FDA Black Box Warning
WARNING: HEMATOLOGIC REACTIONS Quinine sulfate use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported. The risk associated with quinine sulfate use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit [see Indications and Usage (1) and Warnings and Precautions (5.1) ] . WARNING: HEMATOLOGIC REACTIONS See full prescribing information for complete boxed warning Quinine sulfate use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported. The risk associated with quinine sulfate use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit. ( 1 , 5.1 )
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
Macrolide antibiotics (erythromycin, troleandomycin) (CYP3A4 inhibitors) Increased quinine plasma levels have been observed when used concomitantly [see Clinical Pharmacology (12.3) ] . Concomitant administration of macrolide antibiotics such as erythromycin or troleandomycin with quinine sulfate should be avoided [see Warnings and Precautions (5.4) ] .
Source: FDA drug label - quinine
Ketoconazole (CYP3A4 inhibitor) No change in the quinine sulfate dosage regimen is necessary with concomitant ketoconazole [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - quinine
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
Ritonavir Increased quinine plasma levels have been observed when used concomitantly [see Clinical Pharmacology (12.3) ] . Concomitant administration of ritonavir with quinine sulfate should be avoided. Ritonavir Ritonavir has significant effect on quinine pharmacokinetics [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - quinine
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
Urinary alkalizers (acetazolamide, sodium bicarbonate) Urinary alkalinizing agents may increase plasma quinine concentrations.
Source: FDA drug label - quinine
Tetracycline Tetracycline may be concomitantly administered with quinine sulfate [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - quinine
Macrolide antibiotics (erythromycin, troleandomycin) (CYP3A4 inhibitors) Increased quinine plasma levels have been observed when used concomitantly [see Clinical Pharmacology (12.3) ] . Concomitant administration of macrolide antibiotics such as erythromycin or troleandomycin with quinine sulfate should be avoided [see Warnings and Precautions (5.4) ] .
Source: FDA drug label - quinine