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Drug Interactions between Nallpen and Vosevi

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

nafcillin velpatasvir

Applies to: Nallpen (nafcillin) and Vosevi (sofosbuvir / velpatasvir / voxilaprevir)

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 isoenzymes may decrease the plasma concentrations of velpatasvir, which has been shown in vitro to be metabolized by CYP450 2B6, 2C8, and 3A4. The interaction has been studied with efavirenz, a moderate CYP450 2B6 and 3A4 inducer. In 14 healthy volunteers, administration of sofosbuvir-velpatasvir 400 mg -100 mg once daily with efavirenz/emtricitabine/tenofovir disoproxil fumarate 600 mg/200 mg/300 mg once daily decreased mean velpatasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 47%, 53% and 57%, respectively, compared to administration of sofosbuvir-velpatasvir alone. No clinically relevant pharmacokinetic changes were observed for sofosbuvir or its predominant circulating metabolite, GS-331007.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of sofosbuvir-velpatasvir with potent or moderate CYP450 inducers is not recommended.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2016) "Product Information. Epclusa (sofosbuvir-velpatasvir)." Gilead Sciences

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Moderate

velpatasvir voxilaprevir

Applies to: Vosevi (sofosbuvir / velpatasvir / voxilaprevir) and Vosevi (sofosbuvir / velpatasvir / voxilaprevir)

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations of voxilaprevir, which is a substrate of the hepatic uptake transporters. When a single 100 mg dose of voxilaprevir was administered with a single 600 mg dose of the potent OATP 1B1/1B3 inhibitor cyclosporine (n=24), mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 19.0- and 9.4-fold, respectively. Inhibition of P-glycoprotein (P-gp)- and breast cancer resistance protein (BCRP)-mediated intestinal transport and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute to the overall interaction with cyclosporine. The safety of such high levels of voxilaprevir has not been established.

MANAGEMENT: Caution and monitoring are advised when voxilaprevir is used with OATP 1B1 or 1B3 inhibitors.

References

  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences

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Drug and food interactions

Moderate

nafcillin food

Applies to: Nallpen (nafcillin)

ADJUST DOSING INTERVAL: Certain penicillins may exhibit reduced gastrointestinal absorption in the presence of food. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: The interacting penicillin should be administered one hour before or two hours after meals. Penicillin V and amoxicillin are not affected by food and may be given without regard to meals.

References

  1. Neu HC (1974) "Antimicrobial activity and human pharmacology of amoxicillin." J Infect Dis, 129, s123-31
  2. Welling PG, Huang H, Koch PA, Madsen PO (1977) "Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects." J Pharm Sci, 66, p. 549-52
  3. McCarthy CG, Finland M (1960) "Absorption and excretion of four penicillins." N Engl J Med, 263, p. 315-26
  4. Cronk GA, Wheatley WB, Fellers GF, Albright H (1960) "The relationship of food intake to the absorption of potassium alpha-phenoxyethyl penicillin and potassium phenoxymethyl penicillin from the gastrointestinal tract." Am J Med Sci, 240, p. 219-25
  5. Klein JO, Sabath LD, Finland M (1963) "Laboratory studies on oxacillin. I: in vitro activity against staphylococci and some other bacterial pathogens. II: absorption and urinary excretion in normal young." Am J Med Sci, 245, p. 399-411
  6. Neuvonen PJ, Elonen E, Pentikainen PJ (1977) "Comparative effect of food on absorption of ampicillin and pivampicillin." J Int Med Res, 5, p. 71-6
View all 6 references

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Moderate

voxilaprevir food

Applies to: Vosevi (sofosbuvir / velpatasvir / voxilaprevir)

ADJUST DOSING INTERVAL: Administration with food enhances the oral bioavailability of sofosbuvir, velpatasvir, and voxilaprevir. Relative to fasting conditions, mean sofosbuvir systemic exposure (AUC) increased by 64% to 144%, mean velpatasvir AUC increased by 40% to 166%, and mean voxilaprevir AUC increased by 112% to 435% when the combined sofosbuvir/velpatasvir/voxilaprevir formulation is administered with food.

MANAGEMENT: Sofosbuvir/velpatasvir/voxilaprevir should be administered with food.

References

  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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