Tenec

Each tablet contains Diazepam (Tenec) 2 mg, 5 mg and 10 mg, respectively. Each ampoule contain Diazepam (Tenec) 10 mg/2 mL. It also contains the following excipients: Tablets: Lactose. Ampoules: Benzyl alcohol.

A widely used non-cardioselective beta-adrenergic antagonist. R,S-Propranolol (Tenec) Hydrochloride is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety.

Diazepam (Tenec) Rectal Gel is a gel formulation of Diazepam (Tenec) intended for rectal administration in the management of selected, refractory, patients with epilepsy, on stable regimens of AEDs, who require intermittent use of Diazepam (Tenec) to control bouts of increased seizure activity.

Evidence to support the use of Diazepam (Tenec) Rectal Gel was adduced in two controlled trials that enrolled patients with partial onset or generalized convulsive seizures who were identified jointly by their caregivers and physicians as suffering intermittent and periodic episodes of markedly increased seizure activity, sometimes heralded by nonconvulsive symptoms, that for the individual patient were characteristic and were deemed by the prescriber to be of a kind for which a benzodiazepine would ordinarily be administered acutely. Although these clusters or bouts of seizures differed among patients, for any individual patient the clusters of seizure activity were not only stereotypic but were judged by those conducting and participating in these studies to be distinguishable from other seizures suffered by that patient. The conclusion that a patient experienced such unique episodes of seizure activity was based on historical information.

Hypertension

Propranolol (Tenec) hydrochloride tablets USP are indicated in the management of hypertension. It may be used alone or used in combination with other antihypertensive agents, particularly a thiazide diuretic. Propranolol (Tenec) hydrochloride tablets USP are not indicated in the management of hypertensive emergencies.

Angina Pectoris Due to Coronary Atherosclerosis

Propranolol (Tenec) hydrochloride tablets USP are indicated to decrease angina frequency and increase exercise tolerance in patients with angina pectoris.

Atrial Fibrillation

Propranolol (Tenec) hydrochloride tablets USP are indicated to control ventricular rate in patients with atrial fibrillation and a rapid ventricular response.

Myocardial Infarction

Propranolol (Tenec) hydrochloride tablets USP are indicated to reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable.

Migraine

Propranolol (Tenec) hydrochloride tablets USP are indicated for the prophylaxis of common migraine headache. The efficacy of Propranolol (Tenec) in the treatment of a migraine attack that has started has not been established, and Propranolol (Tenec) is not indicated for such use.

Essential Tremor

Propranolol (Tenec) hydrochloride tablets USP are indicated in the management of familial or hereditary essential tremor. Familial or essential tremor consists of involuntary, rhythmic, oscillatory movements, usually limited to the upper limbs. It is absent at rest, but occurs when the limb is held in a fixed posture or position against gravity and during active movement. Propranolol (Tenec) hydrochloride tablets USP cause a reduction in the tremor amplitude, but not in the tremor frequency. Propranolol (Tenec) hydrochloride tablets USP are not indicated for the treatment of tremor associated with Parkinsonism.

Hypertrophic Subaortic Stenosis

Propranolol (Tenec) hydrochloride tablets USP improve NYHA functional class in symptomatic patients with hypertrophic subaortic stenosis.

Pheochromocytoma

Propranolol (Tenec) hydrochloride tablets USP are indicated as an adjunct to alpha-adrenergic blockade to control blood pressure and reduce symptoms of catecholamine-secreting tumors.

Diazepam (Tenec) is a benzodiazepine (ben-zoe-dye-AZE-eh-peen). Diazepam (Tenec) affects chemicals in the brain that may be unbalanced in people with certain conditions.

Diazepam (Tenec) injection is used to treat anxiety disorders, alcohol withdrawal symptoms, or muscle spasms. Diazepam (Tenec) injection is also used to treat a seizure emergency called status epilepticus.

Diazepam (Tenec) injection is sometimes used as a sedative to help you relax before having surgery or other medical procedure.

Diazepam (Tenec) may also be used for purposes not listed in this medication guide.

Propranolol (Tenec) is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. Lowering blood pressure may reduce the risk of stroke and heart attacks.

Propranolol (Tenec) is also used to treat severe chest pain (angina), migraine headaches, or hypertrophic subaortic stenosis (thickened heart muscle).

Propranolol (Tenec) may also be used to treat irregular heartbeats, tremors, or pheochromocytoma (adrenal gland tumor). It may also be used to reduce the risk of death in patients who have heart attacks.

