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Drug Interactions between nirmatrelvir / ritonavir and primidone

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

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Interactions between your drugs

Major

primidone ritonavir

Applies to: primidone and nirmatrelvir / 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)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
Major

primidone nirmatrelvir

Applies to: primidone and nirmatrelvir / ritonavir

CONTRAINDICATED: Coadministration with drugs that are potent inducers of CYP450 3A4 may decrease the plasma concentrations of nirmatrelvir 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 nirmatrelvir. According to the manufacturer, coadministration of nirmatrelvir-ritonavir (300 mg-100 mg twice daily for 5 doses) with the potent CYP450 3A4 inducer carbamazepine (300 mg twice daily for 16 doses) (n=9) decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) of nirmatrelvir by approximately 55% and 43%, respectively. Data are unavailable for other, less potent inducers. In addition, the plasma concentrations and pharmacologic effects of the concomitant inducer may be affected; however, clinical data are lacking.

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

References (1)
  1. US Food and Drug Administration (2021) FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION FOR PAXLOVID. https://www.fda.gov/media/155050/download

Drug and food interactions

Major

primidone food

Applies to: primidone

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 (5)
  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
Moderate

ritonavir food

Applies to: nirmatrelvir / 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)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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

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