Caverject^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Pfizer, Inc. (USA)

Manufactured By

Pfizer Manufacturing Belgium, NV (Belgium)

Contact Information

Pfizer Innovations LLC (Russia)

ATC Code

G04BE01 (Alprostadil)

Active Substance

Alprostadil (Rec.INN registered by WHO)

Dosage Forms

	Caverject®	Lyophilisate for preparation of solution for intracavernous injection 10 mcg: vial 1 pc. in a set with solvent
		Lyophilisate for preparation of solution for intracavernous injection 20 mcg: vial 1 pc. in a set with solvent

Dosage Form, Packaging, and Composition

Vials (1) in a set with solvent in a syringe, injection needles (2 pcs.) and wipes (2 pcs.) – plastic boxes.

Clinical-Pharmacological Group

Drug used for erectile dysfunction. Prostaglandin E₁ drug

Pharmacotherapeutic Group

Vasodilating agent – synthetic prostaglandin E₁ analogue

Pharmacological Action

A prostaglandin E₁ drug used for erectile dysfunction.

During intracavernous injection (into the penis), Alprostadil inhibits α₁-adrenoreceptors of penile tissues, relaxes the musculature of the cavernous bodies, increases blood flow and improves microcirculation.

Alprostadil induces erection by relaxing the trabecular smooth muscle of the corpora cavernosa and dilating the cavernous arteries, which leads to the expansion of lacunar spaces and obstruction of blood flow due to compression of venules against the tunica albuginea (occlusion of penile veins).

Alprostadil inhibits platelet aggregation.

The onset of action of the drug is 5-10 minutes after injection, the duration of action is 1-3 hours.

Indications

• Erectile dysfunction of neurogenic, vascular, psychogenic or mixed etiology;
• Diagnosis of erectile dysfunction (as an adjunct to other diagnostic tests).

ICD codes

Dosage Regimen

The first injections of the drug should be performed in a doctor’s office by specially trained medical personnel. Self-injections can only be started after detailed patient instruction and mastery of the self-injection technique.

The doctor should carefully assess the patient’s skills and ability to perform this procedure. Intracavernous administration should be performed with observance of aseptic rules.

The drug is used by direct intracavernous injection using needles size 27-30 G, 13 mm long. The drug is injected into the dorsolateral part of the proximal third of the penis.

Initial dose selection

The dose is selected individually by careful titration under medical supervision. The following administration scheme (see Table 1) should be followed, taking into account the erectile response, until a dose is reached that causes an erection of duration sufficient for sexual intercourse, but not more than 60 minutes.

If there is no response to a certain dose, the next higher dose can be administered after 1 hour. If there is a response, the interval between doses should be at least 1 day. The patient should remain in the doctor’s office until complete detumescence (cessation of erection, reduction in penis size) occurs.

Table 1

Maintenance therapy

The dose selected for self-injections should cause an erection in the patient sufficient for sexual intercourse, lasting no more than 1 hour. If the duration of erection exceeds 1 hour, the dose should be reduced.

Self-administration of the drug at home should begin with the dose established in the doctor’s office. If necessary, dose adjustment should be performed only after consultation with a doctor and in accordance with the dose selection instructions. The lowest effective dose should be administered.

The recommended frequency of injections is no more than 3 times per week, but not more than once/day. Erection usually occurs 5-20 minutes after injection.

The average dose of alprostadil by the end of 6 months of therapy is 20.7 mcg. In most patients, the maintenance dose was 5-20 mcg. The use of doses above 60 mcg is not recommended.

As an adjunct for the diagnosis of erectile dysfunction, a single dose of the drug that causes a normal erection is used.

The drug is used in pharmacological tests, as an adjunct during duplex or Doppler ultrasound examination, in the xenon-133 washout test, radioisotope phallography and penile arteriography, which allows visualization and assessment of the condition of the penile vessels.

Rules for using the drug

Preparation of the solution for intracavernous injection

Only the supplied solvent or water for injection with 0.9% benzyl alcohol should be used for dilution. After dilution in 1 ml of solvent, the volume of the resulting solution is 1.13 ml.

1 ml of this solution contains 10.5 mcg or 20.5 mcg of alprostadil, however, after injection, 10 mcg or 20 mcg of alprostadil enters the body, respectively, since 0.5 mcg is lost due to adsorption on the walls of the syringe and vial.

After reconstitution of the drug, no substances should be added to the vial. Before administration, the solution should be visually checked for the presence of particles or discoloration.