Propranolol (Tenec) oral solution is used to treat proliferating infantile hemangioma.

Propranolol (Tenec) is a beta-blocker. It works by affecting the response to nerve impulses in certain parts of the body, like the heart. As a result, the heart beats slower and decreases the blood pressure. When the blood pressure is lowered, the amount of blood and oxygen is increased to the heart.

Propranolol (Tenec) is available only with your doctor's prescription.

This section is intended primarily for the prescriber; however, the prescriber should also be aware of the dosing information and directions for use provided in the patient package insert.

A decision to prescribe Diazepam (Tenec) rectal gel involves more than the diagnosis and the selection of the correct dose for the patient.

First, the prescriber must be convinced from historical reports and/or personal observations that the patient exhibits the characteristic identifiable seizure cluster that can be distinguished from the patient's usual seizure activity by the caregiver who will be responsible for administering Diazepam (Tenec) rectal gel.

Second, because Diazepam (Tenec) rectal gel is only intended for adjunctive use, the prescriber must ensure that the patient is receiving an optimal regimen of standard anti-epileptic drug treatment and is, nevertheless, continuing to experience these characteristic episodes.

Third, because a non-health professional will be obliged to identify episodes suitable for treatment, make the decision to administer treatment upon that identification, administer the drug, monitor the patient, and assess the adequacy of the response to treatment, a major component of the prescribing process involves the necessary instruction of this individual.

Fourth, the prescriber and caregiver must have a common understanding of what is and is not an episode of seizures that is appropriate for treatment, the timing of administration in relation to the onset of the episode, the mechanics of administering the drug, how and what to observe following administration, and what would constitute an outcome requiring immediate and direct medical attention.

Calculating Prescribed Dose

The Diazepam (Tenec) rectal gel dose should be individualized for maximum beneficial effect. The recommended dose of Diazepam (Tenec) rectal gel is 0.2-0.5 mg/kg depending on age. See the dosing table for specific recommendations.

How supplied

Diazepam (Tenec) Rectal Gel rectal delivery system is a non-sterile, prefilled, unit dose, rectal delivery system. The rectal delivery system includes a plastic applicator with a flexible, molded tip available in two lengths, designated for convenience as 10 mg delivery system and 20 mg delivery system. The available doses from 20 mg delivery system are 12.5 mg, 15 mg, 17.5 mg, and 20 mg. The available doses from 10 mg delivery system are 5 mg, 7.5 mg and 10 mg. The Diazepam (Tenec) Rectal Gel delivery system is available in the following three presentations:

Each twin pack contains two Diazepam (Tenec) Rectal Gel delivery systems, two packets of lubricating jelly, and administration and disposal Instructions available on the bottom of the package. Diazepam (Tenec) Rectal Gel is also packed with Instructions for Caregivers upon receipt from pharmacy.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

Diazepam (Tenec) Rectal Gel 10 mg delivery system and 20 mg delivery system

Distributed by: TEVA PHARMACEUTICALS USA, INC., North Wales, PA 19454. Manufactured By: DPT Laboratories, LTD., San Antonio, TX 78215, 9435000. Revised: Feb 2015

General

Propranolol (Tenec) hydrochloride extended-release capsules provide Propranolol (Tenec) hydrochloride in a sustained-release capsule for administration once daily. If patients are switched from Propranolol (Tenec) hydrochloride tablets to Propranolol (Tenec) hydrochloride extended-release capsules, care should be taken to assure that the desired therapeutic effect is maintained. Propranolol (Tenec) hydrochloride extended-release capsules should not be considered a simple mg-for-mg substitute for Propranolol (Tenec) hydrochloride tablets. Propranolol (Tenec) hydrochloride extended-release capsules have different kinetics and produce lower blood levels. Retitration may be necessary, especially to maintain effectiveness at the end of the 24-hour dosing interval.

Hypertension

The usual initial dosage is 80 mg Propranolol (Tenec) hydrochloride extended-release capsules once daily, whether used alone or added to a diuretic. The dosage may be increased to 120 mg once daily or higher until adequate blood pressure control is achieved. The usual maintenance dosage is 120 to 160 mg once daily. In some instances a dosage of 640 mg may be required. The time needed for full hypertensive response to a given dosage is variable and may range from a few days to several weeks.

