Adults
Treatment of rheumatoid arthritis, discoid and systemic lupus erythematosus, and dermatological conditions
caused or aggravated by sunlight.
Paediatric Population
Treatment of juvenile idiopathic arthritis (in combination with other therapies), discoid and systemic lupus
erythematosus.
 

Adults (including the elderly)
The minimum effective dose should be employed. This dose should not exceed 6.5mg/kg/day (calculated from
ideal body weight and not actual body weight) and will be either 200mg, 300mg or 400mg per day.
In patients able to receive 400mg daily:
Initially 400mg daily in divided doses. The dose can be reduced to 200mg when no further improvement is
evident. The maintenance dose should be increased to 300mg or 400mg daily if the response lessens.
Paediatric Population
The minimum effective dose should be employed and should not exceed 6.5mg/kg/day based on ideal body
weight. The 200mg tablet is therefore not suitable for use in children with an ideal body weight of less than
31kg.
Each dose should be taken with a meal or glass of milk.
Hydroxychloroquine is cumulative in action and will require several weeks to exert its beneficial effects,
whereas minor side effects may occur relatively early. For rheumatic disease treatment should be discontinued
if there is no improvement by 6 months. In light-sensitive diseases, treatment should only be given during
periods of maximum exposure to light.
The tablets are for oral administration.
 

Visual Effects
The occurrence of retinopathy is very uncommon if the recommended daily dose is not exceeded. The
administration of doses in excess of the recommended maximum is likely to increase the risk of retinopathy,
and accelerate its onset.
All patients should have an ophthalmological examination before initiating treatment with Hydroxychloroquine.
Thereafter, ophthalmological examinations must be repeated at least every 12 months.
The examination should include testing visual acuity, careful ophthalmoscopy, fundoscopy, central visual field
testing with a red target, and colour vision.
This examination should be more frequent and adapted to the patient in the following situations:
o daily dosage exceeds 6.5mg/kg lean body weight. Absolute body weight used as a guide to dosage could
result in an overdosage in the obese
o renal insufficiency
o visual acuity below 6/8
o age above 65 years
o cumulative dose more than 200g.
Hydroxychloroquine should be discontinued immediately in any patient who develops a pigmentary
abnormality, visual field defect, or any other abnormality not explainable by difficulty in accommodation or
presence of corneal opacities. Patients should continue to be observed for possible progression of the
changes.
Patients should be advised to stop taking the drug immediately and seek the advice of their prescribing doctor if
any disturbances of vision are noted, including abnormal colour vision.
Cardiac Effects
Cases of cardiomyopathy resulting in cardiac failure, in some cases with fatal outcome, have been reported in
patients treated with Hydroxychloroquine (see section 4.8 and 4.9). Clinical monitoring for signs and symptoms
of cardiomyopathy is advised and Hydroxychloroquine should be discontinued if cardiomyopathy develops.
Chronic toxicity should be considered when conduction disorders (bundle branch block / atrio-ventricular heart
block) as well as biventricular hypertrophy are diagnosed (see section 4.8).
Caution is required in the following circumstances
Hydroxychloroquine should be used with caution in patients taking medicines which may cause adverse ocular
or skin reactions.
Carefully consider the benefits and risks before prescribing hydroxychloroquine for any patients taking
azithromycin or other macrolide antibiotics, because of the potential for an increased risk of cardiovascular
events and cardiovascular mortality (see section 4.5).
Caution should also be applied when it is used in the following:
o 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.
o patients with severe gastrointestinal, neurological or blood disorders.
o caution is also advised in patients with a sensitivity to quinine, those with glucose-6-phosphate
dehydrogenase deficiency, those with porphyria cutanea tarda which can be exacerbated by
hydroxychloroquine and in patients with psoriasis since it appears to increase the risk of skin reactions.
o patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicine.
Blood Disorders
Although the risk of bone marrow depression is low, periodic blood counts are advisable as anaemia, aplastic
anaemia, agranulocytosis, a decrease in white blood cells, and thrombocytopenia have been reported.
Hydroxychloroquine sulfate should be discontinued if abnormalities develop.
Toxic effects in children
Small children are particularly sensitive to the toxic effects of 4-aminoquinolines; therefore patients should be
warned to keep Hydroxychloroquine sulfate out of the reach of children.
Hypoglycaemia
Hydroxychloroquine has been shown to cause severe hypoglycaemia including loss of consciousness that
could be life threatening in patients treated with and without antidiabetic medications. Patients treated with
hydroxychloroquine should be warned about the risk of hypoglycaemia and the associated clinical signs and
symptoms. Patients presenting with clinical symptoms suggestive of hypoglycaemia during treatment with
hydroxychloroquine should have their blood glucose level checked and treatment reviewed as necessary.
Muscoskeletal effects
All patients on long-term therapy should undergo periodic examination of skeletal muscle function and tendon
reflexes. If weakness occurs, the drug should be withdrawn.
Dermatological reactions
Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
have been reported with the use of Hydroxychloroquine.
Patients should be advised of the signs and symptoms and if symptoms or signs of SJS or TEN are present,
Hydroxychloroquine treatment should be discontinued.
If the patient has developed SJS or TEN with the use of Hydroxychloroquine, Hydroxychloroquine must not be
restarted in this patient at any time
Extrapyramidal disorders
Extrapyramidal disorders may occur with Hydroxychloroquine sulfate (see section 4.8).
Suicidal behaviour and psychiatric disorders
Suicidal behaviour and psychiatric disorders have been reported in some patients treated with
hydroxychloroquine (see section 4.8). Psychiatric side effects typically occur within the first month after the start
of treatment with hydroxychloroquine and have been reported also in patients with no prior history of psychiatric
disorders. Patients should be advised to seek medical advice promptly if they experience psychiatric symptoms
during treatment.
 

