Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local, or emergency room immediately.
Proper storage of Andogablin solution:
Store Andogablin solution at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Andogablin solution out of the reach of children and away from pets.
Overdose of Andogablin in details
When a dose is taken in higher dose than the recommended doses, it is called Overdose. Overdose always needs a clinical supervision. Any medicine or drug when consumed in Overdose produces untoward side effects on one or various organs in the body. A medicine is excreted in the kidney or metabolized in the liver most of the times. This process goes without any hurdles when taken in normal dose, but when taken in an overdose, the body is not able to metabolize it or send it out properly which causes the effects of anoverdose.
Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans
In the postmarketing experience, the most commonly reported adverse events observed with Andogablin when taken in overdose include reduced consciousness, depression/anxiety, confusional state, agitation, and restlessness. Seizures and heart block have also been reported. Deaths have been reported in the setting of lone Andogablin overdose and in combination with other CNS depressants.
Treatment or Management of Overdose
There is no specific antidote for overdose with Andogablin. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with Andogablin.
Andogablin can be removed by hemodialysis. Standard hemodialysis procedures result in significant clearance of Andogablin (approximately 50% in 4 hours).
What should I avoid while taking Andogablin?
Avoid drinking alcohol. It may increase certain side effects of Andogablin.
Avoid driving or hazardous activity until you know how Andogablin will affect you. Your reactions could be impaired.
Warnings are a mix of Precautions. Contraindications and interactions and serious harmful effects associated with the medicine intake. A diabetic or Hypertensive patient need to be warned about few drug interactions. A known hypersensitivity patient needs to be careful about the reactions or anaphylactic shock. A pregnant woman or a breastfeeding woman should be warned of certain medications. A Hepatitis [liver disease] patient or a cardiac patient should avoid few drugs.
There have been postmarketing reports of angioedema in patients during initial and chronic treatment with Andogablin. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue Andogablin immediately in patients with these symptoms.
Exercise caution when prescribing Andogablin to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema.
There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with Andogablin. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue Andogablin immediately in patients with these symptoms.
Withdrawal of Antiepileptic Drugs (AEDs)
As with all AEDs, withdraw Andogablin gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. If Andogablin is discontinued, taper the drug gradually over a minimum of 1 week.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including Andogablin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5–100 years) in the clinical trials analyzed.
Table 2 shows absolute and relative risk by indication for all evaluated AEDs.
Table 2. Risk by indication for antiepileptic drugs in the pooled analysis
Placebo Patients with Events Per 1000 Patients
Drug Patients with Events Per 1000 Patients
Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients
Risk Difference: Additional Drug Patients with Events Per 1000 Patients
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Andogablin or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Inform patients, their caregivers, and families that Andogablin and other AEDs increase the risk of suicidal thoughts and behavior and advise them of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report behaviors of concern immediately to healthcare providers.
Andogablin treatment may cause peripheral edema. In short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications such as hypertension or congestive heart failure. Peripheral edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function.
In controlled clinical trials the incidence of peripheral edema was 6% in the Andogablin group compared with 2% in the placebo group. In controlled clinical trials, 0.5% of Andogablin patients and 0.2% placebo patients withdrew due to peripheral edema.
Higher frequencies of weight gain and peripheral edema were observed in patients taking both Andogablin and a thiazolidinedione antidiabetic agent compared to patients taking either drug alone. The majority of patients using thiazolidinedione antidiabetic agents in the overall safety database were participants in studies of pain associated with diabetic peripheral neuropathy. In this population, peripheral edema was reported in 3% (2/60) of patients who were using thiazolidinedione antidiabetic agents only, 8% (69/859) of patients who were treated with Andogablin only, and 19% (23/120) of patients who were on both Andogablin and thiazolidinedione antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on thiazolidinediones only; 4% (35/859) of patients on Andogablin only; and 7.5% (9/120) of patients on both drugs.
As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, exercise caution when co-administering Andogablin and these agents.
Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, exercise caution when using Andogablin in these patients.
Dizziness and Somnolence
Andogablin may cause dizziness and somnolence. Inform patients that Andogablin-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery.
In the Andogablin controlled trials, dizziness was experienced by 30% of Andogablin-treated patients compared to 8% of placebo-treated patients; somnolence was experienced by 23% of Andogablin-treated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of Andogablin therapy and occurred more frequently at higher doses. Dizziness and somnolence were the adverse reactions most frequently leading to withdrawal (4% each) from controlled studies. In Andogablin-treated patients reporting these adverse reactions in short-term, controlled studies, dizziness persisted until the last dose in 30% and somnolence persisted until the last dose in 42% of patients.
