Plaquenil Hydroxychloroquine Sulfate 200 mg Tablet, 12-count — NDC 67296-1781-1 (Billing 67296-1781-01)

WARNINGS Resistant strains of malaria: PLAQUENIL is not effective against chloroquine-resistant strains of P. falciparum (see CLINICAL PHARMACOLOGY – Microbiology ). Ocular: Irreversible retinal damage has been observed in some patients who had received hydroxychloroquine sulfate. Significant risk factors for retinal damage include daily doses of hydroxychloroquine sulfate greater than 6.5 mg/kg (5 mg/kg base) of actual body weight, durations of use greater than five years, subnormal glomerular filtration, use of some concomitant drug products such as tamoxifen citrate and concurrent macular disease.

A baseline ocular examination is recommended within the first year of starting PLAQUENIL. The baseline exam should include: best corrected distance visual acuity (BCVA), an automated threshold visual field (VF) of the central 10 degrees (with retesting if an abnormality is noted), and spectral domain ocular coherence tomography (SD-OCT). For individuals 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 PLAQUENIL 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 PLAQUENIL 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 PLAQUENIL may prevent life-threatening complications. PLAQUENIL prolongs the QT interval.

Ventricular arrhythmias and torsades de pointes have been reported in patients taking PLAQUENIL (see OVERDOSAGE ). Therefore, PLAQUENIL 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 PLAQUENIL 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 PLAQUENIL. Neuropsychiatric events, including suicidality: Suicidal behavior has been rarely reported i… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS The following adverse reactions have been identified during post-approval use of PLAQUENIL or other 4-aminoqunoline compounds. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders: Bone marrow failure, anemia, aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia.

Hemolysis reported in individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Cardiac disorders: Cardiomyopathy which may result in cardiac failure and in some cases a fatal outcome (see WARNINGS and OVERDOSAGE ). PLAQUENIL prolongs the QT interval.

Ventricular arrhythmias and torsade de pointes have been reported in patients taking PLAQUENIL (see OVERDOSAGE and DRUG INTERACTIONS ). Ear and labyrinth disorders: Vertigo, tinnitus, nystagmus, nerve deafness, 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 PLAQUENIL may precipitate attacks of psoriasis. It may be associated with pyrexia and hyperleukocytosis. To report SUSPECTED ADVERSE REACTIONS, contact Concordia Pharmaceuticals at 1-877-370-1142 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions Digoxin : Concomitant PLAQUENIL and digoxin therapy may result in increased serum digoxin levels: serum digoxin levels should be closely monitored in patients receiving combined therapy. Insulin or antidiabetic drugs : As PLAQUENIL may enhance the effects of a hypoglycemic treatment, a decrease in doses of insulin or antidiabetic drugs may be required. Drugs that prolong QT interval and other arrhythmogenic drugs : PLAQUENIL prolongs the QT interval and should not be administered with other drugs that have the potential to induce cardiac arrhythmias.

Also, there may be an increased risk of inducing ventricular arrhythmias if PLAQUENIL is used concomitantly with other arrhythmogenic drugs. Mefloquine and other drugs known to lower the convulsive threshold : PLAQUENIL can lower the convulsive threshold. Co-administration of PLAQUENIL with other antimalarials known to lower the convulsion threshold (e.g., mefloquine) may increase the risk of convulsions.

Antiepileptics : The activity of antiepileptic drugs might be impaired if co-administered with PLAQUENIL. Methotrexate : Combined use of methotrexate with PLAQUENIL has not been studied and may increase the incidence of adverse effects. Cyclosporin : An increased plasma cyclosporin level was reported when cyclosporin and PLAQUENIL were co-administered.

The following interactions have been observed on treatment with the structurally related substance chloroquine phosphate, and therefore cannot be ruled out for hydroxychloroquine. Praziquantel : Chloroquine has been reported to reduce the bioavailability of praziquantel. Antacids and kaolin : Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed.

Cimetidine : Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level. Concomitant use of cimetidine should be avoided. Ampicillin : In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin.

PRECAUTIONS General: Use with caution in patients with gastrointestinal, neurological, or blood disorders, and in those with a sensitivity to quinine. Hepatic/Renal Disease: Antimalarial compounds should be used with caution in patients with hepatic disease or alcoholism, or in conjunction with known hepatotoxic drugs. A reduction in dosage may be necessary in patients with hepatic or renal disease, as well as in those taking medicines known to affect these organs.

Hematologic Effects/Laboratory Tests: Antimalarial compounds should be used with caution in patients with hepatic disease or alcoholism or in conjunction with known hepatotoxic drugs. Periodic blood cell counts should be performed if patients are given prolonged therapy. If any severe blood disorder such as aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia, appears which is not attributable to the disease under treatment, consider discontinuation of PLAQUENIL.

PLAQUENIL should be administered with caution in patients having glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Dermatologic Effects: Dermatologic reactions to PLAQUENIL may occur and, therefore, proper care should be exercised when it is administered to any patient receiving a drug with a significant tendency to produce dermatitis. Drug Interactions Digoxin : Concomitant PLAQUENIL and digoxin therapy may result in increased serum digoxin levels: serum digoxin levels should be closely monitored in patients receiving combined therapy.

Insulin or antidiabetic drugs : As PLAQUENIL may enhance the effects of a hypoglycemic treatment, a decrease in doses of insulin or antidiabetic drugs may be required. Drugs that prolong QT interval and other arrhythmogenic drugs : PLAQUENIL prolongs the QT interval and should not be administered with other drugs that have the potential to induce cardiac arrhythmias. Also, there may be an increased risk of inducing ventricular arrhythmias if PLAQUENIL is used concomitantly with other arrhythmogenic drugs.

Mefloquine and other drugs known to lower the convulsive threshold : PLAQUENIL can lower the convulsive threshold. Co-administration of PLAQUENIL with other antimalarials known to lower the convulsion threshold (e.g., mefloquine) may increase the risk of convulsions. Antiepileptics : The activity of antiepileptic drugs might be impaired if co-administered with PLAQUENIL.

Methotrexate : Combined use of methotrexate with PLAQUENIL has not been studied and may increase the incidence of adverse effects. Cyclosporin : An increased plasma cyclosporin level was reported when cyclosporin and PLAQUENIL were co-administered. The following interactions have been observed on treatment with the structurally related substance chloroquine phosphate, and therefore cannot be ruled out for hydroxychloroquine.

Praziquantel : Chloroquine has been reported to reduce the bioavailability of praziquantel. Antacids and kaolin : Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed. Cimetidine : Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level.

Concomitant use of cimetidine should be avoided. Ampicillin : In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin. Information for Patients: Patients should be informed of the early signs and symptoms of toxicity such as rash or visual changes.

Patients must see their physicians promptly in case of the appearance of these or of any unusual effects. Periodic laboratory tests may be recommended in some patients. Patients should be fully informed of the potential risks of the use of PLAQUENIL, especially in pregnancy and in children.

Carcinogenesis, mutagenesis, impairment of fertility: Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of PLAQUENIL. The mutagenic potential of hydroxychloroquine was not evaluated. However,… [Excerpted — this section continues on DailyMed.]