9R)-quinine
9R)-quinine Uses, Dosage, Side Effects, Food Interaction and all others data.
9R)-quinine is a cinchona alkaloid and a 4-methanolquinoline. It rapidly acts on blood schizontocide by interfering with lysosomal function or nucleic acid synthesis in the Plasmodia spp. It has no activity against exoerythrocytic forms.
9R)-quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. 9R)-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.
| Trade Name | 9R)-quinine |
| Availability | Prescription only |
| Generic | Quinine |
| Quinine Other Names | (8S,9R)-quinine, 6'-Methoxycinchonidine, Chinin, Chinine, Chininum, Quinina, Quinine |
| Related Drugs | doxycycline, clindamycin, hydroxychloroquine, Plaquenil, Cleocin |
| Type | |
| Formula | C20H24N2O2 |
| Weight | Average: 324.4168 Monoisotopic: 324.183778022 |
| Protein binding | Approximately 70% |
| Groups | Approved |
| Therapeutic Class | Anti-malarial drugs |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
9R)-quinine Sulfate, is an antimalarial drug used only for treatment of uncomplicated Plasmodium falciparum malaria. 9R)-quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented
9R)-quinine Sulfate oral capsules are not approved for:
- Treatment of severe or complicated P. falciparum malaria.
- Prevention of malaria.
- Treatment or prevention of nocturnal leg cramps
9R)-quinine Dihydrochloride is used for the acute treatment of malaria. It may also be used in the treatment of Babesiosis in conjunction with clindamycin.
9R)-quinine is also used to associated treatment for these conditions: Malaria caused by Plasmodium falciparum
How 9R)-quinine works
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.
Dosage
9R)-quinine dosage
Intravenous:
- Adult: Initially, 20 mg/kg to max 1.4 g over 4 hr with maintenance infusion started after 8 hr. Maintenance infusions: 10 mg/kg to max 700 mg over 4 hr 8 hrly. Loading dose should not be given if patient has received quinine, quinidine, halofantrine or mefloquine during the previous 24 hr.
- Child:≤5 mg/kg/hr by slow IV infusion.
Oral:
- Adult: 648 mg given every 8 hr for 7 days.
- Child: ≥8 yr10 mg/kg 8 hrly for 7 days.
Should be taken with food. Take with food to minimise GI discomfort.
Reconstitutions
Dilute in NaCl 0.9% to a concentration of diHCl 60-100 mg/mL.
Side Effects
Headache, nausea, disturbed vision, impaired hearing, tinnitus, abdominal pain, vomiting, diarrhoea, vertigo; flushing skin with intense pruritus, urticaria; fever, dyspnoea, agranulocytosis, palpitations, rashes; myalgia, muscle weakness, asthma, asthenia, disorientation, angioedema; haemoglobinuria; hypoprothrombinaemia, hypoglycaemia, hypotension, renal failure.
Toxicity
9R)-quinine is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. 9R)-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.
Precaution
Patients with cardiac conduction defects, heart block or AF. Pregnancy and lactation.
Interaction
Reduced renal clearance of amantadine. Reduced clearance with cimetidine. Increased anticoagulant effect of warfarin and other anticoagulants. Reduced plasma levels of ciclosporin. Increased plasma levels of digoxin. Increased risk of myopathy and rhabdomyolysis with atorvastatin. May enhance hypoglycaemic effects of oral antidiabetics.
Food Interaction
- Take with food. Food reduces irritation.
[Minor] Coadministration with grapefruit juice does not appear to affect the pharmacokinetics of quinine in a clinically relevant manner.
