FDA label 8bc4df4b-1f3b-46a4-a17a-011d24b1e2b9

WARNING: AVOID USE IN PREGNANCY When pregnancy is detected, discontinue Exforge HCT as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury or death to the developing fetus [see Warnings and Precautions (5.1)]. WARNING: AVOID USE IN PREGNANCY When pregnancy is detected, discontinue Exforge HCT as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury or death to the developing fetus. (5.1)

5 WARNINGS AND PRECAUTIONS Avoid fetal or neonatal exposure (5.1) Symptomatic hypotension with volume- or salt-depletion. Correct volume-depletion prior to administration (5.2) Increased angina and/or myocardial infarction (5.3) Avoid in patients with severely impaired hepatic (2.1, 5.4) or renal function (creatinine clearance ≤30 mL/min) (2.1, 5.5) Observe for signs of fluid or electrolyte imbalance (5.10) Thiazide diuretics may cause an exacerbation or activation of systemic lupus erythematosus (5.8) Hydrochlorothiazide has been associated with acute angle-closure glaucoma (5.11) 5.1 Fetal/Neonatal Morbidity and Mortality Exforge HCT can cause harm to the fetus when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Drugs that act on the renin angiotensin system can cause fetal and neonatal morbidity and mortality when used in pregnancy. In several dozen published cases, ACE inhibitor use during the second and third trimesters of pregnancy was associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death [see Use in Specific Populations (8.1)]. 5.2 Hypotension in Volume- or Salt-Depleted Patients Excessive hypotension, including orthostatic hypotension, was seen in 1.7% of patients treated with the maximum dose of Exforge HCT (10/320/25 mg) compared to 1.8% of valsartan/HCTZ (320/25 mg) patients, 0.4% of amlodipine/valsartan (10/320 mg) patients, and 0.2% of HCTZ/amlodipine (25/10 mg) patients in a controlled trial in patients with moderate to severe uncomplicated hypertension. In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur in patients receiving angiotensin receptor blockers. Correct this condition prior to administration of Exforge HCT. Exforge HCT has not been studied in patients with heart failure, recent myocardial infarction, or in patients undergoing surgery or dialysis. Patients with heart failure or post-myocardial infarction patients given valsartan commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. In controlled trials in heart failure patients, the incidence of hypotension in valsartan-treated patients was 5.5% compared to 1.8% in placebo-treated patients. In the Valsartan in Acute Myocardial Infarction Trial (VALIANT), hypotension in post-myocardial infarction patients led to permanent discontinuation of therapy in 1.4% of valsartan-treated patients and 0.8% of captopril-treated patients. Since the vasodilation induced by amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration. Do not initiate treatment with Exforge HCT in patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy. If excessive hypotension occurs with Exforge HCT, the patient should be placed in a supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized. 5.3 Increased Angina and/or Myocardial Infarction Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration or severity of angina or acute myocardial infarction upon starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated. 5.4 Impaired Hepatic Function Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function. As the majority of valsartan is eliminated in the bile, patients with mild-to-moderate hepatic impairment, including patients with biliary obstructive disorders, showed lower valsartan clearance (higher AUCs). In patients with impaired hepatic function or progressive liver disease, minor alterations of fluid and electrolyte balance, such as those resulting from diuretic use, may precipitate hepatic coma. Therefore, avoid the use of Exforge HCT in patients with severe hepatic impairment. When administering Exforge HCT to patients with mild-to-moderate hepatic impairment, including patients with biliary obstructive disorders, monitor for worsening of hepatic or renal function, including fluid status and electrolytes, and adverse reactions. 