Not all side effects for insulin may be reported.

You should always consult a doctor or healthcare

professional for medical advice. Side effects can be reported to the FDA here.

Applies to insulin: injectable liquid, injectable solution, subcutaneous suspension

Endocrine

Hypoglycemia is the most common and serious side effect of insulin, occurring in approximately 16% of
type 1 and 10% of type II diabetic patients (the incidence varies greatly depending on the populations
studied, types of insulin therapy, etc). Although there are counterregulatory endocrinologic responses to
hypoglycemia, some responses are decreased, inefficient, or absent in some patients. Severe
hypoglycemia usually presents first as confusion, sweating, or tachycardia, and can result in coma,
seizures, cardiac arrhythmias, neurological deficits, and death. Blood or urine glucose monitoring is
recommended in patients who are at risk of hypoglycemia or who do not recognize the signs and
symptoms of hypoglycemia. The risk for developing hypoglycemia is higher in patients receiving intensive
or continuous infusion insulin therapy. The association between insulin and dyslipidemia is currently
being evaluated.[Ref]

Permanent neuropsychological impairment has been associated with recurrent episodes of severe
hypoglycemia.

In one retrospective study of 600 randomly selected patients with insulin-treated diabetes mellitus, the
only reliable predictors of severe hypoglycemia were a history of hypoglycemia, a history of
hypoglycemia-related injury or convulsion, and the duration of insulin therapy. Those with a history of
hypoglycemia had been treated with insulin for 17.4 years, which was significantly longer than the 14.3
years in the insulin-treated patients without a history of hypoglycemia.

Human insulin does not appear to be associated with hypoglycemic episodes more often than animal
insulin. Caution is recommended when switching from animal (either bovine or pork) to purified porcine
insulin or biosynthetic human insulin, however, because of increased potency or bioavailability.[Ref]

Ocular

An unusual ocular disturbance during the beginning of therapy is bilateral presyopia (blurry vision). This
is thought to be due to changes in the osmotic equilibrium between the lens and the ocular fluids, and is
usually self-limited.

Dermatologic

Dermatologic reactions to insulin can result in lipohypertrophy (insulin is lipogenic) or lipoatrophy

(probably immunologically-mediated). The incidence of lipoatrophy is markedly decreased with the use
of purer forms of pork insulin or biosynthetic human insulin and when injection sites are alternated.
Without proper hygiene, subcutaneous insulin injections may be complicated by infection.[Ref]

Hypersensitivity

Hypersensitivity reactions--either local or systemic--are becoming rare (less than 1% of patients) due to
the use of purer forms of pork insulin or biosynthetic human insulin. Local reactions may present as
erythema, swelling, heat, or subcutaneous nodules. They usually occur within the first two weeks of
therapy, then disappear. True allergy to insulin is rare, and sensitization is usually associated with specific
animal proteins in bovine and less pure forms of porcine insulins.[Ref]

A diabetic patient with true allergy to insulin can undergo desensitization. Desensitization kits and
protocols are available from some insulin manufacturers.[Ref]

Immunologic

Immunologic responses to insulin, particularly animal insulin formulations, include the formation of anti-
insulin antibodies. The presence of these antibodies causes the elimination half-life of insulin to increase.

Immunologic analysis of anaphylaxis to some insulin preparations in some cases has revealed markedly
elevated serum levels of lgE and lgG to protamine, but not to regular insulin.[Ref]

Cardiovascular
The cardiovascular consequences of hyperinsulinemia are being evaluated. Given the high frequency of
both microvascular and macrovascular diseases in patients with diabetes, some experts are evaluating
insulin as a possible atherogenic agent. Controversy and continued study surround the role of
hyperinsulinemia as the precursor of hypertension.

Other cardiovascular risk factors that are accentuated in persons with carbohydrate intolerance and
hypertension include abnormalities in platelet function, clotting factors, the fibrinolytic system, and
dyslipidemia. The relationship between diabetes, insulin, and these disorders is currently under
investigation.