Angina Pectoris

Starting with 80 mg Propranolol (Tenec) hydrochloride extended-release capsules once daily, dosage should be gradually increased at three- to seven-day intervals until optimal response is obtained. Although individual patients may respond at any dosage level, the average optimal dosage appears to be 160 mg once daily. In angina pectoris, the value and safety of dosage exceeding 320 mg per day have not been established.

If treatment is to be discontinued, reduce dosage gradually over a period of a few weeks.

Migraine

The initial oral dose is 80 mg Propranolol (Tenec) hydrochloride extended-release capsules once daily. The usual effective dose range is 160 to 240 mg once daily. The dosage may be increased gradually to achieve optimal migraine prophylaxis. If a satisfactory response is not obtained within four to six weeks after reaching the maximal dose, Propranolol (Tenec) hydrochloride extended-release capsules therapy should be discontinued. It may be advisable to withdraw the drug gradually over a period of several weeks depending on the patient's age, comorbidity, and dose of Propranolol (Tenec) hydrochloride extended-release capsules.

Hypertrophic Subaortic Stenosis

The usual dosage is 80 to 160 mg Propranolol (Tenec) hydrochloride extended-release capsules once daily.

See also:
What is the most important information I should know about Diazepam (Tenec)?

You should not use this medication if you are allergic to Diazepam (Tenec) or similar medicines (Ativan, Klonopin, Restoril, Xanax, and others), or if you have myasthenia gravis, severe liver disease, narrow-angle glaucoma, a severe breathing problem, or sleep apnea.

Do not use Diazepam (Tenec) if you are pregnant. It could harm the unborn baby.

Do not start or stop taking Diazepam (Tenec) during pregnancy without your doctor's advice. Diazepam (Tenec) may cause harm to an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby. Tell your doctor right away if you become pregnant while taking Diazepam (Tenec) for seizures.

Before you take Diazepam (Tenec), tell your doctor if you have glaucoma, asthma or other breathing problems, kidney or liver disease, seizures, or a history of drug or alcohol addiction, mental illness, depression, or suicidal thoughts.

Do not drink alcohol while taking Diazepam (Tenec). This medication can increase the effects of alcohol.

Never take more of this medication than your doctor has prescribed. An overdose of Diazepam (Tenec) can be fatal.

Diazepam (Tenec) may be habit forming. Never share Diazepam (Tenec) with another person, especially someone with a history of drug abuse or addiction.

See also:
What is the most important information I should know about Propranolol (Tenec)?

Propranolol (Tenec) must not be used if there is a history of bronchial asthma or bronchospasm.

Bronchospasm can usually be reversed by beta-2 agonist bronchodilators such as salbutamol. Large doses of the beta-2-agonist bronchodilator may be required to overcome the beta-blockade produced by Propranolol (Tenec) and the dose should be titrated according to the clinical response; both intravenous and inhalational administration should be considered. The use of intravenous aminophylline and/or the use of ipratropium, (given by nebuliser), may also be considered. Glucagon (1 to 2 mg given intravenously) has also been reported to produce a bronchodilator effect in asthmatic patients. Oxygen or artificial ventilation may be required in severe cases.

Propranolol (Tenec) as with other beta-blockers must not be used in patients with any of the following: Known hypersensitivity to the substance; bradycardia; cardiogenic shock; hypotension; metabolic acidosis; after prolonged fasting; severe peripheral arterial circulatory disturbances; second or third degree heart block; sick sinus syndrome; untreated (with an alpha adrenoceptor antagonist) phaeochromocytoma; uncontrolled heart failure; Prinzmetal's angina.

Propranolol (Tenec) must not be used in patients prone to hypoglycaemia, i.e., patients after prolonged fasting or patients with restricted counter-regulatory reserves. Patients with restricted-counter regulatory reserves may have reduced autonomic and hormonal responses to hypoglycaemia which includes glycogenolysis, gluconeogenesis and/or impaired modulation of insulin secretion. Patients at risk for an inadequate response to hypoglycaemia includes individuals with malnutrition, prolonged fasting, starvation, chronic liver disease, diabetes and concomitant use of drugs which block the full response to catecholamines.

