Results

Mutations: None
Comorbidities: None
Comedications: Phenobarbital
Treatment history: None
Current regimen: DRV/c/TAF/FTC (Symtuza)
Adherence: Penalize regimens with IV/IM dosing
CD4: Unknown
Viral load: High (100,000 - 500,000)
HLA-B5701: Negative
Tropism: Unknown
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Because there are salvage regimens in consideration, please consider seeking ID consultation or contact the National Clinical Consultation Center partners.
Regimen Weighted Score Active Drugs Total Pills Frequency (x/day)
DTG+TDF/FTC 3.25 2 3 2
DRV/r+TDF/FTC 3.45 2 3 1
RAL+EFV/TDF/FTC 5.95 3 3 1
RAL+TDF/FTC 6.35 2 3 1
DRV/r+EFV/TDF/FTC 6.55 3 3 1
DTG+DRV/r 6.9 2 4 2
RAL+DRV/r+TDF/FTC 7.1 3 5 1
DTG+EFV/TDF/FTC 7.15 3 3 2
RAL+DRV/r 7.45 2 4 1
DTG+DRV/r+TDF/FTC 7.55 3 5 2
EFV/TDF/FTC 7.9 2 1 1
DRV/r+EFV 8.3 2 3 1
RAL+DRV/r+EFV 9.15 3 5 1
DTG+FOS+TDF/FTC 9.4 3 5 2
RAL+IBA+TDF/FTC 9.6 3 3 1

Report

Preferred regimen based on the HIV-ASSIST algorithm: DTG+TDF/FTC

DTG+TDF/FTC had the lowest weighted score (3.25) among all regimens HIV-ASSIST evaluated. In general, lower HIV-ASSIST weighted scores are considered preferable with respect to achieving viral suppression and maximizing tolerability. Your patient may have other considerations we did not factor and this report should not be considered a guarantee of likely success with this patient. Please use clinical judgement in making final ARV selections. Other regimens you may wish to consider are listed below. A full list of ARV regimens analyzed by the HIV-ASSIST algorithm can be found by clicking the Expert Tab above.

Regimen Weighted Score Active Drugs Total Pills Frequency (x/day)
DTG+TDF/FTC 3.25 2 3 2

The rationale behind why this regimen was chosen by our algorithm as the most appropriate is shown below:

Other highly ranked regimens

Other highly ranked regimens based on the HIV-ASSIST algorithm are shown below. For full details on these regimens, please click on the Expert Tab above.

Regimen Weighted Score Active Drugs Total Pills Frequency (x/day)
DRV/r+TDF/FTC 3.45 2 3 1
RAL+EFV/TDF/FTC 5.95 3 3 1
RAL+TDF/FTC 6.35 2 3 1
DRV/r+EFV/TDF/FTC 6.55 3 3 1

Mutations

Based on the Stanford Database, we assign penalties to various regimens based on inputted (i.e., genotypic) and assumed archived mutations. We consider drugs with summed mutation scores between 10 and 29 to have low-level resistance, scores between 30 and 59 to have intermediate-level resistance, and scores above 60 to have high-level resistance.

* signifies an assumed archived mutation based on prior treatment experience.
NRTI Mutation(s) 3TC FTC ABC TAF TDF AZT D4T DDI
M184V* 60 60 15 -10 -10 -10 -10 10
Total 60 60 15 -10 -10 -10 -10 10
NNRTI Mutation(s) EFV ETR RPV NVP DOR
Total 0 0 0 0 0
PI Mutation(s) LPVr FPVr TPVr SQVr IDVr NFV ATVr ATVc ATV DRV DRVr DRVc
Total 0 0 0 0 0 0 0 0 0 0 0 0
INSTI Mutation(s) RAL EVGc DTG BIC CAB
Total 0 0 0 0 0
EI Mutation(s) MVC IBA FOS
Total 0 0 0

Comorbidities, Side Effects, and Pregnancy Interactions

HIV-ASSIST incorporates a mathematical penalty into our algorithms for ARVs that are less preferred due to comorbidities or side-effects, based on recommendations from DHHS guidelines and HIV-ASSIST clinician and pharmacist expertise. In general, higher penalties suggest that the listed ARV is less favored in the presence of the stated comorbidity or side effect.