Andogablin treatment may cause weight gain. In Andogablin controlled clinical trials of up to 14 weeks, a gain of 7% or more over baseline weight was observed in 9% of Andogablin-treated patients and 2% of placebo-treated patients. Few patients treated with Andogablin (0.3%) withdrew from controlled trials due to weight gain. Andogablin associated weight gain was related to dose and duration of exposure, but did not appear to be associated with baseline BMI, gender, or age. Weight gain was not limited to patients with edema.
Although weight gain was not associated with clinically important changes in blood pressure in short-term controlled studies, the long-term cardiovascular effects of Andogablin-associated weight gain are unknown.
Among diabetic patients, Andogablin-treated patients gained an average of 1.6 kg (range: -16 to 16 kg), compared to an average 0.3 kg (range: -10 to 9 kg) weight gain in placebo patients. In a cohort of 333 diabetic patients who received Andogablin for at least 2 years, the average weight gain was 5.2 kg.
While the effects of Andogablin-associated weight gain on glycemic control have not been systematically assessed, in controlled and longer-term open label clinical trials with diabetic patients, Andogablin treatment did not appear to be associated with loss of glycemic control (as measured by HbA1C).
Abrupt or Rapid Discontinuation
Following abrupt or rapid discontinuation of Andogablin, some patients reported symptoms including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea. Taper Andogablin gradually over a minimum of 1 week rather than discontinuing the drug abruptly.
In standard preclinical in vivo lifetime carcinogenicity studies of Andogablin, an unexpectedly high incidence of hemangiosarcoma was identified in two different strains of mice. The clinical significance of this finding is unknown. Clinical experience during Andogablin's premarketing development provides no direct means to assess its potential for inducing tumors in humans.
In clinical studies across various patient populations, comprising 6396 patient-years of exposure in patients >12 years of age, new or worsening-preexisting tumors were reported in 57 patients. Without knowledge of the background incidence and recurrence in similar populations not treated with Andogablin, it is impossible to know whether the incidence seen in these cohorts is or is not affected by treatment.
In controlled studies, a higher proportion of patients treated with Andogablin reported blurred vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases with continued dosing. Less than 1% of patients discontinued Andogablin treatment due to vision-related events (primarily blurred vision).
Prospectively planned ophthalmologic testing, including visual acuity testing, formal visual field testing and dilated funduscopic examination, was performed in over 3600 patients. In these patients, visual acuity was reduced in 7% of patients treated with Andogablin, and 5% of placebo-treated patients. Visual field changes were detected in 13% of Andogablin-treated, and 12% of placebo-treated patients. Funduscopic changes were observed in 2% of Andogablin-treated and 2% of placebo-treated patients.
Although the clinical significance of the ophthalmologic findings is unknown, inform patients to notify their physician if changes in vision occur. If visual disturbance persists, consider further assessment. Consider more frequent assessment for patients who are already routinely monitored for ocular conditions.
Creatine Kinase Elevations
Andogablin treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for Andogablin-treated patients and 28 U/L for the placebo patients. In all controlled trials across multiple patient populations, 1.5% of patients on Andogablin and 0.7% of placebo patients had a value of creatine kinase at least three times the upper limit of normal. Three Andogablin treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and Andogablin is not completely understood because the cases had documented factors that may have caused or contributed to these events. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Discontinue treatment with Andogablin if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.
Decreased Platelet Count
Andogablin treatment was associated with a decrease in platelet count. Andogablin-treated subjects experienced a mean maximal decrease in platelet count of 20 × 103/µL, compared to 11 × 103/µL in placebo patients. In the overall database of controlled trials, 2% of placebo patients and 3% of Andogablin patients experienced a potentially clinically significant decrease in platelets, defined as 20% below baseline value and <150 × 103/µL. A single Andogablin treated subject developed severe thrombocytopenia with a platelet count less than 20 × 103/ µL. In randomized controlled trials, Andogablin was not associated with an increase in bleeding-related adverse reactions.
PR Interval Prolongation
Andogablin treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data, the mean PR interval increase was 3–6 msec at Andogablin doses ≥300 mg/day. This mean change difference was not associated with an increased risk of PR increase ≥25% from baseline, an increased percentage of subjects with on-treatment PR >200 msec, or an increased risk of adverse reactions of second or third degree AV block.
Subgroup analyses did not identify an increased risk of PR prolongation in patients with baseline PR prolongation or in patients taking other PR prolonging medications. However, these analyses cannot be considered definitive because of the limited number of patients in these categories.
What should I discuss with my healthcare provider before taking Andogablin?
You should not use Andogablin if you are allergic to Andogablin.