Use Diazepam (Tenec) Rectal Gel as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Diazepam (Tenec) Rectal Gel. Talk to your pharmacist if you have questions about this information.
• A health care provider will teach your caregiver how to use Diazepam (Tenec) Rectal Gel. Be sure your caregiver understands how to use Diazepam (Tenec) Rectal Gel. Contact your health care provider if you or your caregiver have any questions about using Diazepam (Tenec) Rectal Gel.
• To use Diazepam (Tenec) Rectal Gel, place the patient on their side where they cannot fall. Get the syringe. Push up with your thumb and remove the cap from the syringe. Be sure the seal pin is removed with the cap. Lubricate the rectal tip with the lubricating jelly provided.
• Turn the patient on their side facing you. Bend the upper leg forward and separate the buttocks to expose the rectum.
• Gently insert the syringe tip into the rectum. Slowly count to 3 while gently pushing the plunger in until it stops. Slowly count to 3 before removing the syringe from the rectum. Slowly count to 3 while holding the buttocks together to prevent leakage of the medicine.
• Keep the patient on their side facing you. Continue to observe the patient as directed by the patient's doctor.
• Do not reuse the syringe or other materials. Throw away all used materials in the trash can. Keep out of the reach of children and away from pets.
• Contact the patient's doctor at once if seizures continue for 15 minutes after using Diazepam (Tenec) Rectal Gel, unless the patient's doctor tells you otherwise.
• Contact the doctor at once if you are alarmed by the frequency or severity of the seizures, or the color or breathing of the patient.
• Contact the doctor at once if the seizures are different from the patient's usual seizure episodes or if the patient is having unusual or serious problems.
• Do NOT use Diazepam (Tenec) Rectal Gel more often than once every 5 days unless your doctor tells you otherwise.
• Do NOT use Diazepam (Tenec) Rectal Gel more often than 5 times per month unless your doctor tells you otherwise.
• If you miss a dose of Diazepam (Tenec) Rectal Gel, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Diazepam (Tenec) Rectal Gel.

Use Propranolol (Tenec) solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Propranolol (Tenec) solution comes with extra patient information sheets called a Medication Guide and Instructions for Use. Read them carefully. Read them again each time you get Propranolol (Tenec) solution refilled.
• Do NOT shake Propranolol (Tenec) solution before use.
• Use the syringe that comes with Propranolol (Tenec) solution to measure the dose. Ask the pharmacist for help if you are unsure of how to measure the dose.
• Give Propranolol (Tenec) solution right into your child's mouth. If needed, Propranolol (Tenec) solution may be mixed in a small amount of milk or fruit juice and given in a baby's bottle.
• Give Propranolol (Tenec) solution with or right after a feeding.
• Give doses of Propranolol (Tenec) solution at least 9 hours apart.
• The dose of Propranolol (Tenec) solution may need to be changed as your child's weight changes. Have your child's weight checked often. Talk with the doctor before changing your child's dose.
• Give Propranolol (Tenec) solution on a regular schedule to get the most benefit from it. Giving Propranolol (Tenec) solution at the same time each day will help you remember to give it.
• If your child spits up a dose or if you are not sure your child got all of the medicine, do not give another dose. Wait until the next scheduled dose.
• If you miss giving your child a dose of Propranolol (Tenec) solution, give it as soon as possible. If it is almost time for the next dose, skip giving the missed dose and go back to your child's regular dosing schedule. Do not give 2 doses at once.

Ask your health care provider any questions you may have about how to use Propranolol (Tenec) solution.

Diazepam (Tenec) is used to treat anxiety, muscle spasms, and alcohol withdrawal. The injection form is used when prompt relief is desired or when the medication cannot be taken by mouth.

This medication is also used for the short-term treatment of serious seizures that do not stop (status epilepticus). It is not for ongoing daily use to prevent seizures.

Diazepam (Tenec) is also used before a surgery or procedure to cause drowsiness, decrease anxiety, and to help the patient forget what happened during the surgery/procedure.

This medication works by calming the brain and nerves. Diazepam (Tenec) belongs to a class of drugs known as benzodiazepines.

How to use Diazepam (Tenec) injection

This medication is given by injection into a vein or deep into a muscle as directed by your doctor. You should be closely monitored for several hours after receiving this medication.

If you are using this medication at home, learn all preparation and usage instructions from your health care professional. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.

The dosage is based on your medical condition, age, and response to treatment. Giving the medication too fast into a vein can cause serious side effects. If giving this medication into a vein, inject it slowly into a large vein. Do not inject this medication into an artery or into the skin.

If you suddenly stop using this medication, you may have withdrawal symptoms (such as shaking, abdominal/muscle cramps, vomiting, sweating, anxiety, restlessness, seizures). To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used Diazepam (Tenec) for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.