Co-medication Interactions

We have identified the following possible drug interactions which HIV-ASSIST factors into ARV regimen selection, based on recommendations from DHHS guidelines, University of Liverpool HIV Drug Interaction Checker, and HIV-ASSIST clinician and pharmacist expertise. Penalties less than 1.0 are typically those representing minor interactions that can be mediated by dosage adjustments, whereas a penalty of 2.0 represents medically contraindicated ARVs.

Penalty:
0
Liverpool Interaction Status:
Green/Low: No Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenobarbital undergoes CYP-mediated metabolism.
Penalty:
0
Liverpool Interaction Status:
Green/Low: No Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenobarbital undergoes CYP-mediated metabolism.
Penalty:
0.1
Liverpool Interaction Status:
Yellow/Moderate-low: Potential Weak Interaction (Very Low Quality of Evidence)
Liverpool Notes:
Potent enzymatic inducers such as rifampicin, phenobarbital and phenytoin may via their action on UDP-glucuronyltransferases slightly decrease the plasma concentrations of abacavir. Ziagen Summary of Product Characteristics, ViiV Healthcare UK Ltd, December 2018., Summary:Coadministration has not been studied. Abacavir is metabolised by alcohol dehydrogenase and UGT. Phenobarbital may decrease abacavir plasma concentrations due to induction of UGTs, although to a moderate extent. No a priori dose adjustment is required.
Penalty:
2
HIV-ASSIST Notes:
Tenofovir concentrations may be decreased. Avoid co-administration. Consider levetiracetam or valproic acid.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
The co-administration of Descovy is not recommended with phenobarbital. Interaction not studied with either of the components of Descovy. Co-administration of phenobarbital, a P-gp inducer, may decrease tenofovir alafenamide plasma concentrations, which may result in loss of therapeutic effect and development of resistance.Descovy Summary of Product Characteristics, Gilead Sciences Ltd, April 2016. Coadministration is expected to decrease concentrations of tenofovir alafenamide and is not recommended.Descovy US Prescribing Information, Gilead Sciences Inc, April 2016., Summary:Coadministration has not been studied and is not recommended. Phenobarbital, a P-gp inducer, may decrease tenofovir alafenamide plasma concentrations which may result in loss of therapeutic effect and development of resistance.
Penalty:
0
Liverpool Interaction Status:
Green/Low: No Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenobarbital undergoes CYP-mediated metabolism. Phenobarbital is an inducer of P-gp and therefore could reduce the absorption of tenofovir-DF. However, based on the results of the interaction study between tenofovir-DF and rifampicin, another inducer of P-gp, phenobarbital would be expected to cause only a small decrease in tenofovir-DF.
Penalty:
0.25
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied but may decrease zidovudine concentrations as phenobarbital has been shown to induce zidovudine glucuronidation by 4-fold in rats. Monitor response to HIV therapy.
Penalty:
0
Liverpool Interaction Status:
Green/Low: No Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenobarbital undergoes CYP-mediated metabolism.
Penalty:
0
Liverpool Interaction Status:
Green/Low: No Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenobarbital undergoes CYP-mediated metabolism.
Penalty:
1
HIV-ASSIST Notes:
No data. Coadministration may reduce phenobarbital and/or efavirenz concentrations. Use with close monitoring or consider valproic acid or levetiracetam.
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
The interaction of efavirenz with phenobarbital has not been studied. There is the potential for reduction or increase in the plasma concentrations of phenobarbital. When efavirenz is co-administered with an anticonvulsant that is a substrate of CYP450 isoenzymes, periodic monitoring of anticonvulsant levels should be conducted. Sustiva Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, April 2015. When efavirenz is coadministered with phenobarbital, there is the potential for reduction in phenobarbital and/or efavirenz plasma levels. Periodic monitoring of anticonvulsant plasma levels should be conducted. Sustiva Prescribing Information, Bristol-Myers Squibb Company, March 2015., Summary:Specific interaction studies have not been performed. Coadministration may decrease phenobarbital and/or efavirenz concentrations. Periodic monitoring of plasma levels should be conducted.
Penalty:
2
HIV-ASSIST Notes:
