Tovaris Side effects

• Side effects of Tovaris in details
• Tovaris contraindications
• Tovaris reviews

What are the possible side effects of Tovaris?

Get emergency medical help if you have signs of an allergic reaction to Tovaris: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

In rare cases, Tovaris can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.

Also call your doctor at once if you have:

• kidney problems - little or no urinating, painful or difficult urination, swelling in your feet or ankles, feeling tired or short of breath;

• liver problems - nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• signs of a stroke - sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance.

Common Tovaris side effects may include:

• muscle or joint pain;

• diarrhea; or

• upset stomach.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Side effects of Tovaris in details

The following serious adverse reactions are discussed in greater detail in other sections of the label:

Rhabdomyolysis and myopathy

Liver enzyme abnormalities

Clinical Trial Adverse Experiences

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In the Tovaris placebo-controlled clinical trial database of 16,066 patients (8755 Tovaris vs. 7311 placebo; age range 10–93 years, 39% women, 91% Caucasians, 3% Blacks, 2% Asians, 4% other) with a median treatment duration of 53 weeks, 9.7% of patients on Tovaris and 9.5% of the patients on placebo discontinued due to adverse reactions regardless of causality. The five most common adverse reactions in patients treated with Tovaris that led to treatment discontinuation and occurred at a rate greater than placebo were: myalgia (0.7%), diarrhea (0.5%), nausea (0.4%), alanine aminotransferase increase (0.4%), and hepatic enzyme increase (0.4%).

The most commonly reported adverse reactions (incidence ≥ 2% and greater than placebo) regardless of causality, in patients treated with Tovaris in placebo controlled trials (n=8755) were: nasopharyngitis (8.3%), arthralgia (6.9%), diarrhea (6.8%), pain in extremity (6.0%), and urinary tract infection (5.7%).

Table 2 summarizes the frequency of clinical adverse reactions, regardless of causality, reported in ≥ 2% and at a rate greater than placebo in patients treated with Tovaris (n=8755), from seventeen placebo-controlled trials.

Table 2. Clinical adverse reactions occurring in ≥ 2% in patents treated with any dose of Tovaris and at an incidence greater than placebo regardless of causality (% of patients).

Adverse Reaction*	Any dose N=8755	10 mg N=3908	20 mg N=188	40 mg N=604	80 mg N=4055	Placebo N=7311
* Adverse Reaction ≥ 2% in any dose greater than placebo
Nasopharyngitis	8.3	12.9	5.3	7.0	4.2	8.2
Arthralgia	6.9	8.9	11.7	10.6	4.3	6.5
Diarrhea	6.8	7.3	6.4	14.1	5.2	6.3
Pain in extremity	6.0	8.5	3.7	9.3	3.1	5.9
Urinary tract infection	5.7	6.9	6.4	8.0	4.1	5.6
Dyspepsia	4.7	5.9	3.2	6.0	3.3	4.3
Nausea	4.0	3.7	3.7	7.1	3.8	3.5
Musculoskeletal pain	3.8	5.2	3.2	5.1	2.3	3.6
Muscle Spasms	3.6	4.6	4.8	5.1	2.4	3.0
Myalgia	3.5	3.6	5.9	8.4	2.7	3.1
Insomnia	3.0	2.8	1.1	5.3	2.8	2.9
Pharyngolaryngeal pain	2.3	3.9	1.6	2.8	0.7	2.1

Other adverse reactions reported in placebo-controlled studies include:

Body as a whole: malaise, pyrexia; Digestive system: abdominal discomfort, eructation, flatulence, hepatitis, cholestasis; Musculoskeletal system: musculoskeletal pain, muscle fatigue, neck pain, joint swelling; Metabolic and nutritional system: transaminases increase, liver function test abnormal, blood alkaline phosphatase increase, creatine phosphokinase increase, hyperglycemia; Nervous system: nightmare; Respiratory system: epistaxis; Skin and appendages: urticaria; Special senses: vision blurred, tinnitus; Urogenital system: white blood cells urine positive.

Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)

In ASCOT involving 10,305 participants (age range 40–80 years, 19% women; 94.6% Caucasians, 2.6% Africans, 1.5% South Asians, 1.3% mixed/other) treated with Tovaris 10 mg daily (n=5,168) or placebo (n=5,137), the safety and tolerability profile of the group treated with Tovaris was comparable to that of the group treated with placebo during a median of 3.3 years of follow-up.

