Buprenorphine and Lopinavir and ritonavir interaction

Buprenorphine and Lopinavir and ritonavir: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Buprenorphine (BELBUCA) label · effective 2026-01-02

Major

Examples: atazanavir, ritonavir Benzodiazepines : May increase buprenorphine-induced respiratory depression.

Drug interactionsnames Lopinavir and ritonavirView label on DailyMed
Major

Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression.

Drug interactionsby drug classView label on DailyMed
Moderate

Other PIs with CYP3A4 inhibitory activity (atazanavir and atazanavir/ritonavir) resulted in elevated levels of buprenorphine and norbuprenorphine, and patients in one study reported increased sedation.

Drug interactionsnames Lopinavir and ritonavirView label on DailyMed
Moderate

Intervention: Evaluate patients taking BELBUCA and atazanavir with and without ritonavir and reduce the dose of BELBUCA if warranted.

Drug interactionsnames Lopinavir and ritonavirView label on DailyMed
Moderate

Inhibitors of CYP3A4 Clinical Impact: The concomitant use of BELBUCA and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of BELBUCA is achieved.

Drug interactionsby drug classView label on DailyMed

From the Lopinavir and ritonavir (Kaletra) label · effective 2026-07-23

Major

…Hepatitis C direct acting antiviral: elbasvir/grazoprevir HMG-CoA Reductase Inhibitors: lovastatin, simvastatin Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide Non-opioid Analgesic (selective blocker of Nav1.8 sodium channels): suzetrigine PDE5 Inhibitor: sildenafil (Revatio ® ) when used for the treatment of pulmonary arterial hypertension Sedative/Hypnotics:…

Contraindicationsby drug classView label on DailyMed
Major

Postmarketing life-threatening cases of cardiac toxicity (including complete AV block, bradycardia, and cardiomyopathy), lactic acidosis, acute renal failure, CNS depression and respiratory complications leading to death have been reported, predominantly in preterm neonates receiving KALETRA oral solution.

Warnings and precautionsby drug classView label on DailyMed
Major

Sedative/Hypnotics: triazolam, orally administered midazolam ↑ triazolam ↑ midazolam Contraindicated due to potential for prolonged or increased sedation or respiratory depression [see Contraindications ( 4 )] .

Drug interactionsby drug classView label on DailyMed
Moderate

…potential risks, infants should be monitored closely for increases in serum osmolality and serum creatinine, and for toxicity related to KALETRA oral solution including: hyperosmolality, with or without lactic acidosis, renal toxicity, CNS depression (including stupor, coma, and apnea), seizures, hypotonia, cardiac arrhythmias and ECG changes, and hemolysis.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Analgesics Opioid: methadone* fentanyl Non-opioid analgesic (selective blocker of Na v 1.8 sodium channels): suzetrigine ↓ methadone ↑ fentanyl ↑ suzetrigine and active metabolite M6-SUZ Dosage of methadone may need to be increased when co-administered with KALETRA.

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.