Although grapefruit juice is an inhibitor of CYP450 3A4 and quinine is metabolized by this pathway to its major metabolite, 3-hydroxyquinine, a study of ten healthy volunteers found no significant differences in quinine peak plasma concentration (Cmax), time to reach Cmax (Tmax), terminal elimination half-life, systemic exposure (AUC), or apparent oral clearance (Cl Relative to the control period, the apparent renal clearance of quinine was markedly increased by 81% during treatment with half-strength grapefruit juice. However, since renal clearance accounts for approximately 6% of the total clearance of quinine, this change would likely have minimal clinical impact. The lack of a significant interaction is probably due to the fact that grapefruit juice primarily inhibits intestinal rather than hepatic CYP450 3A4, and quinine is not known to undergo significant presystemic metabolism as evidenced by its relatively high oral bioavailability (76% to 88%). Nevertheless, excessive consumption of grapefruit juice and tonic water (which contains quinine) was suspected as the cause of torsade de pointes arrhythmia in a patient with a history of asymptomatic long QT syndrome. Treatment with magnesium sulfate and metoprolol had no effect, but the arrhythmia resolved spontaneously 48 hours after discontinuation of the drinks. Based on current data, moderate grapefruit juice consumption is probably safe for the majority of patients taking quinine.
9R)-quinine Drug Interaction
Moderate: fluticasone / salmeterol, duloxetine, budesonide / formoterolUnknown: aspirin, diphenhydramine, calcium / vitamin d, celecoxib, rosuvastatin, omega-3 polyunsaturated fatty acids, fluticasone nasal, atorvastatin, pregabalin, esomeprazole, acetaminophen, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine
9R)-quinine Disease Interaction
Major: QT prolongation, G-6-PD deficiency, myasthenia gravis, ocular toxicity, thrombocytopenia, tinnitusModerate: liver impairment, renal impairment
Volume of Distribution
- 1.43 ± 0.18 L/kg [Healthy Pediatric Controls]
- 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients]
- 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose]
Elimination Route
76 - 88%
Half Life
Approximately 18 hours
Clearance
- 0.17 L/h/kg [healthy]
- 0.09 L/h/kg [patients with uncomplicated malaria]
- 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal]
- 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal]
- Oral cl=0.06 L/h/kg [elderly subjects]
Elimination Route
9R)-quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine.
Pregnancy & Breastfeeding use
Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Contraindication
Hypersensitivity to quinine, mefloquine or quinidine. Patients with nocturnal leg cramps; prolonged QT interval, tinnitus or optic neuritis, myasthenia gravis, G6PD deficiency, haemolysis and who had suffered from blackwater fever. Concomitant use with ritonavir, mefloquine, rifampicin, class IA and class III antiarrhythmic agents, neuromuscular blocking agents, other drugs known to cause QT prolongation, and Al- and/or Mg-containing antacids.
Special Warning
Renal Impairment:
- Oral:Severe: Initially, 648 mg followed after 12 hr by maintenance doses of 324 mg 12 hrly.
- Intravenous: Severe: Reduce maintenance dose to 5-7 mg/kg of quinine salt 8 hrly.
Hepatic Impairment:
- Mild to moderate: No dosage adjustment needed.
- Intravenous: Severe: Reduce maintenance dose to 5-7 mg/kg of quinine salt 8 hrly.
Acute Overdose
Symptoms: GI effects, CNS disturbances, oculotoxicity, cardiotoxicity,; tinnitus, abdominal pain, diarrhoea, vertigo, pulmonary oedema, hypotension, sweating, flushing, nausea, vomiting, headache, slightly disturbed vision, deafness, vasodilatation and adult resp distress syndrome.
Management: Administer multiple dose of activated charcoal within 1 hr or perform gastric lavage. Symptomatic (e.g. maintaining BP, respiration and renal function, treating arrhythmias) and supportive treatment.
Storage Condition
Store between 20-25° C. Protect from light.
Innovators Monograph
You find simplified version here 9R)-quinine
9R)-quinine contains Quinine see full prescribing information from innovator 9R)-quinine Monograph, 9R)-quinine MSDS, 9R)-quinine FDA label
FAQ
What is 9R)-quinine used for?
9R)-quinine is used to treat malaria caused by Plasmodium falciparum. Plasmodium falciparum is a parasite that gets into the red blood cells in the body and causes malaria.
How safe is 9R)-quinine?
Experts consider 9R)-quinine safe to consume in small doses.The FDA also specify that manufacturers must place 9R)-quinine on the label for consumers to easily see.
How does 9R)-quinine work?
9R)-quinine works by killing the parasite or preventing it from growing.
What are the common side effects of 9R)-quinine?