Collaborative Tovaris Diabetes Study (CARDS)

In CARDS involving 2,838 subjects (age range 39–77 years, 32% women; 94.3% Caucasians, 2.4% South Asians, 2.3% Afro-Caribbean, 1.0% other) with type 2 diabetes treated with Tovaris 10 mg daily (n=1,428) or placebo (n=1,410), there was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 3.9 years. No cases of rhabdomyolysis were reported.

Treating to New Targets Study (TNT)

In TNT involving 10,001 subjects (age range 29–78 years, 19% women; 94.1% Caucasians, 2.9% Blacks, 1.0% Asians, 2.0% other) with clinically evident CHD treated with Tovaris 10 mg daily (n=5006) or Tovaris 80 mg daily (n=4995), there were more serious adverse reactions and discontinuations due to adverse reactions in the high-dose Tovaris group (92, 1.8%; 497, 9.9%, respectively) as compared to the low-dose group (69, 1.4%; 404, 8.1%, respectively) during a median follow-up of 4.9 years. Persistent transaminase elevations (≥3 × ULN twice within 4–10 days) occurred in 62 (1.3%) individuals with Tovaris 80 mg and in nine (0.2%) individuals with Tovaris 10 mg. Elevations of CK (≥ 10 × ULN) were low overall, but were higher in the high-dose Tovaris treatment group (13, 0.3%) compared to the low-dose Tovaris group (6, 0.1%).

Incremental Decrease in Endpoints through Aggressive Lipid Lowering Study (IDEAL)

In IDEAL involving 8,888 subjects (age range 26–80 years, 19% women; 99.3% Caucasians, 0.4% Asians, 0.3% Blacks, 0.04% other) treated with Tovaris 80 mg/day (n=4439) or simvastatin 20–40 mg daily (n=4449), there was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 4.8 years.

Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL)

In SPARCL involving 4731 subjects (age range 21–92 years, 40% women; 93.3% Caucasians, 3.0% Blacks, 0.6% Asians, 3.1% other) without clinically evident CHD but with a stroke or transient ischemic attack (TIA) within the previous 6 months treated with Tovaris 80 mg (n=2365) or placebo (n=2366) for a median follow-up of 4.9 years, there was a higher incidence of persistent hepatic transaminase elevations (≥ 3 × ULN twice within 4–10 days) in the Tovaris group (0.9%) compared to placebo (0.1%). Elevations of CK (>10 × ULN) were rare, but were higher in the Tovaris group (0.1%) compared to placebo (0.0%). Diabetes was reported as an adverse reaction in 144 subjects (6.1%) in the Tovaris group and 89 subjects (3.8%) in the placebo group.

In a post-hoc analysis, Tovaris 80 mg reduced the incidence of ischemic stroke (218/2365, 9.2% vs. 274/2366, 11.6%) and increased the incidence of hemorrhagic stroke (55/2365, 2.3% vs. 33/2366, 1.4%) compared to placebo. The incidence of fatal hemorrhagic stroke was similar between groups (17 Tovaris vs. 18 placebo). The incidence of non-fatal hemorrhagic strokes was significantly greater in the Tovaris group (38 non-fatal hemorrhagic strokes) as compared to the placebo group (16 non-fatal hemorrhagic strokes). Subjects who entered the study with a hemorrhagic stroke appeared to be at increased risk for hemorrhagic stroke [7 (16%) Tovaris vs. 2 (4%) placebo].

There were no significant differences between the treatment groups for all-cause mortality: 216 (9.1%) in the Tovaris 80 mg/day group vs. 211 (8.9%) in the placebo group. The proportions of subjects who experienced cardiovascular death were numerically smaller in the Tovaris 80 mg group (3.3%) than in the placebo group (4.1%). The proportions of subjects who experienced non-cardiovascular death were numerically larger in the Tovaris 80 mg group (5.0%) than in the placebo group (4.0%).

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Tovaris. 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.

