)] | Maintain Zydelig dose. | Maintain Zydelig dose. Monitor ANC at least weekly. | Interrupt Zydelig. Monitor ANC at least weekly until ANC ≥0.5 Gi/L, then may resume Zydelig at 100 mg BID. |
Thrombocytopenia | Platelets 50 to <75 Gi/L | Platelets 25 to <50 Gi/L | Platelets <25 Gi/L |
[see Adverse Reactions (6.1)] | Maintain Zydelig dose. | Maintain Zydelig dose. Monitor platelet counts at least weekly. | Interrupt Zydelig. Monitor platelet count at least weekly. May resume Zydelig at 100 mg BID when platelets ≥25 Gi/L. |
No dosage modification is recommended for lymphocytosis, which has been observed in some patients taking Zydelig. This observed lymphocytosis is a pharmacodynamic effect and should not be considered progressive disease in the absence of other clinical findings.
Fatal and serious pneumonitis occurred in patients treated with Zydelig
If symptomatic pneumonitis or organizing pneumonia is diagnosed, initiate appropriate treatment with corticosteroids and permanently discontinue Zydelig
Table 1 presents the dosage modification for specific adverse reactions.
For other severe or life-threatening adverse reactions, withhold Zydelig until resolution. If resuming Zydelig after interruption for other severe or life-threatening toxicities, reduce the dosage to 100 mg orally twice daily. Permanently discontinue Zydelig for recurrence of other severe or life-threatening Zydelig-related toxicity upon rechallenge.
| Abbreviations: ANC: absolute neutrophil count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; ULN, upper limit of normal; CMV, cytomegalovirus; DRESS, drug reaction with eosinophilia and systemic symptoms; PCR: polymerase chain reaction; PJP: Pneumocystis jirovecii pneumonia; SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis | |||
ALT/AST | >3–5 × ULN | >5–20 × ULN | >20 × ULN |
[see Warnings and Precautions (5.1)] | Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. | Withhold Zydelig. Monitor at least weekly until ALT/AST are ≤1 × ULN, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
Bilirubin | >1.5–3 × ULN | >3–10 × ULN | >10 × ULN |
[see Warnings and Precautions (5.1)] | Maintain Zydelig dose. Monitor at least weekly until ≤1 × ULN. | Withhold Zydelig. Monitor at least weekly until bilirubin is ≤1 × ULN, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
DiarrheaModerate diarrhea: increase of 4–6 stools per day over baseline; severe diarrhea: increase of ≥7 stools per day over baseline. | Moderate diarrhea | Severe diarrhea or hospitalization | Life-threatening diarrhea |
[see Warnings and Precautions (5.2)] | Maintain Zydelig dose. Monitor at least weekly until resolved. | Withhold Zydelig. Monitor at least weekly until resolved, then may resume Zydelig at 100 mg BID. | Discontinue Zydelig permanently. |
Pneumonitis | Any symptomatic pneumonitis | ||
[see Warnings and Precautions (5.3)] | Discontinue Zydelig in patients with any severity of symptomatic pneumonitis. | ||
Infections | Grade 3 or higher sepsis or pneumonia | ||
[see Warnings and Precautions (5.4)] | Interrupt Zydelig until infection has resolved. | ||
Evidence of CMV infection or viremia | |||
| Interrupt Zydelig in patients with evidence of active CMV infection of any grade or viremia (positive PCR or antigen test) until the viremia has resolved. If Zydelig is resumed, monitor patients by PCR or antigen test for CMV reactivation at least monthly. | |||
Evidence of PJP infection | |||
| Interrupt Zydelig in patients with suspected PJP infection of any grade. Permanently discontinue Zydelig if PJP infection is confirmed. | |||
Intestinal Perforation | Evidence of intestinal perforation | ||
[see Warnings and Precautions (5.5)] | Permanently discontinue Zydelig in patients who experience intestinal perforation. | ||
Severe Cutaneous Reactions | Suspected/Confirmed SJS, TEN, DRESS, or other severe or life-threatening (Grade ≥3) cutaneous reactions | ||
[see Warnings and Precautions (5.6)] | Interrupt Zydelig in patients with suspected SJS, TEN, or DRESS until the etiology of the reaction has been determined. Permanently discontinue Zydelig in patients with confirmed SJS, TEN, or DRESS, or other severe or life-threatening (Grade ≥3) cutaneous reactions. | ||
Hypersensitivity Reactions | Evidence of hypersensitivity reactions | ||
[see Warnings and Precautions (5.7)] | Permanently discontinue Zydelig in patients who develop serious hypersensitivity reactions. | ||
Neutropenia | ANC 1.0 to <1.5 Gi/L | ANC 0.5 to <1.0 Gi/L | ANC <0.5 Gi/L |
[see Warnings and Precautions (5.8)] | Maintain Zydelig dose. | Maintain Zydelig dose. Monitor ANC at least weekly. | Interrupt Zydelig. Monitor ANC at least weekly until ANC ≥0.5 Gi/L, then may resume Zydelig at 100 mg BID. |
Thrombocytopenia | Platelets 50 to <75 Gi/L | Platelets 25 to <50 Gi/L | Platelets <25 Gi/L |
[see Adverse Reactions (6.1)] | Maintain Zydelig dose. | Maintain Zydelig dose. Monitor platelet counts at least weekly. | Interrupt Zydelig. Monitor platelet count at least weekly. May resume Zydelig at 100 mg BID when platelets ≥25 Gi/L. |
No dosage modification is recommended for lymphocytosis, which has been observed in some patients taking Zydelig. This observed lymphocytosis is a pharmacodynamic effect and should not be considered progressive disease in the absence of other clinical findings.