Insulin may contribute to the pathogenesis of hypertension by stimulating the sympathetic nervous
system, promoting renal sodium retention, and/or stimulating vascular smooth muscle hypertrophy. It
may induce dyslipidemia by promoting hepatic synthesis of very low density lipoproteins (VLDLs).

Insulin may stimulate heart rate in the absence of hypoglycemia.[Ref]

General

General weight gain is associated with insulin use, sometimes presenting as edema associated with
abrupt restoration of glucose control in a patient whose control was previously poor. Weight gain may be
due to more efficient use of calories during insulin therapy, suggesting additional benefits of dietary and
exercise modifications. Patients on intensive insulin therapy may be more likely to experience weight
gain.[Ref]

Intensive insulin therapy causes an increase in body fat as a result of the elimination of glycosuria and
reduction in 24-hour energy expenditure. The reduction in 24-h energy expenditure is the result of an
insulin-associated decrease in triglyceride/free fatty acid cycling and nonoxidative glucose and protein
metabolism.[Ref]

Metabolic

The metabolic side effects of insulin therapy may be particularly important in patients who are being
treated for diabetic ketoacidosis (DKA). Insulin increases the intracellular transport of phosphate, which
often results in hypophosphatemia during treatment of DKA. Hypokalemia and hypomagnesemia have
been associated with DKA, and may be due to insulin.[Ref]

Rare cases of hypophosphatemia have been associated with the use of glucose, insulin, and potassium
infusions during the treatment of myocardial infarction.[Ref]

Renal

The renal effects from insulin-induced hypoglycemia include significantly decreased renal plasma flow,
glomerular filtration rate, and significantly increased urinary albumin excretion rate. These changes are
reversible upon resolution of hypoglycemia.
Hypoglycemia is associated with increased plasma dopamine, epinephrine, and plasma renin activity.
Acute changes in renal function during insulin-induced hypoglycemia, therefore, may result from direct
stimulation of the efferent sympathetic nerves to the kidney and hormonal counterregulatory
mechanisms.

Hematologic

The effects of insulin-induced hypoglycemia on hemostasis may explain some of the clinical observations
of embolic phenomenon during treatment of diabetic ketoacidosis.

Limited data show that diabetics have a significantly lower basal concentration of tissue plasminogen
activator.[Ref]

The hematologic effects from insulin-induced hypoglycemia include an enhanced increase in the
concentration of von Willebrand factor. Increased von Willebrand factor, combined with hypoglycemia-
associated decreased plasma volume and increased plasma viscosity, may predispose patients to
reduced peripheral perfusion or embolic phenomenon. A single case of insulin-induced hemolytic
anemia has been reported.[Ref]

Gastrointestinal

Rare cases of gastrointestinal distress have been associated with insulin. GI distress tends to resolve with
dose reduction.[Ref]

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(1981): 296-8

---------------

The Pharmaceutical industry in India is valued at Rs. 90,000 Crore and is growing at the rate of 12 – 14 %
per annum. Exports are growing at 25 % Compound Annual Growth Rate (CAGR) every year. The total
export of Pharma products is to the extent of Rs. 40,000 Crore. India is now being recognized as the
‘Global pharmacy of Generic Drugs’ & has distinction of providing generic quality drugs at affordable
cost. India is also emerging rapidly as a hub of Global Clinical trials & a destination for Drug Discovery &
Development.

Further, more & more new drugs are being introduced into the country which include New Chemical
Entities (NCE), high tech pharma products, vaccines as well as new dosage forms, new routes of drug
administrations and new therapeutic claims of existing drugs. This is reflected in the fact that total
number of applications received & processed have more than doubled from around 10,000 in the Year
2005 to 22,806 in Year 2009 at CDSCO, HQ, New Delhi.This includes increase in New Drug Applications,
Global Clinical Trials , Market Authorization of Vaccine & Biotech products from 1200 ,100 ,10 in Year
2005 to 1753, 262 & 137 in the Year 2009 respectively.

Such rapid induction of NCEs and high tech Pharma products in the market throw up the
challenges of monitoring Adverse Drug Reactions (ADRs) over large population base.

