Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-108556 · Präparat HOS-093047

Trizivir contains abacavir, lamivudine and zidovudine, therefore any interactions identified for these individually are relevant to Trizivir. Clinical studies have shown that there are no clinically significant interactions between abacavir, lamivudine and zidovudine.

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

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-108557 · Präparat HOS-093047

Abacavir is metabolised by UDP-glucuronyltransferase (UGT) enzymes and alcohol dehydrogenase; co-administration of inducers or inhibitors of UGT enzymes or with compounds eliminated through alcohol dehydrogenase could alter abacavir exposure. Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure. Lamivudine is cleared renally. Active renal secretion of lamivudine in the urine is mediated through organic cation transporters (OCTs); co-administration of lamivudine with OCT inhibitors may increase lamivudine exposure.

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

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-108558 · Präparat HOS-093047

Abacavir, lamivudine and zidovudine are not significantly metabolised by cytochrome P450 enzymes (such as CYP 3A4, CYP 2C9 or CYP 2D6) nor do they induce this enzyme system. Lamivudine and zidovudine do not inhibit cytochrome P450 enzymes. Abacavir shows limited potential to inhibit metabolism mediated by CYP3A4 and has been shown in vitro not to inhibit CYP2C9 or CYP 2D6 enzymes. In vitro studies have shown that abacavir has potential to inhibit cytochrome P450 1A1 (CYP1A1). Therefore, there is little potential for interactions with antiretroviral protease inhibitors, non-nucleosides and other medicinal products metabolised by major P450 enzymes.

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): protease (HOS-085623)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-108559 · Präparat HOS-093047

Interaction studies have only been performed in adults. The list below should not be considered exhaustive but is representative of the classes studied.

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

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-108560 · Präparat HOS-093047

Drugs by Therapeutic Area Interaction Recommendation Geometric mean change concerning co- (%) administration (Possible mechanism) ANTIRETROVIRAL MEDICINAL PRODUCTS Didanosine/Abacavir Interaction not studied. No dosage adjustment Didanosine/Lamivudine Interaction not studied. necessary. Didanosine/Zidovudine Interaction not studied. Stavudine/Abacavir Interaction not studied. Combination not Stavudine/Lamivudine Interaction not studied. 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): stavudine (HOS-088080) didanosine (HOS-085836)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-108561 · Präparat HOS-093047

8 Stavudine/Zidovudine In vitro antagonism of anti-HIV activity between stavudine and zidovudine could result in decreased efficacy of both drugs. ANTI-INFECTIVE PRODUCTS Atovaquone/Abacavir Interaction not studied. As only limited data available Atovaquone/Lamivudine Interaction not studied. the clinical significance is Atovaquone/Zidovudine Zidovudine AUC 33% unknown. (750 mg twice daily with Atovaquone AUC  food/200 mg thrice daily) Clarithromycin/Abacavir Interaction not studied. Separate administration of Clarithromycin/Lamivudine Interaction not studied. Trizivir and clarithromycin by Clarithromycin/Zidovudine Zidovudine AUC 12% at least 2 hours (500 mg twice daily/100 mg every 4 hours) Trimethoprim/sulfamethoxazole Interaction not studied. No Trizivir dosage adjustment (Co-trimoxazole)/Abacavir necessary, unless patient has Trimethoprim/sulfamethoxazole Lamivudine: AUC 40% renal impairment (See Section (Co-trimoxazole)/Lamivudine 4.2). (160mg/800mg once daily for 5 Trimethoprim: AUC  days/300mg single dose) Sulfamethoxazole: AUC  When concomitant administration with co- (organic cation transporter trimoxazole is warranted, inhibition) patients should be monitored Trimethoprim/sulfamethoxazole Interaction not studied. clinically. High doses of (Co-trimoxazole)/Zidovudine trimethoprim/ sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis have not been studied and should be avoided.

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): sulfamethoxazole (HOS-084533) atovaquone (HOS-086266) trimethoprim (HOS-085184) stavudine (HOS-088080) clarithromycin (HOS-084517)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-108562 · Präparat HOS-093047

ANTIFUNGALS Fluconazole/Abacavir Interaction not studied. As only limited data are Fluconazole/Lamivudine Interaction not studied. available the clinical Fluconazole/Zidovudine Zidovudine AUC 74% significance is not known. (400 mg once daily/200 mg Monitor for signs of thrice daily) (UGT inhibition) zidovudine toxicity (see section 4.8). ANTIMYCOBACTERIALS Rifampicin/Abacavir Interaction not studied. Insufficient data to recommend dosage Potential to slightly decrease adjustment. abacavir plasma concentrations through UGT induction.