To make sure Andogablin is safe for you, tell your doctor if you have::
lung disease, such as chronic obstructive pulmonary disease (COPD);
a mood disorder, depression, or suicidal thoughts;
a bleeding disorder, or low levels of platelets in your blood;
kidney disease (or if you are on dialysis);
diabetes (unless you are taking Andogablin to treat diabetic neuropathy);
drug or alcohol addiction; or
a severe allergic reaction (angioedema).
Do not give this medicine to a child without medical advice.
Andogablin is not approved for use by anyone younger than 18 years old to treat nerve pain caused by diabetes or shingles (herpes zoster).
Some people have thoughts about suicide while taking Andogablin. Your doctor will need to check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.
It is not known if Andogablin will harm your unborn baby. You and your healthcare provider will have to decide if you should take Andogablin while you are pregnant.
If you are pregnant, your name may be listed on a pregnancy registry to track the effects of Andogablin on the baby.
Andogablin can decrease sperm count and may affect fertility in men (your ability to have children). In animal studies, Andogablin also caused birth defects in the offspring of males treated with this medicine. However, it is not known whether these effects would occur in humans. Ask your doctor about your risk.
You should not breastfeed while using Andogablin.
Certain people who are very sick or very old or who are sensitive show an exacerbation of side effect of the drug which can turn dangerous at times. So, it is very important to remember the precautions while taking the medicine. Pregnancy and Breastfeeding are also special categories wherein extra care or precaution is needed when taking a drug. Few patients may have a hypersensitivity reaction to few medications, and that can be life-threatening rarely. Penicillin hypersensitivity is one example. Diarrhea, rashes are few other symptoms which need a watch. A patient with other co-existing diseases like liver disease, heart disease, kidney disease should take special precautions.
As with all antiepileptic drugs (AEDs), Andogablin should be withdrawn gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. Following abrupt or rapid discontinuation of Andogablin, some patients reported symptoms including insomnia, nausea, headache, diarrhea, flu syndrome, nervousness, depression, pain, sweating and dizziness. If Andogablin is discontinued, this should be done gradually over a minimum of 1 week. Concerning discontinuation of long-term treatment of Andogablin, there are no data of the incidence and severity of withdrawal symptoms in relation to duration of use and dosage of Andogablin.
There are insufficient data for the withdrawal of concomitant antiepileptic medicinal products, once seizure control with Andogablin in the add-on situation has been reached.
Andogablin treatment caused weight gain and edema, primarily described as peripheral edema. As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering Andogablin and these agents. Therefore, dosage adjustment of these antidiabetics may be required.
Because there are limited data on congestive heart failure, patients with New York Heart Association (NYHA) Class III or IV cardiac status, Andogablin should be used with caution in these patients.
Andogablin treatment was associated with creatine kinase elevations. Prescribers should instruct patients to promptly report unexplained muscle pain, tenderness or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Andogablin treatment should be discontinued if myopathy is diagnosed or suspected, or if markedly elevated creatine kinase levels occur.
Andogablin treatment was associated with decrease in platelet count and mild PR interval prolongation.
Patients should be counseled that Andogablin may cause visual disturbances. Patients should be informed that if changes in vision occur, they should notify their physician.
Patients who require concomitant treatment with central nervous system (CNS) depressants eg, opiates or benzodiazepines should be informed that they may experience additive CNS side effects eg, somnolence.
Patients should be told to avoid consuming alcohol while taking Andogablin, as Andogablin may potentiate the impairment of motor skills and sedation of alcohol.
Men being treated with Andogablin who plan to father a child should be informed of the potential risk of male-mediated teratogenicity.
Diabetic patients should be instructed to pay particular attention to skin integrity while being treated with Andogablin. Some animals treated with Andogablin developed skin ulcerations, although no increased incidence of skin lesions associated with Andogablin was observed in clinical trials.
Effects on the Ability to Drive or Operate Machinery: Andogablin causes dizziness and somnolence. Patients should be informed that Andogablin-related dizziness and somnolence may impair their ability to perform tasks eg, driving or operating machinery.
Use in pregnancy & lactation: There are no adequate and well-controlled studies in pregnant women. Andogablin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known if Andogablin is excreted in human milk; it is, however, present in the milk of rats. Because many drugs are excreted in human milk, and because of the potential for tumorigenicity shown for Andogablin in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Use in children: The safety and efficacy of Andogablin in pediatric patients have not been established.
What happens if I miss a dose of Andogablin?
When you miss a dose, you should take it as soon as you remember, but you should take care that it should be well spaced from the next dose. You should not take an extra dose at the time of the second dose as it will become a double dose. The double dose can give unwanted side effects, so be careful. In chronic conditions or when you have a serious health issue, if you miss a dose, you should inform your health care provider and ask his suggestion.
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
DailyMed. "PREGABALIN: 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).