Possible decrease in anticonvulsant and ETR possible. Do not coadminister. Consider alternative anticonvulsant.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Moderate Quality of Evidence)
Liverpool Notes:
The combination is not recommended. Coadministration has not been studied. Phenobarbital is expected to decrease plasma concentrations of etravirine. Intelence Summary of Product Characteristics, Janssen-Cilag Ltd, March 2019. Etravirine should not be used in combination with phenobarbital as co-administration may cause significant decreases in etravirine plasma concentrations and loss of therapeutic effect of etravirine. Intelence US Prescribing Information, Janssen Therapeutics, July 2019., Summary:Etravirine should not be used in combination with phenobarbital as it is expected to decrease etravirine concentrations.
Penalty:
2
HIV-ASSIST Notes:
Possible decrease in RPV level. Contraindicated. Do not coadminister. Consider alternative anticonvulsant treatment.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Moderate Quality of Evidence)
Liverpool Notes:
Coadministration with phenobarbital has not been studied. Significant decreases in rilpivirine plasma concentrations are expected due to induction of CYP3A enzymes. Rilpivirine must not be used in combination with phenobarbital as co-administration may result in loss of therapeutic effect of rilpivirine. Edurant Summary of Product Characteristics, Janssen-Cilag Ltd, January 2019. Coadministration is contraindicated due to the potential for significant decreases in rilpivirine plasma concentrations due to CYP3A enzyme induction, which may result in loss of virologic response. Edurant US Prescribing Information, Janssen Therapeutics, May 2019., Summary:Coadministration is contraindicated as significant decreases in rilpivirine plasma concentrations may occur.
Penalty:
2
HIV-ASSIST Notes:
Possible decrease in anticonvulsant and NVP possible. Monitor anticonvulsant and NVP levels and virologic responses or consider alternative anticonvulsant.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied. Phenobarbital induces CYP3A4 and is expected to significantly decrease nevirapine exposure, and therefore lead to loss of therapeutic effect and possible development of resistance.
Penalty:
2
HIV-ASSIST Notes:
Possible decrease in DOR level. Contraindicated. Do not coadminister. Consider alternative anticonvulsant treatment.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Co-administration with medicinal products that are strong cytochrome P450 (CYP) 3A enzyme inducers is contraindicated as significant decreases in doravirine plasma concentrations are expected to occur, which may decrease the effectiveness of doravirine. These medicinal products included phenobarbital. Pifeltro Summary of Product Characteristics, Merck Sharp & Dohme Ltd, November 2018. Co-administration is contraindicated with phenobarbital. Co-administration is expected to decrease doravirine concentrations. At least a 4-week cessation period is recommended prior to initiation of doravirine. Pifeltro US Prescribing Information, Merck & Co Inc, August 2018.>, Summary:Coadministration is contraindicated. Phenobarbital is a strong inducer of CYP3A4 and is expected to substantially decrease doravirine exposure which may result in loss of therapeutic effect and development of resistance. An alternative anticonvulsant should be considered. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.
Penalty:
1.9
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Do not coadminister with LPVr once daily. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Concentrations of lopinavir may be decreased due to CYP3A induction by phenobarbital. Caution should be exercised in administering phenobarbital with lopinavir/ritonavir. Phenobarbital levels should be monitored when co-administering with lopinavir/ritonavir. When co-administered with phenobarbital an increase of Kaletra dosage may be envisaged. Dose adjustment has not been evaluated in clinical practice. Kaletra must not be administered once daily in combination with phenobarbital.Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021. Coadministration of anticonvulsants, such a phenobarbital, may result in decreased concentrations of lopinavir. Kaletra may be less effective due to decreased plasma concentrations in patients taking these agents concomitantly and should be used with caution. Kaletra ONCE DAILY in combination with phenobarbital is not recommended.Kaletra Prescribing Information, AbbVie Inc, October 2020., Summary:Lopinavir/ritonavir should not be administered once-daily in combination with phenobarbital. Coadministration may result in a marked decrease in concentrations of lopinavir/ritonavir. Monitor phenobarbital concentrations. An increase of lopinavir/ritonavir dosage may be envisaged, but has not been evaluated.