Adverse reactions associated with Tovaris therapy reported since market introduction, that are not listed above, regardless of causality assessment, include the following: anaphylaxis, angioneurotic edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), rhabdomyolysis, myositis, fatigue, tendon rupture, fatal and non-fatal hepatic failure, dizziness, depression, peripheral neuropathy, and pancreatitis.

There have been rare reports of immune-mediated necrotizing myopathy associated with statin use.

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

Pediatric Patients (ages 10–17 years)

In a 26-week controlled study in boys and postmenarchal girls (n=140, 31% female; 92% Caucasians, 1.6% Blacks, 1.6% Asians, 4.8% other), the safety and tolerability profile of Tovaris 10 to 20 mg daily was generally similar to that of placebo.

What is the most important information I should know about Tovaris?

• Tovaris may cause liver problems. Rarely, severe and sometimes fatal liver problems have been reported in patients taking "statin" medicines, including Tovaris. Your risk of developing liver problems may be greater if you drink alcohol daily or in large amounts, or if you have a history of liver problems. Check with your doctor before drinking alcohol while you are taking Tovaris. Tell your doctor right away if you experience symptoms of liver problems (eg, dark urine; pale stools; severe or persistent nausea, loss of appetite, or stomach pain; unusual tiredness; yellowing of the skin or eyes).
• Do NOT take more than the recommended dose without checking with your doctor. Doing so may cause an increase in the risk of severe side effects.
• Follow the diet and exercise program given to you by your health care provider.
• Tell your doctor or dentist that you take Tovaris before you receive any medical or dental care, emergency care, or surgery.
• Women who may become pregnant should use effective birth control while taking Tovaris. Check with your doctor if you have questions about using birth control.
• Muscle problems (myopathy) may occur with Tovaris. Report any unexplained muscle pain, tenderness, or weakness to your doctor right away, especially if you also have a fever or general body discomfort. Tell your doctor if you have muscle problems that persist even after your doctor has told you to stop taking Tovaris.
• Diabetes patients - Tovaris may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.
• Lab tests, including blood cholesterol levels, creatine phosphokinase (CPK) levels, and liver function, may be performed while you use Tovaris. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.
• Use Tovaris with caution in the ELDERLY; they may be more sensitive to its effects, especially muscle problems.
• Tovaris should be used with extreme caution in CHILDREN younger than 10 years old and in those who have not reached puberty; safety and effectiveness in these children have not been confirmed.
• PREGNANCY and BREAST-FEEDING: Do not use Tovaris if you are pregnant. It may cause harm to the fetus. Avoid becoming pregnant while you are taking it. If you think you may be pregnant, contact your doctor right away. It is not known if Tovaris is found in breast milk. Do not breast-feed while taking Tovaris.

Tovaris contraindications

Active liver disease, which may include unexplained persistent elevations in Hepatic Transaminase Levels

Hypersensitivity to any Component of this Medication

Pregnancy

Women who are pregnant or may become pregnant. Tovaris calcium may cause fetal harm when administered to a pregnant woman. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of Tovaris calcium use during pregnancy; however in rare reports, congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, Tovaris revealed no evidence of teratogenicity. Tovaris CALCIUM SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING AGE ONLY WHEN SUCH PATIENTS ARE HIGHLY UNLIKELY TO CONCEIVE AND HAVE BEEN INFORMED OF THE POTENTIAL HAZARDS. If the patient becomes pregnant while taking this drug, Tovaris calcium should be discontinued immediately and the patient apprised of the potential hazard to the fetus.

Nursing Mothers

It is not known whether Tovaris is excreted into human milk; however a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require Tovaris calcium treatment should not breastfeed their infants.

References

1. DailyMed. "AMLODIPINE BESYLATE; ATORVASTATIN CALCIUM: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
2. European Chemicals Agency - ECHA. "(3R,5R)-7-[2-(4-Fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid: The information provided here is aggregated from the "Notified classification and labelling" from ECHA's C&L Inventory. ". https://echa.europa.eu/information-o... (accessed September 17, 2018).
3. HSDB. "ATORVASTATIN". https://toxnet.nlm.nih.gov/cgi-bin/s... (accessed September 17, 2018).

Reviews

The results of a survey conducted on ndrugs.com for Tovaris are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Tovaris. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

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Information checked by Dr. Sachin Kumar, MD Pharmacology