All medicines (pharmaceuticals and vaccines) have side effects. Some of these side effects are known,
while many are still unknown even though that medicine has been in clinical use for several years. It is
important to monitor both the known and hitherto unknown side effects of medicines in order to
determine any new information available in relation to their safety profile. In a vast country like India
with a population of over 1.2 Billion with vast ethnic variability, different disease prevalence patterns,
practice of different systems of medicines, different socioeconomic status, it is important to have a
standardized and robust pharmacovigilance and drug safety monitoring programme for the nation.
Collecting this information in a systematic manner and analyzing the data to reach a meaningful
conclusion on the continued use of these medicines is the rationale to institute this program for India.

-----
Prescription Drug Deaths Increase Dramatically

A growing number of overdoses of legal opioids, sedatives and tranquilizers led to a 65 percent increase
in hospitalizations over seven years

By Katherine Harmon | April 6, 2010

prescription drugs painkillers deaths overdose

ISTOCKPHOTO/ZUZLIK

The number of deaths and hospitalizations caused by prescription drugs has risen precipitously in the
past decade, with overdoses of pain medications, in particular opioids, sedatives and tranquilizers, more
than doubling between 1999 and 2006, according to a new study.

In fact, by 2006, overdoses of opioid analgesics alone (a class of pain relievers that includes morphine
and methadone) were already causing more deaths than overdoses of cocaine and heroin combined.

"Teens and others have different attitudes in using these drugs," often presuming the prescription
substances are safer and less addictive than illegal drugs such as cocaine or heroin, says Jeffrey Coben, a
professor of emergency and community medicine at the West Virginia University School of Medicine in
Morgantown and lead author of the new study. "I think that's a false assumption. Aside from the fact
they can be taken orally rather than injected…[many prescription drugs] really are every bit as powerful,
addictive and dangerous as heroin," he notes, adding that, "when you combine them with other
sedatives, that mix can become particularly lethal."

Using data collected by the Nationwide Inpatient Sample, which gathers hospital patient information for
about 8 million people every year, Coben and his colleagues were able to assess what drugs were
implicated in the majority of poisonings—and in many cases whether the poisonings were intentional or
not. The team selected opioids, sedatives and tranquilizers as the focus of the analysis because these
substances are "contributing the majority of prescription drug overdose deaths," Coben says. These
categories of prescription drugs can kill and injure people by suppressing breathing, depriving the body
of oxygen.

For prescription opioids, sedatives and tranquilizers—commonly prescribed for pain management—the
number of hospitalizations for poisonings increased 65 percent between 1999 and 2006 (the first and
last years, respectively, for which data were comparable and collected). The number of hospitalizations
for all poisonings, including illegal drugs, other prescription medications and miscellaneous substances,
increased during this time period as well, but that jump (33 percent) was about half the rate of those for
the prescription pain drugs.

Unintentional poisonings from these drugs climbed 37 percent during the seven-year period, the
researchers found. Intentional overdoses, in which people meant to inflict self-harm or death, jumped
130 percent (a far cry more than the 53 percent increase of intentional poisoning from other substances
in the same time period). Intent was not listed in all cases and can be subject to reporting error. The
results are detailed online April 6 in the American Journal of Preventive Medicine.

No accident

Poisonings, from prescription drugs and other substances, are classified in medical records as injurious
or accidental deaths. But regardless of whether the incidents are listed as unintentional or intentional,
they are rarely true mistakes, noted Leonard Paulozzi, a medical epidemiologist with the U.S. Centers for
Disease Control and Prevention, in congressional testimony in 2007. "Most unintentional drug poisoning
deaths are not 'accidents' caused by toddlers or the elderly taking too much medication," he noted.
"These deaths are largely due to the misuse and abuse of prescription drugs."

Accidents overall were the fifth most common cause of death in the U.S. as of 2005 (accounting for
117,809 deaths—4.8 percent—that year), according to the National Vital Statistics Report [pdf]. Of injury
deaths, poisoning is the second most common cause of death in the U.S., having doubled between 1985
and 2004, according to a 2007 Department of Health and Human Services analysis [pdf]. Among people
35 to 54 years old, poisoning is the most common accidental death—even more so than auto-related
deaths.

