CLOFELINE (tablets 0.000075 g and 0.00015 g)

Tabulettae Clophelini 0,000075 et 0,00015

International nonproprietary name (INN)

Clonidine.

Pharmacotherapeuticgroup

Alfa- adrenoceptor agonist.

Composition

1 tablet contains 0.00075 or 0.00015 g of clofeline (clonidine).

Pharmacological effect

Pharmacodynamics

Clofeline is antihypertensive agent controlling neurogenic regulation of vascular tone. It stimulates pre- and post-synaptic a₂-adrenoreceptors, and also is similar to imidazoline receptors.

Clofeline stimulates central a₂-adrenoreceptors and imidazoline I₁-receptors, localized in neuron nuclear of the solitary tract, and decreases the tone of vasomotoric center, pulsation in the symptomatic chain of the peripheral nervous system at the pre-synaptic level. Concurrentlyitincreasesvagusnervetone.

The main manifestation of clofeline action is hypotensive effect developing usually in 1-2 h. After drug oral intake and retaining after single intake during 6Ч8 h. Marked and resistant hypotensia is a result of the decreased cardiac output, lower frequency of cardiac contraction and peripheral resistance of the vessels, renal vessels inclusive.

The drug manifests an apparent sedative and to some extent analgesic action.

The important characteristic за clofeline is its activity to decrease (and release) self-vegetative development of opiate and alcohol abstinence. It reduces fear sense, cardiovascular and other disorders gradually disappear. It is supposed that these effects are substantially determined by the reduction of central adrenergiс activity.

Pharmacokinetics

Clofeline is rapidly and completely absorbed in the gastrointestinal tract; concentration peak is observed in 1.5Ч2.5 h. Half-life is 12-16 h. under regular renal function and up to 41 h. under renal failure. It easily penetrates through histohematogenous barriers (hematoencephalic, ophthalmic and others. Plasmaproteinbindingis20Ч40%. It metabolizes in liver (about 50% of the absorbed dose). It is mainly renal excreted, 40-60% unmodified, 20% intestines excretion.

Indicationsforusage

Clofeline is administered as antihypertensive agent for various types of hypertensia, and most widely for relief hypertension strokes.

It may be administered for complex therapy in patients with abstinence syndrome of opiomania.

It may be used for menopausal face rush of blood, TourettТs syndrome.

Administration and dosage

Dosing and pattern of clofeline therapy is determined individually only.

The drug is effective in very low doses. For oral intake as antihypertensive agent clofeline is usually administered starting with 0.075 mg (1/2 tablet) 2Ч4 times a day. If hypotensive effect is not sufficient, increase single dose every 1-2 days by 0.0375 mg (by 1/4 тtablet) to 0.15Ч0.3 mg (1Ч2 tablets) per intake up to 3Ч4 рtimes a day. Usually single daily dose is 0.3Ч0.45 mg (2Ч3 tablets), sometimes Ч 1.2 mg (8 tablets).

In acute arterial hypertenisa begin with 0.15 mg (1 tablet), increasing gradually the dose by 0.075 мг (1/2 tablet) to get antihypertensive effect but max.daily dose is NMT 1.2 mg (8 tablets).

If clofeline is not effective at the dose of 0.45Ч0.6 mg (3Ч4 tablets) a day, it is advisable to administer additionally saluretic agents in low doses, beta- adrenoceptor antagonists, vasodilaters of direct action (hydralasine, minoxydile), post-synaptic a₁- adrenoceptor antagonists (prasosine). In elderly patients, in particular with atherosclerosis of coronary vessels; due to possible hypersensitivity to the drug begin dosing in such patients with 0.0375 mg (1/4 tablet).

The duration of the course is from several weeks to 6-12 months and more.

Due to risk of the withdrawal syndrome reduce clofeline dose gradually to the complete cancellation of the intake.

In case of clofeline treatment of alcoholic or opiate abstinence, administer the drug orally in hospital 0.15Ч0.3 mg (1Ч2 тtablets) 3 times a day with an interval 6-8 h. during 5-7 days. Under side effect reduce gradually the dose (within 2-3 days), then if necessary cancel the drug.

Special indications

During treatment avoid dangerous activities with higher concentration and psycomotor reaction.

Alcohol is prohibited during clofeline treatment.

Abrupt cancellation of clofeline therapy may cause the withdrawal syndrome.

The drug is not administered in patients who cannot take it regularly (to avoid the withdrawal syndrome).

Adverse reaction

Cardiovascular system: rare edema, bradycardia.

Digestive system: reduce gastric secretion, dry mouth, rare constipation.

—NS

†and peripheral nervous system: fatigue, sleepiness, inhibited psycomotor reaction, rare nervousness, anxiety, depression, vertigo, paresthesia.

—о стороны репродуктивной системы:rareinhibitedlibido, impotence.

јллергические реакции:skineruption, itch.

Other:stuffy.

Contraindications

Hypersensitivity to clofeline, cardiogenic shock, arterial hypotensia, apparent atherosclerosis of coronary vessels, obliterating diseases of peripheral arteries, marked sinus bradycardia, AV-block II-II grade, sick sinus syndrome, depression (also in past history).

Limitations of usage: pregnancy, lactation (cancel breast feeding), activities requiring higher psyco- and/or physical reaction.

Safety measures

Dose and pattern is determined individually only.

Interaction with other drugs

Avoid concurrent administration of clofeline and antidepressants (reduced hypotensive action) and neuroleptics (increased sedative effect, possible development of marked depression), benzodiazepine as it increases clofeline depressive action. Hypotensive effect of clofeline is reduced under nifedipin (antagonistic influence on intrecellular ion current —а ²⁺).

Clofeline therapy with beta- adrenoceptor antagonists: to eliminate undesirable hypertensia under termination of the therapy first terminate the treatment with beta- adrenoceptor antagonists, then slowly decrease the dose of clofeline.

Overdose

Symptoms: impairment of consciousness, collapse, bradycardia, increase of QRS complex, possible delay of AV-conductivity and syndrome за early repolarization.

Treatment: symptomatic therapy, maintaining vital functions.

Dosageform

Tablets 0.00075 g and 0.00015 g. 50 or 100 tablets in a jar. 10 tablets in blister. 2 or 5 blisters in pack. 50 tablets in vial.