When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.

Along with its benefits, this medication may rarely cause abnormal drug-seeking behavior (addiction). This risk may be increased if you have abused alcohol or drugs in the past. Use this medication exactly as prescribed to lessen the risk of addiction.

Use: Labeled Indications

Angina, chronic stable: To decrease angina frequency and increase exercise tolerance in patients with angina pectoris.

Cardiac arrhythmias: Control of supraventricular arrhythmias (eg, atrial fibrillation and flutter, atrioventricular nodal reentrant tachycardia) and ventricular tachycardias (eg, catecholamine-induced arrhythmias, digoxin toxicity).

Essential tremor: Management of familial or hereditary essential tremor.

Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2018]).

Migraine headache prophylaxis: Prophylaxis of common migraine headache.

Myocardial infarction, early treatment and secondary prevention: To reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable.

Obstructive hypertrophic cardiomyopathy: Symptomatic treatment of obstructive hypertrophic cardiomyopathy (formerly known as hypertrophic subaortic stenosis).

Pheochromocytoma: As an adjunct to alpha-adrenergic blockade to control blood pressure and reduce symptoms of catecholamine-secreting tumors.

Proliferating infantile hemangioma (Propranolol (Tenec)): Treatment of proliferating infantile hemangioma requiring systemic therapy.

Off Label Uses

Akathisia, antipsychotic-induced

Data from a limited number of patients in 5 randomized, double-blind, controlled studies support the use of Propranolol (Tenec) in antipsychotic-induced akathisia.

Based on the American Association for the Study of Liver Diseases guidelines on the management of portal hypertensive bleeding in cirrhosis and the British Society of Gastroenterology guidelines on the management of variceal hemorrhage in cirrhotic patients, use of nonselective beta-blockers, such as Propranolol (Tenec), is effective and recommended for primary and secondary prophylaxis of variceal hemorrhage.

See also:
What other drugs will affect Diazepam (Tenec)?

If Diazepam (Tenec) rectal gel is to be combined with other psychotropic agents or other CNS depressants, careful consideration should be given to the pharmacology of the agents to be employed particularly with known compounds which may potentiate the action of Diazepam (Tenec), such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants.

The clearance of Diazepam (Tenec) and certain other benzodiazepines can be delayed in association with cimetidine administration. The clinical significance of this is unclear.

Valproate may potentiate the CNS-depressant effects of Diazepam (Tenec).

There have been no clinical studies or reports in literature to evaluate the interaction of rectally administered Diazepam (Tenec) with other drugs. As with all drugs, the potential for interaction by a variety of mechanisms is a possibility.

Effect of Other Drugs on Diazepam (Tenec) Metabolism: In vitro studies using human liver preparations suggest that CYP2C19 and CYP3A4 are the principal isozymes involved in the initial oxidative metabolism of Diazepam (Tenec). Therefore, potential interactions may occur when Diazepam (Tenec) is given concurrently with agents that affect CYP2C19 and CYP3A4 activity. Potential inhibitors of CYP2C19 (e.g., cimetidine, quinidine, and tranylcypromine) and CYP3A4 (e.g., ketoconazole, troleandomycin, and clotrimazole) could decrease the rate of Diazepam (Tenec) elimination, while inducers of CYP2C19 (e.g., rifampin) and CYP3A4 (e.g., carbamazepine, phenytoin, dexamethasone and phenobarbital) could increase the rate of elimination of Diazepam (Tenec).

Effect of Diazepam (Tenec) on the Metabolism of Other Drugs : There are no reports as to which isozymes could be inhibited or induced by Diazepam (Tenec). But, based on the fact that Diazepam (Tenec) is a substrate for CYP2C19 and CYP3A4, it is possible that Diazepam (Tenec) may interfere with the metabolism of drugs which are substrates for CYP2C19, (e.g. omeprazole, propranolol, and imipramine) and CYP3A4 (e.g. cyclosporine, paclitaxel, terfenadine, theophylline, and warfarin) leading to a potential drug-drug interaction.

See also:
What other drugs will affect Propranolol (Tenec)?

Propranolol (Tenec) hvdrochloride (Propranolol (Tenec)® (Propranolol (Tenec)) )

Patients receiving catecholamine-depleting drugs such as reserpine should be closely observed if Inderide is administered. The added catecholamine-blocking action may produce an excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension.