5.5 Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar outcomes have been reported with valsartan. In studies of ACE inhibitors in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported. In a 4-day trial of valsartan in 12 hypertensive patients with unilateral renal artery stenosis, no significant increases in serum creatinine or blood urea nitrogen were observed. There has been no long-term use of valsartan in patients with unilateral or bilateral renal artery stenosis, but an effect similar to that seen with ACE inhibitors should be anticipated. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function. Avoid use of Exforge HCT in severe renal disease (creatinine clearance ≤30 mL/min). The usual regimens of therapy with Exforge HCT may be followed if the patient’s creatinine clearance is >30 mL/min. There is no experience in the use of Exforge HCT in patients with a recent kidney transplant. 5.6 Heart Failure Exforge HCT has not been studied in patients with heart failure. Studies with amlodipine : In general, calcium channel blockers should be used with close monitoring, including close follow-up of fluid status, electrolytes, renal function, and blood pressure in patients with heart failure. Amlodipine (5-10 mg per day) has been studied in a placebo-controlled trial of 1,153 patients with NYHA Class III or IV heart failure on stable doses of ACE inhibitor, digoxin, and diuretics. Follow-up was at least 6 months, with a mean of about 14 months. There was no overall adverse effect on survival or cardiac morbidity (as defined by life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure). Amlodipine has been compared to placebo in four 8-12 week studies of patients with NYHA class II/III heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or LVEF. Studies with valsartan: Some patients with heart failure have developed increases in blood urea nitrogen, serum creatinine, and potassium on valsartan. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or valsartan may be required. In the Valsartan Heart Failure Trial, in which 93% of patients were on concomitant ACE inhibitors, treatment was discontinued for elevations in creatinine or potassium (total of 1.0% on valsartan vs. 0.2% on placebo). In the Valsartan in Acute Myocardial Infarction Trial (VALIANT), discontinuation due to various types of renal dysfunction occurred in 1.1% of valsartan-treated patients and 0.8% of captopril-treated patients. Evaluation of patients with heart failure or post-myocardial infarction should always include assessment of renal function. 5.7 Hypersensitivity Reaction Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history. 5.8 Systemic Lupus Erythematosus Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus. 5.9 Lithium Interaction Lithium generally should not be given with thiazides [see Drug Interactions, Hydrochlorothiazide, Lithium (7)]. 5.10 Electrolytes and Metabolic Imbalances Amlodipine -Valsartan - Hydrochlorothiazide In the controlled trial of Exforge HCT in moderate to severe hypertensive patients, the incidence of hypokalemia (serum potassium <3.5 mEq/L) at any time post-baseline with the maximum dose of Exforge HCT (10/320/25 mg) was 10% compared to 25% with HCTZ/amlodipine (25/10 mg), 7% with valsartan/HCTZ (320/25 mg), and 3% with amlodipine/valsartan (10/320 mg). One patient (0.2%) discontinued therapy due to an adverse event of hypokalemia in each of the Exforge HCT and HCTZ/amlodipine groups. The incidence of hyperkalemia (serum potassium >5.7 mEq/L) was 0.4% with Exforge HCT compared to 0.2-0.7% with the dual therapies. Monitor serum electrolytes periodically based on Exforge HCT use and other factors such as renal function, other medications, or history of prior electrolyte imbalances. Hydrochlorothiazide All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance: hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present, or after prolonged therapy. Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis. Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice. Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy. In diabetic patients, dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy. The antihypertensive effects of the drug may be enhanced in the postsympathectomy patient. If progressive renal impairment becomes evident, consider withholding or discontinuing Exforge HCT therapy or substituting other antihypertensive therapy. Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Exforge HCT should be discontinued or non-thiazide antihypertensive therapy substituted before carrying out tests for parathyroid function. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy. 5.11 Acute Myopia and Secondary Angle-Closure Glaucoma Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

6 ADVERSE REACTIONS Most common adverse events (≥2% incidence) are dizziness, peripheral edema, headache, dyspepsia, fatigue, muscle spasms, back pain, nausea and nasopharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. In the controlled trial of Exforge HCT, where only the maximum dose (10/320/25 mg) was evaluated, safety data were obtained in 582 patients with hypertension. Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall frequency of adverse reactions was similar between men and women, younger (<65 years) and older ( > 65 years) patients, and black and white patients. In the active controlled clinical trial, discontinuation because of adverse events occurred in 4.0% of patients treated with Exforge HCT 10/320/25 mg compared to 2.9% of patients treated with valsartan/HCTZ 320/25 mg, 1.6% of patients treated with amlodipine/valsartan 10/320 mg, and 3.4% of patients treated with HCTZ/amlodipine 25/10 mg. The most common reasons for discontinuation of therapy with Exforge HCT were dizziness (1.0%) and hypotension (0.7%). The most frequent adverse events that occurred in the active controlled clinical trial in at least 2% of patients treated with Exforge HCT are presented in the table below: Preferred Term Aml/Val/HCTZ 10/320/25 mg N=582 n (%) Val/HCTZ 320/25 mg N=559 n (%) Aml/Val 10/320 mg N=566 n (%) HCTZ/Aml 25/10 mg N=561 n (%) Dizziness 48 (8.2) 40 (7.2) 14 (2.5) 23 (4.1) Edema 38 (6.5) 8 (1.4) 65 (11.5 ) 63 (11.2) Headache 30 (5.2) 31 (5.5) 30 (5.3) 40 (7.1) Dyspepsia 13 (2.2) 5 (0.9) 6 (1.1) 2 (0.4) Fatigue 13 (2.2) 15 (2.7) 12 (2.1) 8 (1.4) Muscle spasms 13 (2.2) 7 (1.3) 7 (1.2) 5 (0.9) Back pain 12 (2.1) 13 (2.3) 5 (0.9) 12 (2.1) Nausea 12 (2.1) 7 (1.3) 10 (1.8) 12 (2.1) Nasopharyngitis 12 (2.1) 13 (2.3) 13 (2.3) 12 (2.1) Orthostatic events (orthostatic hypotension and postural dizziness) were seen in 0.5% of patients. Other adverse reactions that occurred in clinical trials with Exforge HCT (>0.2%) are listed below. It cannot be determined whether these events were causally related to Exforge HCT. Cardiac Disorders: tachycardia Ear and Labyrinth Disorders: vertigo, tinnitus Eye Disorders: vision blurred Gastrointestinal Disorders: diarrhea, abdominal pain upper, vomiting, abdominal pain, toothache, dry mouth, gastritis, hemorrhoids General Disorders and Administration Site Conditions: asthenia, non-cardiac chest pain, chills, malaise Infections and Infestations: upper respiratory tract infection, bronchitis, influenza, pharyngitis, tooth abscess, gastroenteritis viral, respiratory tract infection, rhinitis, urinary tract infection Injury, Poisoning and Procedural Complications: back injury, contusion, joint sprain, procedural pain Investigations: blood uric acid increased, blood creatine phosphokinase increased, weight decreased Metabolism and Nutrition Disorders: hypokalaemia, diabetes mellitus, hyperlipidemia, hyponatremia Musculoskeletal and Connective Tissue Disorders: pain in extremity, arthralgia, musculoskeletal pain, muscular weakness, musculoskeletal weakness, musculoskeletal stiffness, joint swelling, neck pain, osteoarthritis, tendonitis Nervous System Disorders: parasthesia, somnolence, syncope, carpal tunnel syndrome, disturbance in attention, dizziness postural, dysgeusia, head discomfort, lethargy, sinus headache, tremor Psychiatric Disorders: anxiety, depression, insomnia Renal and Urinary Disorders: pollakiuria Reproductive System and Breast Disorders: