Криксиван

HIV感染症の治療には、抗レトロウイルス薬と組み合わせた ⁇ риксиванが適応となります。. この適応症は、約1年間の2つの臨床試験に基づいており、次のことを示しています。1)AIDSを定義する病気または死亡のリスクの低減。 2)HIV RNAの長期抑制。

⁇ риксиванの推奨用量は、8時間ごとに経口で800 mg(通常は2つの400 mgカプセル)です。.

⁇ риксиванは8時間間隔で服用する必要があります。. 最適な吸収のために、 ⁇ риксиванは食事なしで投与する必要がありますが、食事の1時間前または2時間後に水と一緒に投与する必要があります。. あるいは、 ⁇ риксиванは、スキムミルク、ジュース、コーヒー、お茶などの他の液体と一緒に、または軽食と一緒に投与することもできます。.、ゼリー、ジュース、コーヒーをスキムミルクと砂糖で乾かします。またはコーンフレーク、スキムミルク、砂糖。. (見る。 臨床薬理学。, 経口吸収に対する食物の影響。.)

適切な水分補給を確実にするために、成人は24時間の間に少なくとも1.5リットル(約48オンス)の液体を飲むことをお勧めします。.

併用療法。 (見る。 臨床薬理学。, 薬物相互作用。、および/または。 注意:。 薬物相互作用。.)

デラビルジン。

1日3回デラビルジン400 mgを投与する場合は、 ⁇ риксиванを8時間ごとに600 mgに減らすことを検討する必要があります。.

ジダノシン。

インディナビルとジダノシンを同時に投与する場合は、空腹時に少なくとも1時間おきに投与する必要があります(ジダノシンについては、製造元の製品の通達を参照してください)。.

イトラコナゾール。

1日2回イトラコナゾール200 mgを同時に投与する場合は、8時間ごとに ⁇ риксиванを600 mgに減らすことをお勧めします。.

ケトコナゾール。

ケトコナゾールを同時に投与する場合は、 ⁇ риксиванを8時間ごとに600 mgに減らすことをお勧めします。.

リファブチン。

リファブチンと ⁇ риксиванを同時投与する場合は、リファブチンを標準用量の半分に減らし(リファブチンのメーカーの製品通達に相談してください)、8時間ごとに ⁇ риксиванから1000 mgへの用量増加をお勧めします。.

肝不全。

肝硬変による軽度から中等度の肝不全の患者では、 ⁇ риксиванの投与量を8時間ごとに600 mgに減らす必要があります。.

腎結石症/尿路結石症。

適切な水分補給に加えて、腎結石症/尿路結石症を経験した患者の医療管理には、一時的な中断が含まれる場合があります(例:.、1〜3日)または治療の中止。.

⁇ риксиванは、そのコンポーネントのいずれかに対して臨床的に有意な過敏症の患者には禁 ⁇ です。.

⁇ риксиванによるCYP3A4の阻害は、以下の薬物の血漿濃度の上昇をもたらし、深刻なまたは生命を脅かす反応を引き起こす可能性があります。

表7: ⁇ риксиванとの薬物相互作用:禁 ⁇ の薬物。

WARNINGS

ALERT: Find out about medicines that should NOT be taken with Криксиван. This statement is included on the product's bottle label.

Nephrolithiasis/Urolithiasis

Nephrolithiasis/urolithiasis has occurred with Криксиван therapy. The cumulative frequency of nephrolithiasis is substantially higher in pediatric patients (29%) than in adult patients (12.4%; range across individual trials: 4.7% to 34.4%). The cumulative frequency of nephrolithiasis events increases with increasing exposure to Криксиван; however, the risk over time remains relatively constant. In some cases, nephrolithiasis/urolithiasis has been associated with renal insufficiency or acute renal failure, pyelonephritis with or without bacteremia. If signs or symptoms of nephrolithiasis/urolithiasis occur, (including flank pain, with or without hematuria or microscopic hematuria), temporary interruption (e.g., 1- 3 days) or discontinuation of therapy may be considered. Adequate hydration is recommended in all patients treated with Криксиван. (See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION, Nephrolithiasis/Urolithiasis.)

Hemolytic Anemia

Acute hemolytic anemia, including cases resulting in death, has been reported in patients treated with Криксиван. Once a diagnosis is apparent, appropriate measures for the treatment of hemolytic anemia should be instituted, including discontinuation of Криксиван.

