Tofranil-pm

Imipramine comes as a tablet and a capsule to take by mouth. When imipramine tablets or capsules are used to treat depression, they are usually taken one or more times a day and may be taken with or without food. When imipramine tablets are used to prevent bedwetting in children, they are usually taken one hour before bedtime. Children who wet the bed early in the evening may be given one dose in the mid-afternoon and another dose at bedtime. Try to take imipramine at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take imipramine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may start you on a low dose of imipramine and gradually increase your dose.

It may take 1-3 weeks or longer for you to feel the full benefit of imipramine. Continue to take imipramine even if you feel well. Do not stop taking imipramine without talking to your doctor. Your doctor will probably want to decrease your dose gradually.

Serious side effects have been reported with Tofranil-PM including the following:

• QT prolongation. This is a condition when changes in the electrical activity of your heart occur, causing irregular heartbeats that can be life threatening. Talk to your healthcare provider about other medicines you are taking before you start taking Tofranil-PM. Tell your healthcare provider right away if you have any signs or symptoms of QT prolongation:
  • feeling faint
  • lightheadedness
  • dizziness
  • feeling like your heart is beating irregularly or quickly
• Serotonin Syndrome. Serotonin syndrome has been reported with Tofranil-PM, alone but particularly with concomitant use of other serotonergic medications. Tell your healthcare provider right away if you have some or all of the following symptoms of serotonin syndrome.
  • mental status changes ( agitation, hallucinations, delirium, and coma)
  • autonomic instability (tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia)
  • neuromuscular changes (tremor, rigidity, myoclonus, hyperreflexia, incoordination)
  • seizures
  • gastrointestinal symptoms (nausea, vomiting, diarrhea).
• Clinical Worsening and Suicide Risk. Tell your healthcare provider right away if you have any of the following signs or symptoms especially if they are new, worse, or worry you:
  •   thoughts about suicide or dying
  •   attempts to commit suicide
  •   new or worse depression/anxiety
  •   feeling very agitated or restless
  •   panic attacks
  •   trouble sleeping (insomnia)
  •   acting on dangerous impulses
  •   other unusual changes in behavior or mood

Tofranil-PM can cause drowsiness and dizziness. Do not drive or operate heavy machinery until you know how Tofranil-PM affects you.

Do not take Tofranil-PM if you:

• are allergic to Tofranil-PM or to any of its ingredients
• take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take a MAOI, including the antibiotic linezolid.
• stopped taking a MAOI in the last 2 weeks unless directed to do so by your physician.
• are in an acute recovery period after a myocardial infarction.

It is very important that your doctor check your progress at regular visits to allow for changes in your dose and to check for any unwanted effects. Blood tests may be needed to check for any unwanted effects. Check with your doctor right away if you start having a fever or sore throat while taking this medicine.

Do not take imipramine with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], linezolid [Zyvox®], methylene blue injection, phenelzine [Nardil®], selegiline [Eldepryl®, or tranylcypromine [Parnate®]). Do not start taking imipramine during the 2 weeks after you stop a MAO inhibitor and wait 2 weeks after stopping imipramine before you start taking a MAO inhibitor. If you do take them together or do not wait 2 weeks, you may develop confusion, agitation, restlessness, stomach or intestinal symptoms, a sudden high body temperature, an extremely high blood pressure, or severe convulsions.

Imipramine may cause some teenagers and young adults to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Some people may have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. If you, your child, or your caregiver notice any of these side effects, tell your doctor or your child's doctor right away. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Imipramine may cause a serious condition called serotonin syndrome if taken together with some medicines. Do not use imipramine with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), lithium (Eskalith®, Lithobid®), methylene blue injection, tryptophan, St. John's wort, or some pain or migraine medicines (eg, rizatriptan, sumatriptan, tramadol, Frova®, Imitrex®, Maxalt®, Relpax®, Ultram®, Zomig®). Check with your doctor first before taking any other medicines with imipramine.

Do not suddenly stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This will decrease the chance of having withdrawal symptoms such as agitation, breathing problems, chest pain, confusion, diarrhea, dizziness or lightheadedness, fast heartbeat, headache, increased sweating, muscle pain, nausea, restlessness, runny nose, trouble in sleeping, trembling or shaking, unusual tiredness or weakness, vision changes, or vomiting.

