Interactions between Harliku and Hydroxychloroquine
1 drug interaction and 19 additional warnings found for the following 2 drugs:
- Harliku (nitisinone)
- hydroxychloroquine
Drug interactions
Moderate drug interactions
Moderate:
hydroxychloroquine nitisinone
Applies to: hydroxychloroquine and Harliku (nitisinone)
Monitor
Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of and exposure to, nitisinone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of nitisinone, which has been shown in in vitro studies to be metabolized by this isoenzyme. However, data evaluating the interaction are not available.
Management
Until more information is available, caution is advised if nitisinone is used concomitantly with CYP450 3A4 inhibitors. Pharmacologic response to nitisinone should be monitored whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the nitisinone dosage adjusted as necessary. Patients should be monitored for the development of adverse effects.
References (3)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
hydroxychloroquine Food/Lifestyle
Applies to: hydroxychloroquine
Generally avoid
Theoretically, grapefruit and grapefruit juice may increase the plasma concentrations of hydroxychloroquine or chloroquine and the risk of toxicities such as QT interval prolongation and ventricular arrhythmias. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Following coadministration with cimetidine, a weak to moderate CYP450 3A4 inhibitor, a 2-fold increase in chloroquine exposure occurred. Since chloroquine and hydroxychloroquine have similar structures and metabolic elimination pathways, a similar interaction may be observed with hydroxychloroquine. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
Adjust dosing interval
Administration with food or milk may reduce the incidence of hydroxychloroquine-related gastrointestinal adverse effects.
Management
Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract during hydroxychloroquine or chloroquine therapy. Hydroxychloroquine should be administered with food or milk to reduce the occurrence of gastrointestinal upset.
References (5)
- (2024) "Product Information. Hydroxychloroquine Sulfate (hydroxychloroquine)." Dr. Reddy's Laboratories Inc
- (2023) "Product Information. Plaquenil (hydroxychloroquine)." Sanofi-Aventis Canada Inc
- (2024) "Product Information. Quinoric (hydroxychloroquine)." Bristol Laboratories Ltd
- (2024) "Product Information. Hydroxychloroquine (GH) (hydroxychloroquine)." Generic Health Pty Ltd
- (2023) "Product Information. HIDROXICLOROQUINA RATIOPHARM (hidroxicloroquina)." RATIOPHARM ESPANA S.A.
Moderate:
nitisinone Food/Lifestyle
Applies to: Harliku (nitisinone)
Monitor
Grapefruit or grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
Management
Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.
References (32)
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- Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
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- Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
- (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
- Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
- Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
- Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
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- Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
- Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
- Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
- Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
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- Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
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- Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
Disease interactions
17 potential interactions Applies to: 17 conditions, including Seizures, Arrhythmia, Psoriasis, Hypoglycemia, and Myasthenia Gravis.
Alcoholism
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Alcoholism.
Aminoquinolines may concentrate in the liver. Isolated cases of abnormal liver function and fulminant hepatic failure have been reported. Therapy with aminoquinolines should be administered cautiously in patients with hepatic disease or alcoholism and in patients receiving other hepatotoxic drugs. Periodic evaluation of hepatic function should be performed during prolonged therapy.
Arrhythmia
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Arrhythmia.
The use of 4-aminoquinolines such as hydroxychloroquine and chloroquine prolong the QT interval. Ventricular arrhythmias and torsades de pointes have been reported in patients taking these agents. Care should be exercised in patients with a prolonged QT interval at baseline or at increased risk for arrythmia. A baseline electrocardiogram should be obtained to assess for QT interval prolongation and other abnormalities. It is recommended to use appropriate diagnostic tools such as ECG to monitor patients during therapy.
Bone Marrow Depression/Low Blood Counts
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.
Adverse hematologic effects including neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia have been rarely associated with 4-aminoquinolines. Therapy with 4-aminoquinolines should be administered cautiously in patients with preexisting bone marrow suppression. A complete blood count should be performed periodically in patients on prolonged therapy. If any severe blood disorder appears which is not attributable to the disease under treatment, discontinuance of the drug should be considered.
Cardiomyopathy
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Cardiomyopathy.
Cardiomyopathy has been rarely reported with high daily dosages of hydroxychloroquine. Therapy with hydroxychloroquine should be monitored in patients with heart conditions. If cardiotoxicity is suspected, it is recommended to discontinue treatment with hydroxychloroquine to prevent life-threatening complications.
Diabetes Mellitus
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Diabetes Mellitus.
Hydroxychloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening in patients treated with or without antidiabetic. Care should be exercised when using hydroxychloroquine in diabetic patients. Patients presenting with clinical symptoms suggestive of hypoglycemia during treatment with hydroxychloroquine should have their blood glucose checked and treatment instituted as necessary.
G-6-PD Deficiency
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with G-6-PD Deficiency.
Hemolysis and acute renal failure have been reported during use of aminoquinolines in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Therapy with aminoquinolines should be administered cautiously in these patients. Blood cell counts and hemoglobin determinations should be performed regularly. Aminoquinoline therapy should be discontinued immediately if signs suggestive of hemolytic anemia occur, such as marked darkening of the urine or sudden decrease in hemoglobin concentration or erythrocytic count.
Hearing Loss
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Hearing Loss.
The use of 4-aminoquinolines has been associated rarely with ototoxicity. Nerve-type deafness, which is usually irreversible, has occurred during long-term, high-dose therapy. Deafness may not be apparent until several weeks after 4-aminoquinoline therapy. Tinnitus and reduced hearing have been reported in patients with preexisting auditory damage. Therapy with 4-aminoquinolines should be administered cautiously in such patients. If new auditory defects develop or if hearing loss becomes worse, therapy should be immediately discontinued and the patient closely monitored.
