No pharmaceutical opinion available for this interaction.
Ritonavir may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Nifedipine.
3A4 (main) and 2D6 (to a lesser extend)
1A2 and UGT (moderate); 2B6, 2C9 and 2C19 (weak)
3A4 (potent) and 2D6 (weak) Transportors: P-gp, OATP1A2 and OATP1B1
3A4 (major) > 2D6 (minor)
1A2 (moderate) > 2C9, 3A4et 2D6 (weak)
Possible increase of adverse effects.
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.
Diuretics, ACE inhibitors and some ARBs (if no contranindications).
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.
When possible, monitor the effects on blood pressure, heart rate and ECG.
Advise patient to consult quickly if lower limb edema, sudden weight gain, difficulty breathing, chest pain or tightness, or hypotension (dizziness, orthostatic effects).
Ref #2773 : Concomitant administration of nifedipine with cimetidine or ranitidine caused an increase of about 80% with cimetidine and 70% with ranitidine. The monograph recommends avoiding the combination of felodipine with potent CYP3A4 inhibitors.
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 51-year-old man with HIV infection who was receiving extended-release nifedipine (60 mg/day) developed symptomatic orthostasis and heart block after starting antiretroviral therapy that included nelfinavir (1250 mg twice daily). Other medication included losartan-hydrochlorothiazide, atenolol, clopidogrel , aspirin , zidovudine and lamivudine. He experienced dizziness, fatigue, and hypotension and developed complete heart block with a junctional escape rhythm. Electrocardiogram abnormalities abated within 24 hours of discontinuing antiretroviral therapy. Medication was changed to nifedipine (60 mg/day), losartan and atenololhowever, the patient developed orthostatic symptoms after restarting nelfinavir. He was switched successfully to an efavirenz-based regimen (efavirenz 600 mg once daily, stavudine 40 mg twice daily, didanosine 400 mg/day). Subsequent administration of antiretroviral therapy containing indinavir/ritonavir (800/100 mg twice daily) with extended-release nifedipine resulted in recurrence of his orthostatic symptoms. Drug therapy at that time consisted of nifedipine (60 mg/day), atenolol losartan and zidovudine and abacavir . Discontinuation of atenolol, and nifedipine dosage reduction to 30 mg/day were effective in managing his orthostatic changes.