erectile dysfunction Respiratory, Thoracic and Mediastinal Disorders: dyspnea, nasal congestion, cough, pharyngolaryngeal pain Skin and Subcutaneous Tissue Disorders: pruritus, hyperhidrosis, night sweats, rash Vascular Disorders: hypotension Isolated cases of the following clinically notable adverse reactions were also observed in clinical trials: anorexia, constipation, dehydration, dysuria, increased appetite, viral infection. Amlodipine Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. Other adverse reactions not listed above that have been reported in <1% but >0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain were: Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, postural hypotension, vasculitis Central and Peripheral Nervous System: neuropathy peripheral, tremor Gastrointestinal: anorexia, dysphagia, pancreatitis, gingival hyperplasia General: allergic reaction, hot flushes, malaise, rigors, weight gain Musculoskeletal System: arthrosis, muscle cramps Psychiatric: sexual dysfunction (male and female), nervousness, abnormal dreams, depersonalization Skin and Appendages: angioedema, erythema multiforme, rash erythematous, rash maculopapular Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus Urinary System: micturition frequency, micturition disorder, nocturia Autonomic Nervous System: sweating increased Metabolic and Nutritional: hyperglycemia, thirst Hemopoietic: leukopenia, purpura, thrombocytopenia Other adverse reactions reported with amlodipine at a frequency of ≤0.1% of patients include: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia. Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina. Adverse reactions reported for amlodipine for indications other than hypertension may be found in its full prescribing information. Valsartan Valsartan has been evaluated for safety in more than 4,000 hypertensive patients in clinical trials. In trials in which valsartan was compared to an ACE inhibitor with or without placebo, the incidence of dry cough was significantly greater in the ACE inhibitor group (7.9%) than in the groups who received valsartan (2.6%) or placebo (1.5%). In a 129 patient trial limited to patients who had dry cough when they had previously received ACE inhibitors, the incidences of cough in patients who received valsartan, HCTZ, or lisinopril were 20%, 19%, and 69% respectively (p<0.001). Other adverse reactions, not listed above, occurring in >0.2% of patients in controlled clinical trials with valsartan are: Digestive: flatulence Respiratory: sinusitis, pharyngitis Urogenital: impotence Adverse reactions reported for valsartan for indications other than hypertension may be found in the prescribing information for Diovan. Hydrochlorothiazide Other adverse reactions not listed above that have been reported with hydrochlorothiazide, without regard to causality, are listed below: Body as a Whole : weakness Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation Hematologic: aplastic anemia, agranulocytosis, hemolytic anemia Hypersensitivity: photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions Metabolic: glycosuria, hyperuricemia Nervous System/Psychiatric: restlessness Renal: renal failure, renal dysfunction, interstitial nephritis Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis Special Senses: transient blurred vision, xanthopsia. 6.2 Post-Marketing Experience Amlodipine With amlodipine, gynecomastia has been reported infrequently and a causal relationship is uncertain. Jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of amlodipine. Valsartan The following additional adverse reactions have been reported in post-marketing experience with valsartan or valsartan/hydrochlorothiazide: Blood and Lymphatic: There are very rare reports of thrombocytopenia. Hypersensitivity: There are rare reports of angioedema. Digestive: Elevated liver enzymes and very rare reports of hepatitis Renal: Impaired renal function Clinical Laboratory Tests: Hyperkalemia Dermatologic: Alopecia Vascular: Vasculitis Nervous System: Syncope Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers. 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.

