Large-scale trial establishes benefits of long-term management of prostate disease (PART V OF V).

WEST POINT, Pa.--(BUSINESS WIRE)--Nov. 1, 1995-- -0- Pregnancy

Pregnancy Category X

See CONTRAINDICATIONS.

PROSCAR is not indicated for use in women. Administration of finasteride to pregnant rats at doses ranging from 100 microg/kg/day to 100 mg/kg/day (1-1000 times the recommended human dose) resulted in dose-dependent development of hypospadias in 3.6 to 100% of male offspring. Pregnant rats produced male offspring with decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development when given finasteride at > or =30 microg/kg/day (> or =3/10 of the recommended human dose) and decreased anogenital distance when given finasteride at > or =3 microg/kg/day (> or =3/100 of the recommended human dose). The critical period during which these effects can be induced in male rats has been defined to be days 16-17 of gestation. The changes described above are expected pharmacological effects of drugs belonging to the class of 5a-reductase inhibitors and are similar to those reported in male infants with a genetic deficiency of 5a-reductase. No abnormalities were observed in female offspring exposed to any dose of finasteride in utero.

No developmental abnormalities have been observed in first filial generation (F1) male or female offspring resulting from mating finasteride-treated male rats (80 mg/kg/day; 61 times the human exposure) with untreated females. Administration of finasteride at 3 mg/kg/day (30 times the recommended human dose) during the late gestation and lactation period resulted in slightly decreased fertility in F1 male offspring. No effects were seen in female offspring. No evidence of malformations has been observed in rabbit fetuses exposed to finasteride in utero from days 6-18 of gestation at doses up to 100 mg/kg/day (1000 times the recommended human dose). However, effects on male genitalia would not be expected since the rabbits were not exposed during the critical period of genital system development.

Nursing Mothers

PROSCAR is not indicated for use in women.

It is not known whether finasteride is excreted in human milk.

Pediatric Use

PROSCAR is not indicated for use in children.

Safety and effectiveness in children have not been established.

ADVERSE REACTIONS 

PROSCAR is generally well tolerated; adverse reactions usually have been mild and transient.

Twelve-Month Controlled Clinical Trials

In North American and international clinical trials, 543 patients were treated with 5 mg of PROSCAR for 12 months. Seven of these patients (1.3%) were discontinued due to adverse experiences that were considered to be possibly, probably or definitely drug-related; only 1 of these patients (0.2%) discontinued therapy with PROSCAR because of a sexual adverse experience.

The following clinical adverse reactions were reported as possibly, probably or definitely drug-related in > or =1% of patients treated for 12 months with 5 mg/day of PROSCAR or placebo, respectively: impotence (3.7%, 1.1%), decreased libido (3.3%, 1.6%), decreased volume of ejaculate (2.8%, 0.9%).

The adverse experience profile for an additional 547 patients treated with 1 mg/day of PROSCAR for 12 months was similar to that observed in patients treated for 12 months with 5 mg/day of PROSCAR.

Long-Term Open Extensions

The adverse experience profile for approximately 1100 patients who were maintained on PROSCAR 5 mg/day for 24 months and 400 patients treated for 36 months was similar to that observed in the controlled studies. In addition, a similar safety profile was observed in 50 patients treated with PROSCAR 5 mg/day for 48 months. There is no evidence of increased adverse experiences with increased duration of treatment with PROSCAR. The annual incidence of drug related sexual adverse experiences decreased with duration of treatment. Sexual adverse experiences resolved with continued treatment in over 60% of patients who reported them.

The following additional adverse effects have been reported in post-marketing experience:

- breast tenderness and enlargement

- hypersensitivity reactions, including lip swelling and skin rash

OVERDOSAGE

Patients have received single doses of PROSCAR up to 400 mg and multiple doses of PROSCAR up to 80 mg/day for three months without adverse effects. Until further experience is obtained, no specific treatment for an overdose with PROSCAR can be recommended.

Significant lethality was observed in male and female mice at single oral doses of 1500 mg/m2 (500 mg/kg) and in female and male rats at single oral doses of 2360 mg/m2 (400 mg/kg) and 5900 mg/m2 (1000 mg/kg), respectively.

DOSAGE AND ADMINISTRATION

The recommended dose is 5 mg once a day.

Although early improvement may be seen, at least 6-12 months of therapy with PROSCAR may be necessary in some patients to assess whether a beneficial response has been achieved. Periodic follow-up evaluations should be performed to determine whether a clinical response has occurred.

PROSCAR may be administered with or without meals.

No dosage adjustment is necessary for patients with renal impairment or for the elderly (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

HOW SUPPLIED

No. 3094 PROSCAR tablets 5 mg are blue, modified apple-shaped, film-coated tablets, with the code MSD 72 on one side and PROSCAR on the other. They are supplied as follows:

NDC 0006-0072-31 unit of use bottles of 30

(6505-01-362-5331, 5 mg 30's)

NDC 0006-0072-58 unit of use bottles of 100

(6505-01-362-7422, 5 mg 100's)

NDC 0006-0072-28 unit dose packages of 100

(6505-01-362-5332, 5 mg individually sealed 100's).

Storage and Handling

Store at room temperatures below 30 C (86 F). Protect from light and keep container tightly closed.

If the film coating of PROSCAR tablets has been broken (e.g., crushed), the tablets should not be handled by a woman who is pregnant or who may become pregnant because of the potential for absorption of finasteride and the subsequent potential risk to a male fetus (see CLINICAL PHARMACOLOGY, Pharmacokinetics; WARNINGS, Exposure of Women -- Risk to Male Fetus; and PRECAUTIONS, Information for Patients and Pregnancy). -0- Dist. by: Merck & Co. Inc., West Point, PA 19486, USA Manufactured by: MERCK SHARP & DOHME Ltd. Hoddesdon, Herts, U.K. EN11 9BU Issued December 1994 Printed in USA

CONTACT: Merck & Co., Inc., West Point

John Bloomfield, 215/652-7485 (business)

215/669-5568 (residence)

Christopher Smith, 212/878-4655 (business)

908/604-0411 (residence)

Heather Berg, 212/878-4682 (business)

201/601-3145 (residence)