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): fluconazole (HOS-087945)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-108563 · Präparat HOS-093047

Drugs by Therapeutic Area Interaction Recommendation Geometric mean change concerning co- (%) administration (Possible mechanism) Rifampicin/Lamivudine Interaction not studied. Insufficient data to Rifampicin/Zidovudine Zidovudine AUC 48% recommend dosage adjustment.

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

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-108564 · Präparat HOS-093047

9 (600 mg once daily/200 mg (UGT induction) thrice daily) ANTICONVULSANTS Phenobarbital/Abacavir Interaction not studied. Insufficient data to recommend dosage Potential to slightly decrease adjustment. abacavir plasma concentrations through UGT induction. Phenobarbital/Lamivudine Interaction not studied. Phenobarbital/Zidovudine Interaction not studied.

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): phenobarbital (HOS-085617)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-108565 · Präparat HOS-093047

Potential to slightly decrease zidovudine plasma concentrations through UGT induction.

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

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-108566 · Präparat HOS-093047

Phenytoin/Abacavir Interaction not studied. Insufficient data to recommend dosage Potential to slightly decrease adjustment. abacavir plasma concentrations through UGT induction. Monitor phenytoin Phenytoin/Lamivudine Interaction not studied. concentrations. Phenytoin/Zidovudine Phenytoin AUC  Valproic acid/Abacavir Interaction not studied. As only limited data are Valproic acid/Lamivudine available the clinical Interaction not studied. Valproic acid/Zidovudine Zidovudine AUC 80%significance is not known. (250 mg or 500 mg thrice Monitor for signs of daily/100 mg thrice daily) (UGT inhibition) zidovudine toxicity (see section 4.8). ANTIHISTAMINES (HISTAMINE H2 RECEPTOR ANTAGONISTS) Ranitidine/Abacavir Interaction not studied. No dosage adjustment Ranitidine/Lamivudine Interaction not studied. necessary.

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): valproic acid (HOS-088515) histamine (HOS-088516) ranitidine (HOS-085660) phenytoin (HOS-084531)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-108567 · Präparat HOS-093047

Clinically significant interaction unlikely. Ranitidine eliminated only in part by renal organic cation transport system. Ranitidine/Zidovudine Interaction not studied Cimetidine/Abacavir Interaction not studied. No dosage adjustment Cimetidine/Lamivudine Interaction not studied. necessary.

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): cimetidine (HOS-085835) ranitidine (HOS-085660)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-108568 · Präparat HOS-093047

Clinically significant interaction unlikely. Cimetidine eliminated only in part by renal organic cation transport system. Cimetidine/Zidovudine Interaction not studied.

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): cimetidine (HOS-085835)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10–11

HOS-108569 · Präparat HOS-093047

10 Drugs by Therapeutic Interaction Recommendation Area Geometric mean change concerning co- (%) administration (Possible mechanism) CYTOTOXICS Cladribine/Lamivudine Interaction not studied. Therefore, the concomitant use of lamivudine with In vitro lamivudine inhibits the cladribine is not intracellular phosphorylation of recommended (see section cladribine leading to a potential 4.4). risk of cladribine loss of efficacy in case of combination in the clinical setting. Some clinical findings also support a possible interaction between lamivudine and cladribine. OPIOIDS Methadone/Abacavir Abacavir: AUC  As only limited data are (40 to 90 mg once daily for 14 Cmax 35% available the clinical days/600 mg single dose, then significance is not known. 600 mg twice daily for 14 Methadone: CL/F 22% Monitor for signs of days) zidovudine toxicity (see Methadone/Lamivudine Interaction not studied. section 4.8). Methadone/Zidovudine Zidovudine AUC 43% (30 to 90 mg once Methadone AUC  Methadone dosage adjustment daily/200 mg every 4 hours) unlikely in majority of patients; occasionally methadone re-titration may be required. RETINOIDS Retinoid compounds Interaction not studied. Insufficient data to (e.g. isotretinoin)/Abacavir recommend dosage Possible interaction given adjustment. common pathway of elimination via alcohol dehydrogenase. Retinoid compounds Interaction not studied. (e.g. isotretinoin)/Lamivudine No drug interaction studies Retinoid compounds Interaction not studied. (e.g. isotretinoin)/Zidovudine URICOSURIC Probenecid/Abacavir Interaction not studied. As only limited data are Probenecid/Lamivudine Interaction not studied. available the clinical Probenecid/Zidovudine Zidovudine AUC 106% significance is not known. (500 mg four times Monitor for signs of daily/2 mg/kg thrice daily) (UGT inhibition) zidovudine toxicity (see section 4.8). MISCELLANEOUS Ethanol/Abacavir Abacavir: AUC 41% No dosage adjustment (0.7 g/kg single dose/600 mg Ethanol: AUC  necessary. single dose) (Inhibition of alcohol dehydrogenase) Ethanol/Lamivudine Interaction not studied. Ethanol/Zidovudine Interaction not studied.