Penalty:
1.9
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Do not coadminister with FPVr once daily or unboosted FPV. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Phenobarbital should be used with caution. Coadministration has not been studied but is expected to decrease amprenavir concentrations. Telzir may be less effective due to decreased amprenavir plasma concentrations in patients taking this medicinal product concomitantly.Telzir Summary of Product Characteristics, ViiV Healthcare UK Ltd, January 2021. Use with caution. Fosamprenavir may be less effective due to decreased amprenavir plasma concentrations in patients taking this drug concomitantly. Lexiva Prescribing Information, ViiV Healthcare, October 2020., Summary:Coadministration has not been studied. Phenobarbital induces CYP3A4 and fosamprenavir may be less effective due to decreased plasma concentrations. Use with caution in combination with fosamprenavir/ritonavir as ritonavir may decrease plasma levels of phenobarbital due to CYP2C9 and CYP2C19 induction. A dose adjustment of phenobarbital may be required. Close monitoring of patient's virologic response should be exercised. Periodic monitoring of fosamprenavir plasma concentrations should be conducted.
Penalty:
1.9
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
No interaction study performed. Phenobarbital induces CYP3A4 and should be used with caution in combination with tipranavir, co-administered with low-dose ritonavir. Aptivus Summary of Product Characteristics, Boehringer Ingelheim Ltd, July 2020. Caution should be used when prescribing phenobarbital. Tipranavir may be less effective due to decreased tipranavir plasma concentration in patients taking these agents concomitantly. Aptivus Prescribing Information, Boehringer Ingelheim, June 2020. A 49 year old HIV+ male patient was stable on phenobarbital (100 mg daily) with a baseline phenobarbital concentration of 16 µg/ml (therapeutic range 15-40 µg/ml). Four weeks after commencing abacavir, didanosine and tipranavir/ritonavir (500/200 mg twice daily), the patient had an episode of seizures and phenobarbital concentrations were found to be 8.1 µg/ml. Phenobarbital was increased to 150 mg daily and a subsequent plasma concentration was 17 µg/ml. The patient remained on this regimen for approximately one year during which phenobarbital concentrations were consistently at the lower end of the therapeutic range, but there were no further episodes of seizures. The trough tipranavir concentration after four weeks of therapy was 34837 ng/ml and was consistent with a population mean value of 30760 ng/ml. Clinically significant drug interaction between tipranavir/ritonavir and phenobarbital in an HIV-infected subject. Bonora S, Calcagno A, Fontana S, et al. Clin Infect Dis, 2007, 45: 1654-1655. , Summary:Phenobarbital induces CYP3A4 and should be used with caution in combination with tipranavir/ritonavir. Tipranavir may be less effective due to decreased tipranavir plasma concentrations.
Penalty:
2
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Penalty:
1.9
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Indinavir inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of these anticonvulsants. Concomitant use of medicinal products that are inducers of CYP3A4, such as carbamazepine, phenobarbital and phenytoin may reduce indinavir plasma concentrations. Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with indinavir.Crixivan Summary of Product Characteristics, Merck Sharp & Dohme Ltd, October 2018. Use with caution. Indinavir may not be effective due to decreased indinavir concentrations in patients taking these agents concomitantly. Crixivan Prescribing Information, Merck & Co Inc, May 2018., Summary:Coadministration has not been studied. Phenobarbital induces CYP3A4 and indinavir may be less effective due to decreased plasma concentrations. Coadministration with unboosted indinavir is not recommended. Use with caution in combination with indinavir/ritonavir as ritonavir may decrease plasma levels of phenobarbital due to CYP2C9 and CYP2C19 induction. A dose adjustment of phenobarbital may be required. Close monitoring of patient's virologic response should be exercised. Periodic monitoring of indinavir plasma concentrations should be conducted.
Penalty:
1.9