This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants (medicines that cause drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies or colds, sedatives, tranquilizers, or sleeping medicines, prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

Before having any kind of surgery, tell the medical doctor in charge that you are using this medicine. Taking imipramine together with medicines used during surgery may increase the risk of side effects.

This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests, or if you have any questions, check with your doctor.

This medicine may make your skin more sensitive to sunlight. Use a sunscreen when you are outdoors. Avoid sunlamps and tanning beds.

This medicine may cause some people to become drowsy or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are drowsy or not alert.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Dry mouth.
• Hard stools (constipation).
• Upset stomach or throwing up.
• Not hungry.
• Loose stools (diarrhea).
• Change in taste.
• Stomach cramps.
• Feeling sleepy.
• Weight gain or loss.
• Sweating a lot.
• Flushing.
• Feeling tired or weak.
• Headache.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Monoamine Oxidase Inhibitors (MAOIs)

The use of MAOIs intended to treat psychiatric disorders with Tofranil-PM or within 14 days of stopping treatment with Tofranil-PM is contraindicated because of an increased risk of serotonin syndrome.  The use of Tofranil-PM within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated (see WARNINGS and  DOSAGE AND ADMINISTRATION).

Starting Tofranil-PM in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see WARNINGS and DOSAGE AND ADMINISTRATION).

Myocardial Infarction

The drug is contraindicated during the acute recovery period after a myocardial infarction.

Hypersensitivity to Tricyclic Antidepressants

Patients with a known hypersensitivity to this compound should not be given the drug. The possibility of cross-sensitivity to other dibenzazepine compounds should be kept in mind.

Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for imipramine pamoate should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.

Screening Patients for Bipolar Disorder – A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that imipramine pamoate is not approved for use in treating bipolar depression.

Extreme caution should be used when this drug is given to patients with cardiovascular disease because of the possibility of conduction defects, arrhythmias, congestive heart failure, myocardial infarction, strokes, and tachycardia. These patients require cardiac surveillance at all dosage levels of the drug; patients with increased intraocular pressure, history of urinary retention, or history of narrow-angle glaucoma because of the drug's anticholinergic properties; hyperthyroid patients or those on thyroid medication because of the possibility of cardiovascular toxicity; patients with a history of seizure disorder because this drug has been shown to lower the seizure threshold; patients receiving guanethidine, clonidine, or similar agents, since imipramine pamoate may block the pharmacologic effects of these drugs; patients receiving methylphenidate hydrochloride. Since methylphenidate hydrochloride may inhibit the metabolism of imipramine pamoate, downward dosage adjustment of imipramine pamoate may be required when given concomitantly with methylphenidate hydrochloride.

Since imipramine pamoate may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as operating an automobile or machinery, the patient should be cautioned accordingly.

Tofranil-PM may enhance the CNS depressant effects of alcohol. Therefore, it should be borne in mind that the dangers inherent in a suicide attempt or accidental overdosage with the drug may be increased for the patient who uses excessive amounts of alcohol (see PRECAUTIONS).

Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Tofranil-PM, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular changes (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.

The concomitant use of Tofranil-PM with MAOIs intended to treat psychiatric disorders is contraindicated. Tofranil-PM should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Tofranil-PM. Tofranil-PM should be discontinued before initiating treatment with the MAOI (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).

If concomitant use of Tofranil-PM with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

Treatment with Tofranil-PM and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

Angle-Closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs including Tofranil-PM may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Note: Although the listing which follows includes a few adverse reactions which have not been reported with this specific drug, the pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when imipramine is administered.

Cardiovascular: Orthostatic hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, ECG changes, precipitation of congestive heart failure, stroke.

Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis.

Neurological: Numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures, alterations in EEG patterns; tinnitus.

Anticholinergic: Dry mouth, and, rarely, associated sublingual adenitis; blurred vision, disturbances of accommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract.

Allergic: Skin rash, petechiae, urticaria, itching, photosensitization; edema (general or of face and tongue); drug fever; cross-sensitivity with desipramine.

Hematologic: Bone marrow depression including agranulocytosis; eosinophilia; purpura; thrombocytopenia.

Gastrointestinal: Nausea and vomiting, anorexia, epigastric distress, diarrhea; peculiar taste, stomatitis, abdominal cramps, black tongue.

