Chemical formula: C₁₈H₂₆ClN₃O Molecular mass: 335.872 g/mol PubChem compound: 3652
Hydroxychloroquine interacts in the following cases:
Caution should also be applied when it is used in patients with hepatic or renal disease, and in those taking drugs known to affect those organs. Estimation of plasma hydroxychloroquine levels should be undertaken in patients with severely compromised renal or hepatic function and dosage adjusted accordingly.
As with chloroquine, antacids may reduce absorption of hydroxychloroquine so it is advised that a 4 hour interval be observed between hydroxychloroquine and antacid dosaging.
As hydroxychloroquine may enhance the effects of a hypoglycaemic treatment, a decrease in doses of insulin or antidiabetic drugs may be required.
Hydroxychloroquine sulfate may also be subject to several of the known interactions of chloroquine even though specific reports have not appeared.
These include: potentiation of its direct blocking action at the neuromuscular junction by aminoglycoside antibiotics, inhibition of its metabolism by cimetidine which may increase plasma concentration of the antimalarial, antagonism of effect of neostigmine and pyridostigmine, reduction of the antibody response to primary immunisation with intradermal human diploid-cell rabies vaccine.
The activity of antiepileptic drugs might be impaired if co-administered with hydroxychloroquine.
Hydroxychloroquine can lower the convulsive threshold. Co-administration of hydroxychloroquine with other antimalarials known to lower the convulsion threshold (e.g. mefloquine) may increase the risk of convulsions.
There is no information available on the effect hydroxychloroquine on human fertility. In animal studies, chloroquine, a substance related to hydroxychloroquine, showed adverse effects on male fertility.
There is a theoretical risk of inhibition of intra-cellular α-galactosidase activity when hydroxychloroquine is coadministered with agalsidase.
There may be an increased risk of inducing ventricular arrhythmias if hydroxychloroquine is used concomitantly with other arrhythmogenic drugs, such as amiodarone and moxifloxacin.
An increased plasma ciclosporin level was reported when ciclosporin and hydroxychloroquine were co-administered.
Hydroxychloroquine sulfate has been reported to increase plasma digoxin levels: serum digoxin levels should be closely monitored in patients receiving concomitant therapy.
Halofantrine prolongs the QT interval and should not be administered with other drugs that have the potential to induce cardiac arrhythmias, including hydroxychloroquine.
In a single-dose interaction study, chloroquine has been reported to reduce the bioavailability of praziquantel. It is not known if there is a similar effect when hydroxychloroquine and praziquantel are coadministered. Per extrapolation, due to the similarities in structure and pharmacokinetic parameters between hydroxychloroquine and chloroquine, a similar effect may be expected for hydroxychloroquine.
Concomitant use of drugs with known toxic effects on the retina (e.g. tamoxifen) and hydroxychloroquine is not recommended.
A moderate amount of data on pregnant women (between 300 – 1000 pregnancy outcomes), including prospective studies in long-term use with large exposure, have not observed a significant increased risk of congenital malformations or poor pregnancy outcomes.
Hydroxychloroquine crosses the placenta. 4-aminoquinolines in therapeutic doses caused damage to the central nervous system, including ototoxicity (auditory and vestibular toxicity, congenital deafness), retinal haemorrhages and abnormal retinal pigmentation.
In animal studies, reproduction toxicity was found with chloroquine, a substance related to hydroxychloroquine, following high maternal exposition.
Only limited non-clinical data are available for hydroxychloroquine, data on chloroquine have shown developmental toxicity at high supratherapeutic doses and a potential risk of genotoxicity in some test systems.
Therefore, hydroxychloroquine sulfate should be avoided in pregnancy except when, in the judgement of the physician, the individual potential benefits outweigh the potential hazards. Before treatment is started a pregnancy has to be excluded.
Hydroxychloroquine is excreted in breast milk (less than 2% of the maternal dose after bodyweight correction). There are very limited data on the safety in the breastfed infant during hydroxychloroquine long- term treatment; the prescriber should assess the potential risks and benefits of use during breastfeeding, according to indication and duration of treatment.
