DOXEPIN tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DOXEPIN HYDROCHLORIDE (UNII: 3U9A0FE9N5) (DOXEPIN - UNII:5ASJ6HUZ7D)

Available from:

REMEDYREPACK INC.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Doxepin tablets are indicated for the treatment of insomnia characterized by difficulty with sleep maintenance. The clinical trials performed in support of efficacy were up to 3 months in duration. Doxepin is contraindicated in individuals who have shown hypersensitivity to doxepin HCl, any of its inactive ingredients, or other dibenzoxepines. Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors. Do not administer doxepin if patient is currently on MAOIs or has used MAOIs within the past two weeks. The exact length of time may vary depending on the particular MAOI dosage and duration of treatment. Doxepin is contraindicated in individuals with untreated narrow angle glaucoma or severe urinary retention.   Risk Summary Available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage (see Data) . There are risks of poor neonatal adaptation with exposure to tricyclic antidepressants (TCAs), including doxepin, during pregnancy (see Clinical  Considerations). In animal reproduction studies, oral administration of doxepin to rats and rabbits during the period of organogenesis caused adverse developmental effects at doses 65 and 23 times the maximum recommended human dose (MRHD) of 6 mg/day based on AUC, respectively. Oral administration of doxepin to pregnant rats during pregnancy and lactation resulted in decreased pup survival and a delay in pup growth at doses 60 times the MRHD based on AUC (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions Neonates exposed to TCAs, including doxepin, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hyperreflexia, tremor, jitteriness, irritability and constant crying. These findings are consistent with either direct toxic effects of TCAs or possibly a drug discontinuation syndrome. Monitor neonates who were exposed to doxepin in the third trimester of pregnancy for poor neonatal adaptation syndrome . Data Human Data Published epidemiologic studies of pregnant women exposed to TCAs, including doxepin, have not established an association with major birth defects, miscarriage or adverse maternal outcomes. Methodological limitations of these observational studies include small sample size and lack of adequate controls. Animal Data When doxepin (30, 100, and 150 mg/kg/day) was administered orally to pregnant rats during the period of organogenesis, developmental toxicity (increased incidences of fetal structural abnormalities consisting of non-ossified bones in the skull and sternum and decreased fetal body weights) and maternal toxicity were noted at ≥100 mg/kg/day, which produced plasma exposures (AUCs) of doxepin and nordoxepin (the primary metabolite in humans) approximately 65 and 53 times, respectively, the plasma AUCs at the MRHD. The plasma exposures at the no-effect dose for embryo-fetal developmental toxicity in rats (30 mg/kg/day) are approximately 6 and 5 times the plasma AUCs for doxepin and nordoxepin, respectively, at the MRHD. When doxepin (10, 30, and 60 mg/kg/day) was administered orally to pregnant rabbits during the period of organogenesis, fetal body weights were reduced at the highest dose in the absence of maternal toxicity, which produced plasma AUCs of doxepin and nordoxepin approximately 23 and 56 times, respectively, the plasma AUCs at the MRHD. The plasma exposures at the no-effect dose for developmental effects (30 mg/kg/day) are approximately 8 and 25 times the plasma AUCs for doxepin and nordoxepin, respectively, at the MRHD. Oral administration of doxepin (10, 30, and 100 mg/kg/day) to rats throughout pregnancy and lactation resulted in decreased pup survival and transient growth delay at the highest dose, which produced plasma AUCs of doxepin and nordoxepin approximately 60 and 39 times, respectively, the plasma AUCs at the MRHD. The plasma exposures at the no-effect dose for adverse effects on pre- and postnatal development in rats (30 mg/kg/day) are approximately 2 and 1 times the plasma AUCs for doxepin and nordoxepin, respectively, at the MRHD. Risk Summary Data from the published literature report the presence of doxepin and nordoxepin in human milk. There are reports of excess sedation, respiratory depression, poor sucking and swallowing, and hypotonia in breastfed infants exposed to doxepin. There are no data on the effects of doxepin on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, clinicians should advise patients that breastfeeding is not recommended during treatment with doxepin. Clinical Considerations Infants exposed to doxepin through breast milk should be monitored for excess sedation, respiratory depression and hypotonia. Infertility Based on results from animal fertility studies conducted in rats, doxepin may reduce fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1)] . It is unknown if the effects are reversible. The safety and effectiveness of doxepin in pediatric patients have not been evaluated. A total of 362 subjects who were ≥ 65 years and 86 subjects who were ≥ 75 years received doxepin in controlled clinical studies. No overall differences in safety or effectiveness were observed between these subjects and younger adult subjects. Greater sensitivity of some older individuals cannot be ruled out. Sleep-promoting drugs may cause confusion and over-sedation in the elderly. A starting dose of 3 mg is recommended in this population and evaluation prior to considering dose escalation is recommended [ see  Dosage and Administration ( 2.2) ]. Patients with hepatic impairment may display higher doxepin concentrations than healthy individuals. Initiate doxepin treatment with 3 mg in patients with hepatic impairment and monitor closely for adverse daytime effects [ see  Clinical Pharmacology ( 12.3) ]. Doxepin has not been studied in patients with obstructive sleep apnea. Since hypnotics have the capacity to depress respiratory drive, precautions should be taken if doxepin is prescribed to patients with compromised respiratory function. In patients with severe sleep apnea, doxepin is ordinarily not recommended for use. Doxepin is not a controlled substance. Doxepin is not associated with abuse potential in animals or in humans. Physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of doxepin (e.g., incrementation of dose, drug-seeking behavior). In a brief assessment of adverse events observed during discontinuation of doxepin following chronic administration, no symptoms indicative of a withdrawal syndrome were observed. Thus, doxepin does not appear to produce physical dependence.