<table ID="if36040b2-5fb4-4800-8897-878ce88ef857"> <col width="108"/> <col width="94"/> <col width="72"/> <col width="72"/> <col width="72"/> <tbody> <tr> <td> <content styleCode="bold">Preferred Term</content> </td> <td align="center"> <content styleCode="bold">Aml/Val/HCTZ</content> <content styleCode="bold"> 10/320/25 mg</content> <content styleCode="bold"> N=582</content> <content styleCode="bold"> n (%)</content> </td> <td align="center"> <content styleCode="bold">Val/HCTZ</content> <content styleCode="bold"> 320/25 mg</content> <content styleCode="bold"> N=559</content> <content styleCode="bold"> n (%)</content> </td> <td align="center"> <content styleCode="bold">Aml/Val</content> <content styleCode="bold"> 10/320 mg</content> <content styleCode="bold"> N=566</content> <content styleCode="bold"> n (%)</content> </td> <td align="center"> <content styleCode="bold">HCTZ/Aml</content> <content styleCode="bold"> 25/10 mg</content> <content styleCode="bold"> N=561</content> <content styleCode="bold"> n (%)</content> </td> </tr> <tr> <td styleCode="Toprule "> <content styleCode="bold">Dizziness</content> </td> <td styleCode="Toprule " align="center"> <content styleCode="bold">48 (8.2)</content> </td> <td styleCode="Toprule " align="center"> <content styleCode="bold">40 (7.2)</content> </td> <td styleCode="Toprule " align="center"> <content styleCode="bold">14 (2.5)</content> </td> <td styleCode="Toprule " align="center"> <content styleCode="bold">23 (4.1)</content> </td> </tr> <tr> <td> <content styleCode="bold">Edema </content> </td> <td align="center"> <content styleCode="bold">38 (6.5)</content> </td> <td align="center"> <content styleCode="bold"> 8 (1.4)</content> </td> <td align="center"> <content styleCode="bold"> 65 (11.5</content> <content styleCode="bold">)</content> </td> <td align="center"> <content styleCode="bold"> 63 (11.2)</content> </td> </tr> <tr> <td> <content styleCode="bold">Headache</content> </td> <td align="center"> <content styleCode="bold">30 (5.2)</content> </td> <td align="center"> <content styleCode="bold">31 (5.5)</content> </td> <td align="center"> <content styleCode="bold">30 (5.3)</content> </td> <td align="center"> <content styleCode="bold">40 (7.1)</content> </td> </tr> <tr> <td> <content styleCode="bold">Dyspepsia</content> </td> <td align="center"> <content styleCode="bold">13 (2.2)</content> </td> <td align="center"> <content styleCode="bold"> 5 (0.9)</content> </td> <td align="center"> <content styleCode="bold"> 6 (1.1)</content> </td> <td align="center"> <content styleCode="bold"> 2 (0.4)</content> </td> </tr> <tr> <td> <content styleCode="bold">Fatigue</content> </td> <td align="center"> <content styleCode="bold">13 (2.2)</content> </td> <td align="center"> <content styleCode="bold">15 (2.7)</content> </td> <td align="center"> <content styleCode="bold">12 (2.1)</content> </td> <td align="center"> <content styleCode="bold"> 8 (1.4)</content> </td> </tr> <tr> <td> <content styleCode="bold">Muscle spasms</content> </td> <td align="center"> <content styleCode="bold">13 (2.2)</content> </td> <td align="center"> <content styleCode="bold"> 7 (1.3)</content> </td> <td align="center"> <content styleCode="bold"> 7 (1.2)</content> </td> <td align="center"> <content styleCode="bold"> 5 (0.9)</content> </td> </tr> <tr> <td> <content styleCode="bold">Back pain</content> </td> <td align="center"> <content styleCode="bold">12 (2.1)</content> </td> <td align="center"> <content styleCode="bold">13 (2.3)</content> </td> <td align="center"> <content styleCode="bold"> 5 (0.9)</content> </td> <td align="center"> <content styleCode="bold">12 (2.1)</content> </td> </tr> <tr> <td> <content styleCode="bold">Nausea</content> </td> <td align="center"> <content styleCode="bold">12 (2.1)</content> </td> <td align="center"> <content styleCode="bold"> 7 (1.3)</content> </td> <td align="center"> <content styleCode="bold">10 (1.8)</content> </td> <td align="center"> <content styleCode="bold">12 (2.1)</content> </td> </tr> <tr> <td> <content styleCode="bold">Nasopharyngitis</content> </td> <td align="center"> <content styleCode="bold">12 (2.1)</content> </td> <td align="center"> <content styleCode="bold">13 (2.3)</content> </td> <td align="center"> <content styleCode="bold">13 (2.3)</content> </td> <td align="center"> <content styleCode="bold">12 (2.1)</content> </td> </tr> </tbody> </table>