Self-injection procedure (for the patient)

1. Wash your hands with soap and water.
2. Remove the plastic protective cap from the vial.
3. Using one of the supplied alcohol-impregnated wipes, wipe the rubber stopper of the vial (the second wipe will be needed later). Discard the used wipe.
4. Unpack the larger needle marked 22G11/2, without removing its plastic protective cap. Attach the needle to the syringe by pressing the base of the needle onto the syringe firmly.
5. Carefully remove the protective cap from the needle.
6. Holding the syringe with the needle up, bring the syringe plunger to the “1 ml” mark (to remove excess solvent from the syringe).
7. Pierce the rubber stopper of the vial in its center with the needle and press the plunger down to inject the solvent into the vial.
8. Holding the syringe and vial gently as one unit, achieve complete dissolution of the powder with light circular motions. Do not use the drug if the resulting solution is cloudy, discolored, or contains any particles.
9. Turn the vial upside down without removing the syringe. Making sure the needle tip is below the liquid level, slowly pull the syringe plunger towards you until the solution level reaches the required mark on the syringe.
10. To remove air bubbles, tap the syringe lightly, or inject the solution back into the vial, and then slowly draw it back into the syringe.
11. Remove the needle from the vial and carefully place the protective cap on it.
12. Open the package with the smaller needle (27G1/2), but do not remove the needle, set the package aside.
13. Remove the larger needle along with the protective cap from the syringe and set it aside for later disposal.
14. Holding the syringe in one hand, take the smaller needle from the opened package, without removing its plastic protective cap, and attach it to the syringe as you attached the larger needle.

A cross-section of the penis shows the injection sites.

Veins, arteries, nerves

Corpora cavernosa (two)

Injection sites

Insertion of the needle into one of the corpora cavernosa

Urethra

Penis, top view; injection sites are shaded.

Injection sites

The drug should be injected into one of the two areas of the penis called the corpora cavernosa.

1. The self-administration procedure should be performed in a sitting, standing, or semi-recumbent position.
2. Perform injections only in the places indicated on diagrams A and B. Avoid hitting visible veins. Repeat injections should be performed alternately on one and the other side of the penis. Each time, a new point on the corresponding side should be chosen for the injection.
3. Grasp the head of the penis with your thumb and forefinger. Pull the penis and hold it firmly with your fingers so that it does not slip out during the procedure. Men who have not been circumcised should retract the foreskin to accurately determine the injection site.
4. Thoroughly clean the skin at the injection site with the unused alcohol-impregnated wipe. Set this wipe aside.
5. Hold the syringe with your thumb and forefinger, without placing your thumb on the plunger. With a confident movement, insert the needle at a 90°C (194°F) angle into the injection site indicated by your doctor (Fig.1).

1. Press the plunger with your thumb or forefinger. With a slow, confident movement, inject the entire contents of the syringe.
2. Remove the needle from the penis. Holding the penis from both sides, press the alcohol-impregnated wipe to the injection site and hold for about 3 minutes. If blood appears, press the wipe until the bleeding stops.
3. After using the contents of this package, all materials should be discarded following appropriate safety rules. The plastic packaging of the Caverject^® drug can be used as follows: place the used syringe, needles and vial in the plastic container. Remove the red plastic locking device from the container and set it aside. Then close the container tightly; a click should be heard. Remove the cut-out central part of the label (where the red lock is drawn) to expose the slot. To lock the container, fully push the red locking device into the slot. When the locking device snaps into place, the container is securely locked and can be discarded. The container containing the used syringe, needles and vial cannot be included in the waste recycling process.

Adverse Reactions

Local reactions pain and burning in the penis; prolonged erection (duration 4-6 hours) was noted in 4% of patients; penile fibrosis, including penile angulation, formation of fibrous nodules and Peyronie’s disease in 3-4% of patients; hematoma at the injection site in 3% of patients and ecchymosis at the injection site in 2% of patients (these side effects are usually associated with the injection technique, not with the action of alprostadil).

Less than 1% – priapism (erection duration more than 6 hours; frequency is 0.4%; in most cases, spontaneous penile relaxation was observed), balanitis, hemorrhages at the injection site, inflammation, itching and swelling at the injection site, bleeding from the urethra, feeling of warmth in the penis, numbness, fungal infection, irritation, skin hyperesthesia, phimosis, erythema, “venous leakage” from the cavernous bodies, painful erection, impaired ejaculation.

Systemic reactions most frequently – increased blood pressure, dizziness, headache, back pain, upper respiratory tract infections, flu-like syndrome, sinusitis, nasal congestion, cough, prostatitis, pain syndrome.