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) isotretinoin (HOS-108570) probenecid (HOS-085208) ethanol (HOS-089988) cladribine (HOS-085842)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-108571 · Präparat HOS-093047

11  Sorbitol solution (3.2 g, 10.2 g, Single dose lamivudine oral When possible, avoid chronic 13.4 g)/ Lamivudine solution 300 mg coadministration of Trizivir with medicinal products Lamivudine: containing sorbitol or other AUC  14%; 32%; 36% osmotic acting poly-alcohols or monosaccharide alcohols Cmax  28%; 52%, 55%. (e.g. xylitol, mannitol, lactitol, maltitol). Consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided. Riociguat/Abacavir Riociguat  Riociguat dose may need to be reduced. Consult the In vitro, abacavir inhibits riociguat prescribing CYP1A1. Concomitant information for dosing administration of a single dose recommendations. of riociguat (0.5 mg) to HIV patients receiving the combination of abacavir/dolutegravir/lamivudine (600 mg/50 mg/300 mg once daily) led to an approximately three-fold higher riociguat AUC(0-∞) when compared to historical riociguat AUC(0-∞) reported in healthy subjects. Abbreviations:  = Increase; =decrease; = no significant change; AUC=area under the concentration versus time curve; Cmax=maximum observed concentration; CL/F=apparent oral clearance

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): maltitol (HOS-085849) riociguat (HOS-086293) dolutegravir (HOS-089992) xylitol (HOS-085846) mannitol (HOS-085847) lactitol (HOS-085848) sorbitol (HOS-085845)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-108572 · Präparat HOS-093047

Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV although the exact mechanism remains to be elucidated. The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.4). Consideration should be given to replacing zidovudine in a combination ART regimen if this is already established. This would be particularly important in patients with a known history of zidovudine induced anaemia.

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): ribavirin (HOS-088127)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-108573 · Präparat HOS-093047

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products (e.g. systemic pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine and doxorubicin) may also increase the risk of adverse reactions to zidovudine (see section 4.8). If concomitant therapy with Trizivir and any of these medicinal products is necessary then extra care should be taken in monitoring renal function and haematological parameters and, if required, the dosage of one or more agents should be reduced.

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): flucytosine (HOS-088525) vinblastine (HOS-086220) vincristine (HOS-086219) amphotericin (HOS-088524) pentamidine (HOS-085605) ganciclovir (HOS-085194) doxorubicin (HOS-084538) pyrimethamine (HOS-088523) dapsone (HOS-088141)

Wechselwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-108574 · Präparat HOS-093047

Limited data from clinical trials do not indicate a significantly increased risk of adverse reactions to zidovudine with cotrimoxazole (see interaction information above relating to lamivudine and co- trimoxazole), aerosolised pentamidine, pyrimethamine and acyclovir at doses used in prophylaxis.

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): pentamidine (HOS-085605) pyrimethamine (HOS-088523) acyclovir (HOS-088527)

Nebenwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-108575 · Präparat HOS-093047

Summary of the safety profile

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

Nebenwirkungen · Trizivir

TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-108576 · Präparat HOS-093047

Adverse reactions have been reported with abacavir, lamivudine and zidovudine used separately or in combination for therapy of HIV disease. Because Trizivir contains abacavir, lamivudine and zidovudine, the adverse reactions associated with these compounds may be expected.

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