ne sulfate tablets do not prevent relapses of p. vivax or p. ovale because it is not active against the hypnozoite forms of these parasites. for radical cure of p. vivax and p. ovale infections, concomitant therapy with an 8-aminoquinoline compound is necessary (see clinical pharmacology – microbiology ). prior to prescribing hydroxychloroquine sulfate tablets for the treatment or prophylaxis of malaria, consult the centers for disease control and prevention (cdc) malaria website (http://www.cdc.gov/malaria). lupus erythematosus hydroxychloroquine sulfate tablets are indicated for the treatment of chronic discoid lupus erythematosus and systemic lupus erythematosus in adults. rheumatoid arthritis hydroxychloroquine sulfate tablets are indicated for the treatment of acute and chronic rheumatoid arthritis in adults.

s with significant risk factors (daily dose of hydroxychloroquine sulfate greater than 5.0 mg/kg base of actual body weight, subnormal glomerular filtration, use of tamoxifen citrate or concurrent macular disease) monitoring should include annual examinations which include bcva, vf and sd-oct. for individuals without significant risk factors, annual exams can usually be deferred until five years of treatment. in individuals of asian descent, retinal toxicity may first be noticed outside the macula. in patients of asian descent, it is recommended that visual field testing be performed in the central 24 degrees instead of the central 10 degrees. it is recommended that hydroxychloroquine be discontinued if ocular toxicity is suspected and the patient should be closely observed given that retinal changes (and visual disturbances) may progress even after cessation of therapy. cardiac effects, including cardiomyopathy and qt prolongation : postmarketing cases of life-threatening and fatal cardiomyopathy have been reported with use of hydroxychloroquine sulfate as well as with use of chloroquine. patients may present with atrioventricular block, pulmonary hypertension, sick sinus syndrome or with cardiac complications. ecg findings may include atrioventricular, right or left bundle branch block. signs or symptoms of cardiac compromise have appeared during acute and chronic treatment. clinical monitoring for signs and symptoms of cardiomyopathy is advised, including use of appropriate diagnostic tools such as ecg to monitor patients for cardiomyopathy during hydroxychloroquine sulfate therapy. chronic toxicity should be considered when conduction disorders (bundle branch block/atrio-ventricular heart block) or biventricular hypertrophy are diagnosed. if cardiotoxicity is suspected, prompt discontinuation of hydroxychloroquine sulfate may prevent life-threatening complications. hydroxychloroquine sulfate prolongs the qt interval. ventricular arrhythmias and torsades de pointes have been reported in patients taking hydroxychloroquine sulfate (see overdosage ). therefore, hydroxychloroquine sulfate should not be administered with other drugs that have the potential to prolong the qt interval (see drug interactions ). worsening of psoriasis and porphyria use of hydroxychloroquine sulfate in patients with psoriasis may precipitate a severe attack of psoriasis. when used in patients with porphyria the condition may be exacerbated. the preparation should not be used in these conditions unless in the judgment of the physician the benefit to the patient outweighs the possible hazard. proximal myopathy and neuropathy: skeletal muscle myopathy or neuropathy leading to progressive weakness and atrophy of proximal muscle groups, depressed tendon reflexes, and abnormal nerve conduction, have been reported. muscle and nerve biopsies have been associated with curvilinear bodies and muscle fiber atrophy with vacuolar changes. assess muscle strength and deep tendon reflexes periodically in patients on long-term therapy with hydroxychloroquine sulfate. neuropsychiatric events, including suicidality: suicidal behavior has been rarely reported in patients treated with hydroxychloroquine sulfate. hypoglycemia : hydroxychloroquine sulfate has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening in patients treated with or without antidiabetic medications (see drug interactions and adverse reactions). patients treated with hydroxychloroquine sulfate should be warned about the risk of hypoglycemia and the associated clinical signs and symptoms. patients presenting with clinical symptoms suggestive of hypoglycemia during treatment with hydroxychloroquine sulfate should have their blood glucose checked and treatment reviewed as necessary.

g/kg base), not to exceed 400 mg (310 mg base), at 6 hours, 24 hours and 48 hours after the initial dose. hydroxychloroquine sulfate filmcoated tablets cannot be divided, therefore they should not be used to treat patients who weigh less than 31 kg. for radical cure of p. vivax and p. malariae infections, concomitant therapy with an 8-aminoquinoline compound is necessary. lupus erythematosus the recommended adult dosage is 200 to 400 mg (155 to 310 mg base) daily, administered as a single daily dose or in two divided doses. doses above 400 mg a day are not recommended. the incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded. rheumatoid arthritis the action of hydroxychloroquine is cumulative and may require weeks to months to achieve the maximum therapeutic effect (see clinical pharmacology). initial adult dosage 400 mg to 600 mg (310 to 465 mg base) daily, administered as a single daily dose or in two divided doses. in a small percentage of patients, side effects may require temporary reduction of the initial dosage. maintenance adult dosage: when a good response is obtained, the dosage may be reduced by 50 percent and continued at a maintenance level of 200 mg to 400 mg (155 to 310 mg base) daily, administered as a single daily dose or in two divided doses. do not exceed 600 mg or 6.5 mg/kg (5 mg/kg base) per day, whichever is lower, as the incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded. corticosteroids and salicylates may be used in conjunction with hydroxychloroquine sulfate, and they can generally be decreased gradually in dosage or eliminated after a maintenance dose of hydroxychloroquine sulfate has been achieved.

