Can Hydroxychloroquine cause pain?

ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Cardiomyopathy and Ventricular Arrhythmias [see Warnings and Precautions ( 5.1 )] Retinal Toxicity [see Warnings and Precautions ( 5.2 )] Serious Skin Reactions [see Warnings and Precautions ( 5.3 )] Worsening of Psoriasis [ see Warnings and Precautions ( 5.4 )] Risks Associated with Use in Porphyria [see Warnings and Precautions ( 5.5 )] Hematologic Toxicity [see Warnings and Precautions ( 5.6 )] Hemolytic Anemia Associated with G6PD [see Warnings and Precautions ( 5.7 )] Skeletal Muscle Myopathy or Neuropathy [see Warnings and Precautions ( 5.8 )] Neuropsychiatric Reactions Including Suicidality [see Warnings and Precautions ( 5.9 )] Hypoglycemia [see Warnings and Precautions ( 5.10 )] Renal Toxicity [see Warnings and Precautions ( 5.11 )] The following adverse reactions have been identified during post-approval use of 4- aminoquinoline drugs, including hydroxychloroquine sulfate. 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 depression, anemia, aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia - Cardiac disorders: Cardiomyopathy, cardiac failure, QT-interval prolongation, ventricular tachycardia, torsades de pointes, atrioventricular block, bundle branch block, sick sinus syndrome, pulmonary hypertension - Ear and labyrinth disorders : Vertigo, tinnitus, nystagmus, sensorineural hearing loss - Eye disorders : Retinopathy, retinal pigmentation changes (typically bull's eye appearance), visual field defects (paracentral scotomas), macular degeneration, corneal edema, corneal opacities, decreased dark adaptation - Gastrointestinal disorders : Nausea, vomiting, diarrhea, abdominal pain - General disorders : Fatigue - Hepatobiliary disorders : Abnormal liver function tests, fulminant hepatic failure - Immune system disorders : Urticaria, angioedema, bronchospasm - Metabolism and nutrition disorders : Anorexia, hypoglycemia, weight loss - Musculoskeletal and connective tissue disorders : Proximal myopathy, depressed tendon reflexes, abnormal nerve conduction - Nervous system disorders : Ataxia, dizziness, headache, seizure, extrapyramidal disorders (dystonia, dyskinesia, tremor) - Neuro psychiatric disorders: Affect/emotional lability, irritability, nervousness, psychosis, suicidal ideation, suicidal behavior, depression, hallucinations, anxiety, agitation, confusion, delusions, paranoia, mania and sleep disorders (insomnia, night terrors, nightmares) - Skin and subcutaneous tissue disorders : Alopecia, hair color changes, rash, pruritus, photosensitivity, psoriasis exacerbation, hyperpigmentation, exfoliative dermatitis, erythema multiforme, acute generalized exanthematous pustulosis, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) The most common adverse reactions reported are: nausea, vomiting, diarrhea, and abdominal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or w w w.fd a .g o v/ m e d w a t ch .

WARNINGS AND PRECAUTIONS Cardiomyopathy and Ventricular Arrhythmias : Fatal or life-threatening cardiomyopathy and ventricular arrhythmias were reported. ( 5.1 ) Retinal Toxicity : Irreversible retinal damage is related to cumulative dosage and treatment duration. Baseline retinal exam and exams during treatment are recommended. ( 5.2 ) Serious Skin Reactions : Stevens Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis have been reported. ( 5.3 ) Worsening of Psoriasis : Avoid in patients with psoriasis. ( 5.4 ) Risks Associated with Use in Porphyria : Avoid in patients with porphyria. Hepatotoxicity was reported in patients with porphyria cutanea tarda ( 5.5 ). Hematologic Toxicity : Discontinue if myelosuppression occurs. ( 5.6 ) Renal Toxicity : Consider phospholipidosis as a possible cause of renal injury in patients with underlying connective tissue disorders. Discontinue hydroxychloroquine sulfate tablets if renal toxicity is suspected or demonstrated by tissue biopsy in any organ system. ( 5.1 , 5.8 , 5.11 ) 5.1 Cardiomypathy and Ventricular Arrhythmias Fatal and life-threatening cases of cardiotoxicity, including cardiomyopathy, have been reported in patients treated with hydroxychloroquine sulfate tablets. Signs and symptoms of cardiac compromise have occurred during acute and chronic hydroxychloroquine sulfate tablets treatment. In multiple cases, endomyocardial biopsy showed association of the cardiomyopathy with phospholipidosis in the absence of inflammation, infiltration, or necrosis. Drug-induced phospholipidosis may occur in other organ systems [see Warnings and Precautions ( 5.8 , 5.11 )]. Patients may present with ventricular hypertrophy, pulmonary hypertension and conduction disorders including sick sinus syndrome. ECG findings include atrioventricular, right or left bundle branch block. Hydroxychloroquine sulfate tablets has a potential to prolong the QT interval. Ventricular arrhythmias (including torsades de pointes) have been reported in hydroxychloroquine sulfate tablets-treated patients. The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded [see Adverse Reactions (6) , Overdosage (10) ]. Avoid hydroxychloroquine sulfate tablets administration in patients