Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual tablets Suboxone 8 mg/2 mg sublingual tablets Suboxone 16 mg/4 mg sublingual tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-115867 · Präparat HOS-094369

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.*

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28

HOS-115881 · Präparat HOS-094369

Summary of the safety profile

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28

HOS-115882 · Präparat HOS-094369

The most commonly reported treatment-related adverse reactions reported during the pivotal clinical studies were constipation and symptoms commonly associated with drug withdrawal (i.e. insomnia, headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated liver function tests were considered serious.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28

HOS-115883 · Präparat HOS-094369

The most commonly reported treatment-related adverse reactions associated with the sublingual or buccal administration of buprenorphine/naloxone were oral hypoesthesia and oral mucosal erythema, respectively. Other treatment-related adverse reactions reported by more than one patient were constipation, glossodynia and vomiting.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28

HOS-115884 · Präparat HOS-094369

Tabulated list of adverse reactions

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28

HOS-115885 · Präparat HOS-094369

Adverse reactions reported during post-marketing surveillance are also included.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28

HOS-115886 · Präparat HOS-094369

The frequency of possible undesirable effects listed below is defined using the following convention: Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), Not known (cannot be estimated from the available data).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28

HOS-115887 · Präparat HOS-094369

Table 1: Treatment-related adverse reactions reported in clinical trials and post-marketing surveillance of buprenorphine/naloxone

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28

HOS-115888 · Präparat HOS-094369

System Organ Very common Common Uncommon Not Known Class Infections and Influenza, Urinary tract infestations Infection, infection, Pharyngitis, Vaginal infection Rhinitis Blood and Anaemia, lymphatic system Leukocytosis, disorders Leukopenia, Lymphadenopathy , Thrombocytopenia Immune system Hypersensitivity Anaphylactic disorders shock Metabolism and Decreased nutrition appetite, disorders Hyperglycaemia, Hyperlipidaemia, Hypoglycaemia Psychiatric Insomnia Anxiety, Abnormal dreams, Hallucination disorders Depression, Agitation, Libido decreased, Apathy, Nervousness, Depersonalisation, Drug dependence,

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 28–30

HOS-115889 · Präparat HOS-094369

28 System Organ Very common Common Uncommon Not Known Class Thinking Euphoric mood, abnormal Hostility Nervous system Headache Migraine, Amnesia, Hepatic disorders Dizziness, Disturbance in encephalopathy, Hypertonia, attention, Syncope Paraesthesia, Hyperkinesia, Somnolence Seizure, Speech disorder, Tremor Eye disorders Amblyopia, Conjunctivitis, Lacrimal disorder Miosis, Vision blurred Ear and labyrinth Vertigo disorders Cardiac disorders Angina pectoris, Bradycardia, Myocardial infarction, Palpitations, Tachycardia Vascular Hypertension, Hypotension Orthostatic disorders Vasodilatation hypotension Respiratory, Cough Asthma, Bronchospasm, thoracic and Dyspnoea, Respiratory mediastinal Yawning depression disorders Gastrointestinal Constipation, Abdominal pain, Hypoaesthesia Glossitis, disorders Nausea Diarrhoea, oral, Stomatitis, Dyspepsia, Glossodynia, Dental caries Flatulence, Mouth ulceration, Oral mucosal Oedema mouth, erythema, Oral pain, Vomiting Paraesthesia oral, Tongue discolouration Hepatobiliary Hepatic function Hepatitis, disorders abnormal Hepatitis acute, Jaundice, Hepatic necrosis, Hepatorenal syndrome Skin and Hyperhidrosis Pruritus, Acne, Angioedema subcutaneous Rash, Alopecia, tissue disorders Urticaria Dermatitis exfoliative, Dry skin, Skin mass Musculoskeletal Back pain, Arthritis and connective Arthralgia, tissue disorders Muscle spasms, Myalgia Renal and urinary Urine Albuminuria, disorders abnormality Dysuria, Haematuria, 29  System Organ Very common Common Uncommon Not Known Class Nephrolithiasis, Urinary retention Reproductive Erectile Amenorrhoea, system and breast dysfunction Ejaculation disorders disorder, Menorrhagia, Metrorrhagia General disorders Drug withdrawal Asthenia, Hypothermia Drug withdrawal and syndrome Chest pain, syndrome administration Chills, neonatal site conditions Pyrexia, Malaise, Pain, Oedema peripheral