Product summary:

Doxepin Tablets are available as follows: 6 mg – Each gray, round, film-coated, unscored tablet imprinted with ‘ ’ on one side and ‘316’ on the other side contains doxepin hydrochloride, USP equivalent to 6 mg of doxepin base. NDC: 70518-3495-00 NDC: 70518-3495-01 PACKAGING: 30 in 1 BOX PACKAGING: 1 in 1 POUCH Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

DOXEPIN- DOXEPIN TABLET, FILM COATED
REMEDYREPACK INC.
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MEDICATION GUIDE
Doxepin (dox' e pin)
Tablets
What is the most important information I should know about doxepin
tablets?
Doxepin tablets can cause serious side effects including:
After taking doxepin tablets, you may get up out of bed while not
being fully awake and do an activity that you do not know you
are doing. The next morning, you may not remember that you did
anything during the night.You have a higher chance for doing
these activities if you drink alcohol or take other medicines that
make you sleepy with doxepin tablets. Reported activities
include:
• driving a car ("sleep-driving")
• making and eating food
• talking on the phone
• having sex
• sleep-walking
Stop takingdoxepin tablets and call your healthcare provider right
away if you find out that you have done any of the above
activities after taking doxepin tablets.
Important:
•
Take doxepin tablets exactly as prescribed
•
Do not take more doxepin tablets than prescribed.
Take doxepin tablets 30 minutes before bedtime. After taking doxepin
tablets, you should only do activities needed to get ready
for bed.
What are doxepin tablets?
Doxepin Tablets are a prescription medicine used to treat adults who
have trouble staying asleep.
It is not known if doxepin tablets are safe and effective in children.
Do not take doxepin tablets if you:
• are allergic to any of the ingredients in doxepin tablets. See the
end of this Medication Guide for a complete list of ingredients
in doxepin tablets.
• take a monoamine oxidase inhibitor (MAOI) medicine or have taken
an MAOI in the last 14 days (2 weeks). Ask your
healthcare provider if you are not sure if your medicine is an MAOI.
• have an eye problem called narrow angle glaucoma that is not being
treated or have trouble urinating that is severe.
Before taking doxepin tablets, tell your healthcare provider about all
of your medical conditions, including if you:
• have a history of depression, mental illness, or suicidal thoughts

Summary of Product characteristics

DOXEPIN- DOXEPIN TABLET, FILM COATED
REMEDYREPACK INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DOXEPIN TABLETS SAFELY
AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR DOXEPIN TABLETS.
DOXEPIN TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1969
INDICATIONS AND USAGE
Doxepin tablets are indicated for the treatment of insomnia
characterized by difficulties with sleep
maintenance. ( 1, 14)
DOSAGE AND ADMINISTRATION
Initial dose: 6 mg, once daily for adults ( 2.1) and 3 mg, once daily
for the elderly. ( 2.1, 2.2)
Take within 30 minutes of bedtime. Total daily dose should not exceed
6 mg. ( 2.3)
Should not be taken within 3 hours of a meal. ( 2.3, 12.3)
DOSAGE FORMS AND STRENGTHS
3 mg and 6 mg tablets. Tablets notscored. ( 3)
CONTRAINDICATIONS
Hypersensitivity to doxepin hydrochloride, inactive ingredients, or
other dibenzoxepines. ( 4.1)
Co-administration with Monoamine Oxidase Inhibitors (MAOIs): Do not
administer if patient is taking
MAOIs or has used MAOIs within the past two weeks. ( 4.2)
Untreated narrow angle glaucoma or severe urinary retention. ( 4.3)
WARNINGS AND PRECAUTIONS
Need to Evaluate for Co-morbid Diagnoses: Reevaluate if insomnia
persists after 7 to 10 days of use. (
5.1)
Abnormal thinking, behavioral changes, complex behaviors: May include
“Sleep-driving” and
hallucinations. Immediately evaluate any new onset behavioral changes.
( 5.2)
Depression: Worsening of depression or suicidal thinking may occur.
Prescribe the least amount
feasible to avoid intentional overdose. ( 5.3)
CNS-depressant effects: Use can impair alertness and motor
coordination. Avoid engaging in
hazardous activities such as operating a motor vehicle or heavy
machinery after taking drug. ( 5.4) Do
not use with alcohol. ( 5.4, 7.3)
Potential additive effects when used in combination with CNS
depressants or sedating antihistamines.
Dose reduction may be needed. ( 5.4, 7.4)
Patients with severe sleep apnea: Doxepin is ordinarily not
recommended for use i