What happens if I overdose Dygab?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local, or emergency room immediately.
Proper storage of Dygab solution:
Store Dygab 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 Dygab solution out of the reach of children and away from pets.
Overdose of Dygab in details
- Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans
- In the postmarketing experience, the most commonly reported adverse events observed with Dygab 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 Dygab overdose and in combination with other CNS depressants.
- Treatment or Management of Overdose
- There is no specific antidote for overdose with Dygab. 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 Dygab.
- Dygab can be removed by hemodialysis. Standard hemodialysis procedures result in significant clearance of Dygab (approximately 50% in 4 hours).
What should I avoid while taking Dygab?
Avoid drinking alcohol. It may increase certain side effects of Dygab.
Avoid driving or hazardous activity until you know how Dygab will affect you. Your reactions could be impaired.
Dygab warnings
Angioedema
There have been postmarketing reports of angioedema in patients during initial and chronic treatment with Dygab. 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 Dygab immediately in patients with these symptoms.
Exercise caution when prescribing Dygab 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.
Hypersensitivity
There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with Dygab. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue Dygab immediately in patients with these symptoms.
Withdrawal of Antiepileptic Drugs (AEDs)
As with all AEDs, withdraw Dygab gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. If Dygab is discontinued, taper the drug gradually over a minimum of 1 week.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including Dygab, 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.
| Indication | 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 |
|---|---|---|---|---|
| Epilepsy | 1.0 | 3.4 | 3.5 | 2.4 |
| Psychiatric | 5.7 | 8.5 | 1.5 | 2.9 |
| Other | 1.0 | 1.8 | 1.9 | 0.9 |
| Total | 2.4 | 4.3 | 1.8 | 1.9 |
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 Dygab 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 Dygab 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.
Peripheral Edema
Dygab 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 Dygab group compared with 2% in the placebo group. In controlled clinical trials, 0.5% of Dygab 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 Dygab 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 Dygab only, and 19% (23/120) of patients who were on both Dygab and thiazolidinedione antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on thiazolidinediones only; 4% (35/859) of patients on Dygab 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 Dygab 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 Dygab in these patients.
Dizziness and Somnolence
Dygab may cause dizziness and somnolence. Inform patients that Dygab-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery.
In the Dygab controlled trials, dizziness was experienced by 30% of Dygab-treated patients compared to 8% of placebo-treated patients; somnolence was experienced by 23% of Dygab-treated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of Dygab 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 Dygab-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.
Weight Gain
Dygab treatment may cause weight gain. In Dygab controlled clinical trials of up to 14 weeks, a gain of 7% or more over baseline weight was observed in 9% of Dygab-treated patients and 2% of placebo-treated patients. Few patients treated with Dygab (0.3%) withdrew from controlled trials due to weight gain. Dygab 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 Dygab-associated weight gain are unknown.
Among diabetic patients, Dygab-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 Dygab for at least 2 years, the average weight gain was 5.2 kg.
While the effects of Dygab-associated weight gain on glycemic control have not been systematically assessed, in controlled and longer-term open label clinical trials with diabetic patients, Dygab 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 Dygab, some patients reported symptoms including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea. Taper Dygab gradually over a minimum of 1 week rather than discontinuing the drug abruptly.
Tumorigenic Potential
In standard preclinical in vivo lifetime carcinogenicity studies of Dygab, 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 Dygab'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 Dygab, it is impossible to know whether the incidence seen in these cohorts is or is not affected by treatment.
Ophthalmological Effects
In controlled studies, a higher proportion of patients treated with Dygab 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 Dygab 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 Dygab, and 5% of placebo-treated patients. Visual field changes were detected in 13% of Dygab-treated, and 12% of placebo-treated patients. Funduscopic changes were observed in 2% of Dygab-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
Dygab treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for Dygab-treated patients and 28 U/L for the placebo patients. In all controlled trials across multiple patient populations, 1.5% of patients on Dygab and 0.7% of placebo patients had a value of creatine kinase at least three times the upper limit of normal. Three Dygab treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and Dygab 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 Dygab if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.
Decreased Platelet Count
Dygab treatment was associated with a decrease in platelet count. Dygab-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 Dygab patients experienced a potentially clinically significant decrease in platelets, defined as 20% below baseline value and <150 × 103/µL. A single Dygab treated subject developed severe thrombocytopenia with a platelet count less than 20 × 103/ µL. In randomized controlled trials, Dygab was not associated with an increase in bleeding-related adverse reactions.
PR Interval Prolongation
Dygab treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data, the mean PR interval increase was 3–6 msec at Dygab 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 Dygab?
You should not use Dygab if you are allergic to Dygab.
To make sure Dygab 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;
-
heart problems (especially congestive heart failure);
-
a bleeding disorder, or low levels of platelets in your blood;
-
kidney disease (or if you are on dialysis);
-
diabetes (unless you are taking Dygab 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.
-
Dygab 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 Dygab. 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 Dygab will harm your unborn baby. You and your healthcare provider will have to decide if you should take Dygab while you are pregnant.
If you are pregnant, your name may be listed on a pregnancy registry to track the effects of Dygab on the baby.
Dygab can decrease sperm count and may affect fertility in men (your ability to have children). In animal studies, Dygab 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 Dygab.
Dygab precautions
As with all antiepileptic drugs (AEDs), Dygab should be withdrawn gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. Following abrupt or rapid discontinuation of Dygab, some patients reported symptoms including insomnia, nausea, headache, diarrhea, flu syndrome, nervousness, depression, pain, sweating and dizziness. If Dygab is discontinued, this should be done gradually over a minimum of 1 week. Concerning discontinuation of long-term treatment of Dygab, there are no data of the incidence and severity of withdrawal symptoms in relation to duration of use and dosage of Dygab.
There are insufficient data for the withdrawal of concomitant antiepileptic medicinal products, once seizure control with Dygab in the add-on situation has been reached.
Dygab 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 Dygab 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, Dygab should be used with caution in these patients.
Dygab 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. Dygab treatment should be discontinued if myopathy is diagnosed or suspected, or if markedly elevated creatine kinase levels occur.
Dygab treatment was associated with decrease in platelet count and mild PR interval prolongation.
Patients should be counseled that Dygab 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 Dygab, as Dygab may potentiate the impairment of motor skills and sedation of alcohol.
Men being treated with Dygab 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 Dygab. Some animals treated with Dygab developed skin ulcerations, although no increased incidence of skin lesions associated with Dygab was observed in clinical trials.
Effects on the Ability to Drive or Operate Machinery: Dygab causes dizziness and somnolence. Patients should be informed that Dygab-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. Dygab should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known if Dygab 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 Dygab 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 Dygab in pediatric patients have not been established.
What happens if I miss a dose of Dygab?
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.
References
- 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).
- DrugBank. "Pregabalin". http://www.drugbank.ca/drugs/DB00230 (accessed September 17, 2018).
- MeSH. "Anticonvulsants". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
Reviews
Consumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
