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Prandin

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Prandin




Side Effects
Interactions

SIDE EFFECTS

The following serious adverse reaction is also described elsewhere in the labeling:

Hypoglycemia [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

PRANDIN has been administered to 2931 individuals during clinical trials. Approximately 1500 of these individuals with type 2 diabetes have been treated for at least 3 months, 1000 for at least 6 months, and 800 for at least 1 year. The majority of these individuals (1228) received PRANDIN in one of five 1-year, active-controlled trials. Over one year, 13% of PRANDIN patients were discontinued due to adverse reactions. The most common adverse reactions leading to withdrawal were hyperglycemia, hypoglycemia, and related symptoms.

Table 1 lists the common adverse reactions for PRANDIN patients compared to placebo in trials 12 to 24 weeks duration.

Table 1: Adverse Reactions (%) occurring ≥ 2% in PRANDIN Treated Patients from Pool of 12 to 24 Week Placebo Controlled

  PRANDIN
N=352
Placebo
N=108
Upper Respiratory Infection 16 8
Headache 11 10
Sinusitis 6 2
Arthralgia 6 3
Nausea 5 5
Diarrhea 5 2
Back Pain 5 4
Rhinitis 3 3
Constipation 3 2
Vomiting 3 3
Paresthesia 3 3
Chest pain 3 1
Bronchitis 2 1
Dyspepsia 2 2
Urinary tract infection 2 1
Tooth disorder 2 0
Allergy 2 0
* See trial descriptions in Clinical Trials (14)

Hypoglycemia

In clinical trials with PRANDIN, hypoglycemia is the most commonly observed adverse reaction. Mild or moderate hypoglycemia occurred in 31% of PRANDIN treated patients and 7% of placebo treated patients [see WARNINGS AND PRECAUTIONS].

Hypoglycemia was reported in 16% of 1228 PRANDIN patients, 20% of 417 glyburide patients, and 19% of 81 glipizide patients in 1year controlled trials. Of PRANDIN-treated patients with symptomatic hypoglycemia, none developed coma or required hospitalization.

In a 24-week placebo controlled trial, patients who were naïve to oral hypoglycemic agent therapy and patients with a HbA1c below 8% at baseline had a higher frequency of hypoglycemia.

Weight Gain

There was no average gain in body weight when patients previously treated with oral hypoglycemic agents were switched to PRANDIN. The average weight gain in patients treated with PRANDIN and not previously treated with sulfonylurea drugs was 3.3%.

Cardiovascular Events

The incidence of total serious cardiovascular adverse events, including ischemia, was higher for PRANDIN (51/1228 or 4%) than for sulfonylurea drugs (13/498 or 3%) in controlled comparator clinical trials.

Table 2: Summary of Serious Cardiovascular Events in Trials Comparing PRANDIN to Sulfonylureas (% of total patients with events)

  PRANDIN SU *
Total Exposed 1228 498
Serious CV Events 4% 3%
Cardiac Ischemic Events 2% 2%
Deaths due to CV Events 0.5% 0.4%
* : glyburide and glipizide

Seven controlled clinical trials included PRANDIN combination therapy with NPH-insulin (n=431), insulin formulations alone (n=388) or other combinations (sulfonylurea plus NPH-insulin or PRANDIN plus metformin) (n=120). There were six serious adverse events of myocardial ischemia in patients treated with PRANDIN plus NPH-insulin from two studies, and one event in patients using insulin formulations alone from another study [see WARNINGS AND PRECAUTIONS].

Combination Therapy With Thiazolidinediones

Hypoglycemia

During 24-week treatment clinical trials of PRANDIN-rosiglitazone or PRANDIN-pioglitazone combination therapy (a total of 250 patients in combination therapy), hypoglycemia (blood glucose < 50 mg/dL) occurred in 7% of patients in combination therapy compared to 7% for PRANDIN monotherapy, and 2% for thiazolidinedione monotherapy.