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Penalty:
1.9
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Do not coadminister with unboosted ATV. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Ritonavir may decrease plasma levels of phenobarbital due to CYP2C9 and CYP2C19 induction. Due to phenobarbital inducing effect, a reduction in Reyataz exposure cannot be ruled out. Phenobarbital should be used with caution in combination with Reyataz/ritonavir. When Reyataz/ritonavir is coadministered with phenobarbital, a dose adjustment of phenobarbital may be required. Close monitoring of patient's virologic response should be exercised. Coadministration of Reyataz without ritonavir is not recommended with phenobarbital. Reyataz Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, October 2018. Ritonavir is expected to decrease plasma levels of phenobarbital. When Reyataz with ritonavir is coadministered with phenobarbital, a dose adjustment of phenobarbital may be required. Plasma concentrations of atazanavir may be decreased when phenobarbital is administered with Reyataz without ritonavir. Coadministration of phenobarbital and Reyataz without ritonavir is not recommended. Reyataz US Prescribing Information, Bristol-Myers Squibb Company, March 2018., Summary:Coadministration has not been studied. Phenobarbital induces CYP3A4 and could decrease atazanavir/ritonavir plasma concentrations. Use with caution in combination with atazanavir/ritonavir as ritonavir may decrease plasma levels of phenobarbital due to CYP2C9 and CYP2C19 induction. A dose adjustment of phenobarbital may be required. Close monitoring of patient's virologic response should be exercised. Periodic monitoring of atazanavir plasma concentrations should be conducted.
Penalty:
2
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Contraindicated with ATV/c. Use alternative anticonvulsant
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration is contraindicated with medicinal products that are strong inducers of the CYP3A4 isoform of cytochrome P450 (e.g. phenobarbital) due to the potential for decreased plasma concentrations of atazanavir and/or cobicistat, leading to loss of therapeutic effect and possible development of resistance to atazanavir. Evotaz Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, November 2018. Coadministration is contraindicated due to potential for decreased atazanavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Evotaz US Prescribing Information Bristol-Myers Squibb Company, March 2018., Summary:Coadministration has not been studied. Phenobarbital induces CYP3A4 and could decrease atazanavir/cobicistat exposure, leading to loss of therapeutic effect and possible development of resistance. Coadministration is contraindicated in the European SmPC, but the US Prescribing Information advises for clinical and virological monitoring if coadministered. This interaction checker reflects the more cautious option.
Penalty:
2
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Do not coadminister with unboosted ATV. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Ritonavir may decrease plasma levels of phenobarbital due to CYP2C9 and CYP2C19 induction. Due to phenobarbital inducing effect, a reduction in Reyataz exposure cannot be ruled out. Phenobarbital should be used with caution in combination with Reyataz/ritonavir. When Reyataz/ritonavir is coadministered with phenobarbital, a dose adjustment of phenobarbital may be required. Close monitoring of patient's virologic response should be exercised. Coadministration of Reyataz without ritonavir is not recommended with phenobarbital. Reyataz Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, October 2018. Ritonavir is expected to decrease plasma levels of phenobarbital. When Reyataz with ritonavir is coadministered with phenobarbital, a dose adjustment of phenobarbital may be required. Plasma concentrations of atazanavir may be decreased when phenobarbital is administered with Reyataz without ritonavir. Coadministration of phenobarbital and Reyataz without ritonavir is not recommended. Reyataz US Prescribing Information, Bristol-Myers Squibb Company, March 2018., Summary:Coadministration has not been studied and is not recommended. Phenobarbital induces CYP3A4 and is expected to significantly decrease atazanavir plasma concentrations, and therefore lead to loss of therapeutic effect and possible development of resistance. If coadministration is needed, consider boosting with ritonavir and a close monitoring of patient's virologic response.
Penalty:
2