Caution should be exercised when patients receiving a beta blocker are administered a calcium-channel blocking drug, especially intravenous verapamil, for both agents may depress myocardial contractility or atrioventricular conduction. On rare occasions, the concomitant intravenous use of a beta blocker and verapamil has resulted in serious adverse reactions, especially in patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction.

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by nonsteroidal anti-inflammatory drugs has been reported.

Hypotension and cardiac arrest have been reported with the concomitant use of Propranolol (Tenec) and haloperidol.

Aluminum hydroxide gel greatly reduces intestinal absorption of Propranolol (Tenec).

Alcohol, when used concomitantly with Propranolol (Tenec), may increase plasma levels of Propranolol (Tenec).

Phenytoin, phenobarbitone, and rifampin accelerate Propranolol (Tenec) clearance.

Chlorpromazine, when used concomitantly with Propranolol (Tenec), results in increased plasma levels of both drugs.

Antipyrine and lidocaine have reduced clearance when used concomitantly with Propranolol (Tenec).

Thyroxine may result in a lower than expected TS concentration when used concomitantly with Propranolol (Tenec).

Cimetidine decreases the hepatic metabolism of Propranolol (Tenec), delaying elimination and increasing blood levels.

Theophylline clearance is reduced when used concomitantly with Propranolol (Tenec).

Hydrochlorothiazide

Thiazide drugs may increase the responsiveness to tubocurarine.

Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged. Hypokalemia may develop during concomitant use of corticosteroids or ACTH.

Drug/Laboratory Test Interactions

Hydrochlorothiazide

Thiazides may decrease serum FBI levels without signs of thyroid disturbance.

Thiazides should be discontinued before carrying out tests for parathyroid function.

See also:
What are the possible side effects of Diazepam (Tenec)?

Diazepam (Tenec) rectal gel adverse event data were collected from double-blind, placebo-controlled studies and open-label studies. The majority of adverse events were mild to moderate in severity and transient in nature.

Two patients who received Diazepam (Tenec) rectal gel died seven to 15 weeks following treatment; neither of these deaths was deemed related to Diazepam (Tenec) rectal gel.

The most frequent adverse event reported to be related to Diazepam (Tenec) rectal gel in the two double-blind, placebo-controlled studies was somnolence (23%). Less frequent adverse events were dizziness, headache, pain, abdominal pain, nervousness, vasodilatation, diarrhea, ataxia, euphoria, incoordination, asthma, rhinitis, and rash, which occurred in approximately 2-5% of patients.

Approximately 1.4% of the 573 patients who received Diazepam (Tenec) rectal gel in clinical trials of epilepsy discontinued treatment because of an adverse event. The adverse event most frequently associated with discontinuation (occurring in three patients) was somnolence. Other adverse events most commonly associated with discontinuation and occurring in two patients were hypoventilation and rash. Adverse events occurring in one patient were asthenia, hyperkinesia, incoordination, vasodilatation and urticaria. These events were judged to be related to Diazepam (Tenec) rectal gel.

In the two domestic double-blind, placebo-controlled, parallel-group studies, the proportion of patients who discontinued treatment because of adverse events was 2% for the group treated with Diazepam (Tenec) rectal gel, versus 2% for the placebo group. In the Diazepam (Tenec) rectal gel group, the adverse events considered the primary reason for discontinuation were different in the two patients who discontinued treatment; one discontinued due to rash and one discontinued due to lethargy. The primary reason for discontinuation in the patients treated with placebo was lack of effect.

Adverse Event Incidence In Controlled Clinical Trials

Table 1 lists treatment-emergent signs and symptoms that occurred in > 1% of patients enrolled in parallel-group, placebo-controlled trials and were numerically more common in the Diazepam (Tenec) rectal gel group. Adverse events were usually mild or moderate in intensity.

The prescriber should be aware that these figures, obtained when Diazepam (Tenec) rectal gel was added to concurrent antiepileptic drug therapy, cannot be used to predict the frequency of adverse events in the course of usual medical practice when patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescribing physician with one basis to estimate the relative contribution of drug and non-drug factors to the adverse event incidences in the population studied.