Common side effects of 9R)-quinine are include:
- nausea.
- restlessness.
- difficulty hearing or ringing in the ears.
- confusion.
- nervousness.
Is 9R)-quinine safe during pregnancy?
You should not avoid taking 9R)-quinine because you are pregnant. The risk of harm to you and your baby from malaria is likely to be far greater than any possible risk from taking quinine. There is no convincing scientific evidence that 9R)-quinine is harmful to an unborn baby.
Is 9R)-quinine safe during breastfeeding?
Because of the low levels of 9R)-quinine in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. The dosage in milk is far below those required to treat an infant for malaria.
Can I drive after taking 9R)-quinine?
9R)-quinine may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly. Do not use to treat any condition that has not been checked by your doctor.
When should be best taken of 9R)-quinine?
9R)-quinine usually is taken with food three times a day (every 8 hours) for 3 to 7 days. Take 9R)-quinine at around the same times every day.
How much 9R)-quinine can I take daily?
Adults and children 16 years of age and older 648 milligrams (mg) (2 capsules) every 8 hours for 7 days. Children younger than 16 years of age Use and dose must be determined by your doctor.
How long does it take for 9R)-quinine tablets to work?
A reduction in frequency of leg cramps may take up to 4 weeks to become apparent. Patients should be monitored closely during the early stages of treatment for adverse effects. After an initial trial of 4 weeks, treatment should be stopped if there is no benefit.
How long until 9R)-quinine is out of my system?
The limit of sensitivity for quinine in urine, utilizing TLC, is approximately 0.2mg/mL. Laboratory experience indicates that 9R)-quinine may be detected as long as 4 to 5 days after intake.
Can I take 9R)-quinine for a long time?
Long-term off-label use of 9R)-quinine, still prescribed to individuals with muscle cramps despite Food and Drug Administration warnings of adverse events, is associated with an increased risk of death.
When should I stop taking 9R)-quinine?
Stop taking 9R)-quinine and call your doctor at once if you have headache with chest pain and severe dizziness, fast or pounding heartbeats, unusual bruising or bleeding, signs of infection, severe lower back pain, or blood in your urine.
Is 9R)-quinine bad for liver?
The hepatotoxicity of 9R)-quinine is usually mild and resolves within 1 to 4 weeks of stopping. In many instances, jaundice and liver test abnormalities may worsen for a few days after stopping 9R)-quinine, but fatalities have not been reported, and recovery is usually rapid.
Can I just stop taking 9R)-quinine?
After an initial trial of 4 weeks, treatment should be stopped if there is no benefit. Treatment should be interrupted approximately every 3 months to reassess the benefit. In patients taking 9R)-quinine long term, a trial discontinuation may be considered.
How often can I take 9R)-quinine ?
Adults and children aged 12 years and over, 600mg every eight hours for 7 days.
Does 9R)-quinine raise blood pressure?
This tea has been used in folk medicine to treat a variety of problems, and scientists have confirmed that it lowers blood pressure as well as cholesterol.
How does 9R)-quinine work in the body?
brank works by killing the parasite or preventing it from growing.
Is 9R)-quinine bad for heart?
9R)-quinine can cause serious side effects on your heart, kidneys, or blood cells.
Does 9R)-quinine make me sleepy?
9R)-quinine may cause hypoglycemia.
What happens if I miss a dose of 9R)-quinine?
Take the 9R)-quinine of dose as soon as you remember. If you are more than 4 hours late for your dose, skip the missed dose and take the medicine at your next scheduled dose time. Do not take extra medicine to make up the missed dose.
Who should not take 9R)-quinine?
You should not take 9R)-quinine if you have a heart rhythm disorder called Long QT syndrome, a genetic enzyme deficiency called glucose-6-phosphate dehydrogenase deficiency, myasthenia gravis, optic neuritis (inflammation of the nerves in your eyes), if you have taken 9R)-quinine in the past and it caused a blood cell disorder or severe bleeding.
What happen if I overdose on 9R)-quinine?
Symptoms of overdose may include are sudden vision change, confusion, severe trouble hearing, fast/irregular heartbeat, fainting, slow/shallow breathing, seizures, inability to wake up (coma).
