quinine (Quinamm, Aflukin, Chinimetten, Qualaquin)
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Introduction
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
- malaria: 650 mg PO TID for 7 days in conjunction with another agent
- babesiosis: 650 mg every 6-8 hours for 7 days
- pediatrics: 10-25 mg/kg/day divided every 8 hours
- 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
Table
| 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
- bioavailability 76-88%
- 69-92% protein binding
- metabolized in the liver by cyt P450 3A4 & to a minor extent cyt P450 2C19
- elimination 1/2life 2-12 hours (unchanged with ESRD) increased in the elderly
- erythrocytic levels 30-50% of plasma levels
- poor penetration into CSF (CSF levels 2-7% of plasma levels)
elimination via liver
1/2life = 9-13 hours
protein binding = 70 %
Adverse effects
- common (> 10%)
- 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
- QT prolongation, ventricular arrhythmias
- long-term use associated with increased mortality[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
- Al[OH]3 inhibits GI absorption
- rifampin decreases plasma quinine levels
- any drug that inhibits cyt P450 3A4 may increase levels of quinine
- any drug that induces cyt P450 3A4 may diminish levels of quinine
- quinine inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates
- other drugs that prolong QT interval
- neuromuscular blockers (respiratory depression, apnea)
Laboratory
- specimen: plasma (EDTA)
- methods: fluorometry, color, TLC
- interferences: TLC, but not other assays distinguish quinidine from quinine
- tonic water ingestion results in plasma concentrations of quinine < 0.3 ug/mL
- labs with Loincs
Mechanism of action
- inhibits nucleic acid synthesis, protein synthesis & glycolysis in Plasmodium falciparum
- binds hemazoin in parasitized erythrocytes
- precise antimalarial action unknown
- stimulates insulin release from pancreas
Notes
More general terms
Additional terms
- babesiosis
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
- malaria
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 5.2 Sanford Guide to antimicrobial therapy 2001
- ↑ Prescriber's Letter 11(4):20 2004
- ↑ 7.0 7.1 Prescriber's Letter 13(10): 2006 FDA Approves First Quinine Product, Qualaquin To Dispense or Not to Dispense Unapproved Quinine Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221002&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 14(1): 2007 Patient Handout - Quinine and Leg Cramps Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230101&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 AR Scientific (Quinalaquin Marketing) Philadelpha PA 19124
- ↑ 11.0 11.1 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
- ↑ Deprecated Reference
- ↑ 13.0 13.1 13.2 13.3 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: https://www.ncbi.nlm.nih.gov/pubmed/28492890 JAMA. 2017;317(18):1907-1909 - ↑ 14.0 14.1 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/16861345 PMCID: PMC1895854 Free PMC article
- ↑ 16.0 16.1 NEJM Knowledge+
Database
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- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=441073
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=91429
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=8547