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Drug Interactions between clarithromycin and Technivie

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

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Interactions between your drugs

Moderate

clarithromycin ritonavir

Applies to: clarithromycin and Technivie (ombitasvir / paritaprevir / ritonavir)

ADJUST DOSE: Coadministration with ritonavir may increase the plasma concentrations of clarithromycin. The mechanism is ritonavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic conversion of clarithromycin to 14-hydroxyclarithromycin. In 22 healthy volunteers, administration of clarithromycin (500 mg every 12 hours) with ritonavir (200 mg every 8 hours) for 4 days increased the mean peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of clarithromycin by 31%, 77% and 180%, respectively, compared to administration without ritonavir. The formation of 14-hydroxyclarithromycin was nearly completely inhibited, as indicated by a 100% decrease in Cmax, AUC, and Cmin in the presence of ritonavir. In contrast, clarithromycin had only minor effects on the pharmacokinetics of ritonavir.

MANAGEMENT: When coadministered with ritonavir, the clarithromycin dose should not exceed 1 g/day. In addition, the clarithromycin dosage should be reduced by 50% in patients with moderate renal impairment (CrCl 30 to 60 mL/min) and 75% in patients with more severe renal impairment (CrCl below 30 mL/min).

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  2. Ouellet D, Hsu A, Granneman GR, et al. (1996) "Assessment of the pharmacokinetic interaction between ritonavir and clarithromycin." Clin Pharmacol Ther, 59, p. 143
  3. Ouellet D, Hsu A, Granneman GR, Carlson G, Cavanaugh J, Guenther H, Leonard JM (1998) "Pharmacokinetic interaction between ritonavir and clarithromycin." Clin Pharmacol Ther, 64, p. 355-62

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Moderate

clarithromycin paritaprevir

Applies to: clarithromycin and Technivie (ombitasvir / paritaprevir / ritonavir)

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of paritaprevir, which is primarily metabolized by the isoenzyme. In 12 study subjects, ketoconazole 400 mg given once daily increased single-dose paritaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 37% and 98%, respectively. The risk of hyperbilirubinemia may be increased, as paritaprevir can cause elevations in indirect (unconjugated) bilirubin via inhibition of OATP1B1/1B3.

MANAGEMENT: Caution is advised if paritaprevir is prescribed in combination with potent CYP450 3A4 inhibitors. Patients should be monitored for signs and symptoms of hepatotoxicity (i.e., ALT and bilirubin elevations).

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC

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Drug and food interactions

Moderate

ritonavir food

Applies to: Technivie (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: Technivie (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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Minor

clarithromycin food

Applies to: clarithromycin

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References

  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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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

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