Lopinavir / ritonavir

Verapamil

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Lopinavir / ritonavir may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Verapamil.

Lopinavir / ritonavir

Pharmacodynamic effects

Potential increased risk for PR or QT interval prolongation.

Recommendations

See comments.

Alternative solution(s)

Verapamil

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Use this combination with caution.

Start treatment with lower dose possible.

Reduce the dose of the CCB if judged necessary and gradually increase according to clinical response and tolerance.

In patients already being treated with this combination and tolerating it, if deemed appropriate, keep actual treatment and exercise close monitoring of adverse effects.

Or choose an alternative.

Alternative solution(s)

Diuretics, ACE inhibitors and some ARBs (if no contranindications).

Monitor

Adverse effects associated with calcium channel blockers : headache, peripheral edema, gastrointestinal effects, fatigue, hypotension, palpitations, tachycardia or bradycardia (diltiazem and verapamil), dizziness, nervousness, vertigo and drowsiness.

Increased risk of arythmia (particularly diltiazem and verapamil). EKG is recommended.

Advise patient to consult quickly if lower limb edema, sudden weight gain, difficulty breathing, chest pain or tightness, or hypotension (dizziness, orthostatic effects).

Tests

Pharmacokinetic parameters

Comment

Ref #2407: In one study, patients who received indinavir 800 mg + ritonavir 100 mg BID with amlodipine 5 mg QD had an increase in amlodipine AUC of approximately 90%. Other patients received indinavir 800 mg + ritonavir 100 mg BID with diltiazem 120 mg QD and a 26.5% increase in diltiazem AUC was observed. 13 patients in the study, two subjects had an increase in diltiazem AUC of 4 times the normal. By cons, no serious adverse effects on the cardiovascular system was observed.
The searchers therefore recommend, if co-administration is indicated, to initiate treatment with low doses increasing doses with caution according to clinical response and the occurrence of adverse effects.

Ref #2110 : Patient Case. The patient has developed hypotension and progressive kidney insufficiency with the association of Lopinavir/ritonavir with nifedipine (long action). When the patient stopped the intake, the symptoms also stopped. Symptoms started again with an edema several years later when the association was taken again.

Ref #1938: A patient case showed with the association nelfinavir with nifedipine (long action): the patient has shown symptomatic orthostatic hypotension, fatigue, dizziness and a complet heart blocking after the start of nefedipine administration. An improvement of the EKG was noted 24 hours after stopping the intake of nelfinavir. Symptoms started again when nelfinavir was administrated again. This patient showed again orthostatic hypotension with the association indinavir-ritonavir and no symptom with the association efavirenz and nifedipine.

N.B. : Dihydropyridine CCBs are associated with hypotension and generally present no risk of PR or QT interval prolongation. However, the benzothiazepine and phenylalkylamine classed of CCBs, such as diltiazem and verapamil, can be associated with severe bradycardia, and PR and QT interval prolongation.

Reference
  • 2777
    Verapamil (Isoptin), BGP Pharma ULC, Quebec, Canada, 25 mars 2015.
  • 122
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 25 septembre 2018.
  • 2407
    Glesby MJ, Aberg JA, Kendall MA, et al. Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. Clin Pharmacol Ther, 2005, 78(2): 143-53.
  • 2110
    Baeza MT, Merino E, Boix V, and Climent E. Nifedipine - lopinavir/ritonavir severe interaction: a case report. AIDS 2007; 21(1): 119-120.
  • 1938
    Rossi DR, Rathbun RC, and Slater LN. Symptomatic orthostasis with extended-release nifedipine and protease inhibitors. Pharmacother 2002; 22:1312-1316.