Hydiphen

Hydiphen - General Information

A tricyclic antidepressant similar to imipramine that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. [PubChem]

Pharmacology of Hydiphen

Hydiphen, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricylic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: alpha-1 and beta-1 receptors are sensitized, alpha-2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.

Hydiphen for patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with clomipramine hydrochloride and should counsel them in its appropriate use. A patient Medication Guide About Using Antidepressants in Children and Teenagers is available for clomipramine hydrochloride. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have.

Hydiphen Interactions

The risks of using Anafranil in combination with other drugs have not been systematically evaluated. Given the primary CNS effects of Anafranil, caution is advised in using it concomitantly with other CNS-Active drugs. Anafranil should not be used with MAO inhibitors.

Close supervision and careful adjustment of dosage are required when Anafranil is administered with anticholinergic or sympathomimetic drugs.

Several tricyclic antidepressants have been reported to block the pharmacologic effects of guanethidine, clonidine, or similar agents, and such an effect may be anticipated with CMI because of its structural similarity to other tricyclic antidepressants.

The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly.

Drugs Metabolized by P450 2D6: The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the aucasian population (about 7%-10% of Caucasians are so-called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected lasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCAmay become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, paroxetine, and fluvoxamine, inhibit P450 2D6, they may vary in the extent of inhibition. Fluvoxamine has also been shown to inhibit P450 1A2, an isoform also involved in TCAmetabolism. The extent to which SSRI-TCAinteractions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCAtreatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of agents in the tricyclic antidepressant class (which includes Anafranil) with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant agent or the other drug. Furthermore, whenever one of these drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant agent may be required. It is desirable to monitor TCAplasma levels whenever an agent of the tricyclic antidepressant class including Anafranil is going to be co-administered with another drug known to be an inhibitor of P450 2D6 (and/or P450 1A2).

Because Anafranil is highly bound to serum protein, the administration of Anafranil to patients taking other drugs that are highly bound to protein (e.g., warfarin, digoxin) may cause an increase in plasma concentrations of these drugs, potentially resulting in adverse effects. Conversely, adverse effects may result from displacement of protein-bound Anafranil by other highly bound drugs.

Hydiphen Contraindications

Anafranil® (clomipramine hydrochloride capsules USP) is contraindicated in patients with a history of hypersensitivity to Anafranil or other tricyclic antidepressants.

Anafranil should not be given in combination, or within 14 days before or after treatment, with a monoamine oxidase (MAO) inhibitor. Hyperpyretic crisis, seizures, coma, and death have been reported in patients receiving such combinations.

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

Additional information about Hydiphen

Hydiphen Indication: For the treatment of depression, obsessive compulsive disorder (OCD), panic attacks with or without agoraphobia, narcolepsy, chronic pain, and enuresis.
Mechanism Of Action: Hydiphen is a strong, but not completely selective Serotonic-Reuptake-Inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of Noradrenaline-Reuptake. Alpha-1-Receptor blockage and beta-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.
Drug Interactions: Altretamine Risk of severe hypotension
Atazanavir Atazanavir increases the effect and toxicity of tricyclics
Cimetidine Cimetidine increases the effect of tricyclic agent
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clonidine The tricycli decreases the effect of clonidine
Dihydroquinidine barbiturate Quinidine increases the effect of tricyclic agent
Dobutamine The tricyclic increases the sympathomimetic effect
Donepezil Possible antagonism of action
Dopamine The tricyclic increases the sympathomimetic effect
Ephedra The tricyclic increases the sympathomimetic effect
Ephedrine The tricyclic increases the sympathomimetic effect
Epinephrine The tricyclic increases the sympathomimetic effect
Fenoterol The tricyclic increases the sympathomimetic effect
Fluoxetine Fluoxetine increases the effect and toxicity of tricyclics
Fluvoxamine Fluvoxamine increases the effect and toxicity of tricyclics
Galantamine Possible antagonism of action
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine The tricyclic decreases the effect of guanethidine
Isoproterenol The tricyclic increases the sympathomimetic effect
Isocarboxazid Possibility of severe adverse effects
Mephentermine The tricyclic increases the sympathomimetic effect
Metaraminol The tricyclic increases the sympathomimetic effect
Methoxamine The tricyclic increases the sympathomimetic effect
Moclobemide Possible severe adverse reaction with this combination
Norepinephrine The tricyclic increases the sympathomimetic effect
Orciprenaline The tricyclic increases the sympathomimetic effect
Phenylephrine The tricyclic increases the sympathomimetic effect
Phenelzine Possibility of severe adverse effects
Phenylpropanolamine The tricyclic increases the sympathomimetic effect
Pirbuterol The tricyclic increases the sympathomimetic effect
Procaterol The tricyclic increases the sympathomimetic effect
Pseudoephedrine The tricyclic increases the sympathomimetic effect
Quinidine Quinidine increases the effect of tricyclic agent
Quinidine barbiturate Quinidine increases the effect of tricyclic agent
Rasagiline Possibility of severe adverse effects
Rifabutin The rifamycin decreases the effect of tricyclics
Rifampin The rifamycin decreases the effect of tricyclics
Ritonavir Ritonavir increases the effect and toxicity of tricyclics
Rivastigmine Possible antagonism of action
Salbutamol The tricyclic increases the sympathomimetic effect
Sibutramine Increased risk of CNS adverse effects
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Terbutaline The tricyclic increases the sympathomimetic effect
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tranylcypromine Possibility of severe adverse effects
Food Interactions: Take with food to reduce irritation.
Avoid alcohol.
Grapefruit and grapefruit juice should be avoided throughout treatment, grapefruit can modify serum levels of clomipramine and its metabolite desmethyl-clomipramine.
Generic Name: Clomipramine
Synonyms: 3-Chloroimipramine; Chlorimipramine; Clomipramina [INN-Spanish]; Clomipramine HCL; Clomipraminum [INN-Latin]; Monochlorimipramine
Drug Category: Antidepressive Agents, Tricyclic; Serotonin Uptake Inhibitors
Drug Type: Small Molecule; Approved

Other Brand Names containing Clomipramine: Hydiphen; Anafranil;
Absorption: Bioavailability is approximately 50% orally.
Toxicity (Overdose): Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. 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. In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with Anafranil either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg.
Protein Binding: 97%
Biotransformation: Hepatic. The main active metabolite is desmethylclomipramine.
Half Life: Approximately 35 hours.
Dosage Forms of Hydiphen: Tablet Oral
Chemical IUPAC Name: 3-(9-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine
Chemical Formula: C19H23ClN2
Clomipramine on Wikipedia: https://en.wikipedia.org/wiki/Clomipramine
Organisms Affected: Humans and other mammals