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Based on theoretical considerations this anticonvulsant is expected to decrease darunavir and/or cobicistat plasma concentrations (CYP3A induction). Co-administration of darunavir/cobicistat and these anticonvulsants is contraindicated due to the potential for loss of therapeutic effect. Rezolsta Summary of Product Characteristics, Janssen-Cilag Ltd, June 2018. Coadministration is expected to decrease concentrations of darunavir and cobicistat. Coadministration is contraindicated due to the potential for reduced plasma concentrations of darunavir, which may result in loss of therapeutic effect and development of resistance. Prezcobix US Prescribing Information, Janssen Pharmaceuticals Inc, June 2018., Summary:Coadministration has not been studied and is contraindicated. Phenobarbital induces CYP3A4 and could significantly decrease darunavir/ cobicistat concentrations which may result in loss of therapeutic effect and development of resistance. Alternative anticonvulsants should be considered.
Penalty:
1.9
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied. Phenobarbitone is expected to decrease plasma concentrations of darunavir and its pharmacoenhancer due to induction of CYP450 enzymes. Darunavir co-administered with low dose ritonavir should not be used in combination with this medicine. Prezista Summary of Product Characteristics, Janssen-Cilag Ltd, July 2018. Co-administration of darunavir/ritonavir may decrease phenobarbitone concentrations. No significant effect on darunavir concentrations is expected. Phenobarbitone levels should be monitored when co-administering with darunavir/ritonavir. Prezista Prescribing Information, Janssen Pharmaceuticals Inc, January 2018., Summary:The European product label for darunavir/ritonavir contraindicates coadministration with phenobarbital as it may significantly decrease darunavir concentrations. However, the US product label predicts no change in darunavir concentrations, but decreased phenobarbital concentrations and advises monitoring of phenobarbital. [This interaction checker reflects the more cautious option.]
Penalty:
2
HIV-ASSIST Notes:
Substantial decrease in PI level possible. Contraindicated with DRV/c. Use alternative anticonvulsant
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Based on theoretical considerations this anticonvulsant is expected to decrease darunavir and/or cobicistat plasma concentrations (CYP3A induction). Co-administration of darunavir/cobicistat and these anticonvulsants is contraindicated due to the potential for loss of therapeutic effect. Rezolsta Summary of Product Characteristics, Janssen-Cilag Ltd, June 2018. Coadministration is expected to decrease concentrations of darunavir and cobicistat. Coadministration is contraindicated due to the potential for reduced plasma concentrations of darunavir, which may result in loss of therapeutic effect and development of resistance. Prezcobix US Prescribing Information, Janssen Pharmaceuticals Inc, June 2018., Summary:Coadministration has not been studied and is contraindicated. Phenobarbital induces CYP3A4 and could significantly decrease darunavir/ cobicistat concentrations which may result in loss of therapeutic effect and development of resistance. Alternative anticonvulsants should be considered.
Penalty:
1.5
HIV-ASSIST Notes:
Coadministration not studied. Do not use RAL 1200mg once daily. Avoid coadministration. If unavoidable, consider RAL 800 mg BID in patients without RAL-associated mutations and monitor closely
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
The impact of strong inducers of drug metabolizing enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown; therefore, co-administration with raltegravir 1,200 mg once daily is not recommended. Isentress 600 mg Summary of Product Characteristics, Merck Sharp & Dohme Ltd, September 2021. The impact of strong inducers of drug metabolizing enzymes (other than rifampin) on raltegravir is unknown. Coadministration is not recommended with carbamazepine, phenobarbital or phenytoin and twice daily or once daily raltegravir. Isentress Prescribing Information, Merck & Co Inc, August 2021., Summary:Coadministration has not been studied. The impact of strong inducers of drug metabolizing enzymes, such as phenobarbital, on UGT1A1 is unknown. Coadministration of once daily raltegravir (1200 mg once daily) is not recommended as strong inducers are expected to have a more pronounced effect on raltegravir Cmin when raltegravir is given once daily. The US product label for raltegravir does not recommended coadministration with twice daily raltegravir. However, if coadministration with phenobarbital is unavoidable, raltegravir should be used as a twice daily regimen with close monitoring of antiretroviral response. Monitor raltegravir plasma concentrations (when possible).
