Phenytoin FDA Alerts

Taro Pharmaceuticals U.S.A. Issues Voluntary Nationwide Recall of Phenytoin Oral Suspension USP, 125 mg/5mL Due to Possible Underdosing or Overdosing

Feb 21, 2020 | Audience: Patient, Health Professional, Pharmacy

February 21, 2020 -- Taro Pharmaceuticals U.S.A., Inc. (“Taro” or the “Company”) is voluntarily recalling two (2) lots of Phenytoin Oral Suspension USP, 125 mg/5 mL both in 237 mL bottles, to the consumer level. Phenytoin Oral Suspension USP, 125 mg/5 mL is indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and is packaged in amber plastic bottles with an inner seal and a white child proof closure, and each bottle contains 237 mL. The reason for the recall is that product from these two lots of Phenytoin Oral Suspension may not re-suspend when shaken, as instructed for administration, which could result in under or overdosing. This recall is being conducted with the knowledge of the FDA.

The population at risk is primarily infants and young children. In those patients, there is a reasonable probability that inaccurate dosing might result in a serious adverse effect such as intoxication or breakthrough seizures requiring medical intervention. For a small minority of patients, who might have severe or repeated breakthrough seizures, a drop in their phenytoin blood levels could result in life-threatening status epilepticus requiring immediate emergency room treatment. To date, Taro has not received any adverse event reports related to this recall.

The two (2) lots that are being recalled are as follows:

Each bottle is labeled to indicate the name of the product, Phenytoin Oral Suspension USP, 125 mg/5 mL and the NDC #51672-4069-1 (see image of container label below).

Lot 327874 was distributed to wholesale distributors, long-term care providers, a repackager and mail order customers in the U.S. market between May 3 and July 5, 2019. Lot 327876 was distributed to wholesale distributors, long-term care providers and mail order customers in the U.S. market between July 1 and August 21, 2019. These customers may have further distributed these lots to retail pharmacies for prescription dispensing to patients who were prescribed Phenytoin Oral Suspension.

Taro is notifying its distributors and retail customers by phone, e-mail, and letters via U.S. Mail and is arranging for return of any containers or quantities of Phenytoin Oral Suspension Lots # 327874 and 327876 (both with an expiration date of December 2020). Retail customers that have any quantities of these two (2) lots which are being recalled, should stop distribution and return any unsold units to their wholesaler.

Consumers with questions regarding this recall can contact Taro by calling 1-866-705-1553 or by e-mail at TaroPVUS@taro.com, Monday through Friday between 7:00 am and 7:00 pm, U.S. Central Time. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to taking or using this drug product.

Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

• Complete and submit the report Online
• Regular Mail or Fax: Download form or call 1- 800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

This recall is being conducted with the knowledge of the U.S. Food and Drug Administration.

SAFE HARBOR STATEMENT

Certain statements in this release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements that do not describe historical facts or that refer or relate to events or circumstances the Company “estimates,” “believes,” or “expects” to happen or similar language, and statements with respect to the voluntary recall of Phenytoin Oral Suspension USP, 125 mg/5 mL. Although the Company believes the expectations reflected in such forward-looking statements to be based on reasonable assumptions, it can give no assurances that its expectations will be attained. Further updates will be detailed from time to time in the Company’s SEC reports, including its Annual Reports on Form 20-F. Forward-looking statements are applicable only as of the date on which they are made.

Source: FDA

---

Antiepileptic Drugs

May 5, 2009 | Audience: Neuropsychiatric healthcare professionals, other healthcare professionals, patients[UPDATE 05/05/2009] FDA notified healthcare professionals that it approved updated labeling for antiepileptic drugs used to treat epilepsy, psychiatric disorders, and other conditions (e.g., migraine and neuropathic pain syndromes). FDA also required development of a medication guide, to be issued to patients each time the product is dispensed. Since issuing safety alerts on December 16, 2008 and January 31, 2008, FDA has been working with the manufacturers of drugs in this class to better understand the suicidality risk. Eleven antiepileptic drugs were included in a pooled analysis of placebo-controlled clinical studies in which these drugs were used to treat epilepsy as well as psychiatric disorders and other conditions. The increased risk of suicidal thoughts or behavior was generally consistent among the eleven drugs, with varying mechanisms of action and across a range of indications. This observation suggests that the risk applies to all antiepileptic drugs used for any indication.

[UPDATE 12/16/2008] The FDA has completed its analysis of reports of suicidality (suicidal behavior or ideation [thoughts]) from placebo-controlled clinical trials of drugs used to treat epilepsy, psychiatric disorders, and other conditions. Based on the outcome of this review, FDA is requiring that all manufacturers of drugs in this class include a Warning in their labeling and develop a Medication Guide to be provided to patients prescribed these drugs to inform them of the risks of suicidal thoughts or actions.

[Posted 01/31/2008] FDA informed healthcare professionals that the Agency has analyzed reports of suicidality (suicidal behavior or ideation) from placebo-controlled clinical studies of eleven drugs used to treat epilepsy as well as psychiatric disorders, and other conditions. In the FDA's analysis, patients receiving antiepileptic drugs had approximately twice the risk of suicidal behavior or ideation (0.43%) compared to patients receiving placebo (0.22%). The increased risk of suicidal behavior and suicidal ideation was observed as early as one week after starting the antiepileptic drug and continued through 24 weeks. The results were generally consistent among the eleven drugs. The relative risk for suicidality was higher in patients with epilepsy compared to patients who were given one of the drugs in the class for psychiatric or other conditions.

Healthcare professionals should closely monitor all patients currently taking or starting any antiepileptic drug for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.

The drugs included in the analyses include (some of these drugs are also available in generic form):

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

Although the 11 drugs listed above were the ones included in the analysis, FDA expects that the increased risk of suicidality is shared by all antiepileptic drugs and anticipates that the class labeling changes will be applied broadly.

[December 16, 2008; UPDATED May 05, 2009 - Drug Information Page - FDA]
[January 31, 2008 - Healthcare Professional Information Sheet - FDA]

---

Phenytoin (marketed as Dilantin, Phenytek and generics) and Fosphenytoin Sodium (marketed as Cerebyx and generics)

Nov 24, 2008 | Audience: Neurological healthcare professionals[Posted 11/24/2008] FDA is investigating new preliminary data regarding a potential increased risk of serious skin reactions including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) from phenytoin therapy in Asian patients positive for human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais. Until the FDA evaluation is completed, healthcare providers who are considering the use of phenytoin or fosphenytoin should be aware of the risks and benefits described in the current prescribing information for this drug. Healthcare providers should consider avoiding phenytoin and fosphenytoin as alternatives for carbamazepine in patients who test positive for HLA-B*1502. A summary of the data currently being analyzed by FDA, and information for patients and healthcare professionals to consider, can be found in the links provided below.

[November 24, 2008 - Information for Healthcare Professionals - FDA]

---