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 30

HOS-115890 · Präparat HOS-094369

Investigations Liver function Blood creatinine Transaminases test abnormal, increased increased Weight decreased Injury, poisoning Injury Heat stroke, and procedural Poisoning complications (Intoxication)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 30

HOS-115891 · Präparat HOS-094369

Description of selected adverse reactions

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 30

HOS-115892 · Präparat HOS-094369

In cases of intravenous drug misuse, some adverse reactions are attributed to the act of misuse rather than the medicinal product and include local reactions, sometimes septic (abscess, cellulitis), and potentially serious acute hepatitis, and other infections such as pneumonia, endocarditis have been reported (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 30

HOS-115893 · Präparat HOS-094369

In patients presenting with marked drug dependence, initial administration of buprenorphine can produce a drug withdrawal syndrome similar to that associated with naloxone (see sections 4.2 and 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Suboxone

Suboxone 2 mg/0.5 mg sublingual film Suboxone 4 mg/1 mg sublingual film Suboxone 8 mg/2 mg sublingual film Suboxone 12 mg/3 mg sublingual film · Abschnitt 4.8 · PDF-Seite 30

HOS-115894 · Präparat HOS-094369

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.*

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Prezista

PREZISTA 100 mg/ml oral suspension · Abschnitt 4.5 · PDF-Seite 21–22

HOS-116415 · Präparat HOS-094447

21  Rosuvastatin rosuvastatin AUC ↑ 48%║ When administration of 10 mg once daily rosuvastatin Cmax ↑ 144%║ rosuvastatin and boosted ║ based on published data with PREZISTA is required, it is darunavir/ritonavir recommended to start with the lowest possible dose of rosuvastatin AUC ↑ 93%§ rosuvastatin and titrate up to the rosuvastatin Cmax ↑ 277%§ desired clinical effect while rosuvastatin Cmin ND§ monitoring for safety. § with darunavir/cobicistat 800/150 mg OTHER LIPID MODIFYING AGENTS Lomitapide Based on theoretical considerations Co-administration is boosted PREZISTA is expected to contraindicated (see section 4.3). increase the exposure of lomitapide when co-administered. (CYP3A inhibition) H2-RECEPTOR ANTAGONISTS Ranitidine # Boosted PREZISTA can be darunavir AUC ↔ 150 mg twice daily # darunavir Cmin ↔ co-administered with H2-receptor # darunavir Cmax ↔ antagonists without dose adjustments. IMMUNOSUPPRESSANTS Ciclosporin Not studied. Exposure to these Therapeutic drug monitoring of the Sirolimus immunosuppressants will be increased immunosuppressive agent must be Tacrolimus when co-administered with boosted done when co-administration PREZISTA. occurs. (CYP3A inhibition) Everolimus Concomitant use of everolimus and boosted PREZISTA is not recommended. INHALED BETA AGONISTS Salmeterol Not studied. Concomitant use of Concomitant use of salmeterol and salmeterol and boosted darunavir may boosted PREZISTA is not increase plasma concentrations of recommended. The combination salmeterol. may result in increased risk of cardiovascular adverse event with salmeterol, including QT prolongation, palpitations and sinus tachycardia. NARCOTIC ANALGESICS / TREATMENT OF OPIOID DEPENDENCE Methadone R(-) methadone AUC ↓ 16% No adjustment of methadone individual dose ranging R(-) methadone Cmin ↓ 15% dosage is required when initiating from 55 mg to 150 mg R(-) methadone Cmax ↓ 24% co-administration with boosted once daily PREZISTA. However, adjustment PREZISTA/cobicistat may, in contrast, of the methadone dose may be increase methadone plasma necessary when concomitantly concentrations (see cobicistat SmPC). administered for a longer period of time. Therefore, clinical monitoring is recommended, as maintenance therapy may need to be adjusted in some patients. Buprenorphine/naloxone buprenorphine AUC ↓ 11% The clinical relevance of the 8/2 mg–16/4 mg once buprenorphine Cmin ↔ increase in norbuprenorphine daily buprenorphine Cmax ↓ 8% pharmacokinetic parameters has norbuprenorphine AUC ↑ 46% not been established. Dose norbuprenorphine Cmin ↑ 71% adjustment for buprenorphine may norbuprenorphine Cmax ↑ 36% not be necessary when naloxone AUC ↔ co-administered with boosted PREZISTA but a careful clinical naloxone Cmin ND monitoring for signs of opiate naloxone Cmax ↔ toxicity is recommended.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): methadone (HOS-086198) lomitapide (HOS-086160) cobicistat (HOS-088111) rosuvastatin (HOS-086307) buprenorphine (HOS-086193) salmeterol (HOS-086285) tacrolimus (HOS-085202) ranitidine (HOS-085660) everolimus (HOS-086310) naloxone (HOS-109490) sirolimus (HOS-085172) ritonavir (HOS-084521)

