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quinine (Quinamm, Aflukin, Chinimetten, Qualaquin)

Tradename: Quinamm, Qualaquin. (quinine sulfate) Indications: - malaria - suppression or treatment of chloroquine-resistant Plasmodium falciparum (Qualaquin FDA-approved) [7] - babesiosis - treatment of Babesia microti infection - nocturnal leg cramps* Contraindications: - concurrent use of neuromuscular blocking agents * The risk associated with use of quinine in the absence of evidence of its effectiveness for treatment or prevention of nocturnal leg cramps, outweighs any potential benefit in treating &/or preventing this benign & self-limiting condition. [10,14] Informed consent recommended when prescribing quinine off-label to treat leg cramps. See drugs with special prescribing & dispensing requirements Dosage: 1) malaria: 650 mg PO TID for 7 days in conjunction with another agent 2) babesiosis: 650 mg every 6-8 hours for 7 days 3) pediatrics: 10-25 mg/kg/day divided every 8 hours 4) leg cramps: 324 mg PO QHS Frequently used as a diluent for heroin. Tabs: 324 mg. (only FDA-approved strength) Dosage adjustment in renal failure: creatinine clearance dosage > 50-90 mL/min every 8 hours 10-50 mL/min every 8-12 hours < 10 mL/min every 24 hours * recommendations [5] despite fact that elimination 1/life unchanged with ESRD Pharmacokinetics: 1) bioavailability 76-88% 2) 69-92% protein binding 3) metabolized in the liver by cyt P450 3A4 & to a minor extent cyt P450 2C19 4) elimination 1/2life 2-12 hours (unchanged with ESRD) increased in the elderly 5) erythrocytic levels 30-50% of plasma levels 6) poor penetration into CSF (CSF levels 2-7% of plasma levels) Adverse effects: 1) common (> 10%) - nausea/vomiting, diarrhea, blurred vision, severe headache, tinnitus 2) uncommon (< 1%) - flushing of the skin, anginal symptoms, fever, rash, pruritus, hypoglycemia, epigastric pain, hemolysis*, thrombocytopenia*, hepatitis, night blindness, diplopia, optic atrophy, impaired hearing, hypersensitivity reactions, anaphylaxis, Steven-Johnson syndrome 3) QT prolongation, ventricular arrhythmias 4) long-term use associated with increased mortality [13] - dose-dependent - RR=1.25 < 300 mg/day - RR=1.83 < 400 mg/day - RR=2.24 >= 400 mg/day [13] * TTP/HUS; deaths have resulted [5,11] * quinine-induced thrombocytopenia not associated with platelet clumping [16] * hemolysis in patients with G6PD deficiency Drug interactions: 1) Al[OH]3 inhibits GI absorption 2) rifampin decreases plasma quinine levels 3) any drug that inhibits cyt P450 3A4 may increase levels of quinine 4) any drug that induces cyt P450 3A4 may diminish levels of quinine 5) quinine inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates 6) other drugs that prolong QT interval 7) neuromuscular blockers (respiratory depression, apnea) Laboratory: 1) specimen: plasma (EDTA) 2) methods: fluorometry, color, TLC 3) interferences: TLC, but not other assays distinguish quinidine from quinine 4) tonic water ingestion results in plasma concentrations of quinine < 0.3 ug/mL 5) labs with Loincs - quinine in specimen - quinine in gastric fluid - quinine in blood - quinine in serum/plasma - quinine in urine Mechanism of action: 1) inhibits nucleic acid synthesis, protein synthesis & glycolysis in Plasmodium falciparum 2) binds hemazoin in parasitized erythrocytes 3) precise antimalarial action unknown 4) stimulates insulin release from pancreas Notes: - a liter of tonic water contains ~100 mg of quinine [13]

Interactions

drug interactions drug adverse effects of antimalarials

Related

babesiosis cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) malaria

General

antimalarial skeletal muscle relaxant (tranquilizer)

Properties

MISC-INFO: elimination route LIVER 1/2life 9-13 HOURS therapeutic-range 5-10 UG/ML toxic-range >10 UG/ML protein-binding 70% pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  4. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  5. Sanford Guide to antimicrobial therapy 2001
  6. Prescriber's Letter 11(4):20 2004
  7. Prescriber's Letter 13(10): 2006 FDA Approves First Quinine Product, Qualaquin To Dispense or Not to Dispense Unapproved Quinine Detail-Document#: 221002 (subscription needed) http://www.prescribersletter.com
  8. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  9. Prescriber's Letter 14(1): 2007 Patient Handout - Quinine and Leg Cramps Detail-Document#: 230101 (subscription needed) http://www.prescribersletter.com
  10. AR Scientific (Quinalaquin Marketing) Philadelpha PA 19124
  11. FDA MedWatch, 07/08/2010 Qualaquin (quinine sulfate): New Risk Evaluation and Mitigation Strategy - Risk of serious hematological reactions http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm218424.htm
  12. Deprecated Reference
  13. Schwenk TL Long-Term Quinine Exposure and Mortality NEJM Journal Watch. May 11, 2017 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Fardet L, Nazareth I, Petersen I. Association between long-term quinine exposure and all-cause mortality. PMID: 28492890 JAMA. 2017;317(18):1907-1909
  14. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  15. Bougie DW, Wilker PR, Aster RH. Patients with quinine-induced immune thrombocytopenia have both "drug-dependent" and "drug-specific" antibodies. Blood. 2006 Aug 1;108(3):922-7. PMID: 16861345 PMCID: PMC1895854 Free PMC article
  16. NEJM Knowledge+