Hepatitis

Hepatitis including cases resulting in hepatic failure and death has been reported in patients treated with Криксиван. Because the majority of these patients had confounding medical conditions and/or were receiving concomitant therapy(ies), a causal relationship between Криксиван and these events has not been established.

Hyperglycemia

New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycemia have been reported during post-marketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established.

Risk Of Serious Adverse Reactions Due To Drug Interactions

Initiation of Криксиван, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving Криксиван, may increase plasma concentrations of medications metabolized by CYP3A. Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of Криксиван, respectively. These interactions may lead to:

• Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications.
• Clinically significant adverse reactions from greater exposures of Криксиван.
• Loss of therapeutic effect of Криксиван and possible development of resistance.

See Table 9 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during Криксиван therapy; review concomitant medications during Криксиван therapy; and monitor for the adverse reactions associated with the concomitant medications.

Concomitant use of Криксиван with lovastatin or simvastatin is contraindicated due to an increased risk of myopathy including rhabdomyolysis. Caution should be exercised if Криксиван is used concurrently with atorvastatin or rosuvastatin. Titrate the atorvastatin and rosuvastatin doses carefully and use the lowest necessary dose with Криксиван. (See PRECAUTIONS: DRUG INTERACTIONS.)

Midazolam is extensively metabolized by CYP3A4. Co-administration with Криксиван with or without ritonavir may cause a large increase in the concentration of this benzodiazepine. No drug interaction study has been performed for the co-administration of Криксиван with benzodiazepines. Based on data from other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally. Therefore Криксиван should not be co-administered with orally administered midazolam (see CONTRAINDICATIONS), whereas caution should be used with coadministration of Криксиван and parenteral midazolam. Data from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levels. If Криксиван with or without ritonavir is co-administered with parenteral midazolam, it should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.

Particular caution should be used when prescribing sildenafil, tadalafil, or vardenafil in patients receiving indinavir. Coadministration of Криксиван with these medications is expected to substantially increase plasma concentrations of sildenafil, tadalafil, and vardenafil and may result in an increase in adverse events, including hypotension, visual changes, and priapism, which have been associated with sildenafil, tadalafil, and vardenafil (see CONTRAINDICATIONS and PRECAUTIONS: DRUG INTERACTIONS and PATIENT INFORMATION, and the manufacturer's complete prescribing information for sildenafil, tadalafil, or vardenafil).

Concomitant use of Криксиван and St. John's wort (Hypericum perforatum) or products containing St. John's wort is not recommended. Coadministration of Криксиван and St. John's wort has been shown to substantially decrease indinavir concentrations (see CLINICAL PHARMACOLOGY, DRUG INTERACTIONS) and may lead to loss of virologic response and possible resistance to Криксиван or to the class of protease inhibitors.

PRECAUTIONS

General

Indirect hyperbilirubinemia has occurred frequently during treatment with Криксиван and has infrequently been associated with increases in serum transaminases (see also ADVERSE REACTIONS, Clinical Trials and Post-Marketing Experience). It is not known whether Криксиван will exacerbate the physiologic hyperbilirubinemia seen in neonates. (See Pregnancy.)

Tubulointerstitial Nephritis

Reports of tubulointerstitial nephritis with medullary calcification and cortical atrophy have been observed in patients with asymptomatic severe leukocyturia ( > 100 cells/ high power field). Patients with asymptomatic severe leukocyturia should be followed closely and monitored frequently with urinalyses. Further diagnostic evaluation may be warranted, and discontinuation of Криксиван should be considered in all patients with severe leukocyturia.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Криксиван. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment. Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Coexisting Conditions

Patients with hemophilia: There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. In some patients, additional factor VIII was required. In many of the reported cases, treatment with protease inhibitors was continued or restarted. A causal relationship between protease inhibitor therapy and these episodes has not been established. (See ADVERSE REACTIONS, Post-Marketing Experience.)

Patients with hepatic insufficiency due to cirrhosis: In these patients, the dosage of Криксиван should be lowered because of decreased metabolism of Криксиван (see DOSAGE AND ADMINISTRATION). Patients with renal insufficiency: Patients with renal insufficiency have not been studied.

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Information for Patients

A statement to patients and health care providers is included on the product's bottle label. ALERT: Find out about medicines that should NOT be taken with Криксиван. A Patient Package Insert (PPI) for Криксиван is available for patient information.

Криксиван is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should remain under the care of a physician when using Криксиван.

Patients should be advised to avoid doing things that can spread HIV-1 infection to others.