Wechselwirkungen · Prezista

PREZISTA 75 mg film-coated tablets PREZISTA 150 mg film-coated tablets PREZISTA 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 64–65

HOS-116530 · Präparat HOS-094447

64  Buprenorphine/naloxone buprenorphine AUC ↓ 11% The clinical relevance of the 8/2 mg–16/4 mg once buprenorphine Cmin ↔ increase in norbuprenorphine daily buprenorphine Cmax ↓ 8% pharmacokinetic parameters has norbuprenorphine AUC ↑ 46% not been established. Dose norbuprenorphine Cmin ↑ 71% adjustment for buprenorphine may norbuprenorphine Cmax ↑ 36% not be necessary when naloxone AUC ↔ co-administered with PREZISTA/ritonavir but a careful naloxone Cmin ND clinical monitoring for signs of naloxone Cmax ↔ opiate toxicity is recommended. Fentanyl Based on theoretical considerations Clinical monitoring is Oxycodone boosted PREZISTA may increase plasma recommended when Tramadol concentrations of these analgesics. co-administering boosted (CYP2D6 and/or CYP3A inhibition) PREZISTA with these analgesics. OESTROGEN-BASED CONTRACEPTIVES Drospirenone Not studied with darunavir/ritonavir. When PREZISTA is co- Ethinylestradiol administered with a drospirenone- (3 mg/0.02 mg once containing product, clinical daily) monitoring is recommended due to the potential for hyperkalaemia.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): oxycodone (HOS-109487) buprenorphine (HOS-086193) drospirenone (HOS-116422) naloxone (HOS-109490) fentanyl (HOS-086196) ritonavir (HOS-084521) tramadol (HOS-112871)

Wechselwirkungen · Prezista

PREZISTA 400 mg film-coated tablets PREZISTA 800 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 103–104