Peripheral Edema and Heart Failure

Peripheral edema was reported in 12 out of 250 (4.8%) PRANDIN-thiazolidinedione combination therapy patients and 3 out of 124 (2.4%) thiazolidinedione monotherapy patients, with no cases reported in these trials for PRANDIN monotherapy. There were reports in 2 of 250 patients (0.8%) treated with PRANDIN-thiazolidinedione therapy of episodes of edema with congestive heart failure. Both patients had a prior history of coronary artery disease and recovered after treatment with diuretic agents. No comparable cases in the monotherapy treatment groups were reported.

Weight Gain

Mean weight increases associated with combination, PRANDIN and pioglitazone therapy were 5.5 kg, 0.3 kg, and 2.0 kg respectively. Mean weight increases associated with combination, PRANDIN and rosiglitazone therapy were 4.5 kg, 1.3 kg, and 3.3 kg respectively.

Infrequent Adverse Events (<1% Of Patients)

Less common adverse clinical or laboratory events observed in clinical trials included elevated liver enzymes, thrombocytopenia, leukopenia, and anaphylactoid reactions.

Postmarketing Experience

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

Read the Prandin (repaglinide) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Clinically Important Drug Interactions With PRANDIN

Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with PRANDIN and instructions for preventing or managing them.

Table 3: Clinically Important Drug Interactions with PRANDIN

Gemfibrozil
Clinical Impact: Gemfibrozil significantly increased repaglinide exposures by 8.1 fold [see CLINICAL PHARMACOLOGY]
Intervention: Do not administer PRANDIN to patients receiving gemfibrozil [see CONTRAINDICATIONS].
Clopidogrel
Clinical Impact: Clopidogrel increased repaglinide exposures by 3.9-5.1 fold [see CLINICAL PHARMACOLOGY]
Intervention: Avoid concomitant use of PRANDIN with clopidogrel. If concomitant use can not be avoided, initiate PRANDIN at 0.5 mg before each meal and do not exceed a total daily dose of 4 mg [see DOSAGE AND ADMINISTRATION]. Increased frequency of glucose monitoring may be required during concomitant use.
Cyclosporine
Clinical Impact: Cyclosporine increased low dose repaglinide exposures by 2.5 fold [see CLINICAL PHARMACOLOGY]
Intervention: Daily maximum PRANDIN dose should be limited to 6 mg, and increased frequency of glucose monitoring may be required when PRANDIN is co-administered with cyclosporine.
CYP2C8 and CYP3A4 Inhibitors
Intervention: PRANDIN dose reductions and increased frequency of glucose monitoring may be required when coadministered.
Examples: Drugs that are known to inhibit CYP3A4 include antifungal agents (ketoconazole, itraconazole) and antibacterial agents (clarithromycin, erythromycin). Drugs that are known to inhibit CYP2C8 include trimethoprim, gemfibrozil, montelukast, deferasirox, and clopidiogrel.
CYP2C8 and CYP3A4 Inducers
Intervention: PRANDIN dose increases and increased frequency of glucose monitoring may be required when coadministered.
Examples: Drugs that induce the CYP3A4 and/or 2C8 enzyme systems include rifampin, barbiturates, and carbamezapine
Drugs That May Increase the Risk of Hypoglycemia
Intervention: PRANDIN dose reductions and increased frequency of glucose monitoring may be required when coadministered.
Examples: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory agents (NSAIDs), pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics
Drugs That May Decrease the Blood Glucose Lowering Effect of PRANDIN
Intervention: PRANDIN dose increases and increased frequency of glucose monitoring may be required when coadministered.
Examples: Atypical antipsychotics (e.g., olanzapine and clozapine), calcium channel antagonists, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
Drugs That May Blunt Signs and Symptoms of Hypoglycemia
Intervention: Increased frequency of glucose monitoring may be required when PRANDIN is co-administered with these drugs.
Examples: beta-blockers, clonidine, guanethidine, and reserpine

Read the Prandin Drug Interactions Center for a complete guide to possible interactions

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 3/13/2017

Side Effects
Interactions

Prandin - User Reviews

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