Less than 1% – testicular pain, testicular swelling, feeling of warmth in the testicles, testicular thickening, scrotal redness, scrotal pain, spermatocele, scrotal swelling, hematuria, urination disorder, increased frequency of urination, imperative urge to urinate, pelvic pain, decreased blood pressure, tachycardia, vasodilation, peripheral vascular disorders, supraventricular extrasystole, vasovagal reactions, hypesthesia, muscle weakness, hyperhidrosis, rash, skin itching, nausea, dry mouth, increased serum creatinine level, calf muscle cramps, pupil dilation.

Decreased blood pressure and increased heart rate were observed when using the drug in doses above 20 mcg and 30 mcg, respectively, and appeared to be dose-dependent. However, these changes were not clinically significant; only 3 patients discontinued treatment due to symptomatic hypotension.

Contraindications

• Diseases predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia);
• Anatomical deformities of the penis (penile angulation, cavernous fibrosis, Peyronie’s disease);
• Presence of a penile implant;
• Known hypersensitivity to the components of the drug.

The drug is not used in men for whom sexual activity is contraindicated or not recommended.

In persons under 18 years of age, the safety and efficacy of the drug have not been studied.

Special Precautions

Before starting therapy with Caverject^®, diagnosis of treatable causes of erectile dysfunction should be performed.

Constant monitoring of the patient’s condition undergoing self-treatment should be carried out, especially in the initial period, when dose adjustment may be required.

Every 3 months, the patient is recommended to visit a doctor to assess the effectiveness and safety of treatment and adjust the dose (if necessary).

It is known that after intracavernous administration of vasoactive drugs, including Caverject^®, priapism may develop. To reduce the risk of priapism, the lowest effective dose should be administered.

The patient should immediately inform the doctor about all cases of erection lasting more than 4 hours. Treatment of priapism is carried out in accordance with established medical practice.

After intracavernous administration of the drug, penile fibrosis may develop, including penile angulation, formation of fibrous nodules and Peyronie’s disease. The frequency of fibrosis may increase with the duration of drug use.

To detect signs of penile fibrosis or Peyronie’s disease, regular examination of patients with careful examination of the penis is recommended. In patients who develop penile angulation, cavernous fibrosis or Peyronie’s disease, treatment with the drug should be discontinued.

Since slight bleeding is possible during intracavernous injection, patients using Caverject^® should be informed about measures to protect against sexually transmitted and blood-borne infections, including the human immunodeficiency virus (HIV).

Patients receiving anticoagulant therapy such as warfarin or heparin have an increased tendency to bleed after intracavernous injection.

In patients receiving MAO inhibitors and alpha-adrenomimetics, a hypertensive crisis may develop in case of prolonged erection.

In patients with coronary artery disease, chronic heart failure or pulmonary diseases, sexual stimulation and intercourse may lead to exacerbation of the disease.

Compliance of the used dosage form of alprostadil with specific indications for its use should be observed.

No clinically significant effect of Caverject^® on the results of blood and urine laboratory tests has been noted.

The vial with the reconstituted drug is intended for single use and should be discarded after use. The patient should be instructed on the rules for disposal of the needle, syringe and vial.

Overdose

Symptoms pain in the penis, prolonged erection and/or priapism, irreversible deterioration of erectile function.

Treatment if the erection lasts less than 6 hours, medical supervision is necessary, since spontaneous detumescence often occurs; if the erection persists for more than 6 hours, an intracavernous injection of alpha-adrenomimetics (ephedrine, epinephrine, phenylephrine, ethylnorepinephrine) should be administered, or aspiration of blood from the cavernous bodies should be performed, or surgical treatment should be carried out.

The patient should be under medical supervision until systemic phenomena disappear and/or until complete detumescence of the penis occurs.

Drug Interactions

Caverject^® is not intended for mixing or simultaneous administration with other drugs, nor for concomitant use with other medicinal products for the treatment of erectile dysfunction.

The possibility of pharmacokinetic interactions with other medicinal products has not been studied.

Concomitant use with antihypertensive drugs, diuretics, hypoglycemic drugs (including insulin) or non-steroidal anti-inflammatory drugs does not have any effect on the safety or efficacy of Caverject^®.

The safety and efficacy of concomitant use of Caverject^® with other vasoactive drugs have not been studied.

The presence of benzyl alcohol in the solvent reduces the degree of binding to the walls of the vial. In this regard, when using water for injection containing benzyl alcohol, a more stable solution is obtained and more complete administration of the drug is ensured.

Storage Conditions

List B. The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F). The reconstituted solution should be stored in the original vial at a temperature not exceeding 25°C (77°F) for no more than 24 hours. Do not freeze or refrigerate!

Pharmacy dispensing conditions

The drug is dispensed by prescription.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.