HOS-116619 · Präparat HOS-094447

103  Rosuvastatin rosuvastatin AUC ↑ 48%║ When administration of 10 mg once daily rosuvastatin Cmax ↑ 144%║ rosuvastatin and boosted ║ based on published data with PREZISTA is required, it is darunavir/ritonavir recommended to start with the lowest possible dose of rosuvastatin AUC ↑ 93%§ rosuvastatin and titrate up to the rosuvastatin Cmax ↑ 277%§ desired clinical effect while rosuvastatin Cmin ND§ monitoring for safety. § with darunavir/cobicistat 800/150 mg OTHER LIPID MODIFYING AGENTS Lomitapide Based on theoretical considerations Co-administration is boosted PREZISTA is expected to contraindicated (see section 4.3). increase the exposure of lomitapide when co-administered. (CYP3A inhibition) H2-RECEPTOR ANTAGONISTS Ranitidine # Boosted PREZISTA can be darunavir AUC ↔ 150 mg twice daily # darunavir Cmin ↔ co-administered with H2-receptor # darunavir Cmax ↔ antagonists without dose adjustments. IMMUNOSUPPRESSANTS Ciclosporin Not studied. Exposure to these Therapeutic drug monitoring of the Sirolimus immunosuppressants will be increased immunosuppressive agent must be Tacrolimus when co-administered with boosted done when co-administration PREZISTA. occurs. (CYP3A inhibition) Everolimus Concomitant use of everolimus and boosted PREZISTA is not recommended. INHALED BETA AGONISTS Salmeterol Not studied. Concomitant use of Concomitant use of salmeterol and salmeterol and boosted darunavir may boosted PREZISTA is not increase plasma concentrations of recommended. The combination salmeterol. may result in increased risk of cardiovascular adverse event with salmeterol, including QT prolongation, palpitations and sinus tachycardia. NARCOTIC ANALGESICS / TREATMENT OF OPIOID DEPENDENCE Methadone R(-) methadone AUC ↓ 16% No adjustment of methadone individual dose ranging R(-) methadone Cmin ↓ 15% dosage is required when initiating from 55 mg to 150 mg R(-) methadone Cmax ↓ 24% co-administration with boosted once daily PREZISTA. However, adjustment PREZISTA/cobicistat may, in contrast, of the methadone dose may be increase methadone plasma necessary when concomitantly concentrations (see cobicistat SmPC). administered for a longer period of time. Therefore, clinical monitoring is recommended, as maintenance therapy may need to be adjusted in some patients. Buprenorphine/naloxone buprenorphine AUC ↓ 11% The clinical relevance of the 8/2 mg–16/4 mg once buprenorphine Cmin ↔ increase in norbuprenorphine daily buprenorphine Cmax ↓ 8% pharmacokinetic parameters has norbuprenorphine AUC ↑ 46% not been established. Dose norbuprenorphine Cmin ↑ 71% adjustment for buprenorphine may norbuprenorphine Cmax ↑ 36% not be necessary when naloxone AUC ↔ co-administered with boosted PREZISTA but a careful clinical naloxone Cmin ND monitoring for signs of opiate naloxone Cmax ↔ toxicity is recommended.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): methadone (HOS-086198) lomitapide (HOS-086160) cobicistat (HOS-088111) rosuvastatin (HOS-086307) buprenorphine (HOS-086193) salmeterol (HOS-086285) tacrolimus (HOS-085202) ranitidine (HOS-085660) everolimus (HOS-086310) naloxone (HOS-109490) sirolimus (HOS-085172) ritonavir (HOS-084521)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 19

HOS-215323 · Präparat HOS-155418

In a study of HIV infected intravenous drug users, co-administration of efavirenz with methadone resulted in decreased plasma levels of methadone and signs of opiate withdrawal. The methadone dose was increased by a mean of 22% to alleviate withdrawal symptoms. Buprenorphine/naloxone/ Buprenorphine: Despite the decrease in efavirenz AUC: ↓ 50% buprenorphine exposure, no patients exhibited withdrawal Norbuprenorphine: symptoms. Dose adjustment of AUC: ↓ 71% buprenorphine or efavirenz may not be necessary when Efavirenz: co-administered. No clinically significant pharmacokinetic interaction a 90% confidence intervals unless otherwise noted. b 95% confidence intervals.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): methadone (HOS-086198) buprenorphine (HOS-086193) naloxone (HOS-109490)

Wechselwirkungen · Xalkori

XALKORI 200 mg hard capsules XALKORI 250 mg hard capsules XALKORI 20 mg granules in capsules for opening XALKORI 50 mg granules in capsules for opening XALKORI 150 mg granules in capsules for opening · Abschnitt 4.5 · PDF-Seite 16

HOS-126284 · Präparat HOS-096239

In vitro studies indicated that crizotinib is a weak inhibitor of uridine diphosphate glucuronosyltransferase (UGT)1A1 and UGT2B7. Therefore, crizotinib may have the potential to increase plasma concentrations of coadministered medicinal products that are metabolised predominantly by UGT1A1 (e.g., raltegravir, irinotecan) or UGT2B7 (e.g., morphine, naloxone).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): morphine (HOS-086053) naloxone (HOS-109490) raltegravir (HOS-086187) uridine (HOS-085192) irinotecan (HOS-112102)