Quinine Sulfate Interactions

Urinary Alkalizers (Acetazolamide, Sodium Bicarbonate) Urinary alkalinizing agents may increase plasma quinine concentrations.

Source: FDA drug label - quinine sulfate

Atorvastatin (CYP3A4 Substrate) Rhabdomyolysis with acute renal failure secondary to myoglobinuria was reported in a patient taking atorvastatin administered with a single dose of quinine. Quinine may increase plasma concentrations of atorvastatin, thereby increasing the risk of myopathy or rhabdomyolysis. Thus, clinicians considering combined therapy of quinine sulfate with atorvastatin or other HMG-CoA reductase inhibitors ("statins") that are CYP3A4 substrates (e.g., simvastatin, lovastatin) should carefully weigh the potential benefits and risks of each medication.

Source: FDA drug label - quinine sulfate

Macrolide Antibiotics (Erythromycin, Troleandomycin) (CYP3A4 Inhibitors) In a crossover study (N=10), healthy subjects who received a single oral 600 mg dose of quinine sulfate with the macrolide antibiotic, troleandomycin (500 mg every 8 hours) exhibited a 87% higher mean quinine AUC, a 45% lower mean oral clearance of quinine, and a 81% lower formation clearance of the main metabolite, 3-hydroxyquinine, than when quinine was given alone. Erythromycin was shown to inhibit the in vitro metabolism of quinine in human liver microsomes, an observation confirmed by an in vivo interaction study. In a crossover study (N=10), healthy subjects who received a single oral 500 mg dose of quinine sulfate with erythromycin (600 mg every 8 hours for four days) showed a decrease in quinine oral clearance (CL/F), an increase in half-life, and a decreased metabolite (3-hydroxyquinine) to quinine AUC ratio, as compared to when quinine was given with placebo.

Source: FDA drug label - quinine sulfate

Ketoconazole (CYP3A4 Inhibitor) In a crossover study, healthy subjects (N=9) who received a single oral dose of quinine hydrochloride (500 mg) concomitantly with ketoconazole (100 mg twice daily for 3 days) had a mean quinine AUC that was higher by 45% and a mean oral clearance of quinine that was 31% lower than after receiving quinine alone. Although no change in the quinine sulfate dosage regimen is necessary with concomitant ketoconazole, patients should be monitored closely for adverse reactions associated with quinine.

Source: FDA drug label - quinine sulfate

Thus, clinicians considering combined therapy of quinine sulfate with atorvastatin or other HMG-CoA reductase inhibitors ("statins") that are CYP3A4 substrates (e.g., simvastatin, lovastatin) should carefully weigh the potential benefits and risks of each medication.

Source: FDA drug label - quinine sulfate

Although clinical drug interaction studies have not been performed, antimalarial doses (greater than or equal to 600 mg) of quinine may inhibit the metabolism of other drugs that are CYP2D6 substrates (e.g., flecainide, debrisoquine, dextromethorphan, metoprolol, paroxetine ).

Source: FDA drug label - quinine sulfate

Midazolam (CYP3A4 Substrate) In 23 healthy subjects who received multiple doses of quinine sulfate capsules, 324 mg three times daily x 7 days with a single oral 2 mg dose of midazolam, the mean AUC and C max of midazolam and 1-hydroxymidazolam were not significantly affected. This finding indicates that 7-day dosing with quinine sulfate capsules,324 mg every 8 hours did not induce the metabolism of midazolam.

Source: FDA drug label - quinine sulfate

Ritonavir In healthy subjects who received a single oral 600 mg dose of quinine sulfate with the 15 th dose of ritonavir (200 mg every 12 hours for 9 days), there were 4-fold increases in the mean quinine AUC and C max , and an increase in the mean elimination half-life (13.4 hours versus 11.2 hours), compared to when quinine was given alone. Therefore, the concomitant administration of ritonavir with quinine sulfate capsules should be avoided [see also DRUG INTERACTIONS ( 7.2 )] . Ritonavir In healthy subjects who received a single oral 600 mg dose of quinine sulfate with the 15 th dose of ritonavir (200 mg every 12 hours for 9 days), the mean ritonavir AUC, C max , and elimination half-life were slightly but not significantly increased compared to when ritonavir was given alone.

Source: FDA drug label - quinine sulfate

Thus, clinicians considering combined therapy of quinine sulfate with atorvastatin or other HMG-CoA reductase inhibitors ("statins") that are CYP3A4 substrates (e.g., simvastatin, lovastatin) should carefully weigh the potential benefits and risks of each medication.

Source: FDA drug label - quinine sulfate

Tetracycline In 8 patients with acute uncomplicated P. falciparum malaria who were treated with oral quinine sulfate (600 mg every 8 hours for 7 days) in combination with oral tetracycline (250 mg every 6 hours for 7 days), the mean plasma quinine concentrations were about two-fold higher than in 8 patients who received quinine monotherapy. Although tetracycline may be concomitantly administered with quinine sulfate, patients should be monitored closely for adverse reactions associated with quinine sulfate.

Source: FDA drug label - quinine sulfate

Macrolide Antibiotics (Erythromycin, Troleandomycin) (CYP3A4 Inhibitors) In a crossover study (N=10), healthy subjects who received a single oral 600 mg dose of quinine sulfate with the macrolide antibiotic, troleandomycin (500 mg every 8 hours) exhibited a 87% higher mean quinine AUC, a 45% lower mean oral clearance of quinine, and a 81% lower formation clearance of the main metabolite, 3-hydroxyquinine, than when quinine was given alone. Therefore, concomitant administration of macrolide antibiotics such as erythromycin or troleandomycin with quinine sulfate should be avoided [see WARNINGS AND PRECAUTIONS ( 5.3 )] .

Source: FDA drug label - quinine sulfate