TABLE 1: Treatment-Emergent Signs And Symptoms That Occurred In > 1% Of Patients Enrolled In Parallel-Group, Placebo-Controlled Trials And Were Numerically More Common In The Diazepam (Tenec) Rectal Gel Group

Other events reported by 1% or more of patients treated in controlled trials but equally or more frequent in the placebo group than in the Diazepam (Tenec) rectal gel group were abdominal pain, pain, nervousness, and rhinitis. Other events reported by fewer than 1% of patients were infection, anorexia, vomiting, anemia, lymphadenopathy, grand mal convulsion, hyperkinesia, cough increased, pruritus, sweating, mydriasis, and urinary tract infection.

The pattern of adverse events was similar for different age, race and gender groups.

Other Adverse Events Observed During All Clinical Trials

Diazepam (Tenec) rectal gel has been administered to 573 patients with epilepsy during all clinical trials, only some of which were placebo-controlled. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. These categories are used in the listing below. All of the events listed below occurred in at least 1% of the 573 individuals exposed to Diazepam (Tenec) rectal gel.

All reported events are included except those already listed above, events unlikely to be drug-related, and those too general to be informative. Events are included without regard to determination of a causal relationship to Diazepam (Tenec).

BODY AS A WHOLE: Asthenia

CARDIOVASCULAR: Hypotension, vasodilatation

NERVOUS: Agitation, confusion, convulsion, dysarthria, emotional lability, speech disorder, thinking abnormal, vertigo

RESPIRATORY: Hiccup

The following infrequent adverse events were not seen with Diazepam (Tenec) rectal gel but have been reported previously with Diazepam (Tenec) use: depression, slurred speech, syncope, constipation, changes in libido, urinary retention, bradycardia, cardiovascular collapse, nystagmus, urticaria, neutropenia and jaundice. Paradoxical reactions such as acute hyperexcited states, anxiety, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances and stimulation have been reported with Diazepam (Tenec); should these occur, use of Diazepam (Tenec) rectal gel should be discontinued.

Drug Abuse And Dependence

Diazepam (Tenec) is a Schedule IV controlled substance and can produce drug dependence. It is recommended that patients be treated with Diazepam (Tenec) rectal gel no more frequently than every five days and no more than five times per month.

Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving Diazepam (Tenec) or other psychotropic agents because of the predisposition of such patients to habituation and dependence.

Abrupt discontinuation of Diazepam (Tenec) following chronic regular use has resulted in withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating). The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuation of benzodiazepines taken continuously at therapeutic levels for several months.

See also:
What are the possible side effects of Propranolol (Tenec)?

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Hypoglycemia and related events, like hypoglycemic seizure.
• Bronchospasm.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in clinical practice.

Clinical Trials Experience with Propranolol (Tenec) in Infants with proliferating infantile hemangioma

In clinical trials for proliferating infantile hemangioma, the most frequently reported adverse reactions ( > 10%) in infants treated with Propranolol (Tenec) were sleep disorders, aggravated respiratory tract infections such as bronchitis and bronchiolitis associated with cough and fever, diarrhea, and vomiting. Adverse reactions led to treatment discontinuation in fewer than 2% of treated patients.

Overall, 479 patients in the pooled safety population were exposed to study drug in the clinical study program (456 in placebo-controlled trials). A total of 424 patients were treated with Propranolol (Tenec) at doses 1.2 mg/kg/day or 3.4 mg/kg/day for 3 or 6 months. Of these, 63% of patients were aged 91-150 days and 37% were aged 35-90 days at randomization.

The following table lists according to the dosage the most common adverse reactions (treatment-emergent adverse events with an incidence at least 3% greater on one of the two doses than on placebo).

Table 2: Treatment-emergent adverse events occurring at least 3% more often on Propranolol (Tenec) than on placebo.

The following adverse events have been observed during clinical studies, with an incidence of less than 1%:

Cardiac disorders: Second degree atrioventricular heart block, in a patient with underlying conduction disorder, required definitive treatment discontinuation.

Skin and subcutaneous tissue disorders: Urticaria, alopecia

Investigations: Decreased blood glucose, decreased heart rate

Compassionate Use Program

More than 600 infants received Propranolol (Tenec) in a compassionate use program (CUP). Mean age at treatment initiation was 3.6 months. Mean dose of Propranolol (Tenec) was 2.2 mg/kg/day and mean treatment duration was 7.1 months.

The adverse reactions reported in the CUP were similar to the ADRs observed during clinical trials but some were more severe.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Propranolol (Tenec). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

These adverse reactions are as follows:

Blood and lymphatic system disorders: Agranulocytosis

Psychiatric disorders: Hallucination

Skin and subcutaneous tissues disorders: Purpura