Penalty:
2
HIV-ASSIST Notes:
Possible increase in phenobarbital concentrations and decrease in EVG and COBI concentrations expected. Consider alternative anticonvulsant.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Co-administration with phenobarbital is contraindicated as it may result in significantly decreased cobicistat and elvitegravir plasma concentrations, which may result in loss of therapeutic effect and development of resistance.Genvoya Summary of Product Characteristics, Gilead Sciences International Ltd, November 2021. Coadministration with phenobarbital is contraindicated due to potential for decreased concentrations of elvitegravir, cobicistat and tenofovir alafenamide, and loss of therapeutic effect and development of resistance. Genvoya US Prescribing Information, Gilead Sciences Inc, September 2021., Summary:Coadministration has not been studied. Phenobarbital induces CYP3A4 and could significantly decrease elvitegravir/cobicistat concentrations, which may result in loss of therapeutic effect and development of resistance. Coadministration is contraindicated. Alternative anticonvulsants should be considered.
Penalty:
1.5
HIV-ASSIST Notes:
Avoid coadministration. May decrease DTG concentrations due to phenobarbital induction of UGT1A1 and CYP3A. If co-administration cannot be avoided, consider dolutegravir 50 mg twice daily in patients without DTG-associated resistant mutations.
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration with oxcarbazepine, phenytoin or phenobarbital has not been studied but is expected to decreased dolutegravir exposure due to induction of UGT1A1 and CYP3A. A similar reduction in exposure as observed with carbamazepine is expected (AUC, Cmax and Ctrough decreased by 49%, 33% and 73%). The recommended adult dose of dolutegravir is 50 mg twice daily when co-administered with these metabolic inducers. In paediatric patients the weight-based once daily dose should be administered twice daily. Alternative combinations that do not include these metabolic inducers should be used where possible in INI-resistant patients. Tivicay Summary of Product Characteristics, ViiV Healthcare, March 2019. Coadministration may decrease dolutegravir concentrations. Avoid coadministration with dolutegravir because there are insufficient data to make dosing recommendations. Tivicay US Prescribing Information, ViiV Healthcare, July 2019. , Summary:Coadministration has not been studied but is expected to decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by phenobarbital. Interaction studies with dolutegravir and rifampicin (a strong inducer) showed that the effect of induction on dolutegravir concentrations can be overcome by administering an additional 50 mg dose of dolutegravir. The US Prescribing Information for dolutegravir advises to avoid coadministration with phenobarbital due to insufficient data to make dosing recommendations. However, the European SPC recommends that dolutegravir be dosed at 50 mg twice daily, but that alternative combinations should be used where possible in INSTI-resistant patients. This dose adjustment should be maintained for approximately 2 weeks after stopping phenobarbital as the inducing effect may persist after discontinuation of a strong inducer.
Penalty:
2
HIV-ASSIST Notes:
BIC concentrations may be significantly decreased when combined with phenobarbital. Avoid coadministration
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Co-administration is not recommended. The interaction has not been studied with any of the components of Biktarvy. Co-administration may decrease bictegravir and tenofovir alafenamide plasma concentrations due to induction of CYP3A, UGT1A1, and P-gp. Biktarvy Summary of Product Characteristics, Gilead Sciences Ltd, June 2019. Coadministration may decrease concentrations of bictegravir and tenofovir alafenamide. Coadministration with alternative anticonvulsants should be considered. Biktarvy Prescribing Information, Gilead Sciences Inc, August 2019., Summary:Coadministration is not recommended. Phenobarbital is an inducer and therefore is expected to decrease both tenofovir alafenamide and bictegravir exposures which may result in loss of therapeutic effect and development of resistance. Alternative anticonvulsants should be considered.
Penalty:
2