Digoxin
Hydroxychloroquine sulfate has been reported to increase plasma digoxin levels: serum digoxin levels should
be closely monitored in patients receiving combined therapy.
Chloroquine
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.
Antacids
As with chloroquine, antacids may reduce absorption of hydroxychloroquine so it is advised that a 4 hour
interval be observed between Hydroxychloroquine sulfate and antacid dosaging.
Anti-diabetics
As hydroxychloroquine may enhance the effects of a hypoglycaemic treatment, a decrease in doses of insulin
or antidiabetic drugs may be required.
Halofantrine
Halofantrine prolongs the QT interval and should not be administered with other drugs that have the potential to
induce cardiac arrhythmias, including hydroxychloroquine. Also, there may be an increased risk of inducing
ventricular arrhythmias if hydroxychloroquine is used concomitantly with other arrhythmogenic drugs, such as
amiodarone and moxifloxacin.
Ciclosporin
An increased plasma ciclosporin level was reported when ciclosporin and hydroxychloroquine were coadministered.
Tamoxifen
Concomitant use of drugs known to induce retinal toxicity, e.g. tamoxifen and hydroxychloroquine sulfate, is not
recommended (see section 4.4).
Antimalarials
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.
Antiepileptics
Also, the activity of antiepileptic drugs might be impaired if co-administered with hydroxychloroquine.
Praziquantil
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.
Agalsidase
There is a theoretical risk of inhibition of intra-cellular α-galactosidase activity when hydroxychloroquine is coadministered with agalsidase.
Azithromycin and macrolide antibiotics
Observational data have shown that co-administration of hydroxychloroquine with azithromycin in patients with
rheumatoid arthritis is associated with an increased risk of cardiovascular events and cardiovascular mortality.
Carefully consider the balance of benefits and risks before prescribing hydroxychloroquine for any patients
taking azithromycin. Similar careful consideration of the balance of benefits and risks should also be
undertaken before prescribing hydroxychloroquine for any patients taking other macrolide antibiotics, such as
clarithromycin or erythromycin, because of the potential for a similar risk when hydroxychloroquine is coadministered with these medicines.
 

FDA Pregnancy Category N - Not classified
Fertility:
There is no information available on the effect of Hydroxychloroquine sulfate on human fertility. In animal
studies, chloroquine, a substance related to hydroxychloroquine, showed adverse effects on male fertility (see
section 5.3).
Pregnancy:
Although able to cross the placenta, the use of hydroxychloroquine in pregnancy is now considered to convey a
low risk of harm to the foetus with no significant increase in congenital malformations. In SLE there is evidence
that hydroxychloroquine reduces disease activity during pregnancy reinforcing the importance of continuing this
therapy. Indeed, pregnancy itself can induce lupus flares, which can be prevented by hydroxychloroquine.
Preliminary studies have suggested that hydroxychloroquine can reduce the risk of neonatal lupus and
congenital heart block in lupus patients who are anti-Ro positive. A recently published study of pregnant
patients with antiphospholipid syndrome found that exposure to hydroxychloroquine was linked to a significantly
higher live birth rate.
Taken together in autoimmune diseases such as lupus and anti-phospholipid syndrome the balance of benefit
outweighs any potential harm to the foetus and therefore hydroxychloroquine should be continued. In other
diseases the prescribing physician should assess the risk/benefit ratio for hydroxychloroquine and act
accordingly.
Lactation:
Data on safety during breastfeeding are limited but no harmful effects have been observed.
Hydroxychloroquine is excreted in small amounts in breast milk, with estimates of exposure to infants ranging
from <1% to about 3% of the adult dose. All infants exposed to hydroxychloroquine during pregnancy will also
have been exposed during breastfeeding because the half-life of hydroxychloroquine is more than 40 days.
Hydroxychloroquine seems to carry a low risk of harm to the infant. A careful benefit-risk assessment should be
made whether to take hydroxychloroquine therapy whilst breastfeeding, taking into account the benefit of
breastfeeding for the child and the benefit of therapy for the woman.
 