• Do not share needles or other injection equipment.
• Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
• Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.
• Do not breastfeed. We do not know if Криксиван can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Patients should be advised to remain under the care of a physician when using Криксиван and should not modify or discontinue treatment without first consulting the physician. Therefore, if a dose is missed, patients should take the next dose at the regularly scheduled time and should not double this dose. Therapy with Криксиван should be initiated and maintained at the recommended dosage.

Криксиван may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St. John's wort.

For optimal absorption, Криксиван should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, Криксиван may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal, e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; or corn flakes, skim milk and sugar (see CLINICAL PHARMACOLOGY, Effect of Food on Oral Absorption and DOSAGE AND ADMINISTRATION). Ingestion of Криксиван with a meal high in calories, fat, and protein reduces the absorption of indinavir.

Patients receiving a phosphodiesterase type 5 (PDE5) inhibitor (sildenafil, tadalafil, or vardenafil) should be advised that they may be at an increased risk of PDE5 inhibitor-associated adverse events including hypotension, visual changes, and priapism, and should promptly report any symptoms to their doctors (see CONTRAINDICATIONS and WARNINGS, DRUG INTERACTIONS).

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

Криксиван Capsules are sensitive to moisture. Patients should be informed that Криксиван should be stored and used in the original container and the desiccant should remain in the bottle.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenicity studies were conducted in mice and rats. In mice, no increased incidence of any tumor type was observed. The highest dose tested in rats was 640 mg/kg/day; at this dose a statistically significant increased incidence of thyroid adenomas was seen only in male rats. At that dose, daily systemic exposure in rats was approximately 1.3 times higher than daily systemic exposure in humans. No evidence of mutagenicity or genotoxicity was observed in in vitro microbial mutagenesis (Ames) tests, in vitro alkaline elution assays for DNA breakage, in vitro and in vivo chromosomal aberration studies, and in vitro mammalian cell mutagenesis assays. No treatment-related effects on mating, fertility, or embryo survival were seen in female rats and no treatment-related effects on mating performance were seen in male rats at doses providing systemic exposure comparable to or slightly higher than that with the clinical dose. In addition, no treatment-related effects were observed in fecundity or fertility of untreated females mated to treated males.

Pregnancy

Pregnancy Category C: Developmental toxicity studies were performed in rabbits (at doses up to 240 mg/kg/day), dogs (at doses up to 80 mg/kg/day), and rats (at doses up to 640 mg/kg/day). The highest doses in these studies produced systemic exposures in these species comparable to or slightly greater than human exposure. No treatment-related external, visceral, or skeletal changes were observed in rabbits or dogs. No treatment-related external or visceral changes were observed in rats. Treatmentrelated increases over controls in the incidence of supernumerary ribs (at exposures at or below those in humans) and of cervical ribs (at exposures comparable to or slightly greater than those in humans) were seen in rats. In all three species, no treatment-related effects on embryonic/fetal survival or fetal weights were observed.

In rabbits, at a maternal dose of 240 mg/kg/day, no drug was detected in fetal plasma 1 hour after dosing. Fetal plasma drug levels 2 hours after dosing were approximately 3% of maternal plasma drug levels. In dogs, at a maternal dose of 80 mg/kg/day, fetal plasma drug levels were approximately 50% of maternal plasma drug levels both 1 and 2 hours after dosing. In rats, at maternal doses of 40 and 640 mg/kg/day, fetal plasma drug levels were approximately 10 to 15% and 10 to 20% of maternal plasma drug levels 1 and 2 hours after dosing, respectively.

Indinavir was administered to Rhesus monkeys during the third trimester of pregnancy (at doses up to 160 mg/kg twice daily) and to neonatal Rhesus monkeys (at doses up to 160 mg/kg twice daily). When administered to neonates, indinavir caused an exacerbation of the transient physiologic hyperbilirubinemia seen in this species after birth; serum bilirubin values were approximately fourfold above controls at 160 mg/kg twice daily. A similar exacerbation did not occur in neonates after in utero exposure to indinavir during the third trimester of pregnancy. In Rhesus monkeys, fetal plasma drug levels were approximately 1 to 2% of maternal plasma drug levels approximately 1 hour after maternal dosing at 40, 80, or 160 mg/kg twice daily.

Hyperbilirubinemia has occurred during treatment with Криксиван (see PRECAUTIONS and ADVERSE REACTIONS). It is unknown whether Криксиван administered to the mother in the perinatal period will exacerbate physiologic hyperbilirubinemia in neonates.

