indication

For the treatment of malaria and leg cramps

pharmacology

Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.

mechanism of action

The theorized mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the malaria parasite. Specifically, the drugs interfere with the parasite's ability to break down and digest hemoglobin. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself.

toxicity

Quinine is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. Quinine induces production of antibodies against glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased antibodies against these complexes increases platelet clearance, leading to the observed thrombocytopenia.

biotransformation

Hepatic, over 80% metabolized by the liver.

absorption

76 - 88%

half life

Approximately 18 hours

route of elimination

Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine.

drug interactions

Acenocoumarol: Quinine, a moderate CYP2C9 inhibitor, may increase the serum concentration of acenocoumarol by decreasing its metabolism via CYP2C9.

Anisindione: Quinine may increase the anticoagulant effect of anisindione.

Artemether: Quinine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atomoxetine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Atracurium: The quinine derivative increases the effect of the muscle relaxant

Dicumarol: Quinine may increase the anticoagulant effect of dicumarol.

Digitoxin: Quinine/quinidine increases the effect of digoxin

Digoxin: Quinine/quinidine increases the effect of digoxin

Lumefantrine: Quinine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Metocurine: The quinine derivative increases the effect of the muscle relaxant

Pancuronium: The quinine derivative increases the effect of the muscle relaxant

Succinylcholine: The quinine derivative increases the effect of the muscle relaxant

Tamoxifen: Quinine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.

Tamsulosin: Quinine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Quinine is initiated, discontinued, or dose changed.

Telithromycin: Telithromycin may reduce clearance of Quinine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Quinine if Telithromycin is initiated, discontinued or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Thiothixene: May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.

Toremifene: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Tramadol: Quinine may decrease the effect of Tramadol by decreasing active metabolite production.

Trandolapril: May cause additive hypotensive effects. Monitor for changes in blood pressure if Quinine is initiated, discontinued or dose changed.

Tretinoin: The moderate CYP2C8 inhibitor, Quinine, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Quinine is initiated, discontinued to dose changed.

Vecuronium: Quinine may increase the neuromuscular blocking action of Vecuronium. Risk of respiratory depression and apnea. Concurrent therapy should be avoided.

Voriconazole: Additive QTc prolongation may occur. Concomitant therapy should be avoided.

Vorinostat: Additive QTc prolongation may occur. Concomitant therapy should be avoided.

Warfarin: Quinine, a moderate CYP2C9 inhibitor, may increase the serum concentration of S-warfarin by decreasing its metabolism via CYP2C9.

Ziprasidone: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Zuclopenthixol: Additive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy should be avoided.