HIV-ASSIST Notes:
Coadministration is contraindicated. Cabotegravir is primarily metabolized by UGT1A1 and slightly by UGT1A9. Phenobarbital is a moderate inducer of UGT1A1 and has been evaluated using a PBPK model with 30 mg once daily oral cabotegravir. There was a predicted 28% decrease in cabotegravir exposure.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Metabolic inducers may significantly decrease cabotegravir plasma concentration. Concomitant use is contraindicated. Vocabria (cabotegravir oral and injection) European Summary of Product Characteristics, ViiV Healthcare, January 2021. Coadministration may decrease cabotegravir concentrations. Coadministration is contraindicated with Vocabria due to potential for loss of virologic response and development of resistance. Vocabria (cabotegravir oral) US Prescribing Information, ViiV Healthcare, January 2021. A physiologically based pharmacokinetic (PBPK) model was developed to prospectively assess the impact of phenobarbital (an inducer of UGT1A1) on the pharmacokinetic of oral cabotegravir (30 mg once daily). Drug-drug interaction simulations predicted a 28% decrease in oral cabotegravir exposure, comparable to observed rifabutin data. Utilization of physiologically based pharmacokinetic modelling (PBPK) to predict the effect of UGT enzyme inhibition and induction on the systemic exposure of cabotegravir. Taskar K, Patel P, Cozens S, et al. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, Noordwijk, May 2018, abstract 18., Summary:Coadministration has not been studied. The interaction between phenobarbital (an inducer of UGT1A1) and oral cabotegravir (30 mg once daily) was evaluated using a PBPK model, which predicted a 28% decrease in cabotegravir exposure. Coadministration is contraindicated due to potential for loss of therapeutic effect and development of resistance.
Penalty:
1
HIV-ASSIST Notes:
Possible decrease in MVC level. Avoid co-administration. If co-administration cannot be avoided, consider MVC 600 mg BID (if used without a strong CYP 3A4 inhibitor) or use an alternative anticonvulsant
Liverpool Interaction Status:
Amber/Moderate: Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied, but carbamazepine, phenobarbital, and phenytoin are potent CYP3A4 inducers and would be expected to decrease maraviroc concentrations. Maraviroc dose should be increased to 600 mg twice daily when co-administered with carbamazepine, phenobarbital or phenytoin in the absence of a potent CYP3A4 inhibitor. Celsentri Summary of Product Characteristics, ViiV Healthcare, September 2018. While not studied, potent CYP3A and/or P-gp inducers carbamazepine, phenobarbital, and phenytoin are expected to decrease maraviroc concentrations. The recommended dose of maraviroc when coadministered with carbamazepine (without a potent CYP3A inhibitor) is 600 mg twice daily. No additional maraviroc dose adjustment when coadministered with potent CYP3A inducers is required in patients with CrCl 30-80 mL/min. Maraviroc is contraindicated in patients with severe renal impairment (<30 mL/min) or ESRD on regular hemodialysis who are receiving potent CYP3A inducers. Selzentry US Prescribing Information, ViiV Healthcare, July 2018., Summary:Coadministration has not been studied but is expected to decrease maraviroc concentrations due to induction of CYP3A4. Maraviroc dose should be increased to 600 mg twice daily when co-administered with phenobarbital in the absence of a potent CYP3A4 inhibitor. The US Prescribing Information contraindicates coadministration in patients with creatinine clearance less than 30 ml/min or on haemodialysis.
Penalty:
0
Liverpool Interaction Status:
Green/Low: No Interaction Expected (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Induction of metabolism by phenobarbital is unlikely to affect ibalizumab, a monoclonal antibody binding to the CD4 receptor, which is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies.
Penalty:
1.9
HIV-ASSIST Notes:
May decrease temsavir concentrations. Avoid if possible. Consider levetiracetam or valproic acid.
Liverpool Interaction Status:
RED/High: Do Not Coadminister (Very Low Quality of Evidence)
Liverpool Notes:
Coadministration has not been studied but is contraindicated. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Coadministration of fostemsavir with rifampicin (another strong inducer) substantially decreased temsavir Cmax and AUC by 76% and 88%. A similar effect is expected with the strong inducer phenobarbital therefore coadministration is contraindicated as it may result in a potential loss of therapeutic effect.