"The US Food and Drug Administration (FDA) has removed the final remaining restrictions placed on the use of rosiglitazone.
In 2013, the FDA lifted restrictions the prescribing and use of the diabetes drug rosiglitazone (Avandia, A"...
The following adverse reactions are discussed elsewhere:
- Hypoglycemia [See WARNINGS AND PRECAUTIONS]
- Hypersensitivity and allergic reactions [See WARNINGS AND PRECAUTIONS]
Clinical trial 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.
Table 1: Treatment –emergent adverse events in pooled clinical
trials up to 28 weeks duration in adults with type 1 diabetes (adverse events
with frequency ≥ 5%)
|Upper respiratory tract infection||22.4||23.1|
|*Body System not Specified|
Table 2: Treatment –emergent
adverse events in pooled clinical trials up to 1 year duration in adults with
type 2 diabetes (adverse events with frequency ≥ 5%)
|Upper respiratory tract infection||11.4||13.3|
|Retinal vascular disorder||5.8||7.4|
|*Body System not Specified|
Table 3: Treatment –emergent
adverse events in a 5-year trial of adults with type 2 diabetes (adverse events
with frequency ≥ 10%)
|Upper respiratory tract infection||29||33.6|
|Pain in extremity||13||13.1|
|Urinary tract infection||10.7||10.1|
Table 4: Treatment –emergent
adverse events in a 28-week clinical trial of children and adolescents with
type 1 diabetes (adverse events with frequency ≥ 5%)
|Upper respiratory tract infection||13.8||16|
|*Body System not Specified|
Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including LANTUS [See WARNINGS AND PRECAUTIONS]. Tables 5 and 6 summarize the incidence of severe hypoglycemia in the LANTUS individual clinical trials. Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose below 50 mg/dL ( ≤ 56 mg/dL in the 5-year trial) or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration. The rates of severe symptomatic hypoglycemia in the LANTUS clinical trials (see Section 14 for a description of the study designs) were comparable for all treatment regimens (see Tables 5 and 6). In the pediatric phase 3 clinical trial, children and adolescents with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to the adult trials with type 1 diabetes. (see Table 5) [See Clinical Studies].
Table 5: Severe Symptomatic Hypoglycemia in Patients
with Type 1 Diabetes
|Study A Type 1 Diabetes Adults 28 weeks In combination with regular insulin||Study B Type 1 Diabetes Adults 28 weeks In combination with regular insulin||Study C Type 1 Diabetes Adults 16 weeks In combination with insulin lispro||Study D Type 1 Diabetes Pediatrics 26 weeks In combination with regular insulin|
|Percent of patients (n/total N)||10.6 (31/292)||15.0 (44/293)||8.7 (23/264)||10.4 (28/270)||6.5 (20/310)||5.2 (16/309)||23.0 (40/174)||28.6 (50/175)|
Table 6: Severe Symptomatic
Hypoglycemia in Patients with Type 2 Diabetes
|Study E Type 2 Diabetes Adults 52 weeks In combination with oral agents||Study F Type 2 Diabetes Adults 28 weeks In combination with regular insulin||Study G Type 2 Diabetes Adults 5 years In combination with regular insulin|
|Percent of patients (n/total N)||1.7 (5/289)||1.1 (3/281)||0.4 (1/259)||2.3 (6/259)||7.8 (40/513)||11.9 (60/504)|
Retinopathy was evaluated in the LANTUS clinical studies by analysis of reported retinal adverse events and fundus photography. The numbers of retinal adverse events reported for LANTUS and NPH insulin treatment groups were similar for patients with type 1 and type 2 diabetes.
LANTUS was compared to NPH insulin in a 5-year randomized clinical trial that evaluated the progression of retinopathy as assessed with fundus photography using a grading protocol derived from the Early Treatment Diabetic Retinopathy Scale (ETDRS). Patients had type 2 diabetes (mean age 55 yrs) with no (86%) or mild (14%) retinopathy at baseline. Mean baseline HbA1c was 8.4%. The primary outcome was progression by 3 or more steps on the ETDRS scale at study endpoint. Patients with pre-specified post-baseline eye procedures (pan-retinal photocoagulation for proliferative or severe nonproliferative diabetic retinopathy, local photocoagulation for new vessels, and vitrectomy for diabetic retinopathy) were also considered as 3-step progressors regardless of actual change in ETDRS score from baseline. Retinopathy graders were blinded to treatment group assignment. The results for the primary endpoint are shown in Table 7 for both the per-protocol and Intent-to-Treat populations, and indicate similarity of Lantus to NPH in the progression of diabetic retinopathy as assessed by this outcome.
Table 7: Number (%) of patients with 3 or more step
progression on ETDRS scale at endpoint
|Lantus (%)||NPH (%)||Differencea,b (SE)||95% CI for difference|
|Per-protocol||53/374 (14.2%)||57/363 (15.7%)||-2.0% (2.6%)||-7.0% to +3.1%|
|Intent-to-Treat||63/502 (12.5%)||71/487 (14.6%)||- 2.1% (2.1%)||-6.3% to +2.1%|
|a Difference = Lantus – NPH
b using a generalized linear model (SAS GENMOD) with treatment and baseline HbA1c strata (cutoff 9.0%) as the classified independent variables, and with binomial distribution and identity link function
Insulin initiation and intensification of glucose control
Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.
Long-term use of insulin, including LANTUS, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection or infusion sites within the same region to reduce the risk of lipodystrophy. [See DOSAGE AND ADMINISTRATION].
Weight gain can occur with insulin therapy, including LANTUS, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Insulin, including LANTUS, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
As with any insulin therapy, patients taking LANTUS may experience injection site reactions, including redness, pain, itching, urticaria, edema, and inflammation. In clinical studies in adult patients, there was a higher incidence of treatment-emergent injection site pain in LANTUS-treated patients (2.7%) compared to NPH insulin-treated patients (0.7%). The reports of pain at the injection site did not result in discontinuation of therapy.
Rotation of the injection site within a given area from one injection to the next may help to reduce or prevent these reactions. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique. Most minor reactions to insulin usually resolve in a few days to a few weeks.
Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including LANTUS and may be life threatening.
All insulin products can elicit the formation of insulin antibodies. The presence of such insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose. In phase 3 clinical trials of LANTUS, increases in titers of antibodies to insulin were observed in NPH insulin and insulin glargine treatment groups with similar incidences.
The following adverse reactions have been identified during post-approval use of LANTUS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.
Medication errors have been reported in which other insulins, particularly short-acting insulins, have been accidentally administered instead of LANTUS [See PATIENT INFORMATION]. To avoid medication errors between LANTUS and other insulins, patients should be instructed to always verify the insulin label before each injection.
Read the Lantus (insulin glargine [rdna origin] injection) Side Effects Center for a complete guide to possible side effects
A number of drugs affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.
The following are examples of drugs that may increase the blood-glucose-lowering effect of insulins including LANTUS and, therefore, increase the susceptibility to hypoglycemia: oral anti-diabetic products, pramlintide, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, propoxyphene, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics.
The following are examples of drugs that may reduce the blood-glucose-lowering effect of insulins including LANTUS: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline), glucagon, isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), protease inhibitors and atypical antipsychotic medications (e.g. olanzapine and clozapine).
Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken the bloodglucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.
Read the Lantus Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/17/2013
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