Many experts think that the sheer prevalence of many of these drugs recently has contributed to the
drastic increase in poisonings. Although growing illegal markets and distribution of these drugs might be
a driving factor in their increasingly large role in poisonings and deaths, perfectly legal prescriptions are
probably playing a role as well, Coben says.

"I think the whole issue of the availability of these drugs and whether they're being over-prescribed"
should be investigated, says Susan Baker, a professor at Johns Hopkins Center for Injury Research and
Policy, who was not involved in the new study but coauthored a 2009 report in the same journal about
recent trends in injury mortality.

Many people do rely on pharmacological treatment for withdrawal, anxiety or chronic pain, but when
communities have access to an overabundance of these medications, abuse appears to become more
likely. If doctors prescribe too much medication or too many refills, excess drugs "are going to be sitting
in people's medicine cabinets for someone else to take advantage of," Baker explains. For example,
methadone poisonings were four times as frequent in 2006 as they were in 1999, a time period during
which retail sales grew more than 1,000 percent, Coben and his team found.

Antidote unknown

Although the new report details the stark increase in the reported poisoning data, the true number of
deaths and hospitalizations in which prescription drugs have played a role might be even higher, the
researchers pointed out. The new analysis assessed cases only in which prescription drug overdose was
listed as the primary diagnosis. Some prescription drug–related hospitalizations might be classified under
other primary categories, and those who abuse the drugs were not always labeled as having been
poisoned. Additionally, the researchers explained, many common terms such as overdose, misuse and
abuse are not well standardized in hospitals.

"I don't have any sense that it's getting any better," Coben says. With drug companies reporting strong
overall sales (including a 5.1 percent increase in U.S. sales in 2009 to $300.3 billion for 3.9 billion
individual retail prescriptions), in fact, the problem might be getting worse.
The researchers noted that the details surrounding these hundreds of thousands of overdoses are
unknown. The medical data used for the analysis did not include full toxicology reports that would reveal
drug-drug interactions. And although the researchers found that the majority of the people hospitalized
for poisoning with these prescription drugs were women, they did not have enough other demographic
data to propose possible reasons for the overdose increases.

"What we really need is something other than the coded data," Baker says. She notes that researchers
need to know more about the circumstances in which people are overdosing before effective prevention
measures can be put into place.

"There's a need to have informational interviews with people who have had overdoses and survived
them," Coben says. He hopes that future research will "raise some opportunities for interventions with
these people."

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Comments

LindaSW April 6, 2010, 6:22 AM

Great article. Given the 2006 ONDCP mandate to reduce prescription drug 'abuse' by 15% by 2008, I
would say we, as a s asociety, have failed. Indeed, poisonings are one horrible consequence, but there
are so many others -- addiction, trauma, DUI, loss of productivity, medical and social costs -- yet we as a
society spend much of our resources on the lesser used substances of use -- cocaine, heroin, meth.

There's no one solution, but perhaps reducing the sheer availability at the point of the prescriber -- are a
month's worth of CII opioids really necessary for a tooth extraction? what IS the evidence for prescribing
opioids for arthritis? lower back pain?
Of course, at the other end, treatment for addictions of all kinds is inadequate, and even more so in the
new economy.

Linda Simoni-Wastila

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Richieo April 6, 2010, 8:54 AM

Reducing the availability of legal drugs will not cure the problem, it will only send it to the black market...

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candide April 6, 2010, 10:08 AM

Education is the answer.

For example, APAP (acetaminophen - Tylenol, most of Vicodin) can easily be taken to overdose levels
(destroys the liver), yet most people do not know this.

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jgrosay April 6, 2010, 6:56 PM

Drugs do produce harm sometimes as they are active products, not inert dummys such a placebo, and
this is the reason why you have to work long and hard to obtain a permit to write prescriptions from
Health Regulatory Authorities. If you endorse a situation as in Spain, where pharmacists do openly sell
almost all prescription only drugs under the sole buyer request; who has the moral strenght to
discourage people from bought and use of addiction drugs, and end as in the China under british rule,
when they were several million opium dependents?