with congenital or documented acquired QT prolongation and/or known risk factors for prolongation of the QT interval such as: Cardiac disease, e.g., heart failure, myocardial infarction. Proarrhythmic conditions, e.g., bradycardia (< 50 bpm). History of ventricular dysrhythmias. Uncorrected hypokalemia and/or hypomagnesemia. Concomitant administration with QT interval prolonging agents as this may lead to an increased risk for ventricular arrhythmias [see Drug Interactions (7.1) ]. Therefore, hydroxychloroquine sulfate tablets are not recommended in patients taking other drugs that have the potential to prolong the QT interval. Correct electrolyte imbalances prior to use. Monitor cardiac function as clinically indicated during hydroxychloroquine sulfate tablets therapy. Discontinue hydroxychloroquine sulfate tablets if cardiotoxicity is suspected or demonstrated by tissue biopsy. 5.2 Retinal Toxicity Irreversible retinal damage was observed in some patients treated with hydroxychloroquine sulfate and it is related to cumulative dosage and treatment duration. In patients of Asian descent, retinal toxicity may first be noticed outside the macula. Risk factors for retinal damage include daily hydroxychloroquine sulfate dosages ≥5 mg/kg of actual body weight, durations of use greater than five years, renal impairment, use of concomitant drug products such as tamoxifen citrate, and concurrent macular disease. Within the first year of starting hydroxychloroquine sulfate tablets, a baseline ocular examination is recommended including 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 patients at higher risk of retinal damage, monitoring should include annual examinations which include BCVA, VF and SD-OCT. For patients without significant risk factors, annual retinal exams can usually be deferred until five years of treatment. 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. If ocular toxicity is suspected, discontinue hydroxychloroquine sulfate tablets and monitor the patient closely given that retinal changes and visual disturbances may progress even after cessation of therapy. 5.3 Serious Skin Reactions Serious adverse reactions have been reported with the use of hydroxychloroquine sulfate tablets including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP). Monitor for serious skin reactions, especially in patients receiving a drug that may also induce dermatitis. Advise patients to seek medical attention promptly if they experience signs and symptoms of serious skin reactions such as blisters on the skin, eyes, lips or in the mouth, itching or burning, with or without fever [see Warnings and Precautions ( 5.4 , 5.5 ), Adverse Reactions (6) ]. Discontinue hydroxychloroquine sulfate tablets if these severe reactions occur. 5.4 Worsening of Psoriasis Administration of hydroxychloroquine sulfate tablets to patients with psoriasis may precipitate a severe flare-up of psoriasis. Avoid hydroxychloroquine sulfate tablets in patients with psoriasis, unless the benefit to the patient outweighs the possible risk. 5.5 Risks Associated with Use in Porphyria Administration of hydroxychloroquine sulfate tablets to patients with porphyria may exacerbate porphyria. Avoid hydroxychloroquine sulfate tablets in patients with porphyria. Hepatotoxicity Associated with Porphyria Cutanea Tarda Cases of hepatotoxicity have been reported when hydroxychloroquine was used in patients with porphyria cutanea tarda (PCT). Patients received dosages ranging from 200 mg twice weekly to 400 mg daily. Most of the PCT-related cases presented with marked elevations in transaminases (>20 times upper limit of the reference range) within days to a month of hydroxychloroquine initiation. In some cases, PCT was diagnosed only after the occurrence of treatment-induced liver injury, when hydroxychloroquine was prescribed for an approved indication. Some of the cases were associated with other risk factors for hepatic injury (e.g., alcohol use, concomitant hepatotoxic medications). Measure liver tests promptly in patients who report symptoms that may indicate liver injury, such as fatigue, rash, nausea, dark urine, or jaundice. In this clinical context, if the patient is found to have abnormal serum liver tests (e.g., ALT level greater than three times the upper limit of the reference range, total bilirubin greater than two times the upper limit of the reference range), interrupt treatment with Hydroxychloroquine sulfate tablets, and investigate further to establish the probable cause. The safety and effectiveness of hydroxychloroquine sulfate tablets for the treatment of PCT have not been established and hydroxychloroquine sulfate tablets are not approved for this use. 5.6 Hematologic Toxicity Hydroxychloroquine sulfate tablets may cause myelosuppression including aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia. Monitor blood cell counts periodically in patients on prolonged hydroxychloroquine sulfate tablets therapy. If the patient develops myelosuppression which cannot be attributable to the disease, discontinue the drug. 5.7 Hemolytic Anemia Associated with G6PD Deficiency Hemolysis has been reported in patients with gluco