Welchol Side Effects Center

SIDE EFFECTS

The following important adverse reactions are described below and elsewhere in the labeling:

• Hypertriglyceridemia and Pancreatitis [see WARNINGS AND PRECAUTIONS]
• Gastrointestinal Obstruction [see WARNINGS AND PRECAUTIONS]
• Vitamin K or Fat-Soluble Vitamin deciencies [see WARNINGS AND PRECAUTIONS]

Clinical Studies 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 clinical studies of another drug and may not reflect the rates observed in practice.

Primary Hyperlipidemia

In 7 double-blind, placebo-controlled clinical trials, 807 patients with primary hyperlipidemia (age range 18-86 years, 50% women, 90% Caucasians, 7% Blacks, 2% Hispanics, 1% Asians) and elevated LDL-C were treated with WELCHOL 1.5 g/day to 4.5 g/day from 4 to 24 weeks (total exposure 199 patient-years).

Table 1 Clinical Studies of WELCHOL for Primary Hyperlipidemia: Adverse Reactions Reported in ≥ 2% of Patients and More Commonly than in Placebo

Pediatric Patients 10 To 17 Years Of Age

In an 8-week double-blind, placebo-controlled study, boys and post-menarchal girls, 10 to 17 years of age, with HeFH (n=194), were treated with WELCHOL tablets (1.9-3.8 g, daily) or placebo tablets.

Table 2 Clinical Study of WELCHOL for Primary Hyperlipidemia in HeFH Pediatric Patients: Adverse Reactions Reported in ≥2% of Patients and More Commonly than in Placebo

The reported adverse reactions during the additional 18-week open-label treatment period with WELCHOL 3.8 g per day were similar to those during the double-blind period and included headache (7.6%), nasopharyngitis (5.4%), upper respiratory tract infection (4.9%), influenza (3.8%), and nausea (3.8%).

Type 2 Diabetes Mellitus

In 5 add-on combination and 1 monotherapy double-blind, 12- to 26-week, placebo-controlled clinical trials in patients with type 2 diabetes mellitus, 1022 patients were treated with WELCHOL. The mean exposure duration was 20 weeks (total exposure 393 patient-years). Patients were to receive 3.8 grams of WELCHOL per day. The mean age of patients was 55.7 years, 52.8 percent of the population was male and 61.9% were Caucasian, 4.8% were Asian, and 15.9% were Black or African American. At baseline the population had a mean hemoglobin A1c (HbA1c) of 8.2%, and 26% had past medical history suggestive of microvascular complications of diabetes.

Table 3 shows adverse reactions associated with the use of WELCHOL in patients with type 2 diabetes. These adverse reactions were not present at baseline, occurred more commonly on WELCHOL than on placebo, and occurred in at least 2% of patients treated with WELCHOL.

Table 3 Clinical Studies of WELCHOL for Type 2 Diabetes: Adverse Reactions Reported in ≥2% of Patients and More Commonly than in Placebo

A total of 5.3% of WELCHOL-treated patients and 3.6% of placebo-treated patients were discontinued from the diabetes trials due to adverse reactions. This difference was driven mostly by gastrointestinal adverse reactions such as abdominal pain and constipation.

One patient in the add-on to sulfonylurea trial discontinued due to body rash and mouth blistering that occurred on the first day of dosing of WELCHOL, which may represent a hypersensitivity reaction to WELCHOL.

Hypertriglyceridemia

Patients with fasting serum TG levels above 500 mg/dL were excluded from the diabetes clinical trials. In the diabetes trials, 1292 (67.7%) patients had baseline fasting serum TG levels less than 200 mg/dL, 426 (22.3%) had baseline fasting serum TG levels between 200 and less than 300 mg/dL, 175 (9.2%) had baseline fasting serum TG levels between 300 and 500 mg/dL, and 16 (0.8%) had fasting serum TG levels greater than or equal to 500 mg/dL. The median baseline fasting TG concentration for the study population was 160 mg/dL; the median post-treatment fasting TG was 180 mg/dL in the WELCHOL group and 162 mg/dL in the placebo group. WELCHOL therapy resulted in a median placebo-corrected increase in serum TG of 9.7% (p=0.03) in the monotherapy study and of 5% (p=0.22), 11% (p<0.001), 18% (p<0.001), and 22% (p<0.001), when added to metformin, pioglitazone, sulfonylureas, and insulin, respectively. In comparison, WELCHOL resulted in a median increase in serum TG of 5% compared to placebo (p=0.42) in a 24-week monotherapy lipid-lowering trial.

Fasting TG concentrations ≥500 mg/dL occurred in 0.9% of WELCHOL-treated patients compared to 0.7% of placebo-treated patients in the diabetes trials. Among these patients, the TG concentrations with WELCHOL (median 606 mg/dL; interquartile range 570-794 mg/dL) were similar to that observed with placebo (median 663 mg/dL; interquartile range 542-984 mg/dL). Five (0.6%) patients on WELCHOL and 3 (0.3%) patients on placebo developed TG elevations ≥1000 mg/dL.

Cardiovascular Adverse Reactions

During the diabetes trials, the incidence of patients with serious adverse reactions involving the cardiovascular system was 2.2% (22/1022) in the WELCHOL group and 1% (10/1010) in the placebo group. These overall rates included disparate events (e.g., myocardial infarction, aortic stenosis, and bradycardia); therefore, the significance of this imbalance is unknown.

Post-Marketing Experience

The following additional adverse reactions have been identified during post-approval use of WELCHOL. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse Reactions Resulting From Drug Interactions [See Drug Interactions]

Increased seizure activity or decreased phenytoin levels in patients receiving phenytoin, reduced International Normalized Ratio (INR) in patients receiving warfarin therapy, and elevated thyroid-stimulating hormone (TSH) in patients receiving thyroid hormone replacement therapy

Gastrointestinal: Bowel obstruction (in patients with a history of bowel obstruction or resection), dysphagia or esophageal obstruction (occasionally requiring medical intervention), fecal impaction, pancreatitis, abdominal distension, exacerbation of hemorrhoids, and increased transaminases

Laboratory Abnormalities: Hypertriglyceridemia

DRUG INTERACTIONS

WELCHOL Drug Interactions That Decrease The Exposure Of The Concomitant Medication

Table 4 includes a list of drugs that decrease exposure of the concomitant medication when administered concomitantly with WELCHOL and instructions for preventing or managing them.

Table 4 WELCHOL Drug Interactions that Decrease the Exposure of the Concomitant Medication

WELCHOL Drug Interactions That Increase The Exposure Of The Concomitant Medication

Table 5 WELCHOL Drug Interactions that Increase the Exposure of the Concomitant Medication

Read the entire FDA prescribing information for Welchol (Colesevelam Hcl)