Animal studies showed an impairment of male fertility for chloroquine. There are no data in humans.
Impaired visual accommodation soon after the start of treatment has been reported and patients should be warned regarding driving or operating machinery. If the condition is not self-limiting, it will resolve on reducing the dose or stopping treatment.
The following CIOMS frequency rating is used, when applicable: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).
| System Organ class | Frequency | Adverse reaction |
|---|---|---|
| Blood and lymphatic system disorders | Not known | Bone-marrow depression, anaemia, aplastic anaemia, agranulocytosis, leucopenia and thrombocytopenia |
| Immune system disorders | Not known | Urticaria, angioedema, bronchospasm |
| Metabolism and nutrition disorders | Common | Anorexia |
| Not known | Hypoglycaemia Hydroxychloroquine may precipitate or exacerbate porphyria | |
| Psychiatric disorders | Common | Affect liability |
| Uncommon | Nervousness | |
| Not known | Suicidal behaviour, psychosis, depression, hallucinations, anxiety, agitation, confusion, delusions, mania and sleep disorders | |
| Nervous system disorders | Common | headache |
| Uncommon | dizziness | |
| Not known | Convulsions have been reported with this class of drugs Extrapyramidal disorders such as dystonia, dyskinesia, tremor | |
| Eye disorders | Common | Blurring of vision due to a disturbance of accommodation which is dose dependent and reversible |
| Uncommon | Retinopathy with changes in pigmentation and visual field defects can occur, but appears to be uncommon if the recommended daily dose is not exceeded. In its early form it appears reversible on discontinuation of hydroxychloroquine sulfate. If allowed to develop, there may be a risk of progression even after treatment withdrawal. Patients with retinal changes may be asymptomatic initially, or may have scotomatous vision with paracentral, pericentral ring types, temporal scotomas and abnormal colour vision. Corneal changes including oedema and opacities have been reported. They are either symptomless or may cause disturbances such as haloes, blurring of vision or photophobia. They may be transient and are reversible on stopping treatment. | |
| Not known | Cases of maculopathies and macular degeneration have been reported (the onset ranging from 3 months to several years of exposure to hydroxychloroquine) and may be irreversible | |
| Ear and labyrinth disorders | Uncommon | Vertigo, tinnitus |
| Not known | Hearing loss | |
| Skin and subcutaneous tissue disorders | Common | Skin rash, Pruritus |
| Uncommon | Pigmentation disorders in skin and mucous membranes, bleaching of hair, alopecia These usually resolve readily on stopping treatment. | |
| Not known | • Bullous eruptions including erythema multiforme • Stevens-Johnson syndrome and toxic epidermal necrolysis • Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) • photosensitivity • exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP). AGEP has to be distinguished from psoriasis, although hydroxychloroquine may precipitate attacks of psoriasis. It may be associated with fever and hyperleukocytosis. Outcome is usually favourable after drug withdrawal. | |
| Gastrointestinal disorders | Very common | Abdominal pain, nausea |
| Common | diarrhoea, vomiting These symptoms usually resolve immediately on reducing the dose or on stopping treatment. | |
| Cardiac disorders | Not known | QT interval prolongation in patients with specific risk factors, which may lead to arrhythmia (torsade de pointes, ventricular tachycardia). Cardiomyopathy which may result in cardiac failure and in some cases a fatal outcome Chronic toxicity should be considered when conduction disorders (bundle branch block/atrioventricular heart block) as well as biventricular hypertrophy are found. Drug withdrawal may lead to recovery. |
| Musculoskeletal and connective tissue disorders | Uncommon | Sensory motor disorders |
| Not known | Skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups. Myopathy may be reversible after drug discontinuation, but recovery may take many months. Depression of tendon reflexes and abnormal nerve conduction studies. Phospholipidosis mimicking Fabry disease | |
| Hepatobiliary disorders | Uncommon | Abnormal liver function tests |
| Not known | Fulminant hepatic failure |
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