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Hermit April 6, 2010, 8:38 PM

1) How many OD's included alcohol? "DO NOT USE WITH ALCOHOL" is printed under,"Warnings."

2) How many doctors who know their patients can't tell hypochondriacs and recreational users from real
sufferers of pain? My doctor says he can see it in my face.

3) How many severe pain sufferers have lived in agony after being denied pain relief because some
stranger misintrepreted their desperate plea for relief as drug withdrawel (which may have also been
included?)

4) How many OD's would occurr if realistic drug education included how to use drugs (alcohol too, if
you're going to use it) more safely and sanely rather than the archaic religious message of, "Just Say No."

When an unaccountable military government agency gets to make it's own rules and set it's own budget
and keep confiscated property of the disobedient, it is a rogue agency. Without health or safety data
they are selling fear of substances in replacement of a system where adults make those decisions and
learn to handle or avoid problems.

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Hermit April 6, 2010, 8:50 PM

1) How many OD's included alcohol? "DO NOT USE WITH ALCOHOL" is printed under,"Warnings."

2) How many doctors who know their patients can't tell hypochondriacs and recreational users from real
sufferers of pain? My doctor says he can see it in my face.

3) How many severe pain sufferers have lived in agony after being denied pain relief because some
stranger misinterpreted their desperate plea for pain relief as drug withdrawal (which may have also
been included?)

4) How many OD's would occur if realistic drug education included how to use drugs (alcohol too, if
you're going to use it) more safely and sanely rather than the archaic religious message of, "Just Say No?"

When an unaccountable military government agency gets to make it's own rules and set it's own budget
and keep confiscated property of the disobedient, it is a rogue agency. Without health or safety data
they are selling fear of substances in replacement of a system where adults make those decisions and
learn to handle or avoid their own problems. Prohibition creates the problems and then milks us for
money to "solve" them by assaulting

our own citizens.

What a racket.

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Wizard April 7, 2010, 1:39 AM

When we will realize that the "science" of medicine defined efficacy of treatment by the elimination or
reduction in specific symptoms, even if these symptoms are themselves defenses of the body. This
"efficacy" is akin to unscrewing a warning light in your car and asserted that you've a "scientifically
proven" method of treating cars that are sick.

"Side effects" are not really "side effects." They are the result of the effective suppression of a symptom
and of the disease, creating a more serious illness. An increase in death rates is totally predictable...and
will be getting worse as a result of an increase in polypharmacy.

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l.kost April 7, 2010, 5:07 AM

around the ansyogen break in your life, regressive's effect of cannabis use can delivery in the time,
ecocerebral time-defect

or progressive delucidation...

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jack.123 April 7, 2010, 7:13 AM

Did any body notice if the ones that overdosed were the ones prescribed the medication?People lIke
myself who have cronic pain don't abuse ,because when you over use there isn't enough left for when
you need it,being given just enough to subdue the pain is is the usual treatment,the pain isn't gone just
reduced so it becomes bearable,people stealing these kind of drugs don't understand that the pain
doesn't stop completely and keep taking more untill an overdose happens.You must keep theses kind of
drugs under lock and key to protect freinds and family who don't unerstand the dangers!!!

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pyramus33 April 7, 2010, 8:20 AM

Many people who suffer from chronic pain do not "abuse" the prescription drugs but they are at very
high risk of becoming dependant on these pain killers. What I don't understand is how the government
can continue to label marijuana users as criminals and the dealers that supply these users as scumbags
when studies such as this show how extremely harmful the drugs the government is selling can be. Even
today many senior politicians in the U.S still refuse to agree with the legalization of medicinal marijuana
because they say we have "less harmful alternatives". Really? These drugs are less harmful or habit
forming then marijuana? If so, why are many people going through rapid detoxification processes just to
get off these "safe" drugs? The most recent example of this arrogance in the media was senator John
McKain during the 2008 election. I think it's time we looked at some of these prescription drugs and
decided what should be classified as truly harmful. I can still remember a number of years ago when
pharmacies were being broken into almost every week by oxycontin addicts.

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