Hypoglycemia
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Hypoglycemia.
Hydroxychloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening in patients treated with or without antidiabetic. Care should be exercised when using hydroxychloroquine in diabetic patients. Patients presenting with clinical symptoms suggestive of hypoglycemia during treatment with hydroxychloroquine should have their blood glucose checked and treatment instituted as necessary.
Liver Disease
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Liver Disease.
Aminoquinolines may concentrate in the liver. Isolated cases of abnormal liver function and fulminant hepatic failure have been reported. Therapy with aminoquinolines should be administered cautiously in patients with hepatic disease or alcoholism and in patients receiving other hepatotoxic drugs. Periodic evaluation of hepatic function should be performed during prolonged therapy.
Myasthenia Gravis
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Myasthenia Gravis.
Certain aminoquinolines such as chloroquine, and hydroxychloroquine should be used with caution in patients with myasthenia gravis (MG). These agents may exacerbate or trigger new onset of symptoms in patients with previously diagnosed MG. It is recommended to advise patients with MG about this possible side effect.
Neutropenia
Moderate:
Harliku
The nitisinone in Harliku has a moderate potential interaction with Neutropenia.
In clinical trials, patients treated with oral formulations of nitisinone and dietary restriction developed transient leukopenia (3%), thrombocytopenia (3%), or both (1.5%). No patients developed infections or bleeding as a result of the episodes of leukopenia and thrombocytopenia. Caution is advised especially in patients with low blood cell counts. Platelet and white blood cell counts should be monitored during therapy with nitisinone.
Porphyria
Major:
hydroxychloroquine
Hydroxychloroquine has a major potential interaction with Porphyria.
The use of aminoquinolines in patients with porphyria may exacerbate the condition. Aminoquinolines should not be used in these patients unless the potential benefits are anticipated to outweigh the risks.
Psoriasis
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Psoriasis.
The use of aminoquinolines in patients with psoriasis may precipitate a severe attack of psoriasis. Aminoquinolines should not be used in these patients unless the potential benefits are anticipated to outweigh the risks.
Renal Dysfunction
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Renal Dysfunction.
Hydroxychloroquine is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. A dosage adjustment is not required for patients with renal impairment. Caution and monitoring should be exercised in patients with impaired renal function.
Retinal Disorders
Major:
hydroxychloroquine
Hydroxychloroquine has a major potential interaction with Retinal Disorders.
The use of 4-aminoquinolines is generally considered contraindicated in the presence of retinal or visual field changes, whether attributable to 4-aminoquinoline compounds or to any other etiology. However, in the treatment of acute attacks of malaria caused by susceptible strains of plasmodia, these agents may be considered if potential benefits are anticipated to outweigh the risks. 4-aminoquinolines are oculotoxic and can cause dose-related, irreversible retinal damage and vision loss during and up to several years after long-term or high-dose therapy (e.g., in the treatment of systemic lupus erythematosus or rheumatoid arthritis). Ophthalmologic monitoring, including visual acuity, expert slit-lamp, funduscopic, and visual field tests, is recommended at baseline and every three months during prolonged use. Therapy should be discontinued immediately if abnormalities develop in visual acuity, visual field, or retinal macular areas (e.g., pigmentary changes, loss of foveal reflex), or if the patient experiences visual symptoms such as light flashes and streaks that are not fully explainable by difficulties of accommodation or corneal opacities. Other common symptoms that may indicate retinopathy include nyctalopia, photophobia, blurred distance vision, difficulty reading or seeing (e.g., words or letters disappearing or parts of objects missing; misty vision; fog before the eyes), and missing or blacked out areas in the central or peripheral visual field. Retinal changes and visual disturbances may progress even after cessation of therapy. However, in a number of patients, early retinopathy (macular pigmentation sometimes with central field defects) diminished or regressed completely after therapy was discontinued. Paracentral scotoma to red targets, sometimes termed premaculopathy, is indicative of early retinal dysfunction and is usually reversible with cessation of therapy.
Seizures
Moderate:
hydroxychloroquine
Hydroxychloroquine has a moderate potential interaction with Seizures.
4-aminoquinolines may cause epileptic seizures in susceptible individuals. Patients with epilepsy or an otherwise low seizure threshold may be at greater risk. Therapy with 4-aminoquinolines, particularly chloroquine, should be administered cautiously in patients with epilepsy.
Thrombocytopenia
Moderate:
Harliku
The nitisinone in Harliku has a moderate potential interaction with Thrombocytopenia.
In clinical trials, patients treated with oral formulations of nitisinone and dietary restriction developed transient leukopenia (3%), thrombocytopenia (3%), or both (1.5%). No patients developed infections or bleeding as a result of the episodes of leukopenia and thrombocytopenia. Caution is advised especially in patients with low blood cell counts. Platelet and white blood cell counts should be monitored during therapy with nitisinone.
More resources
Harliku
A total of 255 drugs are known to interact with Harliku.
- Harliku is in the drug class miscellaneous metabolic agents.
- Harliku is used to treat Alkaptonuria.
hydroxychloroquine
A total of 624 drugs are known to interact with hydroxychloroquine.
- Hydroxychloroquine is in the following drug classes: antimalarial quinolines, antirheumatics.
-
Hydroxychloroquine is used to treat the following conditions:
- Dermatomyositis
- Lichen Planopilaris (off-label)
- Lupus
- Lyme Disease, Arthritis
- Malaria
- Malaria Prevention
- Rheumatoid Arthritis
- Sjogren's Disease (off-label)
- Undifferentiated Connective Tissue Disease (off-label)
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.