Endocrine: Gynecomastia in the male; breast enlargement and galactorrhea in the female; increased or decreased libido, impotence; testicular swelling; elevation or depression of blood sugar levels; inappropriate antidiuretic hormone (ADH) secretion syndrome.

Other: Jaundice (simulating obstructive); altered liver function; weight gain or loss; perspiration; flushing; urinary frequency; drowsiness, dizziness, weakness and fatigue; headache; parotid swelling; alopecia; proneness to falling.

Withdrawal Symptoms: Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache and malaise.

Postmarketing Experience

The following adverse drug reaction has been reported during post-approval use of Tofranil-PM. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency.

Eye disorders: angle-closure glaucoma

Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic overdose. Therefore, hospital monitoring is required as soon as possible.

Children have been reported to be more sensitive than adults to an acute overdosage of imipramine pamoate. An acute overdose of any amount in infants or young children, especially, must be considered serious and potentially fatal.

Manifestations

These may vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the interval between drug ingestion and the start of treatment. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity.

Other CNS manifestations may include drowsiness, stupor, ataxia, restlessness, agitation, hyperactive reflexes, muscle rigidity, athetoid and choreiform movements.

Cardiac abnormalities may include tachycardia, and signs of congestive failure. Respiratory depression, cyanosis, shock, vomiting, hyperpyrexia, mydriasis, and diaphoresis may also be present.

Management

Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line, and initiate gastric decontamination. A minimum of 6 hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. There are case reports of patients succumbing to fatal dysrhythmias late after overdose; these patients had clinical evidence of significant poisoning prior to death and most received inadequate gastrointestinal decontamination. Monitoring of plasma drug levels should not guide management of the patient.

Gastrointestinal Decontamination – All patients suspected of tricyclic overdose should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by activated charcoal. If consciousness is impaired, the airway should be secured prior to lavage. Emesis is contraindicated.

Cardiovascular – A maximal limb-lead QRS duration of ≥ 0.10 seconds may be the best indication of the severity of the overdose. Intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used. Concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring. A pH > 7.60 or a pCO2 < 20 mmHg is undesirable.

Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium, or phenytoin. Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).

In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic poisoning.

CNS – In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines, or if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in consultation with a poison control center.

Psychiatric Follow-up – Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate.

Pediatric Management – The principles of management of child and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.

A. Acute: Oral LD50:

Mouse          2185 mg/kg

Rat (F)          1142 mg/kg

       (M)          1807 mg/kg

Rabbit           1016 mg/kg

Dog                  693 mg/kg (Emesis ED50)

B. Subacute:

Two three-month studies in dogs gave evidence of an adverse drug effect on the testes, but only at the highest dose level employed, i.e., 90 mg/kg (10 times the maximum human dose). Depending on the histological section of the testes examined, the findings consisted of a range of degenerative changes up to and including complete atrophy of the seminiferous tubules, with spermatogenesis usually arrested.

Human studies show no definitive effect on sperm count, sperm motility, sperm morphology or volume of ejaculate.

Rat

One three-month study was done in rats at dosage levels comparable to those of the dog studies. No adverse drug effect on the testes was noted in this study, as confirmed by histological examination.

C. Reproduction/Teratogenic:

Oral: Imipramine pamoate was fed to male and female albino rats for 28 weeks through two breeding cycles at dose levels of 15 mg/kg/day and 40 mg/kg/day (equivalent to 2 1/2 and 7 times the maximum human dose).

No abnormalities which could be related to drug administration were noted in gross inspection. Autopsies performed on pups from the second breeding likewise revealed no pathological changes in organs or tissues; however, a decrease in mean litter size from both matings was noted in the drug-treated groups and significant growth suppression occurred in the nursing pups of both sexes in the high group as well as in the females of the low-level group. Finally, the lactation index (pups weaned divided by number left to nurse) was significantly lower in the second litter of the high-level group.

Mallinckrodt, the “M” brand mark, the Mallinckrodt Pharmaceuticals logo,  and other brands are trademarks of a Mallinckrodt company.

© 2014 Mallinckrodt.

Manufactured by
Patheon Inc.
Whitby, Ontario, Canada
L1N 5Z5

Manufactured for
Mallinckrodt Inc.
Hazelwood, MO 63042 USA

Medication Guide - Tofranil-PM™ (imipramine pamoate) capsules

Read the Medication Guide that comes with you or your family member's antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk to your, or your family member's, healthcare provider about:

• all risks and benefits of treatment with antidepressant medicines
• all treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.

