Case 12: More on Oral Minoxidil

A 28-year-old male presents to the office with progressive hair loss for 3 years. His father and maternal grandfather are both bald. He has tried topical minoxidil 5% solution previously but could not comply with daily application. He has a history of OCD and panic disorder relating to needles. He has read on the internet that finasteride is the most effective FDA-approved therapy for male genetic thinning but is worried about the risk of sexual dysfunction and other side effects. On examination with trichoscopy the patient has miniaturized hairs at the frontal and top scalp. A hair pull test is negative.

 
Question 1: What would be the next best step?

1. Biopsy of the scalp.
2. Laboratory bloodwork.
3. Start finasteride 1mg oral daily.
4. Retrial of topical Rogaine.
5. Platelet-Rich Plasma.
6. Oral minoxidil.

Answer: F. The presentation and examination of this patient indicate genetic thinning and so a biopsy or laboratory bloodwork are unnecessary. Given the history of psychiatric disorder in this patient and the strong fear regarding side effects of finasteride, this patient should not be encouraged to begin this medication. If the patient later decides he wants finasteride, a second opinion from a primary doctor or psychiatrist would be highly advisable. The patient had already shown poor compliance with topicals and has needle-phobia and so neither Rogaine nor PRP would be appropriate. Instead, you should consider a discussion about oral minoxidil, complete with information regarding its off-label use and side-effect profile.

 
Question 2: What other patients are good candidates for off-label oral minoxidil?

1. Patients who wash their hair infrequently and find that daily application of topical minoxidil leaves a residue in their hair or that it is just too inconvenient to use.
2. Patients who are having side effects of itching or flaking scalp with topical minoxidil.
3. When other treatments do not seem to be working well enough.
4. Patients who are having side effects to finasteride or just choose not to use this medication.
5. Patients who want to maximize their treatment response.

Answer: All the above. All of these are suitable reasons to consider a discussion of off-label low-dose oral minoxidil once appropriate informed consent is obtained.

 
Question 3: The patient is amenable to starting oral minoxidil. What dose would you initially prescribe?

1. 1.25mg oral minoxidil daily.
2. 2.5mg oral minoxidil daily.
3. 5mg oral minoxidil daily.
4. 10mg oral minoxidil daily.

Answer: B. While studies show that doses of 2.5, 5 or 10mg are effective doses for hair loss in men, initially new medications are often started at the lowest effective dose and then slowly titrated upward after the patient has shown good ability to tolerate the new medication.

 
Question 4: The patient’s sister also has genetic hair loss and for the same reasons as her brother would like to begin oral minoxidil. What dose would you begin with?

1. The same as her brother, 2.5mg PO OD.
2. 5mg a day, as women are generally less sensitive to this medication.
3. O.625mg a day, as women tend to be more sensitive to oral minoxidil.

Answer: C. In female patients, 0.625mg or 1.25mg are the recommended starting doses as women are generally more sensitive to the side effects and will respond to lower doses.

 
Question 5: How should one take 0.625mg?

1. Since 1.25mg is the smallest dose, cut the pills in half and take ½ pill each day.
2. Since 1.25mg is the smallest dose, take a pill every other day so one will be taking 0.65mg a day on average.
3. Cut a 2.5mg pill into 4 parts using a pill-cutter and take a quarter of a pill each day.
4. Cut a 5mg pill into 4 parts and take a ¼ every other day.

Answer: C. Minoxidil should be taken at least every day as the half-life is about 4 hours. The smallest dose it comes in is 2.5 mg, so the easiest way to take 0.625mg is to cut the 2.5mg pill into 4 parts using a pill cutter and take a ¼ pill each day.

 
Question 6: The patient’s girlfriend uses topical minoxidil and asks if she can use oral minoxidil too. You respond:

1. Yes, but you will need to stop the topical minoxidil first to avoid overdose.
2. Yes, but you should initially consider using both topical and oral together.
3. Yes, and you should overlap use of the topical with the oral while it begins to take effect and to see if you can tolerate it before stopping the topical.
4. No, it would be better if you continue with the topical version if you are tolerating it well since oral minoxidil should be avoided in pre-menopausal women.

