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Drug Interactions between dasabuvir / ombitasvir / paritaprevir / ritonavir and Sublocade

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

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Interactions between your drugs

Moderate

buprenorphine ritonavir

Applies to: Sublocade (buprenorphine) and dasabuvir / ombitasvir / paritaprevir / ritonavir

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations and pharmacologic effects of buprenorphine, which is partially metabolized (approximately 30%) by the isoenzyme. The interaction appears to be dependent, in part, on the route of administration of buprenorphine. When administered transdermally, buprenorphine peak plasma concentration (Cmax) and systemic exposure (AUC) were not significantly affected by ketoconazole, a potent CYP450 3A4 inhibitor. However, it was reported in another study that ketoconazole increased the Cmax and AUC of buprenorphine (route unspecified) by approximately 70% and 50%, respectively, and to a lesser extent, of the metabolite norbuprenorphine. The interaction has also been reported with atazanavir/ritonavir. A case series describes three patients who experienced excessive opiate effects of buprenorphine during concomitant antiretroviral therapy with atazanavir, ritonavir, and various nucleoside reverse transcriptase inhibitors. Two of the patients had been on their antiretroviral regimen for several months and reported doped-up feeling, dizziness, and feeling high following initiation of buprenorphine 8 mg/day. The dosage was reduced to 8 mg every other day. One was maintained on this dosage while the other had dosage increased up to 12 mg/day, whereupon he developed hypersomnolence but managed to maintain that dosage. The third patient had been inducted with buprenorphine and titrated to a stable dose of 14 mg/day for two days prior to beginning antiretroviral therapy. The next day, the patient complained of daytime somnolence and decreased mental functioning. His buprenorphine dosage was decreased to 8 mg/day, and he developed tolerance to the sedative effects within 7 days.

MANAGEMENT: Caution is advised if buprenorphine is prescribed with CYP450 3A4 inhibitors. Induction with buprenorphine should begin at a reduced dosage, and dosage escalation should occur more slowly to allow for assessment of opiate effects and development of patient tolerance. In patients who are already stabilized on buprenorphine, pharmacologic response and vital signs should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the buprenorphine dosage adjusted as necessary. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Patients should seek medical attention if potential signs and symptoms of toxicity occur such as dizziness, confusion, fainting, extreme sedation, bradycardia, slow or difficult breathing, and shortness of breath.

References

  1. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc PROD (2001):

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Drug and food interactions

Major

buprenorphine food

Applies to: Sublocade (buprenorphine)

GENERALLY AVOID: Concomitant use of buprenorphine with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may increase the risk of buprenorphine overdose, severe respiratory depression, coma, and death. Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many, but not all, involved abuse or misuse of buprenorphine including intravenous self-injection. The mechanism of interaction probably involves some degree of additive pharmacologic effects. Preclinical studies also suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Coadministration of buprenorphine with some CNS depressants such as alcohol, benzodiazepines, and phenothiazines may also increase the risk of hypotension.

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Extreme caution is advised when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol. Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

References

  1. "Product Information. Suboxone (buprenorphine-naloxone)." Reckitt and Colman Pharmaceuticals Inc (2002):
  2. Kilicarslan T, Sellers EM "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry 157 (2000): 1164-6
  3. Reynaud M, Petit G, Potard D, Courty P "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction 93 (1998): 1385-92
  4. Tracqui A, Kintz P, Ludes B "Buprenorphine-related deaths among drug addicts in France: a report on 20 fatalities." J Anal Toxicol 22 (1998): 430-4
  5. Reynaud M, Tracqui A, Petit G, Potard D, Courty P "Six deaths linked to misuse of buprenorphine-benzodiazepine combinations." Am J Psychiatry 155 (1998): 448-9
  6. Kintz P "A new series of 13 buprenorphine-related deaths." Clin Biochem 35 (2002): 513-6
  7. Martin HA "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs 37 (2011): 200-2
  8. Hakkinen M, Launiainen T, Vuori E, Ojanpera I "Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning." Eur J Clin Pharmacol 68 (2012): 301-9
  9. Substance Abuse and Mental Health Services Administration (US) "Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series, No. 40 http://www.ncbi.nlm.nih.gov/books/NBK64245/" (2013):
  10. Schuman-Olivier Z, Hoeppner BB, Weiss RD, Borodovsky J, Shaffer HJ, Albanese MJ "Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes." Drug Alcohol Depend 132 (2013): 580-6
  11. Ferrant O, Papin F, Clin B, et al. "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int 204 (2011): e8-11
  12. Pirnay S, Borron SW, Giudicelli CP, Tourneau J, Baud FJ, Ricordel I "A critical review of the causes of death among post-morten toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths." Addiction 99 (2004): 978-88
  13. Kintz P "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int 121 (2001): 65-9
  14. Sekar M, Mimpriss TJ "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia 42 (1987): 567-8
  15. Gueye PN, Borron SW, Risede P, et al. "Buprenorphine and midazolalm act in combination to depress respiration in rats." Toxicol Sci 65 (2002): 107-14
  16. US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf" (2016):
View all 16 references

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Moderate

ritonavir food

Applies to: 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. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

paritaprevir food

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

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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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