Fatal and/or serious infections occurred in 48% of patients treated with Zydelig in combination with rituximab or with unapproved combination therapies
Serious or fatal
Fatal and serious intestinal perforation occurred in Zydelig-treated patients. At the time of perforation, some patients had moderate to severe diarrhea. Advise patients to promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting. Discontinue Zydelig permanently in patients who experience intestinal perforation.
Indications and Usage, Relapsed Follicular B-cell non-Hodgkin Lymphoma – Accelerated Approval Indication Removed (Zydelig is indicated, in combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. Zydelig is a kinase inhibitor indicated for the treatment of patients with:
Limitations of use: Zydelig is not indicated and is not recommended for first-line treatment of any patient, including patients with CLL, small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other indolent non-Hodgkin lymphomas. Zydelig is not indicated and is not recommended in combination with bendamustine and rituximab, or in combination with rituximab for the treatment of patients with FL, SLL, and other indolent non-Hodgkin lymphomas. Limitations of Use Zydelig is not indicated and is not recommended for first-line treatment of any patient, including patients with CLL, small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other indolent non-Hodgkin lymphomas. Zydelig is not indicated and is not recommended in combination with bendamustine and rituximab, or in combination with rituximab for the treatment of patients with FL, SLL, and other indolent non-Hodgkin lymphomas. 2/2022 |
Indications and Usage, Relapsed Small Lymphocytic Lymphoma – Accelerated Approval Indication Removed (Zydelig is indicated, in combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. Zydelig is a kinase inhibitor indicated for the treatment of patients with:
Limitations of use: Zydelig is not indicated and is not recommended for first-line treatment of any patient, including patients with CLL, small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other indolent non-Hodgkin lymphomas. Zydelig is not indicated and is not recommended in combination with bendamustine and rituximab, or in combination with rituximab for the treatment of patients with FL, SLL, and other indolent non-Hodgkin lymphomas. Limitations of Use Zydelig is not indicated and is not recommended for first-line treatment of any patient, including patients with CLL, small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other indolent non-Hodgkin lymphomas. Zydelig is not indicated and is not recommended in combination with bendamustine and rituximab, or in combination with rituximab for the treatment of patients with FL, SLL, and other indolent non-Hodgkin lymphomas. 2/2022 |
Zydelig is indicated, in combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.
Recommended dosage: 150 mg orally twice daily. (
The recommended dosage of Zydelig is 150 mg administered orally twice daily with or without food until disease progression or unacceptable toxicity. The optimal and safe dosing regimen for patients who receive treatment longer than several months is unknown.
Swallow tablets whole.
If a planned dose of Zydelig is missed by less than 6 hours, take the missed dose as soon as possible and take the next dose as usual. If a dose of Zydelig is missed by more than 6 hours, skip the missed dose and take the next dose at the usual time.
Tablets:
- 100 mg: orange, oval-shaped, film-coated tablet debossed with "GSI" on one side and "100" on the other side.
- 150 mg: pink, oval-shaped, film-coated tablet debossed with "GSI" on one side and "150" on the other side.
There are no data on the presence of idelalisib or its metabolites in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with Zydelig and for 1 month after the last dose.