Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

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

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. 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.

Abacavir and lamivudine 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 does 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.

ABACAVIR LAMIVUDINE TARO should not be taken with any other medicinal products containing lamivudine (see section 4.4).

The list below should not be considered exhaustive but is representative of the classes studied.

Drugs by Therapeutic Area     Interaction                               Recommendation concerning Geometric mean change (%)                 co-administration
(Possible mechanism)
ANTIRETROVIRAL MEDICINAL PRODUCTS
Didanosine /Abacavir          Interaction not studied.                  No dosage adjustment Didanosine/Lamivudine         Interaction not studied.                  necessary.
Zidovudine/Abacavir           Interaction not studied
Zidovudine/Lamivudine         Lamivudine: AUC ↔
Zidovudine 300 mg single dose Zidovudine: AUC ↔
Lamivudine 150 mg single dose


Emtricitabine/Lamivudine                                         Due to similarities, ABACAVIR
LAMIVUDINE TARO should not be administered concomitantly with other cytidine analogues, such as emtricitabine.

ANTI-INFECTIVE PRODUCTS
Trimethoprim/sulfamethoxazole Interaction not studied.           No ABACAVIR (Co-trimoxazole)/Abacavir                                        LAMIVUDINE TARO dosage adjustment necessary.
Trimethoprim/sulfamethoxazole   Lamivudine: AUC ↑40%
(Co-trimoxazole)/Lamivudine                                      When concomitant administration with
(160 mg/800 mg once daily for   Trimethoprim: AUC ↔              co-trimoxazole is warranted, 5 days/300 mg single dose)      Sulfamethoxazole: AUC ↔          patients should be monitored clinically. High doses of
(organic cation transporter      trimethoprim/ inhibition)                      sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis have not been studied and should be avoided
ANTIMYCOBACTERIALS
Rifampicin/Abacavir             Interaction not studied.         Insufficient data to recommend dosage adjustment.
Potential to slightly decrease abacavir plasma concentrations through UGT induction.
Rifampicin/Lamivudine           Interaction not studied.
ANTICONVULSANTS
Phenobarbital/Abacavir          Interaction not studied.         Insufficient data to recommend dosage adjustment.
Potential to slightly decrease abacavir plasma concentrations through UGT induction.
Phenobarbital/Lamivudine        Interaction not studied.
Phenytoin/Abacavir              Interaction not studied.         Insufficient data to recommend dosage adjustment.
Potential to slightly decrease abacavir plasma concentrations   Monitor phenytoin through UGT induction.           concentrations.
Phenytoin/Lamivudine            Interaction not studied.



ANTIHISTAMINES (HISTAMINE H2 RECEPTOR ANTAGONISTS)
Ranitidine/Abacavir    Interaction not studied. No dosage adjustment
Ranitidine/Lamivudine  Interaction not studied. necessary.

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

Clinically significant interaction unlikely. Cimetidine eliminated only in part by renal organic cation transport system.
CYTOTOXICS
Cladribine/Lamivudine            Interaction not studied.             Therefore, the concomitant use of lamivudine with cladribine
In vitro lamivudine inhibits the     is not recommended (see intracellular phosphorylation of     section 4.4).
cladribine leading to a potential 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 ↔                      No ABACAVIR (40 to 90mg once daily for 14              Cmax ↓35%                  LAMIVUDINE TARO dosage days/600mg single dose, then                                          adjustment necessary.
600mg twice daily for 14 days)   Methadone: CL/F ↑22%
Methadone dosage adjustment
Methadone/Lamivudine             Interaction not studied.             unlikely in majority of patients; occasionally methadone re-titration may be required.
RETINOIDS
Retinoid compounds               Interaction not studied.             Insufficient data to recommend (e.g. isotretinoin)/Abacavir                                          dosage adjustment.
Possible interaction given common pathway of elimination via alcohol dehydrogenase.
Retinoid compounds               Interaction not studied.
(e.g. isotretinoin)/Lamivudine
No drug interaction studies



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.
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 ABACAVIR LAMIVUDINE
Lamivudine:
TARO with medicinal
AUC ↓ 14%; 32%; 36%                         products containing sorbitol or other osmotic acting poly-
Cmax ↓ 28%; 52%, 55%.
alcohols or monosaccharide alcohols (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 riociguat
In vitro, abacavir inhibits prescribing information for
CYP1A1. Concomitant dosing recommendations.
administration of a single dose of riociguat (0.5 mg) to HIV patients receiving the combination of abacavir/dolutegravir/lamivudine
(600mg/50mg/300mg 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 
Paediatric population

Interaction studies have only been performed in adults.