There are no adequate and well-controlled studies in pregnant patients. Криксиван should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

A Криксиван dose of 800 mg every 8 hours (with zidovudine 200 mg every 8 hours and lamivudine 150 mg twice a day) has been studied in 16 HIV-infected pregnant patients at 14 to 28 weeks of gestation at enrollment (study PACTG 358). Given the substantially lower antepartum exposures observed and the limited data in this patient population, indinavir use is not recommended in HIV-infected pregnant patients (see CLINICAL PHARMACOLOGY, Pregnant Patients).

Antiretroviral Pregnancy Registry

To monitor maternal-fetal outcomes of pregnant patients exposed to Криксиван, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.

Nursing Mothers

Studies in lactating rats have demonstrated that indinavir is excreted in milk. Although it is not known whether Криксиван is excreted in human milk, there exists the potential for adverse effects from indinavir in nursing infants. Mothers should be instructed to discontinue nursing if they are receiving Криксиван. This is consistent with the recommendation by the U.S. Public Health Service Centers for Disease Control and Prevention that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV.

Pediatric Use

The optimal dosing regimen for use of indinavir in pediatric patients has not been established. A dose of 500 mg/m² every eight hours has been studied in uncontrolled studies of 70 children, 3 to 18 years of age. The pharmacokinetic profiles of indinavir at this dose were not comparable to profiles previously observed in adults receiving the recommended dose (see CLINICAL PHARMACOLOGY, Pediatric). Although viral suppression was observed in some of the 32 children who were followed on this regimen through 24 weeks, a substantially higher rate of nephrolithiasis was reported when compared to adult historical data (see WARNINGS, Nephrolithiasis/Urolithiasis). Physicians considering the use of indinavir in pediatric patients without other protease inhibitor options should be aware of the limited data available in this population and the increased risk of nephrolithiasis.

Geriatric Use

Clinical studies of Криксиван did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy.

成人の臨床試験。

腎結石症/尿路結石症。, 血尿の有無にかかわらず脇腹の痛みを含みます。 (微視的血尿を含む。) 約12.4%で報告されています。 (301/2429。; 個々の試験の範囲:4.7%から34.4%。) 追跡期間の中央値が47週間の臨床試験で推奨用量で ⁇ риксиванを投与された患者の数。 (範囲:1日から242週間。; 2238患者年のフォローアップ。). 腎結石イベントの累積頻度は、 ⁇ риксиванへの曝露期間とともに増加します。ただし、時間の経過に伴うリスクは比較的一定のままです。. 二重盲検期の臨床試験で腎結石症/尿路結石症を発症した ⁇ риксиванで治療された患者のうち、2.8%(7/246)が水腎症を発症し、4.5%(11/246)がステント配置を受けたと報告されています。. 急性エピソードに続いて、患者の4.9%(12/246)が治療を中止しました。. (見る。 警告。 と。 投与量と投与。, 腎結石症/尿路結石症。.)

主に間接ビリルビンの上昇として報告されている無症候性高ビリルビン血症(総ビリルビン≥2.5 mg / dL)は、 ⁇ риксиванで治療された患者の約14%で発生しています。. 1%未満では、これはALTまたはASTの上昇に関連していました。

高ビリルビン血症および腎結石症/尿路結石症は、2.4 g /日以下の用量と比較して、2.4 g /日を超える用量でより頻繁に発生しました。.

⁇ риксиван単独、 ⁇ риксиванとジドブジンまたはジドブジンおよびラミブジン、ジドブジン単独、またはジドブジンとラミブジンの併用で治療された患者の2%以上で報告された臨床的有害経験を表10に示します。.

表10:患者の2%以上で報告された臨床有害経験。

フェーズIおよびIIの対照試験では、以下の有害事象は、ヌクレオシド類似体に無作為化されたものよりも、 ⁇ риксиванを含む腕に無作為化されたものによって有意に頻繁に報告されました:発疹、上気道感染症、乾燥肌、 ⁇ 頭炎、味覚異常。.

ジドブジンまたはジドブジンとラミブジン、ジドブジンのみ、またはジドブジンとラミブジンの併用で治療された患者で報告された、重度または生命にかかわる強度の選択された検査異常を表11に示します。.

表11:研究028およびACTG 320で報告されている重度または生命にかかわる強度の選択された検査異常。

市販後の経験。

全体としての体:。 体脂肪の再分布/蓄積(参照。 注意。, 脂肪の再分配。).