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.
 

a.  Summary of the safety profile

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).

b.  Tabulated list of adverse reactions

c.  Description of selected side effects

Not applied

d.  Special populations

Not applied

e.  Paediatric population

Not applied

Reporting of side effects

Saudi Arabia

Other GCC states /other countries

Overdosage with the 4-aminoquinolines is dangerous particularly in infants, as little as 1-2g having proved fatal.

The symptoms of overdosage may include headache, visual disturbances, cardiovascular collapse, convulsions, hypokalaemia; rhythm and conduction disorders, including QT prolongation, Torsade de Pointes, ventricular tachycardia and ventricular fibrillation followed by sudden and early respiratory and cardiac arrest. Since these effects may appear soon after taking a massive dose, treatment should be prompt and symptomatic.

The stomach should be immediately evacuated, either by emesis or by gastric lavage. Activated charcoal in a dose at least five times of the overdose may inhibit further absorption if introduced into the stomach by tube following lavage and within 30 minutes of ingestion of the overdose.

Consideration should be given to administration of parenteral diazepam in cases of overdosage; it has been shown to be beneficial in reversing chloroquine cardiotoxicity.

Respiratory support and shock management should be instituted as necessary.

ATC Code: P01BA02

Pharmacotherapeutic group: Anti rheumatic

Antimalarial agents like chloroquine and hydroxychloroquine have several pharmacological actions which may be involved in their therapeutic effect in the treatment of rheumatic disease, but the role of each is not known. These include interaction with sulphydryl groups, interference with enzyme activity (including phospholipase, NADH - cytochrome C reductase, cholinesterase, proteases and hydrolases), DNA binding, stabilisation of lysosomal membranes, inhibition of prostaglandin formation, inhibition of polymorphonuclear cell chemotaxis and phagocytosis, possible interference with interleukin 1 production from monocytes and inhibition of neutrophil superoxide release.

Hydroxychloroquine has actions, pharmacokinetics and metabolism similar to those of chloroquine. Following oral administration, hydroxychloroquine is rapidly and almost completely absorbed. In one study, mean peak plasma hydroxychloroquine concentrations following a single dose of 400mg in healthy subjects ranged from 53-208ng/ml with a mean of 105ng/ml. The mean time to peak plasma concentration was 1.83 hours. The mean plasma elimination half-life varied, depending on the post-administration period, as follows: 5.9 hours at Cmax-10 hours), 26.1 hours (at 10-48 hours) and 299 hours (at 48-504 hours). The parent compound and metabolites are widely distributed in the body and elimination is mainly via the urine, where 3% of the administered dose was recovered over 24 hours in one study.

Animal studies concerning a cancerogenic potential of hydroxychloquine are not available. A mutagenic potential could not be excluded.

Hydroxychloroquine passes the placenta and can induce damage to organs of the fetus. In studies with mice and monkeys, chloroquine, a substance related to hydroxychloroquine, resulted in transplacental transfer and accumulation in the adrenal cortex and the retina. High maternal doses of chloroquine were fetotoxic in rats and caused anophthalmia and microophthalmia. In studies in rats, chloroquine reduced the testosterone secretion, the weight of the testis and epididymis and caused production of abnormal sperm.

-Corn Starch

-Polyvinyl Pyrolidone (Povidone K30)

-Lactose monohydrate

-Magnesium Stearate

-Opadry II white 32F280000

-Purified water

Not applicable.

Do not store above 30°C.

Store in the original package in order to protect from light and moisture.

Available in packs containing 60 tablets

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.