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Drug Interactions between Levsin with Phenobarbital and Viekira XR

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

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Interactions between your drugs

Major

PHENobarbital ritonavir

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital) and Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

CONTRAINDICATED: Coadministration with drugs that are strong inducers of CYP450 3A4 may decrease the plasma concentrations of ritonavir and result in a potential loss of virologic response. The proposed mechanism is increased clearance due to induction of CYP450 3A4, which is the isoenzyme primarily responsible for the metabolism of ritonavir.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of ritonavir with drugs that are strong inducers of CYP450 3A4 is considered contraindicated.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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Major

PHENobarbital ombitasvir

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital) and Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

CONTRAINDICATED: Coadministration with potent inducers of CYP450 isoenzymes may significantly decrease the plasma concentrations of ombitasvir, paritaprevir, ritonavir, and dasabuvir. In 12 study subjects, administration of single-dose ombitasvir, paritaprevir, ritonavir, and dasabuvir with the potent CYP450 inducer carbamazepine (200 mg once daily followed by 200 mg twice daily) decreased ombitasvir peak plasma concentration (Cmax) by 31% and systemic exposure (AUC) by 31%; paritaprevir Cmax by 66% and AUC by 70%; ritonavir Cmax by 83% and AUC by 87%; and dasabuvir Cmax by 55% and AUC by 70%. Loss of therapeutic effects and development of resistance may occur.

MANAGEMENT: Concomitant use of ombitasvir/paritaprevir/ritonavir plus dasabuvir with potent CYP450 inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort is considered contraindicated.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. van Erp NP, Guchelaar HJ, Ploeger BA, Romijn JA, Hartigh J, Gelderblom H (2011) "Mitotane has a strong and a durable inducing effect on CYP3A4 activity." Eur J Endocrinol, 164, p. 621-6
  3. (2012) "Product Information. Xtandi (enzalutamide)." Astellas Pharma US, Inc
  4. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC
View all 4 references

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Major

PHENobarbital dasabuvir

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital) and Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

CONTRAINDICATED: Coadministration with potent inducers of CYP450 isoenzymes may significantly decrease the plasma concentrations of ombitasvir, paritaprevir, ritonavir, and dasabuvir. In 12 study subjects, administration of single-dose ombitasvir, paritaprevir, ritonavir, and dasabuvir with the potent CYP450 inducer carbamazepine (200 mg once daily followed by 200 mg twice daily) decreased ombitasvir peak plasma concentration (Cmax) by 31% and systemic exposure (AUC) by 31%; paritaprevir Cmax by 66% and AUC by 70%; ritonavir Cmax by 83% and AUC by 87%; and dasabuvir Cmax by 55% and AUC by 70%. Loss of therapeutic effects and development of resistance may occur.

MANAGEMENT: Concomitant use of ombitasvir/paritaprevir/ritonavir plus dasabuvir with potent CYP450 inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort is considered contraindicated.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. van Erp NP, Guchelaar HJ, Ploeger BA, Romijn JA, Hartigh J, Gelderblom H (2011) "Mitotane has a strong and a durable inducing effect on CYP3A4 activity." Eur J Endocrinol, 164, p. 621-6
  3. (2012) "Product Information. Xtandi (enzalutamide)." Astellas Pharma US, Inc
  4. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC
View all 4 references

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Drug and food interactions

Major

PHENobarbital food

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
View all 5 references

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Moderate

ritonavir food

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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Moderate

paritaprevir food

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ombitasvir, paritaprevir, ritonavir, and dasabuvir. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a moderate-fat meal (approximately 600 Kcal; 20% to 30% calories from fat) increased the mean systemic exposure (AUC) by 82%, 211%, 49%, and 30%, respectively. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a high-fat meal (approximately 900 Kcal; with 60% calories from fat) increased the mean AUC by 76%, 180%, 44%, and 22%, respectively.

MANAGEMENT: Ombitasvir/paritaprevir/ritonavir plus dasabuvir should always be administered with a meal. The fat or calorie content does not matter.

References

  1. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC

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Moderate

hyoscyamine food

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M (1973) "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol, 6, p. 107-12

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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.


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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.