Answer: B, C. Since oral minoxidil is an off-label treatment, formal guidelines do not yet exist on how to manage patients currently on the topical form and wishing to add-in or switch to the oral version. Most physicians will advise overlap for 3-6 months to make sure there are no side effects before the prior topical medication is discontinued. Since oral minoxidil was historically prescribed at 20-40mg doses for blood pressure, it is unlikely that a low-dose oral minoxidil along with the topical would cause overdose. While the side effect profile is not fully understood for low-dose oral minoxidil, it can be added to a woman’s hair loss regimen if appropriate informed consent about potential risks is reviewed. Neither oral nor topical minoxidil should be used in pregnant women.

 
Question 7: You begin the woman on oral minoxidil 0.625mg a day with a plan to increase to 1.25mg daily if well-tolerated. What medication would you consider adding in conjunction with oral minoxidil?

1. Spironolactone 25mg PO daily.
2. Oral finasteride 1mg PO daily.
3. Birth control if the patient is having unprotected sex.
4. None. Oral minoxidil should always be used a monotherapy.

Answer: A and C. Oral minoxidil should not be used in pregnant women. If a woman plans to become pregnant while on oral minoxidil, then she should consider stopping the medication 3 months prior to conceiving. If a woman is having unprotected sex, it would be advisable to also begin some form of contraception. Many women also report water retention and weight gain while on low-dose oral minoxidil. Spironolactone at a 25mg oral daily dose will function as a diuretic to help mitigate this side effect. It also has anti-androgen properties to help mitigate the excess facial hair growth that may be observed.

 
Question 8: The male patient does not seem to be responding to the 2.5mg dose and the female patient does not seem to be responding to the 0.625mg dose. When would you consider adjusting the dose?

1. If the person’s vital signs are stable, increasing the dose at one month is reasonable.
2. Wait 1-3 months to increase the dose.
3. Wait at least 6 months to increase the dose.

Answer: C. It is common to experience shedding the first three months on minoxidil as the medication initiates a new hair cycle. Actual benefit is usually seen in about 4-6 months, although there are exceptions.

 
Question 9: Both your male patient and his girlfriend are eager to try oral minoxidil as an off-label therapy. What other conditions should you ask about specifically regarding this medication that may warrant caution before prescribing?

1. Are you taking any heart or blood pressure medication?
2. History of EKG changes or arrhythmia?
3. Hypotension?
4. Hypertension?
5. Renal problems?

Answer: All the above. Patients with a cardiac history or renal disease should be warned that oral minoxidil has been associated with reflex tachycardia, EKG changes, pericardial effusion, and congestive heart failure. Sodium and water retention are side effects that lead to weight gain or leg/ankle swelling and very infrequently can cause pulmonary edema, especially in patients with renal conditions. These cardiac and renal side effects are more commonly seen at 10 to 40mg daily dosages and the risk is greatly diminished at the low-dose version used for hair loss. Nonetheless, caution should be advised in these higher risk patients. Ask about hypotension as these patients may be more sensitive to the side effects of oral minoxidil and ask about hypertension as well, as hypertensive patients are likely to be on other medication or would need appropriate medication if not yet treated.

The most common side effect reported is hypertrichosis which is often described as mild and manageable. Other less frequent side effects include dizziness/postural hypotension and blood pressure changes. Although significant cardiopulmonary events are very unlikely in a healthy person at the low dosages of oral minoxidil recommended, providers should remain vigilant and may want to refer patients on oral minoxidil for regular blood pressure, heart rate, and fluid retention monitoring with their primary care provider. At a minimum, the patient’s PCP should be aware that the patient is taking this systemic medication.

 
Question 10: Oral minoxidil is contra-indicated in which of the following condition(s)?

1. Parkinson’s disease.
2. Chronic Lymphocytic Leukemia.
3. Pheochromocytoma.
4. Sickle Cell Trait.
5. Ulcerative Colitis.

Answer: C. Minoxidil tablets are contraindicated in pheochromocytoma because it may stimulate secretion of catecholamines from the tumor through its antihypertensive action.