2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.

3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

• Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
• Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
• Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• feeling very agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood

Visual problems

• eye pain
• changes in vision
• swelling or redness in or around the eye

Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.

Who should not take Tofranil-PM?

Do not take Tofranil-PM if you:

• take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid.
  • Do not take an MAOI within 2 weeks of stopping Tofranil-PM unless directed to do so by your physician.
  • Do not start Tofranil-PM if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.

What else do I need to know about antidepressant medicines?

• Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
• Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
• Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
• Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
• Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child's healthcare provider for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Mallinckrodt, the “M” brand mark, the Mallinckrodt Pharmaceuticals logo, and other brands are trademarks of a Mallinckrodt company. 

© 2014 Mallinckrodt.

Manufactured by
Patheon Inc.
Whitby, Ontario, Canada
L1N 5Z5

Manufactured for
Mallinckrodt Inc.
Hazelwood, MO 63042 USA                                                                                 

Rev 06/2014

MallinckrodtTM

NDC 0406-9926-03

30 Capsules

Tofranil-PM™
(imipramine pamoate) capsules

150 mg*

Rx only

*Each capsule contains imipramine pamoate equivalent to 150 mg of imipramine hydrochloride.

PHARMACIST: PLEASE DISPENSE WITH ATTACHED MEDICATION GUIDE

MallinckrodtTM

Rev 06/2014

2000006593

Applies to imipramine: oral capsule, oral tablet

Along with its needed effects, imipramine (the active ingredient contained in Tofranil-PM) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking imipramine:

• Abdominal or stomach pain
• agitation
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain or discomfort
• clay-colored stools
• cold sweats
• confusion about identity, place, and time
• continuing ringing or buzzing or other unexplained noise in the ears
• cough or hoarseness
• dark urine
• decrease in the frequency of urination
• difficulty in passing urine (dribbling)
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• double vision
• dry mouth
• false beliefs that cannot be changed by facts
• fast, pounding, or irregular heartbeat or pulse
• feeling, seeing, or hearing things that are not there
• feeling that others are watching you or controlling your behavior
• feeling that others can hear your thoughts
• fever with or without chills
• flushed, dry skin
• general feeling of tiredness or weakness
• hearing loss
• hostility
• hyperventilation
• inability to move the arms, legs, or facial muscles
• irritability
• itching or rash
• lack of coordination
• lethargy
• loss of balance control
• lower back or side pain
• mood or mental changes
• muscle spasm or jerking of all extremities
• muscle trembling, jerking, or stiffness
• nightmares
• pain or discomfort in the arms, jaw, back, or neck
• painful or difficult urination
• pinpoint red or purple spots on the skin
• rapid weight gain
• redness of the face, neck, arms, and occasionally, upper chest
• restlessness
• seizures
• shakiness and unsteady walk
• slow speech
• sore throat
• stiffness of the limbs
• stupor
• sweating
• swelling of the face, ankles, legs, or hands
• talking, feeling, and acting with excitement
• trouble sleeping
• twisting movements of the body
• uncontrolled movements, especially of the face, neck, and back
• unusual behavior
• unusual tiredness or weakness
• weakness in the arms, hands, legs, or feet
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking imipramine:

• Bluish color of fingernails, lips, skin, palms, or nail beds
• cold, clammy skin
• decreased awareness or responsiveness
• difficult or troubled breathing
• disorientation
• fast, weak pulse
• hallucinations
• irregular, fast, slow, or shallow breathing
• severe sleepiness

Some side effects of imipramine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bigger, dilated, or enlarged pupils (black part of the eye)
• black tongue
• decreased interest or ability in sexual intercourse
• difficulty having a bowel movement (stool)
• enlargement of the breast
• hives or welts
• increase in sexual ability, desire, drive, or performance
• increased sensitivity of the eyes to light
• increased urge to urinate during the night
• peculiar taste
• redness or other discoloration of the skin
• severe sunburn
• swelling of the testicles
• swelling of the breasts or breast soreness in both females and males
• swollen, painful, or tender lymph glands on the side of the face or neck
• unexpected or excess milk flow from the breasts
• waking to urinate at night