心血管系:。 心筋 ⁇ 塞や狭心症などの心血管障害;脳血管障害。.

消化器系:。 肝機能異常;肝不全の報告を含む肝炎(参照 警告。); ⁇ 炎;黄 ⁇ ;腹部膨満;消化不良。.

血液学:。 血友病患者の自然出血の増加(参照。 注意。);急性溶血性貧血(参照。 警告。).

内分 ⁇ /代謝:。 新たに発症した糖尿病、既存の糖尿病の悪化、高血糖(参照。 警告。).

過敏症:。 アナフィラキシー様反応;じんま疹;血管炎。.

筋骨格系:。 関節痛、周発性関節炎。.

神経系/精神医学:。 口腔感覚異常;うつ病。.

皮膚と皮膚の付属物:。 多形紅斑およびスティーブンス・ジョンソン症候群を含む発疹;色素沈着過剰;脱毛症;陥入した足指の爪および/または爪周囲;そう ⁇ 。.

⁇ 尿生殖器系:。 腎結石症/尿路結石症、場合によっては腎不全または急性腎不全、菌血症を伴うまたは伴わない腎腎炎(参照) 警告。);間質性腎炎は、インディナビル結晶沈着を伴うことがあります。一部の患者では、間質性腎炎は ⁇ риксиванの中止後に解消しませんでした。腎不全;腎不全;白血球尿症(参照) 注意。)、結晶尿症;排尿障害。.

実験室の異常。

血清トリグリセリドの増加;血清コレステロールの増加。.

⁇ риксиванによる急性または慢性の人間の過剰摂取(推奨される総1日量2400 mgの最大23倍)の報告は60件を超えています。. 最も一般的に報告された症状は腎臓でした(例:.、腎結石症/尿路結石症、脇腹の痛み、血尿)および消化器(例:.、吐き気、 ⁇ 吐、下 ⁇ )。.

⁇ риксиванが腹膜または血液透析によって透析可能かどうかは不明です。.

吸収。

インディナビルは空腹時に急速に吸収され、ピーク血漿濃度(Tmax)までの時間は0.8±0.3時間(平均±S.D.)(n = 11)でした。. インディナビル血漿濃度の用量比例的増加よりも、200〜1000 mgの用量範囲で観察された。. 8時間ごとに800 mgの投与計画で。, 血漿濃度時間曲線の下の定常状態領域。 (AUC。) 30,691±11,407nM ⁇ ¢âでした。 (n = 16。) ピーク血漿濃度。 (Cmax。) 12,617±4037 nMでした。 (n = 16。) 投与後8時間の血漿濃度。 (トラフ。) 251±178 nMでした。 (n = 16。).

経口吸収に対する食物の影響。

カロリー、脂肪、タンパク質が豊富な食事(784 kcal、48.6 g脂肪、31.3 gタンパク質)を含むインジナビルの投与により、AUCが77%±8%減少し、Cmaxが84%±7%減少しました(n = 10)。. 軽い食事での投与(例:.、ゼリー、リンゴジュース、スキムミルクと砂糖入りコーヒー、またはコーンフレーク、スキムミルク、砂糖入りコーヒーのドライトーストの食事)は、AUC、Cmax、またはトラフの濃度にほとんどまたはまったく変化しませんでした。.

分布。

インディナビルは、81 nMから16,300 nMの濃度範囲で約60%がヒト血漿タンパク質に結合しました。

代謝。

14C-インディナビルの400 mg投与後、総放射能の83±1%(n = 4)および19±3%(n = 6)がそれぞれ ⁇ 便と尿で回収されました。 ⁇ 便と尿中の親薬物による放射能は、それぞれ19.1%と9.4%でした。. 7つの代謝物が確認されています。1つはグルクロニド抱合体、6つは酸化代謝物です。. In vitro。 研究によると、チトクロームP-450 3A4(CYP3A4)は、酸化代謝産物の形成に関与する主要な酵素です。.

除去。

インディナビルの20%未満が変化せずに尿中に排 ⁇ されます。. 変化のない薬物の平均尿中排 ⁇ は、それぞれ700 mgと1000 mgの単回投与後に10.4±4.9%(n = 10)と12.0±4.9%(n = 10)でした。. インディナビルは1.8±0.4時間の半減期で急速に排除されました(n = 10)。. 8時間ごとに800 mgを複数回投与した後、有意な蓄積は観察されませんでした。.