fness, deafness. eye disorders irreversible retinopathy with retinal pigmentation changes (bull's eye appearance), visual field defects (paracentral scotomas) and visual disturbances (visual acuity), maculopathies (macular degeneration), decreased dark adaptation, color vision abnormalities, corneal changes (edema and opacities) including corneal deposition of drug with or without accompanying symptoms (halo around lights, photophobia, blurred vision). gastrointestinal disorders nausea, vomiting, diarrhea, and abdominal pain. general disorders and administration site conditions fatigue. hepatobiliary disorders liver function tests abnormal, hepatic failure acute. immune system disorders urticaria, angioedema, bronchospasm metabolism and nutrition disorders decreased appetite, hypoglycemia, porphyria, weight decreased. musculoskeletal and connective tissue disorders: sensorimotor disorder, skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups, depression of tendon reflexes and abnormal nerve conduction. nervous system disorders headache, dizziness, seizure, ataxia and extrapyramidal disorders such as dystonia, dyskinesia, and tremor have been reported with this class of drugs. psychiatric disorders affect/emotional lability, nervousness, irritability, nightmares, psychosis, suicidal behavior. skin and subcutaneous tissue disorders rash, pruritus, pigmentation disorders in skin and mucous membranes, hair color changes, alopecia. dermatitis bullous eruptions including erythema multiforme, stevens-johnson syndrome, and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (dress syndrome), photosensitivity, dermatitis exfoliative, acute generalized exanthematous pustulosis (agep). agep has to be distinguished from psoriasis, although hydroxychloroquine sulfate may precipitate attacks of psoriasis. it may be associated with pyrexia and hyperleukocytosis. to report suspected adverse reactions, contact zydus pharmaceuticals usa inc. at 1-877-993-8779 or fda at 1-800-fda-1088 or www.fda.gov/medwatch .

ng the 155 mg infusion and 6 months following the 310 mg infusion. pharmacokinetic parameters were not significantly different over the therapeutic dose range of 155 mg and 310 mg indicating linear kinetics. following chronic oral administration of hydroxychloroquine, significant levels of three metabolites, desethylhydroxychloroquine (dhcq), desethylchloroquine (dcq), and bidesethylhydroxychloroquine (bdcq) have been found in plasma and blood, with dhcq being the major metabolite. the absorption half-life was approximately 3 to 4 hours and the terminal half-life ranged from 40 to 50 days. the long half-life can be attributed to extensive tissue uptake rather than through decreased excretion. peak plasma levels of hydroxychloroquine were seen in about 3 to 4 hours. renal clearance in rheumatoid arthritis (ra) patients taking hydroxychloroquine sulfate for at least six months seemed to be similar to that of the single dose studies in volunteers, suggesting that no change occurs with chronic dosing. range for renal clearance of unchanged drug was approximately 16 to 30% and did not correlate with creatinine clearance; therefore, a dosage adjustment is not required for patients with renal impairment. in ra patients, there was large variability as to the fraction of the dose absorbed (i.e. 30 to 100%), and mean hydroxychloroquine levels were significantly higher in patients with less disease activity. cellular levels of patients on daily hydroxychloroquine have been shown to be higher in mononuclear cells than polymorphonuclear leucocytes. microbiology - malaria mechanism of action the precise mechanism by which hydroxychloroquine exhibits activity against plasmodium is not known. hydroxychloroquine, like chloroquine, is a weak base and may exert its effect by concentrating in the acid vesicles of the parasite and by inhibiting polymerization of heme. it can also inhibit certain enzymes by its interaction with dna. activity in vitro and in clinical infections hydroxychloroquine is active against the erythrocytic forms of chloroquine sensitive strains of plasmodium falciparum, plasmodium malariae, plasmodium ovale, and plasmodium vivax. hydroxychloroquine is not active against the gametocytes and exoerythrocytic forms including the hypnozoite stage ( p. vivax and p. ovale ) of the plasmodium parasites. drug resistance p. falciparum strains exhibiting reduced susceptibility to chloroquine also show reduced susceptibility to hydroxychloroquine. resistance of plasmodium parasites to chloroquine is widespread (see indications and usage – malaria ). patients in whom chloroquine or hydroxychloroquine have failed to prevent or cure clinical malaria or parasitemia, or patients who acquired malaria in a geographic area where chloroquine resistance is known to occur should be treated with another form of antimalarial therapy (see indications and usage – malaria and warnings ). rheumatoid arthritis and systemic lupus erythematosus mechanism of action the mechanisms underlying the anti-inflammatory and immunomodulatory effects of hydroxychloroquine sulfate are unknown.